Current Ophtalmology

Welcome to…
“The Really”
Current Ophthalmology
The Electronic Book that is continuously being up-dated
Third Edition
“August 2000”
MAGDY A. NOFAL
MB ChB (Cairo), FRCSEd, FRCOphth
CONTENTS
How to use the book?
Introduction
New chapter 4 GP’s

Common ophthalmic
presentations
External eye Corneal surgery Cataract surgery

diseases
Glaucoma Medical retina Vitreoretinal surgery
Paediatric Neuroophthalmology Tumours

Ophthalmology of the eye
Ocular adnexa Uveitis Trauma
Double click here for last

minute messages
Copyright © 2000. All rights reserved to the author.
How to use the book?
• In the table of contents, click on any arrow-head pointing to the

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Introduction
“The future is for electronic books!”
My goal of writing this book, is to provide the reader with a book that will
be continuously expanded and updated to meet the rapid developments
in Ophthalmology. In my opinion, the only way to keep up with all the
development is by keeping up with the literature. For busy
ophthalmologists, this can prove difficult.
Nowadays, when medical knowledge is changing with such an alarming

speed, it will be very difficult to provide a continuously expanding and
updated book in the usual printed format. It would be much easier and
more practical to produce such a book in an electronic format. This can
be updated and expanded much faster and easier.
I intend to update my book every three months by producing a new

disc to replace the old one. I hope, by doing this, I will be able to provide
the reader with a Really Current and up to date book. The book is not
intended for the beginner ophthalmologists, it does not contain
ophthalmic basic knowledge. My book is meant to complement other
basic ophthalmology books.
I believe the book can make a useful addition to any ophthalmologist

library “or hard disc”. It will complement other basic text books, and it will
also save on the time spent in the library looking through the ophthalmic
journals. I intend to update the book regularly, add photos and diagrams
and also possibly produce the book on a CD rather than a floppy disc.
I have included a New Chapter, in this edition, about the common

ophthalmic presentations. This chapter has been requested by many
non-ophthalmologists who deal with eye problems e.g. General
Practitioners and Optometrists. This chapter contains basic
Ophthalmology about the most common ophthalmic symptoms.
Magdy A Nofal
August 2000
About The Author
Magdy Nofal is an ophthalmic surgeon in Torbay general hospital, Torquay,

Devon, UK. He was born in Egypt and qualified in medicine in Cairo university
in 19975 (MB ChB). He has been working in the UK since 1980.
The author passed his FRCS Diploma examination in 1983, from the Royal
College of Surgeons in Edinburgh, and was also awarded the fellowship of
the College of Ophthalmologists of the UK in 1990. He spent some time
working in Saudi Arabia. The author’s main interest in Ophthalmology is
anterior segment, oculoplastic and lacrimal surgery.
Magdy Nofal is also the co-author of the book "An update in topics in
Ophthalmology" with Mr. Fathi El-Sayyad, from Cairo, Egypt. This book has
a similar idea as this electronic book. It is, however, renewed every year. The
book is distributed to ophthalmologists and ophthalmic students, in Egypt, for
free. A copy of this book can be obtained by writing to the author.
Magdy Nofal can be contacted by any of these methods:
Postal address
Mr. Magdy A Nofal,
The Eye Clinic, Level 2,
Torbay General Hospital,
Lawes Bridge,
Torbay, TQ 2 7 AA
Devon. UK.
Fax number
UK-01803654287
Tel. number "work"

UK-01803654575
E-mail address
[email protected]
You can also visit his web site at

http://webside.lineone.net/~magdynofal
The Really Current Ophthalmology. Magdy A Nofal.
Common Ophthalmic Presentations NEW

4 General Practitioners and Optometrists
This chapter is aimed at GPs, Optometrists and non-

Ophthalmologists dealing with eye problems. It deals
with the common ophthalmic disorders, basic
manifestations, differential diagnosis, primary care
and the indications for referral to an ophthalmologist.
This chapter of the book is mainly tables, so it would be better if you hide
the table of contents and bookmarks column, on the left of the screen, to
increase the screen area for the text material. You can open the table of
contents again when you want to go to a different destination in the book.
The word “more”, in this chapter, indicates a link, to another part of the
book, for more relevant information. Clicking on it will take you to that
part of the book.
Acute red eye.

Common causes
1. Conjunctivitis
2. Iritis
3. Acute closed angle glaucoma
4. Episcleritis, scleritis.
5. Corneal ulceration, foreign body or abrasion.
Differential diagnosis
Disease Main manifestations What to do? Comments

Conjunctivitis sticky or watery treat with topical see additional points below
discharge, no or mild antibiotics. Refer if
visual loss, bright persistent.
clear cornea, normal
pupil.
Iritis photophobia, may be Refer within a day for often idiopathic. May be
slight decrease of diagnosis and associated with ankylosing
vision, the cornea treatment spondylitis, sarcoidosis. May be
may or may not be associated with posterior uveitis
cloudy, ma be (severe visual loss).
irregular pupil. more
Acute sudden and severe phone and Refer the warn the patient that
glaucoma very painful loss of patient immediately hospitalisation and laser
vision, bluish-red for medical treatment treatment will be needed.
discoloration, very followed by laser
cloudy cornea, dilated treatment peripheral
and fixed pupil, iridotomy.
sickness and
vomiting,
Episcleritis bright red eye, no Refer (to exclude scleritis is rarer. Dull boring pain,
discharge, localised or scleritis), may need bluish-red discoloration, may be
diffuse, with or without topical steroids. visual loss, often associated with
nodules, no severe systemic diseases.
visual loss, bright Refer to diagnose the cause,
cornea, normal pupil. often need systemic immuno-
suppression.
Corneal history of trauma, exclude foreign body Refer, to exclude infection, if the
abrasion pain, foreign body (if you have a symptoms are out of proportion to
sensation, and microscope), topical the degree of staining. more
photophobia, watery antibiotics with
discharge, deep cycloplegic, with or
anterior chamber, + without a pad.
fluorescein staining.
• If conjunctivitis does not resolve in a few days, with topical antibiotics

treatment, consider:
⇒ Viral conjunctivitis
⇒ Allergic conjunctivitis
⇒ Chlamydial conjunctivitis
⇒ Chronic blepharoconjunctivitis
⇒ Dry eyes syndrome
Differential diagnosis of conjunctivitis

Viral history of recent very infectious, often If conjunctival follicle persists
conjunctivitis URTI, often bilateral, self limited, cold for more than 6 weeks think of
watery discharge, compresses and chlamydial infection
conjunctival follicles, antibiotics to prevent (secondary to genital infection)
tender and palpable secondary bacterial which need systemic
lymphadenopathy. infection. tetracycline treatment. Refer
Allergic seasonal, itching, antihistamine, Refer if resistant to exclude
conjunctivitis thick ropy discharge, cromolyn sodium, or vernal disease, may need
papillary reaction. lodoxamide. steroids and other second line
treatment. more
Chronic discharge, lid margin topical antibiotics, lid beware this might lead to
blepharo- thickening, hygiene. marginal corneal ulceration.
conjunctivitis hyperaemia and
crusting.
Chlamydial chronic follicular confirm the diagnosis treat with systemic and topical
conjunctivitis conjunctivitis in a by an tetracycline or azithromycin,
young sexually active immunofluorescent also investigate and treatment
patient, may be studies of a the patient sexual partner.
urethritis or cervicitis, conjunctival swab,
palpable lymph
nodes.
Dry eyes burning, FB artificial tear drops Refer if precipitant for punctal
syndrome sensation, may be and lubricants. occlusion by plugs.
epiphora, worse at
the end of the day,
Rose bengal staining,
decreased Schirmer’s
test and tear break up
time.
• If severe purulent fulminating conjunctivitis occur very rapidly, think of

hyper-acute conjunctivitis:
⇒ Intense chemosis in a few hours with purulent discharge.
⇒ Caused by gonococcus infection
⇒ High risk of corneal perforation
⇒ Refer immediately for definite diagnosis and systemic penicillin (or
ceftriaxone) treatment.
Conjunctivitis in babies
(Ophthalmia neonatorum)
• Purulent conjunctivitis in a new born (ophthalmia neonatorum) should

be referred to the hospital for investigations, possible admission and
treatment.
• Exclude congenital nasolacrimal duct obstruction and glaucoma.
• All patients should gave a full microbiological studies.
Causes and differential diagnosis of Ophthalmia neonatorum
Causes Features What to do?

Chemical rare nowadays, appears within few Nothing if sure
hours after instilling silver nitrate drops,
lasts only 24-36 hours.
Neisseria within the first few days, rapidly hospitalisation under
gonorrhoeae progressive, mother may have an ophthalmologists and
infection. Gram negative intracellular paediatrician, blood and CSF
bacilli culture, parenteral administration
of ceftriaxone or cefotaxime.
Topical antibiotics. All babies
should also be treated for
chlamydial infection. Treat the
mother and her sexual partner.
Chlamydial often presents in the second week of Systemic and topical
life. Basophilic intra-cytoplasmic erythromycin, treat the mother and
inclusion bodies and her sexual partner.
polymorphonuclear leucocytes.
Bacterial gram positive or negative cocci treat according to gram stain and
cytology.
Herpes may have the typical dendrites and skin Topical and systemic acyclovir.
simplex rash.
A short summery of uveitis

Uveitis can be anatomically classified into:
1. Anterior uveitis: the inflammation occurs mainly in the iris and the
anterior chamber
2. Intermediate uveitis: the inflammation occurs mainly in the vitreous
cavity
3. Posterior uveitis: the inflammation occurs mainly in the choroid and the
retina. It may be due to infectious or non-infectious causes.
4. Pan-uveitis: all the previous layers show signs of inflammation.
The common causes of anterior uveitis include:
• Idiopathic, (the most common type).

• Trauma, and postoperative, (easy to diagnose from the history).
• Iritis associated with arthritis, e.g.:
Disease Main manifestations

Ankylosing spondylitis low back pain, abnormal sacroiliac X ray, HLA B27
Psoriasis arthritis iritis with psoriasis is often associated with arthritis, rheumatologist
opinion.
Reiter’s disease chlamydial infection, young adult, conjunctivitis or iritis, polyarthritis,
urethritis, increased ESR, HLA B27
Juvenile rheumatoid often chronic, young girls, whit eye with no pain, bilateral, positive
arthritis antinuclear antibodies, mainly in pauciarticular arthritis, negative
rheumatoid factor, high ESR, associated cataract and glaucoma,
paediatrician opinion.
• other conditions:

Sarcoidosis typically black patients, bilateral, may be granulomatous with
posterior uveitis, abnormal chest X ray, positive gallium scan,
high ACE, positive biopsy. more
Syphilis rash, vascular papules on the iris, positive VDRL, FTA-ABS or
RPR serological test
Tuberculosis typical chest X ray, posterior uveitis may be present.
Lyme disease history of a tick bite, headache, meningitis and facial weakness,
general illness, muscle and joint pain, bull’s eye or erythematous
skin lesions, arthritis, high anti-Borrelia burgdorferi serum titre by
the ELISA test.
Inflammatory bowel diseases chronic intermittent diarrhoea and constipation.
Behcet disease young adults, acute hypopyon in a white eye, aphthous mouth
and genital ulcers, erythema nodosum, positive skin puncture
test, retinal vasculitis, HLA-B27 or HLA-B5 positive. more.
Medications Rifabutin, sulphonamides, cidofovir.
• Investigations of patients with anterior uveitis are often tailored

according to the clinical presentation.
• Anterior uveitis may be a manifestation of associated posterior uveitis
and dilated fundus examination is necessary.
• Other non-inflammatory conditions should be considered as they may
masquerade as uveitis. These conditions are called “Masquerade
Syndrome”.
Masquerade Syndrome

Posterior segment e.g. leukaemia and retinoblastoma in children, malignant
tumours melanoma in adults and old patients, and reticulum cell carcinoma
in elderly patients.
Retinal detachment diagnosed by fundus examination
Juvenile xanthogranuloma children, spontaneous hyphaema, iris nodules, orange skin lesion
Anterior or posterior ultrasound scan is often helpful.
scleritis
Common causes of infectious uveitis

Toxoplasmosis yellow white retinal lesions near to an old pigmented chorioretinal scar
mainly in the peripheral retina, severe vitritis, a negative undiluted
antibody titre exclude the diagnosis in an immunocompetent patient.
more
Histoplasmosis mainly in endemic areas, white choroidal lesions in the posterior pole,
peripapillary atrophy, macular dry degeneration, may be choroidal
neovascular membrane, minimal to no vitritis
Syphilis may mimic anything rely on the serological tests
Tuberculosis variable manifestations, diagnosis is based on lab. tests, a two weeks
trial with Isoniazid should resolve the uveitis
Cat scratch disease unilateral, stellate macular exudates, optic nerve swelling, vitritis,
enlarged lymph nodes, positive Bartonella serology more
Rubella infants of mothers infected in pregnancy, salt and pepper retinal
pigmentation, microphthalmos, cataract, increased antibody titre
Toxocara infection in children, unilateral, macular granuloma, peripheral granuloma, or
endophthalmitis, a negative undiluted serology ELISA test exclude the
disease.
Postoperative or post- more
trauma
Common causes of non-infectious uveitis

Sarcoidosis granulomatous iritis, vitritis, vitreous opacities, sheathing of the retinal
veins, iris or choroidal nodules, optic disc swelling, erythema nodosum,
hilar lymphadenopathy on CXR, raised angiotensin converting
enzyme, positive conjunctival nodule biopsy, others, more
Multiple white dot often in young women, acute unilateral vision loss, history of viral
syndrome illness, multiple white fundus lesions few vitreous cells, enlarged blind
spot, good prognosis for vision.

Recurrent multifocal often young myopic women, unilateral visual loss, bilateral multiple
choroiditis small round inflammatory lesion at the choroid, may be associated with
choroidal neovascular membrane, some activity in the anterior
chamber and the vitreous, respond to systemic steroids, may be
recurrent.
AMPPE young adults after viral illness, acute visual loss, multiple grey
subretinal lesions in the posterior pole, serous retinal detachment, mild
inflammatory signs, may be CNS signs. Self limited.
Behcet disease young adults, bilateral, white eye with iritis and hypopyon, retinal
haemorrhage and vascular sheathing, recurrent mouth and genital
ulcers, erythema nodosum, arthritis. more
Vogt-Koyanagi-Harada dark patients from Asian or American origin, anterior uveitis with mild
syndrome vitritis, serous retinal detachment, optic disc swelling, meningeal signs,
vitiligo and alopecia, hearing loss and tinnitus. more
Birdshot choroiditis middle age women, bilateral multiple creamy yellow lesions in the mid-
retinal periphery, vitritis, positive HLA-A29, cystoid macular oedema
and choroidal neovascular membrane may occur.
intermediate uveitis “pars planitis”
main features Other features treatment others

floaters and blurred vision in iritis, vascular only if the visual acuity is more
a 15-45 years old, sheathing, lens affected by CMO or by severe
photophobia, occasionally opacities, secondary vitritis. Treatment is often by
red eye, bilateral disease. glaucoma, vitreous topical, periocular or systemic
fundus examination reveal haemorrhage, retinal steroids. Retinal cryotherapy or
vitreous snow-banking and detachment. vitrectomy may also be needed
snowball vitreous opacities. in resistant cases.
Corneal fluorescein staining

(corneal ulcer)
Common causes:
1. Bacterial ulcers, the most serious
2. Herpes simplex virus ulcer
3. Fungal ulcer
4. Acanthamoeba ulcer
5. Marginal ulcer
6. Corneal abrasion
Differential diagnosis of keratitis and corneal ulcers

Bacterial red eye, pain, discharge, decreased vision, Refer needs admission,
white infiltrate in case of keratitis or central urgently any central
staining in case of ulceration. infiltrate or ulcer
should be
considered
bacterial until
proved otherwise
by lab. tests. more
Heroes zoster skin rash on one side of the forehead and Start a course if the tip of the
ophthalmicus scalp and pain, headache may precede the of systemic nose is involved
rash, may be associated with corneal acyclovir and with the rash it is
dendrites, keratitis or iritis with or without Refer to likely that the eye
raised IOP. exclude ocular will also be
involvement. affected.
Herpes eye lid vesicles, cold sores, dendritic- Refer topical steroid
simplex shaped ulceration, can only be
prescribed by an
ophthalmologist
at onset and also
in the future.
Fungal feathery infiltrate, satellite lesions, Refer needs admission,
urgently must be
considered after
trauma with
vegetable
material (tree
branches)
Acanthamoeba extreme pain and photophobia for several Refer needs admission,
days (out of proportion to the degree of urgently should be
corneal infiltrate), contact lens wearer, considered in any
stromal ring shaped infiltrate, radial keratitis. contact lens
wearer and in
non-responding
bacterial or viral
ulcers. Keep the
contact lens for
culture. more
Marginal often marginal, mild or no visual loss, may Refer out-patient
keratitis be very painful, associated with blepharitis. treatment,

treatment is by
steroids, make
sure it is not
marginal herpes
simplex ulcer
before using
steroids.
It is safe to say that all patients with central corneal ulceration should be referred
immediately to an ophthalmologist for diagnosis and treatment.
Sudden onset of painful loss of vision.

Common causes
With a red eye Without a red eye

• acute glaucoma • temporal
• keratitis and arthritis
corneal ulcers • optic neuritis

Retrobulbar or sudden loss of vision Refer, needs IV optic neuritis may be caused by
optic neuritis in a 18-45 years old steroids in many causes, young adult
patient, RAPD, demyelinating patients need a neurologists
normal or swollen diseases and an MRI opinion to diagnose of exclude
optic nerve head, for ? CNS MS, in children it is often due to
orbital pain with involvement. more viral infection and complete
ocular movements, spontaneous improvement is
altered perception of often expected.
moving objects,
worsening of vision
with increased body
heat.
Arteritic sudden loss of vision Refer immediately for a very quick action is needed as
anterior in a 50 or older IV and oral steroids permanent and total loss of
ischaemic optic patient with RAPD, (80-100 mg of vision is a major risk even with
neuropathy severe headache and prednisolone daily) the full steroids treatment.
temporal tenderness, and confirmation with
no temporal artery a blood test and/or
pulsation, severely ill temporal artery
patient, no pain with biopsy. Medical
ocular movements, referral is also
pale optic nerve head advisable. More
with flame shaped
haemorrhage, high
ESR and CRP. More
• Anterior ischaemic optic neuropathy may be non-arteritic, vision loss is

often painless and non-progressive, patients are often younger,
altitudinal visual field defect is typical, normal ESR and CRP, steroids
do not often help very much, Refer to exclude the arteritic type.
Sudden onset of painless loss of vision

Common causes:
1. Retinal artery occlusion
2. Retinal vein occlusion
3. Retinal detachment and vitreous haemorrhage.
4. Macular changes
5. Central visual field loss
6. Central serous retinopathy

Retinal artery sudden severe (if central Refer to consider treatment Giant cell arteritis
occlusion retinal artery occlusion) (effective if administered in the often present by
(central or loss of vision, RAPD, first 24 hours), needs carotid anterior ischaemic
branch) whitening of the retina with artery ultrasound to exclude optic neuropathy
a cherry-red spot, source of embolization, but central retinal
segmentation of the retinal exclude giant cell arteritis by artery occlusion
vessels, with or without an ESR. may also be the
retinal emboli. presenting feature
of the disease
Retinal vein diffuse retinal Exclude hypertension, Retinal vein
occlusion haemorrhage, cotton wool diabetes, and other occlusion may be
(central or spots, disc and macular cardiovascular disease, ischaemic or non-
branch) oedema, collateral and consider stopping oral ischaemic. The
new blood vessels. contraceptives, Refer to ischaemic type
exclude glaucoma and has a worst
papilloedema and to consider prognosis and
fluorescein angiography and need a closer
possible laser treatment. follow-up.
Retinal history of floaters and Refer urgently if the central any case with
detachment flashing light, curtain vision is still good (macula is sudden onset of
and vitreous moving across the vision, still on) or if the patient is vitreous
haemorrhage loss of the central or the young or if the detachment is haemorrhage (in a
peripheral vision, retinal of recent onset (better non-diabetic
elevation, with loss of the prognosis after surgery). Refer patient) should be
red reflex, with or without soon if the central vision is lost considered as
vitreous haemorrhage. or if the detachment is of long caused by a
duration. Referral is also useful detachment or
if there is a doubt about retinal tear until
retinoschisis. proved otherwise.
see other types of
detachment
below.
Macular often elderly patients, check blood pressure, Refer 10% of all patients
changes rapid onset of distortion or urgently as fluorescein may benefit from
loss of vision (not as angiography is often needed laser treatment.
sudden as vascular and laser photocoagulation Other methods of
occlusion), subretinal may be possible, treatment are
macular haemorrhage, developing. more
exudates or fluid. History
of similar problem in the

fellow eye.
Central visual history of a recent stroke, check blood pressure and CAT Suspect this when
field loss often bilateral hemianopia scan for any space occupying patients complain
or quadrantonopia, normal lesion and for any treatable of s a sudden
ocular examination and no cause of the stroke, Refer for onset of visual
RAPD. proper visual field testing, loss in both eyes
bitemporal hemianopia needs with good visual
further investigations for the acuity.
pituitary gland. May need a
medical referral.
Central blurred and distorted do not give steroids (it makes it severe cases may
serous vision (rather than loss of worse), Refer for confirmation rarely occur
retinopathy vision), young patients by fluorescein angiography, leading to a
with type A personality, often self limited in about 6-8 widespread
localised detachment of weeks, laser photocoagulation exudative
the serous retina mainly at may be needed in long- detachment.
the macular area, standing case.
Types and causes of retinal detachment
Rhegmatogenous Exudative Traction

history of floaters and/or minimal to severe visual loss with visual field visual loss,
flashing lights, elevation defects, elevation of the retina with no tears, immobile retina,
of the retina with a shifting of the subretinal fluid according to head may result from
retinal tear, pigmented posture, caused by retina or choroidal primary or penetrating ocular
cells in the vitreous, secondary tumours, and also by inflammatory trauma, diabetes or
needs urgent referral for conditions (Vogt-Koyanagi-Harada syndrome and vascular retinal
surgical treatment posterior scleritis) and others. Treated by treating disorders. Needs
the cause. surgical treatment.
Differential diagnosis of the common intraocular tumours more
Tumour Features
Choroidal melanoma may be asymptomatic, floaters or decreased vision of visual field
loss, may be pigmented or non-pigmented, elevated mass, vitreous
haemorrhage, typical ultrasound features.
Choroidal haemangioma in young adults, may be asymptomatic, may present with change of
refraction, red orange lesion, mild elevation, typical fluorescein
angiography features.
Choroidal metastases may be asymptomatic, creamy white colour mass, flat or slightly
elevated, history of cancer mainly in the breast or the lung.
Retinoblastoma children, white nodular mass, may extends in the vitreous or under
the retina, iris neovascularisation, pseudo-hypopyon, vitreous
seeding.
Gradual loss of vision

Common causes:
1. Cataract (by far the most common cause)
2. Macular degeneration
3. Glaucoma
4. Corneal dystrophies
5. Optic neuropathies
Disease Main manifestations What to do?

Cataract slow progressive visual loss, Refer to an optician to check if correction of
glare, loss of contrast sensitivity, refractive error will be enough, opticians
change of refraction towards usually suggest referral to an ophthalmic
myopia in some cases, surgeon to consider surgery if glasses are
opacification of the crystalline not enough.
lens.
Macular Difficulty with near and reading if there are retinal elevation, exudate or
degeneration vision mainly, it only affects the haemorrhage Refer urgently as laser
central vision, distortion of vision, photocoagulation may be effective in
macular drusen, retinal pigment preventing progression. If the degeneration
epithelium atrophy, subretinal is mainly dry and atrophic Refer to consider
elevation, exudate or low visual aid and poorly sighted
haemorrhage. the most common registration.
type of macular degeneration s
the age related type in elderly
patients.
Glaucoma often discovered during routine If in doubt Refer to an optician to measure
eye tests and may not be the IOP and the visual field, referral to an
associated with any symptoms, ophthalmologist is often suggested by the
patients may notice gradual optician.
deterioration of vision and loss of
the peripheral vision, may be
associated with headache if the
IOP is very high, high IOP,
cupped optic nerve head, loss of
peripheral visual field.
Corneal Gradual deterioration of the Refer for diagnosis and consideration of
dystrophies vision associated with corneal corneal graft surgery (or hard contact lens in
changes with no signs of cases of keratoconus).
inflammation or vascularisation
of the cornea, may be inherited.
Some types of corneal
dystrophies may cause recurrent
painful corneal erosions.
Optic painless progressive visual loss, Refer for diagnosis and treatment
neuropathies RAPD, loss of colour vision (by
the Ishihara test), associated
with central scotoma and may be
associated with peripheral visual
field loss.
The main types of stromal corneal dystrophies are:

1. Lattice dystrophy
2. Granular dystrophy
3. Macular dystrophy
4. Keratoconus

Lattice dystrophy refractile branching corneal lines, dots and scarring of the central cornea,
may be recurrent corneal erosions.
Granular white deposits in the central cornea separated by clear areas of healthy
dystrophy cornea, the corneal periphery is often clear, appears in the first decade of
life but become symptomatic later in adulthood.
Macular dystrophy grey white corneal deposits covering the whole cornea with no clear
areas in-between the deposits.
Keratoconus often affects young adults, slowly progressive irregular corneal
astigmatism often discovered by the optician, may be associated with
sudden onset of pain and red eye if corneal hydrops develop. May be
associated with systemic diseases e.g. Down’s syndrome and atopy.
Common causes of optic neuropathies:

1. Non-arteritic ischaemic neuropathy (the arteritic type is often painful
with headache)
2. Tobacco and/or alcohol abuse (malnutrition)
3. Iatrogenic (chloramphenicol, ethambutol, isoniazide, chloroquine,
others)
4. Compressive neuropathy (optic nerve glioma, meningioma)
5. Leber’s neuropathy
6. Dominant optic atrophy
Transient loss of vision

The main causes:
1. Papilloedema
2. Amaurosis fugax (unilateral)
3. Vertebrobasilar insufficiency (Bilateral)
4. Anterior ischaemic optic neuropathy and giant cell arteritis
5. Migraine

Papilloedema visual loss or obscuration lasts only seconds, check BP and Refer
optic disc head swelling, may be associated with urgently for a head MRI
headache and symptoms of raised intracranial
pressure.
Amaurosis fugax monocular loss of vision for few minutes, start aspirin therapy, and
appears as a curtain moving across vision, Refer for investigations
retinal emboli or retinal cotton wool spots including carotid artery
indicating retinal ischaemia, dilated retinal ultrasound.
vessels with mid peripheral retinal
haemorrhage, retinal or disc neovascularisation
indicating ocular ischaemia. may be associated
with systemic neurological manifestations.
Vertebrobasilar Bilateral loss of vision that lasts for minutes or start aspirin therapy, and
insufficiency more, may be associated with flashing lights Refer for investigations
and ataxia, vertigo, and hemiparesis. including carotid artery
ultrasound.
Anterior sudden loss of vision in a 50 or older patient Refer immediately for IV
ischaemic optic with RAPD, severe headache and temporal and oral steroids (80-100
neuropathy (giant tenderness, no temporal artery pulsation, mg of prednisolone daily)
cell arteritis) severely ill patient, no pain with ocular and confirmation with a
movements, pale optic nerve head with flame blood test and/or
shaped haemorrhage, high ESR and CRP. temporal artery biopsy.
Medical referral is also
advisable. more
Migraine young patients, recurrent episodes, often lasts Refer to exclude all the
between 10 and 45 minutes, the diagnosis is other causes.
often made after excluding all the other causes.
Floaters and flashing lights

Common causes of floaters
1. Posterior vitreous detachment
2. Posterior uveitis
3. Vitreous haemorrhage
4. Vitreous degenerative conditions (like asteroid hyalosis)
5. Migraine
Differential diagnosis of floaters and flashing lights

Posterior vitreous seeing floaters, cob webs, Refer to exclude retinal detachment,
detachment circles or tadpole that move retinal breaks or vitreous haemorrhage.
with eye or head movements, the likelihood of having retinal break
may be associated with increases when the floaters are
flashing lights. associated with flashing lights. Posterior
vitreous detachment is untreatable
condition and rarely cause severe visual
problems.
Posterior uveitis Vitritis is associated with Refer to make a diagnosis and treat if
vitreous white cells and needed.
possibly cells in the anterior
chamber too
Vitreous Variable degrees of visual in the absence of diabetic retinopathy
haemorrhage loss depending on the severity and retinal vascular diseases, vitreous
of the haemorrhage, loss of haemorrhage should be considered to
the red reflex. be caused by retinal break until proved
otherwise. Refer to exclude retinal
breaks and vascular retinal diseases.
Vitreous small refractile opacities, of no No need to refer.
degenerative clinical significant.
conditions (asteroid
hyalosis)
Migraine floaters and flashing lights are This diagnosis is often made by
often transient, associated exclusion, no need to refer if confident of
with seeing zig-zag lines, the diagnosis.
headache may or may not be
associated with the floaters
and flashing lights.
Anisocoria
(unequal pupils)
Anisocoria more marked in the dim light

(do the 10% cocaine eye drops test)

Physiological the small pupil dilates with 10% no need to refer.
anisocoria cocaine eye drops.
Horner ptosis, miosis, with or without do the 1 % Hydroxyamphetamine test to
syndrome anhidrosis, no dilatation after differentiate preganglionic (the pupil
10% cocaine eye drops. more dilates), and postganglionic (the pupil
does not dilate) causes. Refer for further
investigations (e.g. CXR and carotid
arteries) especially in recent onset cases.
Anisocoria more marked in the bright light

(do the 0.1% pilocarpine eye drops test)

Traumatic iris damage torn iris sphincter on microscopic examination, No need to
slow near pupil reaction refer.
Third nerve palsy no constriction with 0.1% pilocarpine, constricts Refer for further
with 1% pilocarpine, may be exodeviation and investigations
ptosis.
Adie’s pupil pupil constricts with 0.1% pilocarpine, sector iris No need to
palsy, tonic near reaction. refer.
Pharmacological the pupil constricts with 1% pilocarpine drops. No need to
dilatation. refer.
The cocaine and the Hydroxyamphetamine test

• Put one drop of cocaine 10% in each eye and then examine the pupils
after 15 minutes. If nothing happens repeat the drops and examine
again in 15 minutes. In case of 1 % Hydroxyamphetamine test,
examine the pupils after 30 minutes.
• Hydroxyamphetamine should not be used within 24 hours of using the
cocaine drops.
Ptosis
“droopy upper lid” more
Causes of ptosis
1. Levator muscle dehiscence e.g. old age (the commonest cause),
postoperative, or post-trauma
2. Congenital
3. Myasthenia gravis
4. Third nerve palsy
5. Horner syndrome more
6. Chronic progressive ophthalmoplegia
7. Prolonged use of topical steroids

Levator muscle the upper lid skin crease is Refer for surgical treatment.
dehiscence typically raised, good levator
muscle function,
Congenital onset since birth, the skin Refer soon (if there is a risk of visual
crease is typically normal, deprivation) for vision evaluation,
poor levator function amblyopia treatment and surgical
treatment if indicated.
Myasthenia gravis may be double vision, worse Refer to an ophthalmologist or a
towards the end of the day, neurologist for confirmation by acetyl-
weakness of other facial or choline receptors antibodies and
swallowing muscles. Tensilon test. more
Third nerve palsy pupil may be dilated, the eye Refer. Sudden onset of painful third
may be deviated outwards, nerve palsy with pupil involvement is a
no diurnal variation. real emergency to role out the
possibility of intracranial aneurysm.
Chronic progressive gradual onset, ocular Refer for fundus examination, and
ophthalmoplegia misalignment and limited ECG to exclude Kearns-Sayre
ocular movements, may be syndrome, abetalipoproteinaemia, and
other muscles weakness, no Refsum’s disease, may need a
diurnal variation, normal neurological opinion.
pupils, may be family history.
Kearns-Sayre onset before 20 years of age, retinal pigmentary changes, heart

syndrome block, hearing loss, mental retardation.
Abetalipoproteinaemia retinal pigmentary changes, diarrhoea, ataxia, CNS signs,
acanthocytosis of red blood cells.
Refsum’s disease retinitis pigmentosa-like picture, increased blood phytanic acid, other
neurological signs.
• The Tensilon test: inject 0.2 ml IV of Edrophonium chloride, if an
improvement in the lid position is noticed the test is considered
positive. If no improvement occurs, inject 0.4 ml and notice the lid
margin position again. If no improvement occurs inject another 0.4 ml
and notice the lid margin and any side effects.
• Be prepared with Atropine (0.4 mg IV) and resuscitation equipment.
Proptosis
Proptosis is the hallmark of orbital diseases. Almost all the orbital
diseases present with these typical presentations:
• Proptosis or exophthalmos
• Pain
• Restriction of ocular movements and double vision
• Blurred vision
• Resistance to retropulsion of the globe.
Before diagnosing proptosis, care should be taken to exclude causes of

pseudo-proptosis e.g. high myopia and contralateral enophthalmos.
Radio-imaging plays a very important part in the diagnosis and all
patients with proptosis should be referred to an ophthalmologist for
a CAT or MRI scan .
Common causes of proptosis

1. Thyroid eye disease (the most common cause)
2. Orbital pseudo-tumours
3. Orbital cellulitis
4. Orbital tumours
5. Trauma
6. Varix
7. Arteriovenous fistula
Disease Main manifestations Radio-imaging

Thyroid eye may be unilateral or bilateral, may have a gradual or thickening of the
disease rapid onset, upper lid retraction, lid lag. T3, T4, TSH. extraocular muscles
without involvement of
their tendons.
Orbital often painful, healthy patient with normal white count thickened muscles with
pseudo- and no pyrexia, dramatic response to systemic involvement of their
tumours steroids. tendons, the scleral
orbital fat or the
lacrimal glands may
also be involved.
Orbital pyrexia, high white count. Patients should be followed sinusitis, peri-orbital
cellulitis up daily to watch out for improvement or the possible abscess.
development of cavernous sinus thrombosis
(drowsiness, with nausea and vomiting, decreased
sensation of the fifth cranial nerve, dilated and sluggish
pupils, weakness of the third, fourth, and sixth cranial
nerves), or peri-orbital abscess.
Orbital mass, globe displacement according to the location of a mass is shown
tumours the mass, there may be a primary in the breast or the
bronchus.
Trauma trauma and foreign body may be followed by a
retrobulbar haemorrhage.
Varix due to a large dilated orbital vein by a thrombus, Dilated vein may be
proptosis increases with Valsalva manoeuvre. shown with an
enhanced CAT scan
during Valsalva
manoeuvre
Arteriovenou may follow trauma or may be spontaneous, a bruit may enlarged superior
s fistula be heard, prominent conjunctival vessels and ophthalmic vein, the
chemosis. extraocular muscles
may also be enlarged,
reversed blood flow
may be noticed by
ultrasound Doppler.
Differential diagnosis of the common orbital tumours

in adults
Tumour Ophthalmic features Radio-imaging

Secondary the most common cause of orbital mass, poorly defined mass, bone
tumours common primary sites include breast, lung, destruction.
prostate, and GIT,
Cavernous young adults, slow onset, well defined mass often within
haemangiom the muscle cone, high
a amplitude internal echo by
ultrasound.
Optic nerve middle aged women, slowly progressive visual tubular enlargement of the
sheath loss with mild proptosis and RAPD, optic nerve optic nerve,
meningioma swelling or atrophy with opticociliary shunt
vessels, may be a temporal fossa mass.
Lymphoid middle age to elderly patients, slow irregular mass, no bony
tumours progression and onset, may be associated with erosions,
lymphoid tumours of the anterior segment, not
necessarily associated with systemic disease,
Mucocele frontal headache with a history of sinusitis. frontal or ethmoid sinus
swelling with bone erosions.
Differential diagnosis of the common orbital tumours

in children
Tumour Ophthalmic features Radio-imaging

Dermoid and present since birth, slow progress, often well-defined mass.
epidermoid cyst develops in the outer upper quadrant, smooth
round and non-tender.
capillary from birth till early infancy, slow progress, may irregular mass.
haemangioma enlarge during the first year but often regresses
afterwards, may present a s bluish-red mass
seen through the lid, proptosis may increase
with crying.
Rhabdomyosarcoma often around the age of 7, rapid onset and bone destruction,
progression, malignant and may metastasise, may be well-
history of nose bleeding, urgent biopsy is demarcated mass.
mandatory if this tumour is suspected, needs
referral to a paediatric oncologist.
optic nerve glioma at the age of 2-6 years old, RAPD and fusiform swelling of
decreased vision, optic nerve swelling or the optic nerve, the

atrophy, may be associated with chiasm may also be
neurofibromatosis. involved.
Leukaemia often in the first decade of life, rapid irregular mass,
progression, may be bilateral, may precede temporal fossa mass
blood or bone marrow changes (acute may be present.
myelogenous leukaemia).
Lymphangioma in the first decade of life, slowly progressive, non-capsulated
rapid growth if bleeds, may be increased in size irregular mass, with
with infections, may be other lymphoid tumours cystic multiloculated
elsewhere. areas.
Diabetic retinopathy: ophthalmic features

Peripheral new vessels
indicating sever
retinal ischaemia
Disc new vessels
indicating sever
retinal ischaemia
Yellow hard exudates

indicating lipid
leakage
Small red dots
indicating retinal
micro-aneurysms Large red lesions
indicating retinal
haemorrhage
Macular oedema
indicating leakage
Cotton wool spots

indicating retinal
ischaemia
ophthalmic feature what it means and what to do?

Micro-aneurysms no treatment unless leaking and threatening fixation by macular oedema
Retinal haemorrhage no treatment needed
Yellow hard indicates lipids and macrophages leakage, should be refereed and treated if
exudates threatening fixation
Macular thickening indicates macular oedema, may affect vision, should be refereed, treated if near
enough to fixation
Cotton wool spots indicate ischaemia, needs referral for close observation
Disc or peripheral indicate severe retinal ischaemia, high risk of vitreous haemorrhage and retinal
new vessels detachment and poor visual outcome, needs urgent referral for laser treatment
Vitreous indicates poor visual outcome, needs urgent referral to exclude retinal detachment,
haemorrhage may need vitrectomy.
Acute disc oedema occurs mainly in juvenile diabetics, mild visual loss, no RAPD, often resolves in a few
months, no need for treatment .
Diabetic retinopathy: types of laser treatment
1. Panretinal photocoagulation
(several hundreds to few thousands burns)
indicated in disc and/or peripheral new vessels
2. Grid laser photocoagulation

(few hundreds burns)
indicated in diffuse macular oedema
3. Focal laser photocoagulation

(several burns)
indicated in focal leakage threatening fixation
Ophthalmic features of AIDS
Anterior segment features
Molluscum contagiosum dome-shaped umblicated shiny nodule on the lid margin or

the lid, may be multiple, may be associated with chronic
follicular conjunctivitis and keratitis.
Kaposi sarcoma malignant sub-conjunctival red nodule, occurs in about 30%
of patients.
Severe herpes simplex or in young patients often suspect aids, corneal dendritic
herpes zoster infection ulcers may be peripheral.
Microsporidial keratitis. fine to coarse diffuse chronic keratitis.
Posterior segment features
Retinal micro-angiopathy asymptomatic, cotton wool spots, may be retinal haemorrhage,

micro-aneurysms.
CMV retinitis peripheral opacification of the retina with/without haemorrhage,
often progressive, dense white well demarcated confluent
opacities of the retina, mild vitritis. more
Pneumocystis carinii yellow round choroidal lesions, often bilateral, no vitritis.
choroiditis
Toxoplasmosis more
PORN more
Strabismus
Squint may be convergent (esodeviation) when the two eyes are looking towards
each other, or divergent (exodeviation) when the two eyes are looking away from
each other.
You must, first of all, exclude pseudo-esotropia (the eye appear to be turning in
but they do not actually show and deviation with the cover test).
Causes of pseudo-esotropia:
1. Wide nasal bridge
2. Prominent epicanthus fold
3. Small inter-pupillary distance
You must differentiate between the main two type of squint:
Concomitant squint Incomitant squint

manifest deviation of the eye where the the measured angle of squint varies depending on
deviation angle is nearly the same in all the patient ‘s direction of gaze. This is mainly due to
direction of gaze, the ocular movement a paralytic cause.
seems to normal in this case.
Common causes of concomitant esodeviation

Congenital often positive family history, appears in the first few months, the angle of
deviation if often large, little or no refractive errors, may be associated with
nystagmus, amblyopia may or may not be present. Refer the patient to treat
amblyopia if present and also to align the eyes with surgery.
Accommodative often appears at the age of 2-3 years old, children often have high hyperopia,
refractive moderate to small angle of deviation with is equal to near and far vision, the
deviation disappears on wearing the corrective glasses. Refer for refraction
and treatment of amblyopia if present.
Accommodative the refractive error is not significantly higher than normal, the angle of
non-refractive deviation is larger for near vision than for distant vision. Refer to treat
amblyopia and surgery if needed.
Partial the angle of deviation is decreased but not completely eliminated by wearing
accommodative the corrective glasses. Refer to correct amblyopia and to align the eyes
surgically.
Sensory as in congenital cataract, corneal opacity, optic nerve diseases or intraocular
deprivation tumours. Refer to diagnose and treat the cause.
Divergence diagnosis of exclusion.
insufficiency
Common causes of incomitant esodeviation
1. Neurological diseases e.g. Tumours, hydrocephalus.

2. Thyroid eye disease
3. Orbital trauma
4. Isolated sixth nerve palsy
Common causes of exodeviation

Intermittent the most common type in children, often occur at the age of 4, often
exodeviation progressive from intermittent deviation on distant vision to constant
deviation on near and far vision. Refer for surgical treatment.
Sensory blind eyes, from any cause, tends to diverge. Refer for cosmetic surgery
deprivation if the patient is interested.
Duane syndrome limitation of adduction of the eye with retraction of the globe on attempted
type 2 adduction. Refer for consideration of surgical treatment.
Third nerve palsy pupil may be dilated, the eye may be deviated outwards, no diurnal
variation. Sudden onset of painful third nerve palsy with pupil involvement
is a real emergency to role out the possibility of intracranial aneurysm.
Refer.
Orbital diseases proptosis and ocular motility restriction. Refer for MRI.
Myasthenia gravis may be double vision, worse towards the end of the day, weakness of
other facial or swallowing muscles. Refer to an ophthalmologist or a
neurologist for confirmation by acetyl-choline receptors antibodies and
Tensilon test.
Convergence blurred near vision and headache when reading, straight eyes for
insufficiency distance but exodeviation for near. Refer for convergence exercises.
The cover test

• Ask the patient to look at a distant object. Cover the right eye and see
what happens to the left the eye when it is forced to take up fixation,
then cover the left eye and see what happens to the right eye when it
is forced to take up fixation.
• If the right eye turns inward, when the left eye is covered, this means
that the right the was turning out when both eye were open and then
had to turn in to take up fixation. This means that the patient has a right
divergent squint.
• If the right eye turns outward when the left eye is covered, this means
that the patient has a right convergent squint.
Diplopia
double vision
Care should be taken to differentiate between monocular and binocular
diplopia. In monocular diplopia patients complain of double vision even if
one eye is covered. In binocular diplopia double vision is present only if
both eyes are open.
Common causes of binocular diplopia Common causes of monocular diplopia

1. Isolated third nerve palsy 1. Error of refraction
2. Isolated sixth nerve palsy 2. Lens or corneal opacities
3. Isolated fourth nerve palsy
4. Giant cell arteritis
7. Chronic progressive external ophthalmoplegia
8. Orbital tumours or pseudo-tumours
9. Orbital trauma and blow out fracture.
Differential diagnosis of diplopia
The disease features Tests What to do?

De-compensated common, history of Refer to an optician If symptoms persist despite
phoria difficulty and eye for refraction and proper glasses Refer for
strain for close fine ocular muscle orthoptic assessment.
work, may be balance.
intermittent first,
symptoms may be
more severe if the
patient become ill
or debilitated.
Cranial nerves see next table.
palsy
Myasthenia gravis worse towards the Ice or Tensilon test Refer to an ophthalmologist
end of the day, or a neurologist for
weakness of other confirmation by acetyl-choline
facial or swallowing receptors antibodies and
muscles, normal Tensilon test.
pupil most of the
time, weak
orbicularis muscle..
Thyroid eye may be unilateral or thickening of the Refer to an ophthalmologist
disease bilateral, may have extraocular muscles for medical treatment or
a gradual or rapid without involvement surgical treatment of
onset, upper lid of their tendons. proptosis or associated lid or
retraction, lid lag. extraocular muscles
T3, T4, TSH. disorders.
Chronic gradual onset, Refer for fundus
progressive ocular misalignment examination, and ECG to
external and limited ocular exclude Kearns-Sayre
ophthalmoplegia movements, may syndrome,
be other muscles abetalipoproteinaemia, and
weakness, no Refsum’s disease, may need

diurnal variation, a neurological opinion.
normal pupils, may
be family history.
Giant cell arteritis sudden loss of high ESR and CRP. Refer immediately for IV and
vision in a 50 or oral steroids (80-100 mg of
older patient with prednisolone daily) and
RAPD, severe confirmation with a blood test
headache and and/or temporal artery
temporal biopsy. Medical referral is
tenderness, no also advisable.
temporal artery
pulsation, severely
ill patient, no pain
with ocular
movements, pale
optic nerve head
with flame shaped
haemorrhage,
Orbital tumours or often painful, thickened muscles Refer for MRI diagnosis and
pseudo-tumours healthy patient with with involvement of possible steroids treatment.
normal white count their tendons, the
and no pyrexia, scleral orbital fat or
dramatic response the lacrimal glands
to systemic may also be
steroids. involved.
Differential diagnosis of the isolated cranial nerve palsy
The Features Causes what to do?

nerve
Third diplopia and ptosis, may pupil sparing is often caused by occlusion patch to
nerve be complete or vascular lesion e.g. diabetes, prevent diplopia and
Palsy incomplete, in complete hypertension or giant cell Refer to diagnose the
palsy all eye arteritis. Pupil-involving palsy is cause. Sudden onset of
movements will be lost likely to be caused by a painful third nerve palsy
except outward gaze. In compressive lesion e.g. with pupil involvement is
partial palsy inward, aneurysm, tumour or trauma, it a real neuro-ophthalmic
upward or downward may also be caused by a emergency to exclude
gaze will be affected vascular lesion. intracranial aneurysm.
depending on which MRI scan in all pupil-
branch of the nerve is involving lesion, young
involved. The pupil may patients with no vascular
be dilated and fixed, or cause, incomplete palsy,
may be normal. and patients with no
recovery in 3 months
Sixth horizontal diplopia vascular causes e.g. diabetes, occlusion patch to
nerve worse for distance than hypertension and prevent diplopia and
Palsy for near mainly in the atherosclerosis, trauma, Refer for diagnosis of the
direction of action of the idiopathic. May also be caused cause. MRI in young
involved muscle. by raised intracranial pressure. patients and children, if
In children post-viral palsy is not resolved in no better
common and often have a in 3-4 months or if there
benign course. is a primary cancer.
Fourth vertical or oblique congenital, trauma, vascular occlusion patch to

nerve diplopia, difficulty lesions, demyelinating disease, prevent diplopia and
Palsy reading, the involved idiopathic. refer to diagnose and
eye if typically higher treat the cause if
than the other eye. possible. MRI scan if
there is other suspected
neurological lesion and
in young patients.
If there is multiple ocular motor deficiencies, consider the following:

1. Cavernous sinus syndrome or superior orbital fissure syndrome
3. Chronic progressive ophthalmoplegia
4. Orbital lesions e.g. tumours or pseudo-tumours.
Cavernous sinus/superior orbital fissure syndrome
Ocular features Causes

limitation of ocular motility for any 1. Arteriovenous fistula,
combination of different cranial nerve palsies, 2. intra-cavernous aneurysm or tumours
facial pain and numbness corresponding to 3. fungal infection (mucormycosis) in diabetics
the trigeminal nerve distribution, may be a 4. pituitary apoplexy
Horner syndrome, the pupil may be dilated if 5. herpes zoster
a complete third nerve palsy is present, 6. cavernous sinus thrombosis
proptosis may be present.
Leukocoria (White pupil)
Common causes and differential diagnosis of Leukocoria
Disease Ophthalmic features What to do?

Congenital congenital cataract may be unilateral or Refer urgently to an
cataract bilateral, it may also be an isolated ocular ophthalmologist and a paediatrician
abnormality or may be secondary to a for investigations and surgical
local ophthalmic (persistent hyperplastic treatment. Surgical treatment of a
primary vitreous, trauma, infections, unilateral congenital cataract should
tumours) or systemic (Galactosaemia, be carried out as soon as possible.
Rubella, Lowe’s syndrome) disease. The question about IOL is still
controversial but more surgeons are
implanting IOL at the time of primary
surgery to avoid the postoperative
problem about correcting the
aphakia and avoiding amblyopia.
Retinoblastoma A white nodular retinal mass extending Refer to establish the diagnosis,
into the vitreous or underneath the retina and treat. Most cases can now be
causing retinal detachment, often present treated with chemotherapy and
between 12 and 24 months of age, iris radiotherapy, enucleation may also
neovascularisation, cataract and pseudo- be needed in advanced case.
hypopyon may occur.
Toxocara A history of contact with puppies and Refer for ELISA test to confirm the
eating dirty things. May appear a s a diagnosis, and also possible
localised white elevated granuloma in the steroids treatment or vitrectomy.
posterior pole, as a peripheral granuloma
with macular traction, or as a diffuse
endophthalmitis. Rarely bilateral, often
diagnosed between the ages of 6 months
and 10 years.
Persistent A developmental ophthalmic abnormality. Refer for possible cataract surgery
hyperplastic Present at birth, rarely bilateral often or vitrectomy.
primary associated with microphthalmos, a
vitreous fibrovascular membrane behind the lens
and cataract.
Coats disease A retinal vascular abnormality. Exudative Refer for possible laser treatment,
retinal detachment, mainly in boys, in the or retinal detachment surgery.
first two decades of life, rarely bilateral,
may lead to severe glaucoma .
Retinopathy of ROP predominantly occurs in premature Refer, if not already been refereed
prematurity children (less than 32 weeks of gestation by the obstetrician, for follow up
and less than 1500 grams) who have had and possible laser or cryotherapy
oxygen treatment. treatment (in stage 3) and possible
more surgical treatment of the retinal
detachment (in stages 4 and 5).
Eyelid lumps
Causes of eyelid lumps and swellings

1. Chalazion
2. Basal cell carcinoma
3. Squamous cell carcinoma
4. Sebaceous gland carcinoma
5. Keratoacanthoma
6. Molluscum contagiosum
7. Squamous papilloma
8. Actinic keratosis
9. Seborrheic keratosis
Differential diagnosis of eyelid lumps
Disease features What to do?

Chalazion chronic obstruction of the meibomian glands, painful Treat with topical
and tender, may also be painless, may also be antibiotics and
associated with lid inflammation resembling preseptal warm compresses,
cellulitis. it persistent Refer
for incision and
curettage.
Basal cell The most common eyelid tumour, may present with a Refer for incision or
carcinoma lump, ulcer or diffuse indistinct skin mass. excision biopsy and
lid reconstruction.
Squamous cell Squamous cell carcinoma may present as basal cell Refer for incision or
carcinoma carcinoma, this tumour, however, can metastasise to excision biopsy and
distant organs in the body. lid reconstruction.
Sebaceous gland Must be considered in recurrent chalazion, or in Refer for incision
carcinoma persistent blepharitis in elderly population, the tumour biopsy, excision and
may also be multifocal involving both the upper and lid reconstruction.
the lower lids.
Keratoacanthoma A mass resembling basal cell and squamous cell Refer for surgical
carcinoma with a central ulcer crater, rapid growth, excision.
followed by a slow shrinkage and spontaneous
resolution.
Molluscum Often multiple lesions, umbilicated centre, may be Refer for surgical
contagiosum associated with chronic follicular conjunctivitis. excision.
Squamous Soft elevated or flat sessile lesions, spontaneous Refer for excision
papilloma resolution, some lesion may be a squamous biopsy.
carcinoma.
Actinic keratosis Round, pre-malignant, scaly surface, found in the Refer for excision
exposed areas. biopsy.
Seborrheic Middle age or elderly patients, brown-black well- May be excision by
keratosis demarcated crust-like lesion. a shave biopsy if
needed.
It is suggested that all lid lesions should be sent for histopathology after removal
as clinical diagnosis is not often enough to exclude malignancy.
Other eyelid problems
Entropion inward rotation of the lid margin, Refer for surgical treatment. more
the lid margin and the eye lashes
rubs on the eye causing corneal
irritations, gritty eyes, discomfort
and watering
Ectropion outward rotation of the lid margin, Refer for surgical treatment
watery eye due to irritation and
lacrimal punctum eversion.
Ptosis droopy upper lid, may cover part of Refer for diagnosis of the cause and
the visual field, may cause fatigue treatment . more
when reading.
In-growing irritation and watering eyes. If one or two lashes you can remove them, if
eye lashes more or recurrent Refer for electrolysis,
cryotherapy or surgical treatment.
Epiphora
watery eyes
Common causes and differential diagnosis
The disease Features

Congenital in babies and children, due to failure of canalisation of the lacrimal duct,
nasolacrimal duct spontaneously improves in the majority of cases within the first year. Most
obstruction ophthalmologists wait for spontaneous improvement unless there is a
recurrent conjunctivitis or dacryocystitis when the baby should be referred for
probing with or without closed intubation. more
Acquired may be complicated with recurrent conjunctivitis and dacryocystitis and orbital
Nasolacrimal duct cellulitis. Refer for DCR operation. more
obstruction
Eyelid e.g. ectropion, entropion, lid notches and in-growing eyelashes. Refer for
abnormalities surgical treatment.
Dry eye syndrome excessive drying of the corneal leads to irritation and burning sensation with
reflex lacrimation mainly at the end of the day. may be diagnosed by the
Schirmer’s test. Treated with artificial tear drops. Refer if drops need to be
used too frequently for punctal plugs insertion. more
Blepharitis itching, burning and crusting of the lid margin. Treated with artificial tear
drops with lid hygiene and sometimes with a short course of topical antibiotics
and steroids. May need a long course of tetracycline treatment if rosacea is
suspected. Refer if complicated with marginal corneal ulceration.
Conjunctival pigmentation
Conjunctival pigmentation may be due to local or general causes:
General causes Local causes

1. Ochronosis with Alkaptonuria (due to enzymatic 1. Ocular or oculo-dermal melanosis.
deficiency, often in young adults, associated 2. Primary acquired melanosis.
with dark urine and arthritis). 3. Naevi.
2. Addison’s disease. 4. Malignant melanoma.
3. Agyrosis (history of using silver nitrate drops) 5. Racial pigmentation.
4. Haemochromatosis.
5. Adrenochrome deposits (history of using
Adrenaline or Propine drops).
5. Mascara deposits.
6. Chlorpromazine treatment.
Differential diagnosis of the local causes

Ocular or congenital, it is mainly an episcleral lesion Refer to exclude other uveal
oculo-dermal (i.e. you can see the conjunctiva moving on melanomas as this condition
melanosis top of the lesion), the lesion is often predisposes to uveal tract
unilateral, is often associated with darker malignancy.
ipsilateral iris and choroid, the skin on the
ipsilateral lid may also be pigmented (naevus
of Ota).
Primary appears in the middle age, flat and brown Refer for observation and
acquired patches, may be pre-malignant. detection of malignant changes
melanosis (extension, modularity,
increased vascularity of the
lesion).
Naevi commonly develop at puberty, well watch closely, Refer if there is a
demarcated, the degree of pigmentation may suspicion of malignant
change with time, may have cystic lesions, transformation.
rare in the palpebral conjunctiva, may
undergo malignant transformation.
Malignant in middle aged to elderly population, the Refer to detect for any other
melanoma lesion is often nodular, well vascularised, with associated intraocular malignant
a large conjunctival feeding blood vessel. tumours and to consider excision
biopsy or other surgical or
chemical treatment. more
Contact lens-Related problems

Corneal white corneal lesion which may stain with all cases must be
infiltrate or fluorescein , central lesions are more likely to considered as infectious
ulceration be due to infection than peripheral lesions, until proved otherwise,
severe pain indicate possible infection. Refer for compete
microbiological work out.
Giant papillary itching, mucous, lens intolerance. stop contact lens wear in
conjunctivitis severe cases, use
cromolyn sodium or
Alomide, replace the lens,
more thorough cleaning,
consider daily wear lenses.
Corneal often asymptomatic early in the disease. discontinue lens wear,
vascularisation consider steroid treatment,
refit with highly gas
permeable lens when it is
better.
Tight lens severe discomfort and pain one or two days discontinue wear, may
syndrome after poor fitting of soft contact lens. the lens need cycloplegic drops,
does not move with blinking, may lead to refit with a flatter lens.
corneal oedema and iritis with or without
hypopyon, conjunctival marks may occur at the
edges of the tight lens.
Corneal in long term PMMA contact lens wearers, good discontinue lens wear, refit
warpage vision with contact lens but blurred vision with with gas permeable contact
glasses, blurred vision then occur with both lens when refraction and
contact lens and glasses, discomfort, may or keratometry is stable.
may not be punctate keratopathy.
Contact lens these may lead to corneal and conjunctival change the lens
deposits irritation,
Superior hyperaemia and fluorescein staining of he consider changing the
limbal kerato- upper limbal conjunctiva, infiltrate and cleaning solutions, may
conjunctivitis irregularity at the upper cornea, no corneal need topical steroids if
filaments, no papillary conjunctivitis. severe.
Displaced may be displaced outside the eye or in the evert or double evert the lid
contact superior fornix. to find the lens and
lens examine it for damage or
lost pieces, refit if needed.
Hypersensitivity irritation and conjunctival injection shortly after discontinue wear, use
reaction lens cleaning after using a new type of cleaning preservative-free artificial
solution, SPK, conjunctival follicles, corneal tears, new contact lens and
infiltrates. new preservative-free
solutions.
External Eye Diseases
Infections
bacterial infection
Severe infectious keratitis is a major cause of ocular morbidity in
temperate and tropical regions. Predisposing factors for central corneal
ulceration in these areas include ocular surface disease, contact lens
wear (even without corneal epithelium disruption), previous trauma,
cocaine abuse, and the use of traditional eye medicines. Ulcerative
keratitis also develops in 4.7% of patients with prolonged bullous
keratopathy. Steroid drops and bandage soft contact lens are risk factor
for microbial ulcers in these patients. Prophylactic antibiotic use does not
seem to prevent ulcer development. Conditions associated with systemic
immune suppression should also be considered among the disease that
constitute higher risk factor for patients with infectious keratitis.
Microbial keratitis is a serious complication of contact lens wear. In

certain communities in the USA, contact lens wear was found to be the
most significant risk factor for developing ulcerative keratitis. Contact lens
and also contact lens cases are major sources for corneal infections in
contact lenses wearers. A study of 178 asymptomatic wearers found
microbial contamination in 53% of the cases. Cases hygiene is as
important as lenses hygiene, frequent and regular changes of the cases
may prove to be a necessary measure to prevent contamination.
Among the various types of contact lenses, extended wear soft contact
lenses seem to carry the greatest risks for causing corneal problems.
Overnight extended wear is the most important risk factor for developing
ulcerative keratitis even with disposable contact lenses and good
hygienic measures. Previous reports found that the relative risk of
developing ulcerative keratitis for overnight wear is 21 for soft lenses and
3.6 for daily wear soft lens when compared with gas permeable hard
lenses. 49% to 74% of contact lenses related ulcerative keratitis could be
prevented by not wearing the lenses over night. Corneal hypoxia, caused
by overnight wear with the accumulation of deposits and contamination of
the lens, lead to higher risk of complications and corneal infection.
Daily disposable contact lenses have many advantages over extended

wear contact lenses e.g. minimal handling and less need for hygienic
compliance. It had been hoped that this theoretical advantages might
eliminate the incidence of ulcerative keratitis with this type of contact
lenses, but higher rate of complications may also occur with extended
wear of daily disposable contact lens. The main complications associated
with extended wear of disposable contact lens are, however, sterile
corneal infiltrates. It seems that frequent and regular disposing of lenses

does not completely eliminate complications.
Large central corneal ulceration is more often associated with positive

culture and anterior chamber activity than peripheral ulcers. There has
been some controversy regarding the need for complete work-up in
suspected microbial keratitis. 3 different strategies for management have
previously been proposed:
• Complete laboratory work-up for all cases.

• Complete laboratory work-up only for unusual or severe corneal ulcers.
• Work up, only, if treatment with the common antibiotics fails.
Most authorities consider that complete work-up should be carried out in

all suspicious microbial keratitis. Corneal scrapings should be taken from
all lesions not including the visual axis. The scrapings should be cultured
on blood agar, chocolate agar, Sabouraud, and Thioglycate medium.
Corneal specimens should also be stained with gram and Giemsa stains
as a routine. Optional culture media and special stains for specific
infections can also be carried out in suspected cases. Corneal biopsy
may also be needed in chronically progressive lesions.
Confocal in vivo slit scanning video-microscope is a new confocal

microscope which offer a non-invasive and non-contact imaging of the
corneal layers with good lateral and axial resolution and also good
contrast even in the presence of corneal opacities, without the need for
histological staining. The technique has been shown to give results that
are consistent with histopathological and biochemical techniques. This
technique is, however not as sensitive as biomicroscopy in some
conditions. Microbiologic evaluation of a diagnostic corneal biopsy may
be used in the diagnosis and treatment of patients with progressive
infectious keratitis.
fluoroquinolones
There are several topical fluoroquinolone eye drops available now on the
market. The main preparations are:
• Ciprofloxacin.
• Norfloxacin.
• Ofloxacin.
The three preparations have similar antibiotic spectrum of activity but

ciprofloxacin seems to be more potent than the other two. The greater
potency of ciprofloxacin seems to offset the superior corneal penetration
ability of Ofloxacin. The combination of fluoroquinolone e.g. ciprofloxacin,
norfloxacin, or ofloxacin is superior to any of the fluoroquinolone alone.
Fluoroquinolone preparations should be used with caution in patient with

a history of convulsions, epilepsy, or liver or kidney failure. Frequent
application of ciprofloxacin or norfloxacin drops, especially in patients
with dry eyes or eyes with corneal ulcers may cause a white precipitate
on the ulcerated corneal surface which may lead to the formation of a
firmly adherent plaque which might delay corneal healing.
Ciprofloxacin or ofloxacin is effective as single agent in the treatment of

ulcerative keratitis. They seems to be as effective as, or even better than,
fortified topical antibiotics drops (e.g. Cefazolin and Gentamicin). Mono-
therapy with ciprofloxacin has the advantage of being easier to prepare,
more cost effective, and also being less toxic to the cornea. The use of
fluoroquinolone as a monotherapy may, however, lead to serious
complications (e.g. corneal perforation) especially in deep corneal ulcers
in the elderly patients. Topical ciprofloxacin may also be effective in
cases with non-tuberculous mycobacterium keratitis that does not
respond to amikacin treatment.
Continued use of the drug has lead to the emergence of increasing

resistance among gram positive and gram negative bacteria including
Staphylococci aureus, Streptococci, Pseudomonas and Neisseria
gonorrhoea. It is estimated that about 30.7% of the pathogens causing
bacterial keratitis is developing resistance to the drug. Care should be
taken when using fluoroquinolone as a monotherapy in bacterial keratitis
because of these emerging resistance among many pathogenic bacteria.
Resistant cases may be treated with cefazolin in gram positive infection,
or gentamycin in gram negative infections.
Sparfloxacin is a new member of the fluoroquinolone family of

antibiotics. The drug is particularly active against microbial infections
against which the fluoroquinolone drugs in general have low activity (e.g.
streptococci, mycoplasma, and chlamydia).
chlamydial infection-trachoma
Trachoma is still thought to be the second most common cause for
blindness in the world. It is estimated that there are about 5.9 million
cases of blindness from corneal scarring caused by the disease world-
wide. The disease is mainly confined to poor and crowded areas in the
developing countries. The world health organisation designed a simple
grading scheme for the disease:
• TF, trachoma inflammation-follicles: 5 or more follicles in the upper

tarsal conjunctiva.
• TI, trachoma inflammation-intense: pronounced inflammatory
thickening of the tarsal conjunctiva that obscures more than half of the
normal deep tarsal vessels.
• TS, trachoma scarring: presence of visible scarring in the upper tarsal
conjunctiva.
• TT, trachoma trichiasis: at least one eye lash on the eye ball.
• CO, corneal opacity: easily visible corneal opacity over the pupil
obscuring pupil margin.
The pathogenesis of the disease is not completely known. Tissue

damage may result from immunological and metabolic mechanisms.
Anti-chlamydial antibodies in tears are seen significantly more often in
patients with conjunctivitis than in those with urethritis. Anti-chlamydial Ig
G is found only in tears of patients with conjunctivitis. The detection of
anti-chlamydial Ig G in the tears might be helpful for diagnosis in patients
with suspected chlamydial conjunctivitis who have antigen-negative
conjunctival swabs. The polymerase chain reaction test is likely to play
an increasing role in the diagnosis of ocular C-trachomatis infection
because of its excellent sensitivity and specificity.
There is also evidence that there is an increase in the local production of

cytokines in the conjunctiva in eyes with trachoma. The cytokines may
promote conjunctival scarring. Anti-cytokines treatment may be useful in
the treatment of this disease.
Increased collagen content in the conjunctiva is also a feature of the

inflammatory process. Type V collagen, increased type I, III, and IV
collagen have been demonstrated in the conjunctiva in eyes with
trachoma. Increased levels of the enzyme gelatinase B may also play a
role in the pathogenesis of the disease.
Control of the disease may also carried out by using the SAFE strategy:
community based Surgery

Antibiotics treatment
Face cleanliness
Environmental improvement
Lack of compliance is a major problem in treating trachoma in endemic

areas. Treatment of trachoma, in endemic areas, needs to be simple,
effective and inexpensive. The world health organisation has
recommended mass treatment of children in trachoma endemic areas
with the drug azithromycin. Azithromycin is a relatively new antibiotic
derived from erythromycin. The drug can be administered once a day. A
single dose of oral Azithromycin (20 mg/kg) gives blood level that
reaches the minimum inhibitory concentration of the drug for 6 days.
Prolonged high concentration has been demonstrated in ocular tissue
after a single oral dose of one gram. It is also as effective as a 6 weeks
course of topical tetracycline ointment in managing active trachoma in
endemic areas. The drug has also been found effective in the treatment
of other chlamydial genital infections.
fungal infection
Fungus infection is often caused by fungi that are considered
saprophytic. Candida typically affects compromised corneas. The chronic
use of topical anaesthesia can cause severe morbidity to the eye due to
it’s direct toxic effect on the corneal epithelium and also due to delaying
corneal wound healing. Polymerase chain reaction test may be used in
the diagnosis of some types of fungal keratitis. Endogenous fungal
keratitis may occur after the treatment of fungal endophthalmitis. Fungal
organisms may not be completely eradicated with treatment. Patients
should be monitored for a long period after the treatment of
endophthalmitis. The incidence of ocular involvement (mainly
chorioretinitis) in patients with candidaemia seems to be clinically
significant (26%). It is recommended that ophthalmic follow up should be
undertaken in all patients with candidaemia for at least 2 weeks after an
initial negative ophthalmic examination.
Antifungal drugs (e.g. natamycin 5%, flucytosine, and amphotericin B

drops and ointment), are expensive, and not often readily available.
Treatment with these medications may also be needed for long periods of
time. The treatment of fungal keratitis in developing tropical countries
may be difficult due to the lack of specific anti-fungal medications, and
also lack of appropriate microbiological facilities. Chlorhexidine 0.2%
may be used as the first line of treatment in some cases. The drug is
cheap, readily available, and may be superior to natamycin in the
treatment of filamentary fungus infection.
herpes simplex virus infection

Herpes simplex virus infection can mimic varicella-zoster virus infection.
The differential diagnosis is specially important because incorrect
treatment may aggravate the disease. DNA specific herpes simplex virus
can be detected from the tears of patients by the polymerase chain
reaction when the diagnosis is in doubt.
The typical features of herpes virus infection is by dendritic corneal

epithelial ulceration. Herpes simplex virus iridocyclitis in the absence of
keratitis is thought to be rare and self limited. Chronic iridocyclitis with iris
atrophy may also occur as the primary manifestation of herpes simplex
virus infection without corneal involvement. Unilateral anterior uveitis with
sector atrophy of the iris without associated, or previous, keratitis may
also occur in herpetic eye diseases. Typical feature of this entity is rise of
the intraocular pressure during intraocular inflammation. Recurrent
unilateral anterior uveitis with iris atrophy and/or elevated intraocular
pressure may indicate a herpes simplex virus infection.
Posner-Schlossman (recurrent attacks of unilateral raised IOP with mild

iridocyclitis) has also been linked to varicella-zoster virus,
cytomegalovirus, and herpes simplex virus. Herpes simplex virus may
play a role in the pathogenesis of this syndrome. herpes simplex virus
DNA has been detected in the aqueous of patients with Fuchs
heterochromic iridocyclitis. Herpes simplex infection may play a role in
the pathogenesis of the disease.
Herpes simplex virus keratitis may also affect immunosuppressed

patients e.g. patients with HIV. The incidence and clinical course of HSV
keratitis do not seem to be different among patients positive for HIV
except for the recurrence rate. The recurrence rate is about 2.48 times
more frequent among patients positive for HIV.
Acyclovir is the drug of choice in treating herpes simplex virus keratitis in

Europe. Topical steroids in active herpes simplex virus stromal keratitis
are significantly better than placebo when administered with topical
antiviral medication. The role of systemic antiviral medications in the
treatment of herpes simplex virus keratitis has been controversial. Oral
Acyclovir has recently been shown to reduces the number of
recurrences of herpetic genital and labial infections. Long-term oral
Acyclovir treatment (800 mg / day) is also associated with a reduced rate
and duration of recurrences of herpes simplex virus stromal Keratitis.
Oral acyclovir also appears to be beneficial, in treating epithelial disease
and in providing prophylaxis and preventing recurrences, in the paediatric
patients.
Continued use of Acyclovir lead to the emergence of acyclovir resistant

strains of herpes simplex virus. Ganciclovir ophthalmic gel 0.15%, is a
new drugs that may be used in the treatment herpes simplex virus
infection. It is reported to be equally effective to acyclovir ophthalmic

ointment 3% in treating herpes simplex virus keratitis without significant
side effects. It has the added advantage of having less effect on the
vision being a watery gel rather than an ointment.
Cidofovir eye drops, and Penciclovir eye ointment have also been
successfully tried in the treatment of the epithelial disease in animals and
may prove useful and effective in humans. Cidofovir is highly effective
against epithelial disease when used twice a day. it can also be used to
prevent stromal disease. The drug is not, however, able to treat already
established stromal disease. Carbocyclic Oxetanocin G is a new
antiviral drug that is active against herpes simplex virus, varicella-zoster
virus, CMV, Epstein-Barr virus and HIV virus. Eye drops containing 0.1%
Carbocyclic Oxetanocin seems to be excellent and safe in the treatment
of herpes simplex virus corneal ulcers. The average healing time is about
four days. The drug does not seem to be associated with significant side
effects.
Corneal graft failure after herpes simplex virus keratitis is known to be

associated with the recurrence of herpetic corneal disease within the first
year. Herpes simplex virus infection of the corneal endothelium may
contribute to graft failure in recurrent infection. Postoperative systemic
acyclovir therapy after penetrating keratoplasty for HSV keratitis is
associated with a reduced rate of recurrent HSV dendritic keratitis and
possible graft failure at 1 year of follow-up.
varicella-zoster virus infection

The clinical presentation of herpes zoster ophthalmic infection varies
considerably. About 40% of patients are affected by some form of
anterior segment intraocular inflammation. Many of the iris changes,
associated with disease, are believed to be due to an ischaemic
occlusive vasculitis. Iridoplegic granulomatous iridocyclitis is another
newly described, acute, fulminant uveitis probably caused by varicella-
zoster virus. Acute secondary glaucoma may also be seen in 15% to
43% of the patients. The glaucoma is often dramatic and difficult to
control.
Cases with ocular Zoster without skin rash have been well documented,
this condition has been termed (Zoster Sine Herpete). Accurate diagnosis
of the infection is important as anti-inflammatory treatment may be
required as well as antiviral treatment. Polymerase chain reaction tests
can detect varicella-zoster virus DNA in intraocular material and confirms
the diagnosis when the typical skin rash is absent.
Herpes zoster virus may cause chronic epithelial keratitis in patients with
AIDS. The keratitis is characterised by dendritic lesions, long duration,
and extreme pain. The disease may also occur without skin lesion.
Herpes Zoster infection in young Africans with HIV infection has a poor
visual prognosis. 40% of these patients have visual outcome of light
perception or no light perception only. Severe keratouveitis and
perforation are common and responsible for most cases with poor visual
outcome.
Topical and systemic acyclovir is regarded as the drug of choice in

patients with varicella-zoster infection. The role played by the drug is not,
however completely understood. Topical use, when compared with
systemic use, is associated with more complications and more frequent
anterior uveitis recurrences. The uveitis and corneal hypothesia also
appear to be more severe in patients taking topical treatment. Topical
Acyclovir does not appear to have a prophylactic value in spite of its
better ocular penetration. A retrospective case control study also showed
that oral acyclovir (800 mg 5 times a day, starting within 3 days of the
onset of the rash and taken for 7 days) does not appear to affect the rate
of ocular complication in immune competent patients after Herpes Zoster
eye infection
acanthamoeba keratitis
Acanthamoeba keratitis is often associated with contact lens wear in the
Western world. In the UK the disease is associated with contact lens
wear in 85% of cases. All types of contact lenses may be associated with
the disease. The strongest association is thought to be with daily wear
soft disposable contact lens. In the tropics the disease has been reported
after trauma and mud splashing. Chronic eye disease (e.g. trachoma)
may also compromise the corneal surface and predispose the cornea to
infection without a history of contact lens wear or trauma. Corneal
abrasion seems to be needed for the organism to penetrate the cornea.
Diagnosis of Acanthamoeba keratitis is often made later in non-contact
lens wearers than in contact lens wearers.
Severe pain and photophobia out of proportion to the physical signs is a

characteristic feature of the disease (often due to the accompanying
scleritis and neuritis). Superficial corneal ulceration with perineural
keratitis is the main corneal features. Ring infiltration with stromal
ulceration may also occur. Significant decrease in the corneal sensation
is also a frequent finding in the disease. Acanthamoeba keratitis may
also masquerade as herpetic, or adenoviral keratitis. Acanthamoeba
keratitis may also occur as a secondary or opportunistic infection in
patients with herpetic keratitis.
Current methods of investigations for Acanthamoeba keratitis includes:
• Staining of corneal material with Calcofluor white stain in addition to

gram and Giemsa stains.
• Cultures of corneal scrapings and contact lens and contact lens
containers on non-nutrient agar with E coli overlay. Buffered charcoal-
yeast extract agar is another excellent culture medium that is readily
available.
• Corneal biopsy is also needed if the gram stain and cultures are
negative.
• Confocal microscopy can also be a useful non-invasive method of
examination in patients with suspected Acanthamoeba keratitis. High
contrast round bodies suggestive of Acanthamoeba cysts, and
irregular forms suggestive of Acanthamoeba trophozoites are seen.
Occasionally the confocal microscope can also reveal the
characteristic double walled structure of the Acanthamoeba ectocyst.
Radial kerato-neuritis may also be seen. Confocal microscopy
diagnosis may be confirmed by histological examination and PCR
analysis of epithelial biopsy.
Acanthamoeba scleritis is rare, it may be associated with a poor

prognosis, even with intensive medical and surgical treatment.
Acanthamoeba infection should also be considered in the differential
diagnosis of uveitis and endophthalmitis in AIDS patients. Diagnosis may
be confirmed by finding the Acanthamoeba cysts in aqueous and vitreous
samples. Topical treatment with anti-amoeba drugs does not seem to be

effective.
treatment
The prognosis of Acanthamoeba keratitis has improved due to increased

awareness and early diagnosis of the disease, and also due to the
improvement of treatment. A high level of suspicion (especially in contact
lens wearers) is needed to achieve early diagnosis and effective
treatment. Prompt diagnosis and medical treatment, and avoiding topical
steroids can lead to cure in most cases of Acanthamoeba keratitis with
excellent prognosis for vision. 79% of all eyes and 70% of culture positive
eyes may achieve a final visual acuity of 6/12.
Most patients with Acanthamoeba keratitis can expect a good visual

prognosis and cure by medical treatment alone if diagnosed early. The
current topical anti-amoebic used at present are:
1. Diamidine derivatives e.g. Brolene, and Desomedine.

2. Biguanide derivative e.g. polyhexanide (PHMB), and chlorhexidine.
The most commonly used medical treatment in the UK is
polyhexamethylene biguanide (PHMB) which is non-toxic and effective
against trophozite and cysts forms.
3. Propamide may also be used in combination with the PHMB. The
combination of chlorhexidine and propamidine seems to have an
effective amoebicidal action within the cornea. The use of this
combination may shorten the period and reduce the frequency of using
anti-Acanthamoeba medications and consequently reduce their toxic
side effects and also reduce the development of resistance to these
drugs.
4. Neomycin. The role of Neomycin in the treatment of the disease is
controversial. Neomycin is known to be a poor cysticidal agent but a
good trophozoicidal agent. The addition of Polyhexamethylene
biguanide to neomycin and propamidine may dramatically improve the
clinical response in eyes with Acanthamoeba keratitis.
Medical treatment needs to be used for a long time, recurrences may

occur if the treatment is discontinued after a short period. Corneal
epithelial toxicity seems to be common with all drugs (probably with the
exception of PHMB). Topical steroids are useful in cases with deep
corneal involvement with limbitis and uveitis. Steroids should not,
however not be started till the disease seems to be under control with the
anti-amoebic drugs.
Regular cleaning and replacement of contact lens containers and the

use of sterile commercial cleaning, disinfecting and rinsing solution may
be important and effective in removing the Acanthamoeba from the
contact lenses. Disinfection for more than 3 hours in H2O2 is
recommended. Tap water should not be used in the cleaning process of
the lenses. Sodium salicylate may successfully reduced amoebal

trophozoite attachment to hydrogel lenses. This effect may be due to
inhibition of biofilm formation, direct effect on the amoebae, or due to
alteration in the biofilm–amoebal attachment resulting modification of the
hydrogel lens surface.
About 39% of patients may need therapeutic penetrating keratoplasty,

most of these eyes are associated with delayed diagnosis. Penetrating
keratoplasty is often indicated in quite eyes with gross corneal scarring or
in acute eyes impending perforation. The outcome of surgery is much
better in eyes medically controlled before surgery. Cataract, Intumescent
cataract and glaucoma, graft rejection are the main complications after
surgery. Penetrating keratoplasty have good results in quiet eyes but in
inflamed eyes the results are often compromised by complications .
Others Infections
cat scratch disease
Cat scratch disease is a systemic disease characterised by

lymphadenopathy, fever, and malaise. The disease is probably caused
by Bartonella henselae infection (a gram negative bacilli belonging to
the order Rickettsiales). Transmission from cats to patients often occurs
via flea bites. The disease can also be transmitted by bites from an
infected animal (often a cat or a dog).
Patients often develop an erythematous papule or pastule followed by a

systemic rash within days or weeks. The typical ocular features are
painful regional lymphadenopathy and follicular conjunctivitis. The
disease may also be associated with serous retinal detachment of the
macula, neuroretinitis, a retinal white spot syndrome, intermediate uveitis
and retinal vasculitis, unifocal choroiditis, inflammatory mass of the optic
nerve head producing acute loss of vision and focal choroiditis. An
unusual, well-defined retinal opacification with features of both multiple
retinal arteriolar occlusions and a low-grade retinitis has also been
described.
Rochalimaea henselae infection should be considered in intraocular

anterior and posterior inflammation with optic nerve swellings even in the
absence of a history of cat scratch or lymphadenopathy. Improvement in
the inflammation and in the visual acuity can be achieved by oral
ciprofloxacin, Rifampicin or Doxycycline and steroids. Diagnosis of this
disease can be confirmed by specific enzyme-linked immuno-assay
(ELISA) serologic tests, as well as lymph nodes, conjunctival or skin
biopsy.
mycobacterium keratitis
Non-tuberculous mycobacterium are now recognised as an important

cause of microbial keratitis. Several reports of Mycobacterium fortuitum
and Mycobacterium chelonae keratitis have been published. Corneal
ulcers often develop after foreign body injuries (metallic foreign bodies),
after surgical procedures or after contact lens wear. Clinical features
include satellite or ring infiltrates, crystalline keratopathy and hypopyon.
Mycobacterium keratitis is generally difficult to treat. Amikacin remains
the main line of treatment of mycobacterium keratitis, however, failure of
treatment or resistance may develop. Topical clarithromycin, ciprofloxacin
and combined amikacin and vancomycin may all be clinically useful in
the treatment of this infection. Ciprofloxacin is effective in the treatment
of Mycobacterium keratitis, but the drug appears to be less effective
against M. chelonae than M. fortuitum in vivo studies. Topical
ciprofloxacin may be effective even in cases that does not respond to
amikacin treatment. Lamellar keratectomy should be considered in
medically resistant cases, and also for corneal involvement of 80%
thickness or more. This method of treatment can help to obtain a

specimen for biopsy, eradicate the micro-organism, and facilitate drugs
penetration
Allergic Diseases
atopic keratoconjunctivitis
Atopic keratoconjunctivitis is the most serious, sight-threatening allergic
manifestation of atopic diseases in the eye. Atopy should be considered
in the differential diagnosis of severe keratoconjunctivitis even in the
absence of systemic findings of atopy. About 70% of patients have some
type of keratopathy, 60% have corneal neovascularisation, and 20%
have symblepharon. Conjunctival biopsy and serum Ig E are valuable
measures in making the diagnosis. The impression cytology technique
may also be used. Loss of goblet cells and conjunctival squamous
metaplasia have been previously demonstrated. Cataract,
rhegmatogenous retinal detachment, and keratoconus, may also be
associated with the disease. Higher levels of aqueous flare caused by
the breakdown of blood-aqueous barrier may contribute to the formation
of cataract in patients with atopic dermatitis.
Successful long-term control of symptoms can be achieved with medical

treatment by mast cell stabilisers, antihistamines, and ocular lubrication
(with unpreserved saline solution). Short-term topical or systemic steroid
therapy may be needed during exacerbation. Topical cyclosporin 2%
eye drops may also be used, the drug seems to reduce the severity of
symptoms. The mechanism of action may be due to inhibition of CD 4 T-
lymphocytes. Systemic cyclosporin A may also be an alternative therapy
in severe cases. Some food antigens may contribute to the pathogenesis
of severe atopic dermatitis and its ocular complications.
vernal disease
Vernal keratoconjunctivitis is a chronic eosinophilic disease of the ocular
surface involving Ig E, no-Ig E-mediated mechanisms. The disease often
has a good prognosis. Severe visual impairments may, however, result
from long-standing inflammation. Large giant papillae indicates poor
prognosis for the persistence of the disease and its evolution into a
chronic, perennial condition. A reduction of visual acuity may result from
corneal scarring, or steroid-induced glaucoma.
Multiple mechanisms have been implicated in the pathogenesis of vernal

disease. Histamine is the most significant mediator in this disease.
Histamine is secreted by mast cells and activated basophils. Increased
tear histamine levels is due to increased production by the mast cells and
their de-granulation. Decreased histamine degradation by the enzyme
histaminase in tears and plasma has also been shown in patients with
vernal diseases. Alteration in the ratio between collagen and
proteoglycan and between the different types of collagen also seems to
play a role in the development of the morphological abnormalities
associated with this disease. There is also accumulation of CD 4+ cells,
plasma cells, eosinophils, Ig E cells irrespective of the atopic status of the
patient. The role of the allergen-specific Ig E sensitisation in the
pathogenesis is not clear. Increased expression of adhesion molecules
also play an important role. Adhesion molecules play a key role in the
selective recruitment of different leucocytes population to inflammatory
sites.
Conjunctival eosinophils are considered the histological hallmark of

vernal kerato-conjunctivitis. There seem to be a significant correlation
between eosinophils cationic proteins value, and disease severity in all
conditions. Serum, and tear levels of eosinophils cationic proteins (a
product secreted by activated eosinophils) are significantly higher in
vernal disease patients, and may be used as a marker for ocular
inflammation. Extra-cellular deposition of eosinophils granules major
basic protein has also been found in the conjunctiva in patients with
vernal keratoconjunctivitis. The success of superficial keratectomy in
some forms of vernal keratopathy could be explained in part by the
removal of this protein deposits.
In vernal keratoconjunctivitis patients, the tarsal and bulbar conjunctival

epithelium and sub-epithelium contain more oestrogen and
progesterone receptors than in non atopic controls. Most of the cells
positive for the oestrogen and the progesterone receptors are
eosinophils. Sex hormones through their receptors may influence the
activity of eosinophils. This may explain the natural history of the disease
with the usual spontaneous resolution of activity by the age of about 30
years of age.
clinical features
Patients typically present with redness and itching. Patients with vernal
disease, may also present with acute hydrops as the presenting sign of
keratoconus. Corneal hydrops may indicate undiagnosed keratoconus
especially if associated vernal conjunctivitis. Impression cytology is a
simple, cheap and non-invasive technique that can be used in studying
cellular reaction in eyes with vernal conjunctivitis. In vernal conjunctivitis
the mean number of goblet cells is significantly higher than in controls
and the diameter of the goblet cells seem to be smaller. The disease can
be classified into palpebral and a limbal types. In temperate regions
limbal inflammation is severe, but the palpebral manifestations
predominates.
treatment
Mast cell stabilisers and antihistamines have been used successfully for
many years to reduce the ocular signs and symptoms of the disease.
Cromolyn sodium is the classical treatment of vernal eye disease.
Cromolyn is thought to act by reducing calcium transport across the mast
cells membrane and subsequently inhibiting histamine release. A new
theory hypothesise that cromolyn interferes with protein synthesis and
therefore, with receptors mediated changes in the mast cells.
Nedocromil sodium is a recent inhibitor of activated inflammatory cells

(e.g. eosinophils and mast cells), that seems to be more efficient in
inhibiting activated inflammatory cells than sodium cromoglycate. Unlike
sodium cromoglycate, which appears to stabilise only connective tissue
type mast cells, nedocromil sodium also stabilises mucosal mast cells
which is the predominant type of mast cells in vernal disease. A double
masked comparative study of four times daily 2% Nedocromil sodium,
2% sodium cromoglycate and placebo found that both drugs are effective
in controlling vernal keratoconjunctivitis. The Nedocromil sodium,
however had a more pronounced overall therapeutic effect.
Levocabastine (Livostin) is a newly synthesised histamine H1 receptor

antagonist. A single dose of 0.05% Levocabastine seems to be more
superior than cromolyn 4 times / a day for treating allergic conjunctivitis, it
also has a duration of action of at least 4 hours.
Lodoxamide (Alomide) is a new drug that has been shown to reduce the
ocular signs and symptoms in vernal conjunctivitis, presumably by
inhibiting mast cell de-granulation and the toxic effects of eosinophils-
derived products on corneal epithelium. In a recent study the drug
significantly reduced eosinophils activation and seemed to be more
effective than sodium cromoglycate in reducing clinical signs and
symptoms. Patients treated with lodoxamide seem to have a better
symptoms and signs score than those who are treated with over
cromolyn sodium. Clinical superiority of lodoxamide over cromolyn
sodium may be linked to its greater effect on the CD4+ cells, because
CD4+ cells plays a pivotal role in the pathogenesis of vernal

keratoconjunctivitis.
Topical Cyclosporin eye drops 2% has recently been shown to be

effective in the treatment of vernal kerato-conjunctivitis without significant
side effects. The clinical improvement after Cyclosporin treatment may
result from its immune modulator effects on the components of cell-
mediated and humoural immune response. Within the first month of
treatment, both the symptoms and signs of the disease improve
significantly (particularly papillary proliferation). The drug does not seem
to have an effect on the mast cell or the Ig E-mediated allergic response.
Supra-tarsal injection of steroids may be associated with dramatic

relieve of symptoms and signs in patients with refractive vernal
keratoconjunctivitis. Short acting steroids (Dexamethasone) and long
acting steroids (Triamcinolone) are equally effective but short acting
steroids do not seem to be associated with raised IOP. The steroid is
injected by a 30 gauge needle in the space between the conjunctiva and
the Muller muscle about 1 millimetre above the superior tarsal margin
after a small amount of local anaesthesia.
Olopotadine is a new anti-allergic drug that has a double antihistamine

and mast cell stabiliser action. The drug, in concentrations of 0.05% and
0.1%, has a rapid and prolonged anti-allergic action that may last for up
to 8 hours.
Low dose (0.01%) topical Mitomycin C may be useful in the treatment of

resistant cases with vernal disease. The effect of the drug seems to be
due to its anti-proliferative effects on the conjunctival mast cells.
In vernal keratoconjunctivitis patients, shield corneal ulcers or plaque,

that do not re-epithelialise after controlling the disease activity, should be
treated surgically. A simple scraping of the base and margins of the ulcer
with removal of the inflamed material results in rapid re-epithelialisation.
Complications of delayed corneal healing include bacterial infection,
amblyopia, corneal scarring, vascularisation and possibly perforation.
Corneal Dystrophies
lattice dystrophy
Lattice corneal dystrophy is characterised by the presence of refractile
dots and fine lines in the anterior corneal stroma. The stromal lines
gradually become larger and thicker. The intervening cornea typically
stays clear. There are three clinically and histopathologically distinct
types of lattice dystrophy:
1. Type (I) and type (II) which are autosomal dominant.

2. Type (III) which is autosomal recessive.
Type I tends to have more numerous deep and more central lines into the
stroma than type II, it also progresses more rapidly. Type II manifests by
the age of 20 and rarely needs corneal transplantation, it is often
suspected by the typical facial features of the patient (droopy lids and
protruding lips). Only type II is known to be associated with systemic
Familial Amyloidosis Finnish type (FAF), also called (Meretoja)
syndrome. In lattice dystrophy Type II (Meretoja Syndrome), the corneal
lines are less numerous but thicker than in Type I. The lines are also
radial and extend from the corneal periphery to the centre of the cornea.
Visual acuity are often normal until later years. The vast majority of
families with this disorder originate from Finland. Recently a genetic
defect underlying Meretoja Syndrome has been discovered. The anti-
FAF antiserum should prove useful for rapidly screening corneal buttons
to determine whether there is any evidence of FAF in lattice type II.
Recurrent corneal erosions may occur and patients may be particularly
susceptible to microbial keratitis as a result of repeated epithelial
disturbances and ophthalmologists should remain alert to the possibility
of sight-threatening infective complications.
macular corneal dystrophy

Macular corneal dystrophy is the least frequent types of stromal
dystrophies. It is characterised by the presence of cloudy corneal stroma
in both eyes with superimposed discrete white opacities that enlarge and
merge together with time. The basic metabolic abnormality in macular
corneal dystrophy is an abnormal synthesis of corneal
glycosaminoglycans. Macular corneal dystrophy may be classified into:
1. Type I (no antigenic keratan sulphate activity in the serum and in the
cornea). Type I A, is characterised by the lack of detectable antigenic
keratan sulphate in the serum, and a corneal stroma that does not
react with the keratan sulphate monoclonal antibody but in which
corneal fibroblasts react with keratan sulphate monoclonal antibody.
2. Type II (detectable and normal of serum and corneal levels of
antigenic keratan sulphate activity).
Macular dystrophy is a genetically determined disease. The gene for type

I dystrophy has been located to chromosome 16q22 and it is presumed
that type II is also liked to this location. Both types may occur together in
a single patient. The finding of both type in the same sibling in a family
provides an evidence to the hypothesis that both diseases are localise
din the same chromosome.
avellino corneal dystrophy

Avellino corneal dystrophy is a relatively new type of stromal corneal
dystrophy which was originally described in patients originating from the
Italian province of Avellino. Avellino dystrophy is characterised by
anterior stromal deposits and deep fusiform stromal deposits. The
corneal deposits have been shown to be amyloid material. There is a
substantial phenotype variation in patients with this dystrophy. Granular,
lattice type I and Avellino dystrophies have been independently linked to
the same region on chromosome 5q. Histological evidence also suggests
that these dystrophies are caused by mutation within the same gene. The
three diseases may be phenotypic variations caused by mutation in the
same gene.
schnyder corneal dystrophy

Schnyder dystrophy is an autosomal dominant, bilateral, symmetrical
stromal dystrophy that often affect the anterior 1/3 of the corneal stroma.
It is characterised by the deposition of needle shaped polychromatic
cholesterol crystals. Visual acuity is often not affected. Schnyder
dystrophy is thought to be due to a primary abnormality of the corneal
lipid metabolism resulting in opacification secondary to lipids
accumulation. Phospholipids, unesterfied cholesterol and cholesterol
esters are the main lipids involved. Disturbance in the corneal
metabolism sphingomyelin has also been shown. The severity of the
primary corneal lipids metabolism abnormality may be altered by
systemic hyperlipidaemia.
Only 51% of patients with Schnyder corneal dystrophy actually have

clinical evidence of corneal crystalline deposits. The name (Schnyder
crystalline dystrophy sine crystals) has been proposed for patients
who do not demonstrate these typical corneal crystalline deposits. The
corneal crystalline deposits may disappear in stromal areas underlying
areas of epithelial corneal erosions. In patients with superficial stromal
opacities (without stromal haze) epithelial debridement or excimer photo-
therapeutic keratectomy may be an alternative treatment to penetrating
keratoplasty. The dystrophy may recur after penetrating keratoplasty.
keratoconus
basic science
keratoconus is characterised by corneal ectasia. The anterior and the

posterior corneal curvature are affected in the disease. Electron
microscopy studies show that the earliest stages of the disease occurs in
the corneal epithelium layer. The pathological process in keratoconus
results from enhanced matrix metalloproteinase activity. In vitro and
vivo analysis show that a gelatinase of molecular weight 65000 is the
major protease secreted by normal keratocytes, whereas keratocytes
from keratoconus cornea and traumatised corneas secrete an additional
types of gelatinase with a molecular weight 61000. The enzymatic
abnormalities are mainly seen in the corneal epithelial layer. It has also
been shown that the conjunctival epithelium may be altered in patients
with keratoconus in a manner similar to the corneal epithelium.
clinical features
Keratoconus is often diagnosed at adolescence. In patients with vernal

disease acute hydrops may be the presenting sign of keratoconus. The
presence of corneal hydrops may indicate undiagnosed keratoconus
especially if associated with vernal conjunctivitis. Acute hydrops may also
occur in Down’s Syndrome, and in congenital rubella presumably due to
eye rubbing. It is often caused by a rupture of the corneal endothelium
and the Descemet’s membrane, resulting in corneal oedema and
opacification. Intra-stromal clefts formation have also been described in
some eyes. These clefts seem to close with time but corneal
neovascularisation commonly develop, compromising the results of future
possible penetrating keratoplasty operations.
The use of Botulinum ptosis, topical and sub-conjunctival steroids may

achieve a quick recovery and resolution of hydrops in Down’s Syndrome
patients. Topical steroids may reduce inflammation and subsequent
corneal scarring. Contact lens wear in patients with corneal hydrops
may lead to infectious keratitis and corneal perforations and should not
be worn during the acute phase of the disease. Corneal perforation is
uncommon in uncomplicated disease. Black race and young age at
presentation are also significant risk factors for the progression of the
disease. Sex, laterality, systemic atopic diseases and family history do
not seem to be statistically related to the outcome.
The incidence of "unilateral" keratoconus appears to be very low.

Patients initially diagnosed with unilateral keratoconus, when observed
for a sufficient period of time, commonly had signs of keratoconus
developing in the opposite eye. Videokeratography is useful in detecting
early sub-clinical cases of keratoconus. Videokeratography in most
patients shows an inferior corneal steepening in the fellow eyes. The
possibility that all cases of unilateral keratoconus may eventually become
bilateral should be considered.
Three dimension scanning electron microscopy shows alterations in the

Bowman’s membrane layer specific to keratoconus (lattice like
configuration and collagen scar tissue). Fragmentation of Bowman’s

membrane layer may be an early sign of keratoconus.
treatment
irregular astigmatism is a major problem in the disease. One method of

correcting the irregular astigmatism is by the Piggyback contact lens.
Piggyback contact lens is a PMMA hard contact lens placed on a soft
contact lens base obtaining better fitting and centration with the soft lens
and better optical correction with the hard lens. Animal studies showed
that the oxygen pressure under Piggyback lenses is higher than under
PMMA lenses when used alone.
Corneal grafts in keratoconus patients stabilise quickly and usually

achieve good visual results. Recurrence of keratoconus is a rare cause
of corneal graft failure. Keratoconus recurrence is believed to be due to
either incomplete initial excision of the corneal cone, or due to abnormal
host keratocytes or epithelial cells infiltrating the donor tissue and
causing the pathological changes to recur. A graft in the second eye
seems to increase the risk of failure to the graft in the first eye. Surgery to
the second eye should be delayed as much as possible if there was a
rejection episode affecting the first eye. Prophylactic treatment to the first
eye could be considered at the time of surgery to the second eye. The
overall survival of corneal grafts in the second eye is better than in the
first eye unless there was a history of rejection in the first eye which
increases the risk of rejection in the second eye as well.
posterior keratoconus
Posterior keratoconus is an abnormal variation of the posterior corneal

curvature. This uncommon non-inflammatory disorder is generally
considered a developmental anomaly, although acquired and post-
traumatic varieties also have been described. The distinct topographic
patterns seen probably warrant a further classification of localised
posterior keratoconus into central-paracentral and peripheral varieties.
Dry eye syndrome (KCS)

The prevalence of dry eyes is not exactly known, it varies between
different studies, because studies use different signs or tests in making
the diagnosis. The diagnosis and the grading of dry eye disease is not
often easy. The Ocular surface Disease Index is a 12 item
questionnaire developed by Allergan Inc to provide a rapid assessment
of the symptoms of the disease and the impact of the disease on the
visual function. The index has a good reliability, validity, sensitivity and
specificity. The index could also be used for comparison and assessment
of treatment for this condition.
The disease may be caused by two main mechanisms:
1. Tear deficiency which may be due to Sjogren’s or non-Sjogren’s

syndrome causes.
2. Excessive evaporation, which may be due to oil deficiency , lid
retraction, contact lens wear, or surfaces changes. Evaporation of
tears is higher in patients with dry eyes than in patients with normal
eyes and this increased evaporation seem to account for the majority
of tear loss in these eyes. Lipid secretion from the meibomian glands
are important in reducing the ocular surface water evaporation and
preventing dry eyes.
Conjunctival squamous metaplasia is often observed in the conjunctival

epithelium in eyes with keratoconjunctivitis sicca. The expression of type-
1 growth factor receptors is greatly increased in the conjunctival
epithelium of these eyes. This may explain the conjunctival changes
seen in this disease.
tests
This is a summery of some of the tests used in the study of dry eyes:
Test comment
Tear turn over Tear turn over is the percentage decrease per minute of
fluorescein concentration in tears after the instillation of
fluorescein drops. Tear turn over can be determined by
fluoro-photometry. The tear clearance rate test is a simple
and useful method to estimate basal tear turn over and tear
flow, it can also indirectly measure the tear drainage.
Tear function index Tear function index is the combined values of both tear
secretion and tear drainage tests. It is the value obtained
from dividing the value of Schirmer’s test with local
anaesthesia by the tear clearance rate. This index is more
specific and more sensitive in diagnosing dry eyes
associated with Sjogren’s syndrome than the Schirmer’s or
the tear clearance rate test alone. Tear function index below
96 are consistent with dry eyes and those below 34 are seen
mainly in patients with Sjogren’s syndrome. Meibomian gland

secretions are important in reducing tear evaporation and
preventing dry eye
Rose Bengal Rose Bengal stain is inversely correlated with bulbar
staining conjunctival goblet cell densities and with the absence of
bulbar conjunctival mucous membrane mucin expression.
Preferential distribution of rose bengal staining in the non-
exposed parts of the ocular surface characterise lipid tear
deficiency dry eye and may helps to differentiate it from liquid
tear deficiency. Rose Bengal stain is thought to stain only the
degenerated conjunctival cells and mucous
Lissamine green Lissamine green is a synthetic organic acid dye that is used
staining as a food dye. It has been shown to have the same staining
profile as Rose Bengal with better tolerance by patients.
Meibography Meibography can objectively assess meibomian gland
dysfunction. Patients with meibomian gland drop out have an
increased risk of developing dry eye due to increased tear
evaporation, even if the tear production by the Schirmer’s test
is moderately reduced because the evaporation rate in these
patients is very high.
Infra-red ocular This test can be used in the objective assessment of dry
thermogram eyes. The evaporation of tears reduces the temperature of
the cornea. The mean ocular surface temperature of dry eyes
is greater than normal. There is also a greater variation of
temperature across the ocular surface in dry eyes. The tear
lipid layer pattern is highly correlated with dry eye severity.
Dry eyes are characterised by non-uniform distribution of the
tear lipid interface or by partial exposure of the corneal
surface.
The tear lipid layer this tear pattern can be observed by a special non-invasive
interference pattern and non-contact specular reflection video-recording system.
The study of the tear lipid layer may lead to useful and
reproducible information in the diagnosis of dry eyes. There is
an association between blink rate, maximum blink interval
and ocular surface conditions.
Abnormal pattern of Abnormal pattern of blinking is often considered to be due to
blinking a psychological or emotional disorder. External eye diseases
can also significantly affect patients pattern of blinking. The
use of artificial tear drops may in some patients normalise the
pattern of blinking. The blink rate and the maximum blink
interval, are significantly different in dry eye patients
compared with healthy eyes. An automated non-invasive
blink monitor that allows quantitative analysis of blinking has
described.
H185 monoclonal These antibodies have been linked to a mucin like
antibodies glycoprotein produced by the epithelial cells of the ocular
surface. The binding of H185 monoclonal antibodies to the
epithelial cells seem to be absent or severely reduced in
keratinised ocular surface epithelium. Changes in mucous
contents of tears may occur in various types of external eye

diseases, and dry eyes.
Impression cytology Impression cytology with ELISA and the tumour marker CA
19-9 may be used in the measuring glycoproteins of the
mucin.
management
Ocular surface area and evaporation is greater on looking up than on

looking ahead or down. Increased tear evaporation is thought to be the
main cause of ocular fatigue in VDTs users since they have a greater
exposed ocular surface area and reduced rate of blinking. It is
recommended that VDTs to be placed at a lower level to allow a lesser
exposed surface area and lesser tear evaporation, and also that VDTs
users to keep their eyes partially closed and to blink frequently.
Dry eyes with decreased BUT time may be associated with allergic
conjunctivitis and papillary reaction, raised serum Ig E and history of
allergic diseases. The decreased BUT time seems to be due to a
decrease in the conjunctival goblet cells due to the papillary conjunctival
reaction. A combination of anti-histamine and low dose of steroids may
used if the conventional methods of treatment fail.
Animal studies in dogs showed significant increase in the tear production

in dogs with dry eyes after the administration of topical Cyclosporin.
Patients with renal allograft recipients who are treated with systemic
Cyclosporin, show a significant increase in the tear production. Systemic
Cyclosporin appears to increase tear flow even when no lacrimal auto-
immune disease exists. Topical cyclosporin 0.05% and 0.1%
significantly improve the ocular signs and symptoms of moderate-to-
severe dry eye disease, and decreased the effect of the disease on
vision-related functioning. Cyclosporin A 0.05% and 0.1% appear to be
safe and well tolerated. Administration of 5-mg pilocarpine tablets 4
times daily (20 mg/d) may produce a significant improvement in
symptoms of dry eyes and other xeroses in patients with Sjögren
Syndrome.
Bicarbonate containing solutions are valuable in patients with severe

dry eyes, not only for the comfort of the eyes, but also to promote the
recovery of the ocular surface. Carbomer gel is a water-soluble polymeric
resin that has been reported to maintain the tear film in contact with the
eye for an extended period. The drug appears to be more efficacious
than placebo in improving a number of subjective and objective
symptoms of moderate-to-severe dry eye syndrome. Sodium
hyaluronate, when used 6 times a day dose not appear to offer subjective
advantages to patients more than the conventional tear drops, but it may
have a role in maintaining a healthy corneal epithelium, promotes corneal
epithelial wound healing and protects the corneal epithelium.
Hyaluronan, Fermavisc, (sodium hyaluronate) is a polymer of acetyl

glucosamine and glucuronic acid that is widely distributed in the
connective tissue and vitreous. Topical application of the drug has been
shown to be more beneficial than normal saline in the subjective and
objective improvement in dry eyes.
surgical treatment
Punctal and / or canalicular occlusion may be used in patients with KCS.

A trial of temporary occlusion with collagen plugs may be used.
Permanent closure of the punctum may be accomplished by cautery, or
argon laser. Punctal occlusion by thermal cautery seems to give a
longer lasting effect than occlusion by argon laser. This might be due to
the ability of the thermal cautery to penetrate and coagulate deeper in the
canaliculus than the laser technique. Silicone plugs are a reversible
means of punctal occlusion that can be effective for long term treatment.
Migration of plugs into the lacrimal drainage system requiring surgical
removal has been reported. Permanent occlusion can be complicated by
very symptomatic epiphora.
Transplantation of autologous submandibular gland is a new method

that may be useful in the treatment of severe cases of KCS. It is
associated with a significant increase in the basal tear secretion and
relief of symptoms in patients with KCS.
The orbicularis muscle plays an important role in the pump mechanism of

the lower canaliculus and in tear drainage. It has recently been described
that injection of botulinum into the medial part of the eye lid may
decrease lacrimal drainage (as measured by the drop test) by interfering
with the orbicularis muscle function. This method may have potential in
treating dry eyes and improving patient’s comfort.
vitamin a deficiency and xerophthalmia
Vitamin A deficiency may be associated with protein calorie malnutrition,

with chronic hepatic or biliary disease, cystic fibrosis, and intestinal
disease. Breast feeding appears to be highly protective against this
condition. Vitamin A deficiency is a major cause of morbidity and mortality
among pre-school children in many parts of the world. It is also a leading
preventable causes of childhood blindness in the world. Vitamin A
deficiency may lead to Xerophthalmia which is often associated with
corneal xerosis, Bitot’s spots and corneal ulceration.
Impression cytology is useful technique in the evaluation of vitamin A

deficiency. The test may show alteration in the external eye that is not
seen by fluorescein or rose bengal staining. Diagnosis on the basis of
impression conjunctival cytology should, however, be made with caution
in areas endemic with trachoma, as children with trachoma are likely to
have an abnormal result on impression conjunctival cytology.
The current World Health Organisation protocol for treating children 1

year of age and older with vitamin A is 200,000 IU oral dose every 3 to 6
months for prophylaxis and 3 times of this dose for the treatment of
xerophthalmia. Approximately 8% of children treated prophylactically with
vitamin A have side effects (e.g. nausea, vomiting and fever). Although
these side effects are transient, they may decrease community
compliance with the treatment. The most important factor in predicting
response to treatment is base line serum retinol concentration. Children
with lower pre treatment concentrations are more likely to have
responsive lesions.
Cicatricial diseases
ocular cicatricial pemphigoid

Ocular cicatricial pemphigoid is characterised by conjunctival
inflammation associated with scarring in the form of symblepharon, and
shortening of the inferior fornix. Poor tear film and lid margin disorders,
may then lead to corneal ulceration, infection and ultimately loss of vision.
The disease is believed to be caused by the deposition of sub-epidermis
auto-immune deposits of anti-epithelial basement membrane zone
antibodies. It often affects both eyes, may be asymmetric and very rarely
may be unilateral. Most of the disorders leading to conjunctival and
mucous membrane scarring have an acute phase of activity followed by
scar formation. A chronic form of the disease can also be found in some
patients. The majority of patients with cicatricial pemphigoid have ocular
involvement and about 50% of them develop systemic manifestations.
Systemic manifestations of the disease include mouth, pharynx and
oesophagus lesions as well as nose, sinus and skin involvement. There
is no association between the ocular and system manifestations. Chronic
progressive cicatrising conjunctivitis may also occurs as a part of
paraneoplastic syndromes and also in association with some systemic
and topical medications (pseudo pemphigoid).
Circulating Ig A and Ig G auto-antibodies have been recognised.

Macrophages may also play an important role in the mechanism of the
disease by secreting fibrogenic cytokines (e.g. TGF-B). Blockers of the
fibrogenic cytokines may be of therapeutic importance. In ocular
cicatricial pemphigoid the conjunctiva is infiltrated with neutrophils,
macrophages, Langerhans cells, CD 8+, and CD 4+ in the acute stage,
and mainly by CD 8+ T-cells in the chronic stage. The mechanism of
fibrosis is not known but it may be due to an increased amount of
fibrogenic growth factors. Blister formation and tissue damage may be
caused by the release of eosinophilic granule proteins which may play a
role in the acute phase of the disease.
treatment
The need for treatment depends on disease activity. Super-added

bacterial or toxic conjunctivitis should be excluded and treated. Systemic
immunosuppression treatment is regarded to be the treatment of choice
of the disease. Broad spectrum medication (e.g. steroids) may be more
effective in the treatment of this disease than specific immuno-
suppressant drugs (e.g. cyclosporin). High doses topical steroids alone is
often ineffective in controlling the conjunctival inflammation.
Cylclophosphamide and short term high dose steroid is often effective in
treating severe ocular pemphigoid but may not completely prevent ocular
scarring.
Dapsone is the most effective initial agent for active disease, it is also a
safer treatment in the elderly than steroids. Dapsone commonly induces
significant haemolytic anaemia (more commonly in patients deficient in
the enzyme glucose 6-phosphatase dehydrogenase). Patients are also at
higher risk of agranulocytosis. Dapsone-induced neutropenia may not be
dose dependent and routine white blood cells monitoring (specially 8 to
10 weeks after treatment) in needed. A taste disturbance and tingling
sensation in the mouth and lips has been reported as a side effect of
Dapsone.
Suggested system for treatment of mucous membrane pemphigoid:
severity drug follow up

mild • topical steroids IOP
moderate • sulphapyridine • Full blood count.

• dapsone • urea and electrolytes.
• G6PD screening.
severe • systemic prednisolone • Full blood count.
• cyclophospham (in older • urea and electrolytes.
patients) • blood pressure.
• azathioprine • chest X ray.
• methotrexate • liver function tests.
• cyclosporin (in younger • urine analysis.
patients)
Intravenous immunoglobulin treatment may also be effective in

arresting progress in cicatricial ocular pemphigoid in resistant cases. The
treatment consists of cycles which can be repeated every 2 to 6 weeks.
Each cycle involve administration of 2 to 3 g/Kg body weight of the
immunoglobulin over a 3 days. Other drugs that has been used include
Sulphapyridine and Interferon Alfa-2
In patients with cicatricial obliteration of the conjunctival fornices, surgical

lysis of the adhesion followed by intraoperative application of 0.4 mg
Mitomycin C / ml in saline for 3-5 minutes seems to be useful in
preventing fornices shrinkage. Sub-conjunctival injections of Mitomycin C
might be effective in preventing progression of the disease.
Conjunctival surgery and opening the conjunctiva should be avoided in

the acute stages of the disease when possible. Ocular pemphigoid and
Sjogren’s syndrome have always been difficult to treat because of the
immediate recurrence of the adhesions. Mucous membrane grafts can
successfully protect the corneal surface without provoking the
conjunctiva inflammation in most cases, but in the long term
complications eventually develop in a large number of patient. Mucous
membrane grafts should not be performed in severe keratoconjunctivitis
sicca, very advanced ocular cicatricial pemphigoid or active conjunctiva
inflammation without proper immunosuppressive treatment.
Penetrating keratoplasty in patients with advanced cicatricial

conjunctivitis disease can be performed for tectonic reasons. Visual
restoration is often limited even after intensive medical treatment. The
major causes of failure of the penetrating keratoplasty are epithelial
defects, stromal ulceration, perforation, and infections .
stevens-johnson syndrome
Stevens-Johnson Syndrome is associated with severe purulent
conjunctivitis which often leads to severe conjunctival cicatrization
resulting in trichiasis, symblepharon conjunctival and corneal scarring
and ultimately blindness. Steven-Johnson Syndrome may be caused by
an autoimmune mechanism. The disease has been associated with
certain HLA tissue types (e.g. HLA-BW 44, and HLA-DQB 10601).
Patients with this tissue types may be at higher risk of developing ocular
complications. Drugs (e.g. sulphonamides) are the most frequent
identified aetiological factor in the cicatricial eye diseases
Systemic steroids during the acute phase of the disease appears to have
no effect on the development of ocular manifestations. Topical
antibiotics, steroids, lubricants and symblepharon lysis are required.
Autologous conjunctival transplantation to promote normal trans-
differentiation of the corneal cells has been tried in unilateral cases. In
bilateral cases affecting the conjunctiva and the cornea, transplantation
of the conjunctiva and the cornea from a cadaver eye has also been
suggested. Amniotic membrane transplantation restores adequate
bulbar surface and fornices depth and prevents recurrence of
symblepharon in severe cases of Stevens-Johnson Syndrome. A
combination of allograft limbal transplantation, amniotic membrane
transplantation and tarsorrhaphy followed by the use of serum derived
tear drops may reconstruct the ocular surface and lead to significant
improvement in vision.
Surgery Of The Cornea
Penetrating keratoplasty
The indications for penetrating keratoplasty have changed over the past
20 years. Keratoconus, endothelial failure, corneal scarring secondary to
corneal infection, aphakic bullous keratopathy and interstitial keratitis are
currently the main indications for penetrating keratoplasty in the UK.
Failed grafts are increasing as an indication for penetrating keratoplasty.
Graft clarity and visual acuity results, after repeat transplantation, appear
to be very good.
Preoperative considerations
The most commonly used storage media for donor corneas are the
Optisol medium and organ culture medium. Corneas can be stored in
the Optisol medium for up to 2 weeks (or 21 days in the Optisol GS
medium). Organ culture media have the advantages of longer storage
time, and the ability to detect infection in the donor cornea prior to
transplantation. Penetrating keratoplasty using donor corneas stored (for
up to 11 days) by either method seem to have the same results for up to
2 years after surgery.
Transmission of the donor disease to the recipient, through corneal

transplantation, is a very rare complication after penetrating keratoplasty.
The Eye Bank Association of America has developed certain
contraindications for donor corneal use. These contraindications
include:
1. Death of unknown cause.

2. Certain CNS disease of unknown nature and certain CNS infectious
disease (e.g. Creutzfeldt-Jakob disease and subacute sclerosing pan-
encephalitis).
3. Systemic infections (e.g. Septicaemia, endocarditis, AIDS, syphilis and
viral hepatitis).
4. Intrinsic congenital or acquired eye diseases.
5. Prior anterior segment surgery.
6. Choroid malignant melanoma has traditionally been considered as a
contraindication for donor corneal use. Recent studies, however,
showed that corneas transmitted from eyes with primary choroid
malignant melanoma have similar outcome to corneas transmitted from
healthy eyes, as long as the tumour has not spread to the ciliary body
or the iris.
Hepatitis B, and C, HIV-1 virus, and Creutzfeldt-Jakob disease can be

transmitted through corneal grafts. In HIV patients, serological testing for
HIV does not guarantee against infection, because patients may not test
HIV positive for as long as 6 months after infection. In these diseases, the
polymerase chain reaction may be able to detected the virus DNA in
donors tears and aqueous humour samples.
VZV and HSV-1 may infect the cornea. HSV in a donor cornea may
cause endothelial destruction and both primary graft failure and ulcerative
keratitis after transplantation. PCR and immuno-histochemistry are both
sensitive for the detection of HSV-1 in the cornea. A combination of PCR
and immuno-histochemistry increases the specificity for the diagnosis to
97%.
Other microbial contamination may also be transmitted through corneal

grafts. Immersion of donor corneas in 5 mg / ml solution of povidone-
iodine for 2 minutes significantly reduces microbial contamination without
significantly affecting the corneal structure.
Penetrating keratoplasty is often unsuccessful in patients with severe

ocular surface abnormalities (e.g. chemical burns, ocular cicatricial
pemphigoid or limbal stem cell deficiency). Impression cytology can be
used to diagnose and monitor corneal diseases with limbal stem cell
deficiency. Limbal allograft transplantation (see later sections in this
chapters) and intensive immune-suppression and steroid therapy may be
used for the reconstruction and preparation of corneas affected by these
diseases before corneal grafts are carried out.
Penetrating keratoplasty in children presents special problems.

Postoperative amblyopia often results in poor vision despite good
surgical results. Corneal grafting for congenital opacities In infants should
be performed as early as possible for unilateral as well as bilateral
involvement. Corneal neovascularisation is, however, a recognised
problem in penetrating keratoplasty surgery in children under 2 years of
age. This necessitates early removal of suture with its accompanying
problems. The postoperative course in children may be complex and
patients may require re-grafting.
Late endothelial failure is the commonest cause of graft failure 5 years

after surgery. The most important risk factor for late endothelial failure is
the low endothelial cell count in the donor cornea before surgery or
immediately after the operation. Taking care in choosing the donor
material may play a role in reducing the incidence of late graft failure.
In considering donor materials, it may be difficult to detect eyes that had

undergone previous PRK surgery even with microscopic examination.
Transplantation of corneas after PRK may be associated with high
postoperative hyperopia. Corneal topography by Videokeratography may
be used in detecting eyes that had undergone PRK. Confocal microscopy
may also be used to study corneas after PRK. Stromal changes can be
detected many months after surgery.
Surgical techniques
Astigmatism is a major problem after penetrating keratoplasty. Different

suturing techniques have been devised to reduce postoperative
astigmatism. Corneal grafts may be sutured by a single running suture,
interrupted sutures, or a combination of interrupted and running sutures.
A single running suture often results in more rapid visual rehabilitation

and less early astigmatism compared with the combined interrupted and
running single technique. In using a 24 bites single running sutures
technique, with postoperative sutures adjustment, the postoperative
mean astigmatism is reported to be about 2.7 +/- 2.2 D, compared to 3.9
+/- 2.5 D in the combined running and interrupted sutures technique.
Sutures adjustment can be made on the basis of retinoscopy, and
keratometry. The sutures should be tightened in the flat meridian and
loosened in the steep meridian. Suture adjustment may be done at 2 to 6
weeks after the operation. Continuos suture can also be adjusted during
surgery by using a keratoscope fixed to the microscope (Pollack
keratoscope). This technique allows quicker visual rehabilitation. The
long term benefits of this technique is not known.
The difference between the results of single running suture technique,

and combined running and interrupted technique is insignificant when
all the sutures are removed. Removal of continuos sutures after
penetrating keratoplasty may have unpredictable outcome. Corneal
astigmatism can change unpredictably, and by large degrees when
sutures are removed even up to 6 years after the operation.
The relationship between the donor cornea and the recipient bed seems
to be the most important factor in controlling postoperative astigmatism.
Malposition of the recipient and the donor cornea is a main cause for
postoperative astigmatism. The donor cornea is often cut about 0.5 mm
larger than the recipient corneal bed. It is suggested, however, that the
use of he same size trephine for cutting both the donor and the recipient
cornea may give less astigmatism, and better visual results. It has also
been suggested that cauterisation of the central cornea may improve
the postoperative refractive results of keratoconus patients.
Discrepancy in the corneal wound between donor and recipient cornea,

when cut by mechanical trephine, is one of the major factors influencing
the optical results of penetrating keratoplasty. Excimer and YAG laser
can be used for non-mechanical trephination of donor corneas. Laser
trephination has the advantages of reducing vertical tilt that is often
noticed with the traditional mechanical methods. Orientation notches can
also be produced with the laser which helps in the placing and orientation
of the donor cornea.
Non-mechanical trephination in penetrating keratoplasty with the

excimer laser is associated with less postoperative disruption of the blood
aqueous barriers than the conventional mechanical methods.
Postoperative non-randomised studies showed that laser trephination
produces lower keratometric astigmatism, high regularity of the cornea
surface and better corrected visual acuity. Non-mechanical trephination
with excimer laser for tectonic penetrating keratoplasty can also be used.
Graft failure and rejection
After penetrating keratoplasty the corneal endothelial cell density

decreases rapidly during the first three years after surgery. The mean
endothelial cell density continues to decrease by a 7.8% per year for 3-5
years after surgery compared to a rate of 0.5% in the fellow eyes. The
recipient peripheral cornea may also be affected in graft rejection. Eyes
with IOLs loose more endothelial cells with time.
The main risk factors for non-immune mediated graft failure includes:
1. Prior glaucoma or uveitis.

2. Vitreous surgery in the same time with the graft surgery.
3. Repeat graft surgery.
Allograft rejection accounts for at least 33% of all graft failure. It often
follows an inflammatory event (e.g. loose suture, suture track infection or
recurrent HSV infection). Patients with corneal transplantation may suffer
from recurrent episodes of unilateral or bilateral corneal grafts rejection
during periods of pregnancy and child birth, or after vaccination.
Rejection often occurs in the endothelial cells but may also rarely occur in
the epithelial layer or the stroma.
There are conflicting results regarding the role of human leukocyte

antigen (HLA) matching and A, B, O compatibility in corneal graft
rejection for low and high risk patients. The main antigenic stimulus for
allograft rejection is the major HLA system. There is a large number of
studies indicating that HLA class I matching offers a survival advantages
in high risk corneal grafts, while HLA-DR compatibility may lead to graft
rejection. The relative risk of graft rejection also seems to increase with
increasing mismatch in the HLA-A and B system. Currently it is
recommended that matching for class I (HLA-A and HLA-B) should be
carried out in high risk corneal transplants. The high incidence of graft
rejection in matched grafts indicate that several other histocompatibility
complex genes may play a role in graft rejection.
Steroids are the main drug for treating corneal graft rejections. The role
of systemic versus intensive topical steroids is not completely
understood. Some reports showed that, in cases with severe rejection,
topical steroids is not enough and systemic or intravenous pulse
treatment (500 mg prednisolone) may be needed. Other studies showed

that a single pulse treatment may be more effective than oral treatment.
Some recent reports demonstrated that systemic steroids treatment does
not appear to have any additional benefits over intensive topical steroids
in the treatment of graft rejection in patients with no risk factors. The
difference in the results in these studies may be due to different degrees
of rejection.
In high risk corneas, steroids treatment alone seems to be insufficient in

providing enough immunosuppression. Systemic and topical
cyclosporin may be needed. A 12 months course of the cyclosporin is
needed for maximal effects. Combined IV pulse methylprednisolone and
oral cyclosporin treatment may also be used.
Other drugs that showed beneficial effects in the treatment of graft

rejection include:
The anti-lymphocytes monoclonal antibodies CAMPATH-1H.

FK 506.
Rapamycin.
Mycophenolate.
Interleukin-1 receptors antagonists.
Mycophenolate is an immuno-suppressant that has been used in the

treatment of renal transplant rejection. The drug acts by inhibiting the
formation of guanosine nucleosides and consecutively purine synthesis.
Combined therapy with Mycophenolate and cyclosporin A seems to have
a marginal benefit, over mycophenolate alone, with no major
complications. The drug has also been shown to be effective and safe for
the treatment of corneal graft rejection (when used in combination with a
short course of steroid).
It has also been shown that topical treatment with interleukin-1

receptors antagonists suppresses corneal graft rejection in animal
corneas. The drug seems to reduce graft rejection by preventing activity
of recipient Langerhans cells. The drug may prove to be useful in clinical
practice.
Postoperative glaucoma
IOP increase in the early postoperative period occurs in about 12 % of all

patients undergoing penetrating keratoplasty. The measurement of IOP is
often difficult with the Goldmann applanation tonometer because of the
graft irregularities. Tono-Pen and pneumotonometer seem to be
associated with slight overestimation of the IOP. The minified
Goldmann applanation tonometer (in which the front of the prism is
reduced from 7 mm to 4 mm) seems to be as accurate as the
pneumotonometer and the Tono-Pen in measuring IOP after penetrating
keratoplasty.
Penetrating keratoplasty, cataract and pseudophakia
There is some controversy about the best approach in patients with co-
exiting lens and corneal opacities needing cataract surgery and
penetrating keratoplasty (e.g. Fuchs endothelial dystrophy). Some
authorities argue that triple penetrating keratoplasty, cataract extraction
and IOL implantation is better than consequential penetrating
keratoplasty followed by cataract surgery. The following table
summarises the different advantages and disadvantages for each
approach:
Triple procedure cataract surgery followed by

penetrating keratoplasty
Rapid visual rehabilitation. In Cataract extraction with the open sky
consequential surgery you need to wait technique is unsafe as the eye is at
until all sutures are removed in order to greater risk of expulsive haemorrhage
get a stable and accurate keratometry during the period after removing the
readings. cornea.
Good refractive and visual outcome Despite using regression formulae to
can be achieved by analysing the determine the individual surgeon own
surgeon own results and by using keratometry results, postoperative refractive
regression formulae to determine the results are still more accurate in
anticipated keratometry readings and consequential surgery when accurate
consequently the IOL power. Some biometry can be carried out.
studies showed that, in the absence of
a keratometry value, a keratometry
value of 7.49 mm can be used for
calculation of the power of the implant
as shown in. Videokeratoscopic data of
the peripheral recipient cornea may
result in improved postoperative
refractive outcomes.
Penetrating keratoplasty may hasten ECCE is associated with increased risk
the progression of lens opacities, and of posterior capsule rupture and vitreous
cataract surgery often leads to more loss than small incision
endothelial cell loss. phacoemulsification surgery.
There is no doubt that the triple procedure Other alternative approaches include
is beneficial in some patients who need performing the penetrating keratoplasty
rapid visual recovery (single eye patients), with ECCE followed later by accurate
or in patients for whom two operations biometry and secondary IOL implantation.
might be undesirable.
Deep lamellar keratoplasty

Previous studies demonstrated a progressive endothelial cellular loss
after penetrating keratoplasty surgery. Deep lamellar keratoplasty is a
new procedure in which pathological corneal stroma is completely
excised as far down as Descemet's membrane, at least in the pupillary
region. The operation may reduce the risk of corneal graft rejection,
and may lead to a marked improvement in postoperative visual acuity in
certain selected conditions e.g. keratoconus. Compared with penetrating
keratoplasty, deep lamellar keratoplasty allows endothelial cell counts to
be maintained for a longer period. In deep lamellar keratoplasty, the
postoperative endothelial density appears to be normal in most cases.
Difficult surgical technique is the main drawback of this procedure.
The difficulty in this technique is in determining, accurately, the depth of

the graft in the donor and the recipient cornea. Air injection has been
used to facilitate corneal dissection down to the level of Bowman’s
membrane. Balanced salt solution has recently been injected in the
corneal stroma to facilitate dissection. Fluid injection transfer the cornea
into a solid and opaque tissue that can be easily dissected. Fluid deep
lamellar keratoplasty has recently been reported to be a safe and
effective procedure, especially in bilateral keratoconus. The technique is
difficult and has a slow visual rehabilitation course.
Posterior lamellar keratoplasty
This is a new technique of corneal grafts that has recently been

described in patients with pseudophakic bullous keratopathy and Fuchs’
endothelial dystrophy. The technique involves transplanting the posterior
corneal stroma Descemet’s membrane and the corneal endothelium in
the pupillary area. A micro-keratome is used to create a 9 mm corneal
flap with a 350 micron thickness. A 7 mm trephination of the posterior
lamella is then fashioned. The donor posterior lamella is then
transplanted and sutured to the recipient bed. The corneal flap is sutured
with a continuos suture. It is thought that this procedure may have a
place and some advantages in diseases of the corneal endothelium. The
preservation of the anterior corneal layers preserves the refractive
surface and the refractive power of the eye. If the operation fails, a
penetrating keratoplasty can then be carried out.
Corneal Refractive Surgery
Laser In Situ Keratomileusis (LASIK)

Laser in situ keratomileusis (LASIK) is gaining popularity as a reliable
method for correcting medium and high myopia. The operation involves
excimer laser photoablation of the corneal stroma under a partial
thickness corneal flap, which may be hinged at one point or completely
removed. Flap complications are relatively common but rarely lead to a
permanent decrease in visual acuity. Flapped corneal buttons are more
likely to cause loss of visual acuity than free flaps.
The operation seems to be safe. Intraoperative or postoperative

complications does not appear to lead to serious visual loss in the
majority of patients. There is, however, a concern that Laser in situ
keratomileusis (LASIK) may be associated with so much thinning of the
central corneal stroma which may lead to corneal ectasia and iatrogenic
keratoconus.
Complexity of instruments and surgical technique is a main drawback of

Laser in situ keratomileusis (LASIK) surgery. Picosecond laser Myopic
keratomileusis is a new technique that allows laser application to the
corneal stroma without affecting the epithelium of the Bowman’s
membrane and also without the need for micro-keratome. It has been
shown, in animal model studies, that is possible to cut the corneal stromal
lenticule by the laser without the need for a micro-keratome. The laser
produces plasma formation, shock wave and gas cavitation within the
corneal stroma without affecting the epithelium or the Bowman’s
membrane. The lenticule can then be removed manually through a very
small flap. It has also been shown that this method can produce good
refractive results. The results appear to depend on the corneal thickness,
and may not last for longer than 6 months.
History of contact lens wear is very important in patient candidates of

refractive surgery. There is great individual variation in contact lens-
induced corneal changes among patients. Contact lens wear may lead to
an increase or a decrease in the corneal thickness. A recent study
showed that long-term contact lens wear results in a decrease in the
entire corneal thickness and an increase in the central curvature and in
the corneal surface irregularities.
Precise measurement of the corneal thickness is of great importance in

refractive surgery. Corneal thickness measurements with conventional
pachymetry, and computerised Videokeratography correlate poorly with
the refractive results of lamellar corneal surgery. Partial coherence laser
Doppler interferometer technique measures the central and peripheral
corneal thickness with high precision. This new technique does not seem
to be associated with significant inter-observer variability and is likely to
be more superior to the currently used ultrasound and the conventional
optical pachymetry technique. Very high frequency ultrasound is another

new promising method for studying the micro-anatomy of the cornea
before and after PRK surgery.
The results of LASIK is better for low to moderate myopia than for higher
myopia. Most studies show stability of refraction and adequate
uncorrected visual acuity in a large percentage of patients with myopia up
to 15.00 D. Laser in situ keratomileusis (LASIK) can also be used to
correct higher levels of myopia that cannot be successfully corrected by
PRK or RK procedures. It can also be used to reduce astigmatism and
myopia after penetrating keratoplasty. For myopia greater than 15.00
D, accuracy and patient satisfaction are poor. LASIK for high myopia may
be associated with early regression. Stabilisation often occur between 3
and 6 months. However, patients with high myopia show more
improvement in the visual acuity mainly due to the increase in the size of
images after surgery. Optical coherence tomography studies showed that
corrections of higher degrees of ametropia runs a high risk of producing a
thinner than expected central cornea, particularly, corrections greater
than 12 D.
It has been suggested that deep application of laser may have a

detrimental effect on the corneal endothelium. Recent reports, however
showed that LASIK surgery for up to 14.5D is not associated with
clinically significant corneal endothelial loss for up to 12 weeks after
surgery.
Optical complications (e.g. glare, halo, and monocular diplopia) may

occur in some patients after both PRK and LASIK for moderate to high
myopia. In a randomised prospective, comparative study, between
Laser in situ keratomileusis and PRK, for myopia between 2.5D and
8.00D, both operations achieved a successful refractive outcome. Laser
in situ keratomileusis (LASIK) was, however, associated with better
correction, quicker recovery of vision, more regular postoperative corneal
topography, and less pain. A recent study showed that, for myopia
between 1 and 9.5 D, laser in situ keratomileusis (LASIK), however,
appears to be associated with more postoperative haloes. Corneal
sensitivity at the ablated zone may be more reduced after laser in situ
keratomileusis than after photorefractive keratectomy during the first 3
months after surgery, but it appear to be similar 6 months after either
surgery. Another recent study indicated that PRK patients show an
increase in halo and diplopia symptoms, but not glare, after surgery, and
LASIK patients show an increase in diplopia, but not glare and halo
symptoms. The study also showed that there is a lesser tendency toward
postoperative optical symptoms in LASIK compared with PRK treated
eyes.
The operation appears to be effective and safe, but about 5% of patients

may develop complications. These complications are often mild and
rarely lead to loss of more than two lines of visual acuity. The most
common complication after this procedure is under-correction. The mean

refractive regression after Laser in situ keratomileusis (LASIK), in one
study, was -1.07D (7.6%) from the first week to the third month. Early
regression of refraction after LASIK appears to be a consequence of an
increase in corneal thickness associated with central corneal steepening.
Re-treatment of residual myopia is possible and predictable, but epithelial
in-growth and flap melting are more likely to occur in re-treatment than in
first time treatment. The surgical technique of re-treatment may be more
demanding.
There are conflicting reports on the suitability of refractive laser corneal

surgery in patient with a previous history of herpes simplex virus corneal
infection. Recent reports indicate that reactivation of latent herpes
simplex virus may be triggered by the application of laser treatment.
Diffuse lamellar keratitis is relatively new non-infectious condition that

may complicate surgery. Several different names have been given to this
condition and similar conditions (e.g. interface keratitis, Fine lattice
lines and Sands of the Sahara syndrome). The condition is
characterised by the presence of corneal infiltrate at the interface of the
corneal flap, that typically present 2 to 6 days after surgery. Patient often
present with pain, photophobia, and redness of the eye. The conjunctiva
and the anterior chamber are typically quiet. The cause and the
mechanism of this condition is not completely known. Causes may
include povidone iodine, balanced salt solution, metal particles, or
contamination from the meibomian gland. There is also a theory that this
condition may be caused by contamination, of the surgical interface, by
bacterial cell wall from the instruments or from the irrigating solutions. It
may also be related to endotoxin released from gram-negative biofilm in
sterilizer reservoirs. Intraoperative intra-stromal steroid application, and
intensive topical steroids treatment immediately after the diagnosis is a
safe and effective way to reduce the incidence and severity of this
condition.
Increased intraocular pressure associated with the micro-keratome

vacuum ring used during laser in situ keratomileusis (to stabilise the eye)
may precipitate optic nerve head ischaemia and visual field defect. IOP
monitoring is a very important part in postoperative follow up as many
patients need steroids treatment after surgery. The measurement of the
IOP by a chlorine-disinfected applanation tonometer may be associated
with corneal epithelial changes. It is suggested that non-contact
tonometry is better used in these patients.
Serious vitreoretinal complications after Laser in situ keratomileusis

(LASIK) procedure appear to be rare. Some investigators, however,
reported retinal breaks and asymptomatic retinal detachment after Laser
in situ keratomileusis (LASIK), PRK, and RK surgery. Patients, however,
should be warned about these complications.
Photorefractive Keratotomy (PRK)

PRK is often performed by the argon fluoride excimer laser (193 nm)
which produces a pulsed far-ultraviolet laser which can ablate the corneal
surface with sub-micron accuracy. The excimer laser, however, has
many disadvantages (e.g. the extremely toxic fluoride gas, the apparatus
is heavy, bulky and complicated). Neodymium YAG laser, and ER-YAG
laser have also been used. The neodymium YAG laser has the
advantage of being solid and compact, more cost effective and without
the potential safety hazards of the toxic fluorine gas in the excimer laser.
The ER-YAG is a solid state laser that is easier to handle, less
expensive, and can also be fitted on a slit lamp or an operating
microscope.
Photorefractive keratectomy causes significant refractive changes in the

anterior as well as the posterior corneal surface. It is also associated
with forward shift of the cornea. The thinner, ablated cornea may slightly
bulge forward to steepen both anterior and posterior curvatures. This
may account for the regression toward myopia that is typically found in
the first few days post-treatment. The forward bulging is similar to the
corneal relaxation effects observed after radial keratotomy
Removal of the corneal epithelium is an important part of PRK surgery

before laser ablation to the stroma. Corneal de-epithelialisation may be
carried out by mechanical or chemical (ethanol) methods, or by laser
trans-epithelial debridement. In a rabbit experiment all methods of de-
epithelialisation produced a significant decrease in the stromal
keratocytes associated with acute inflammation. The use of topical
metabolic nutrients (e.g. storage media) after de-epithelialisation may
reduce this effect and increase the re-epithelialisation rate. The
postoperative re-population of the anterior stromal keratocytes seems to
be associated with collagen production which can lead to the formation of
sub-epithelial haze and unpredictable outcome after surgery.
In a recent study, a single intraoperative application of Mitomycin C

(0.02%) for 2 minutes was carried out, after epithelial debridement,
followed by saline irrigation. The eyes were then patched, or a bandage
contact lens placed until epithelial healing was complete. The study
showed that, topical application of Mitomycin C (0.02%) may be a useful
method of preventing recurrence of sub-epithelial fibrosis after epithelial
debridement.
Optical zone centration is critical in corneal refractive surgery. Visual

outcome may be reduced due to poor centration of the ablation zone.
Patients with de-centration of the ablation zone can be retreated with a
repeat, photorefractive keratectomy. Theoretically, the smaller the
diameter of ablation zone the higher the dioptric correction for a given
ablation depth. Some studies showed that The use of large zones in high
myopia (more than 5 mm and depending on the degree of myopia), is
recommended as it gives more precise and stable refractive results.

Other studies showed that photorefractive keratectomy with a 6-mm zone
may be associated with reduction in vision. A multiple zone technique
can also be used to reduce the total depth of ablation necessary to
correct high myopia.
The autonomous technologies corporation (ATC) LADARVISION excimer

laser is a new laser system that combines a small shaping beam with an
eye tracker system. The tracker system detects eye movements and
either stops the laser delivery or guide the laser system to follow the eye
movements without stopping laser delivery to ensure proper centration of
laser ablation. Recent studies showed that treatment, with this new
system, of 1-10D of myopia with or without astigmatism, is associated
with early refractive stability, excellent uncorrected visual acuity, no loss
of best corrected visual acuity and low levels of corneal haze. An active
eye-tracking system alone cannot, however, ensure good centration.
Patient co-operation and fixation are important.
wound healing and corneal haze
Wound healing plays an important part in the visual outcome and in the
visual predictability of PRK surgery. Exposure to Ultraviolet-B during
post-PRK stromal healing exacerbates and prolongs the stromal healing
response. Excessive ocular Ultraviolet-B exposure should be avoided
during the period of postoperative period. PRK does not seem to be
associated with detectable changes in the central corneal endothelial
cells. Previous studies showed that there might be slight increase in the
corneal endothelial cells after surgery, presumably due stopping wearing
contact lenses.
Untreated allergic conjunctivitis seems to be associated with increased

corneal haze after PRK surgery. Treatment of allergic conjunctivitis
before surgery is recommended. Caution should also be taken in
performing PRK in patients with a long history of tranquilliser use. A long
history of tranquilliser intake (e.g. Chlorpromazine) may be associated
with corneal endothelial cells abnormalities, and stromal haze.
Mild anterior corneal stromal haze is often seen after PRK. It usually
appears within 4 weeks after the procedure. A new type of corneal haze,
starting relatively late (4 to 12 months) after PRK, has been reported in
about 1.8% of patients. Although glare and halos appear to be reduced
with the 6 mm treatment, a small number of patients still report
substantial glare or halo after the procedure.
Several distinct patterns of corneal topography have been identified

after PRK. Central islands, and key-hole semicircular patterns are often
noticed in the postoperative period. Central island are areas of higher
refractive power. They can be observed in the cornea several months
after treatment, and represent areas of irregular corneal astigmatism
which may lead to loss of best corrected visual acuity during the early or
late postoperative period.
Although some of the central islands resolve with time due to the healing
response of the cornea, the presence of central islands has been shown
to correlate with poor visual rehabilitation because of the inhomogeneous
refraction across the pupil. The cause of these islands is not known. It is
hypothesised that they are due to local defects in the optics of the laser
machine, resulting in colder spots and less ablation centrally, or may be
due to differences in the hydration between the deep and superficial
layers of the cornea.
Topical steroids, and non-steroidal anti-inflammatory drugs are the main

treatment against excessive haze formation. Gene transfer is a new
technique to modulate wound healing after PRK in order to reduce
postoperative corneal haze. In this technique the keratocytes are
genetically transduced with a herpes simplex virus vector, which makes
these cells more sensitive to ganciclovir. Topical application of ganciclovir
would be highly selective to these cells with causing any damage to other
corneal cells. In an experimental study on rabbits eyes, eyes which were
treated with ganciclovir after transduction developed significantly less
corneal haze than eyes that were not transduced. The use of an
antioxidant to reduce tissue damage may also help minimise
postoperative stromal opacification.
results
Most patients (86%) seek PRK treatment to be able to have good vision
without spectacles or contact lenses. 73% of patients seek treatment
because of difficulties with contact lens use. The procedure is highly
effective, safe and reliable in treating myopia of up to 5.00 D spherical
equivalent. Individual variation in the refractive outcome after PRK is
noticed in many patients, specially patients with high myopia. A recent
study showed that, the operation increases the ocular aberrations and
impairs the visual performance of the treated eyes. Scotopic visual
measures such as low-contrast visual acuity and glare visual acuity suffer
most from the myopia correction.
Age may play a role in the outcome of refractive surgery. In patients

younger than 50 years of age, age does not significantly affect visual
outcome or predictability after myopic photorefractive keratectomy. There
is a significant difference between patients older than 50 and patients
younger than 50 years of age in predictability of the refractive outcome at
3, 6, and 12 months.
Some patients are disappointed even after achieving good visual acuity
due to glare and distortion. Refraction may continue to change for up to
20 months after surgery. It is essential that patients should be counselled
properly before surgery. The accuracy of correction diminishes
significantly with myopia greater than 10 D spherical equivalent and the

potential for loss of best corrected visual acuity is also increased with
increasing pre treatment myopia. Recent studies demonstrated that good
predictable results may also be achieved in myopic eyes up to 9 D. PRK
in myopia higher than 9.5D is associated with more corneal scarring and
refractive regression than in smaller degrees of myopia. Perception of
halos, and night driving problems may be noted by some patients with
high myopia.
Complications of PRK are few and not often vision threatening. A

significant number of patients show refraction regression after PRK. The
risk of regression is higher in patients with higher myopia, patients who
had small diameter treatment area, female patients taking contraceptive
pills, and also in patients who had regression after treatment of the other
eye. The cause of postoperative myopic regression after PRK is not very
clear. It appears to be dependant on the epithelial and stromal healing
process. It may be related epithelial hyperplasia and stromal re-
modelling. The most significant shift in refraction seems to occur in the
first one or two months. Small degrees of refractive changes may also
continue to occur for up to 12 months. It is not known when refraction
stabilises after surgery.
Repeated PRK can be used successfully to improve visual acuity in

cases with refractive regression. Deliberate over-correction may also
reduce the chance of further regression. A second PRK operation can be
carried out six months after the primary operation in patients with
regression. When corneal haze is present, re-treatment is less
predictable with about 40% of patients having over-correction. Patient
with high myopia and those who regressed beyond -3.5 D should be
treated with caution as the risk of further regression is high.
Post-PRK hyperopia is a major problem that is caused mainly by

epithelial hyperplasia and collagen deposition adding to the corneal
thickness. Over-correction of more than 1.0 D of hyperopia occurs in
about 1% of eyes. The over-correction tends not to persist. There does
not seem to be any significant association between over-correction and
age, gender, surgical treatment or the simultaneous correction of
astigmatism.
The effect of topical steroids on the postoperative refraction is not

known. Some studies showed that Dexamethasone may have an initial
effect in reducing myopia after PRK operations when compared with
placebo. The difference between steroids and placebo after discontinuing
the steroids three months after surgery, in these studies was not
significant. Other studies, on the other hand, showed that postoperative
topical steroids play a crucial role in the development of the refractive
results. Steroids may have a beneficial modulating effect on keratocytes
activity during wound healing. This effect may limit the extent of the new
collagen synthesis in the treated cornea and possibly reduce stromal re-
modelling during the healing process. Caution should be taken in using

postoperative steroids because reactivation of viruses may occur after
laser ablation.
Other postoperative complications include IOP rise, epithelial changes,

recurrent corneal erosions. Unlike radial keratotomy, PRK does not
appear to result in diurnal variation in visual acuity, spherical equivalent,
or keratometry readings.
PRK and IOP
Corneal thickness is significantly reduced in patients with normal

pressure glaucoma as compared with patient with primary open angle
glaucoma and individuals with healthy corneas. Underestimation of the
IOP in patients with primary open angle glaucoma who have thin corneas
may lead to a misdiagnosis of NTG, while overestimation of the IOP in
normal subjects who have thick corneas may lead to a misdiagnosis of
ocular hypertension. The measurement of IOP with Goldman tonometry
and non-contact tonometry, after PRK for myopia may be underestimated
(by up to 2.4 +/- 1.23 mm Hg.) because of changes in the corneal
thickness. The decrease in the IOP seems to be related to the degree of
myopia treated. Pneumotonometry can reliably measure the IOP in all
parts of the cornea after surgery, and may be a more accurate method of
measuring the IOP in theses eyes.
Radial keratotomy (RK)

Radial keratotomy usually achieves partial improvement in uncorrected
visual acuity in patients with non-progressive low and moderate amounts
of myopia. Under-correction occurs commonly, and the amount of
correction cannot be predicted accurately for an individual patient. Many
surgeons recommend intentional under-correction followed by repeated
surgery to augment the results.
In eyes with RK, a significant increase in the spherical equivalent

(hyperopic shift) and in the keratometric value is noticed at high
altitudes (12000 to 17000 feet). Patients travelling to high altitudes may
benefit from taking multiple spectacles with increasing plus power lenses.
A higher myopic correction can also be expected in patients who have
the operation at high altitude compared with those at sea level if the
same technique and the same nomogram is used. The mechanism of the
hyperopic shift may be mechanical due to the change in the barometric
pressure, or due to a slower metabolic process in the cornea. Hypoxic
corneal expansion at high altitude with central flattening may also explain
this phenomena. Some patients may also show small diurnal variation in
refraction and visual acuity after surgery. The technique and nomogram
used in RK surgery should take in consideration the height at which the
surgery is carried out.
RK surgery makes the cornea susceptible to trauma and may be

associated with corneal rupture after minor blunt trauma up to 91 months
after surgery. Globe rupture often involves the RK wounds sites. Mini
radial keratotomy refers to a radial keratotomy procedure with the
corneal radial incision limited to within 3.5 millimetres from the centre of
the central clear zone. The corneal integrity is still reduced with mini
radial keratotomy, but corneas with mini radial keratotomy incisions
appear to rupture at a significantly higher pressure than cornea with
conventional radial keratotomy incisions. Mini radial keratotomy may
have an advantage to patients at high risk of minor ocular trauma.
Micro-corneal perforation, corneal ulcer and early onset keratitis following

radial keratotomy are relatively infrequent. Diamond knife contamination
from the eye lashes is an important source of infection during this
procedure. Severe bacterial endophthalmitis and cellulitis have also been
reported. Patients should be informed about this small but potentially
blinding complication.
Intra-stromal Corneal Ring “intacs”

Intra-stromal corneal rings and Intra-stromal corneal ring segments are a
relatively new technique designed to treat low to moderate myopia (1-3
D) by flattening the anterior corneal curvature by inserting corneal rings
into the peripheral corneal stroma. The rings are made of
polymethylmethacrylate. The thickness of the rings seems to be crucial in
determining the amount of myopia corrected. The procedure involves
making corneal incisions, creating stromal channels by a special suction
device and then implantation of the rings in the peripheral corneal stroma.
The rings can be removed from the cornea, if needed, to reverse the
refractive effect of the procedure with minimal disruption to the corneal
stroma. The ring segments can also be exchanged with segments of
different thickness to correct over- and under-correction in the initial
surgery. Clinical studies showed that this technique is safe, effective and
predictable in reducing myopia. Intra-corneal ring segments are also not
associated with clinically significant diurnal variation in visual acuity or
manifest refraction. The technique may be a promising alternative to
current kerato-refractive surgical procedures.
Lens refractive surgery

Several strategies have been used to correct high myopia. Changing the
curvature of the cornea by radial keratotomy, PRK, or by Laser in situ
keratomileusis (LASIK) have been tried with varying degree of
predictability and stability. Another approach for correcting myopia is by
clear lens extraction. This approach carries the same risk as any other
intraocular procedure. It also leads to loss of accommodation. The
incidence of retinal detachment after clear lens extraction, for axial
myopia, is about 7.5%. There is a strong association between the
incidence of the detachment and postoperative laser or surgical
capsulotomy but, apparently, not with primary intraoperative
capsulotomy. The presence of vitreoretinal degeneration should be
considered as a contraindication for this procedure.
A third approach is by implanting a minus power IOL without removing

the clear crystalline lens. Preservation of accommodation is a main
advantage of this technique. The predictability of this approach is good,
but visual acuity and refractive outcomes with clear lensectomy appear to
be associated with more favourable results. Anterior chamber as well as
posterior chamber IOLs have been implanted in phakic myopic eyes. AC
IOL implantation, has been reported to have good safety and good visual
results. Posterior chamber silicon IOL may is associated with a high
incidence of cataract formation.
The procedure may be complicated by:

• Lens rotation.
• Cataract.
• Oval pupil.
• Endothelial cell loss.
• Retinal detachments (in about 4.8% of patients). The time between
implanting surgery and retinal detachment ranges between 1 and 44
months. Conventional scleral surgery is successful in most cases, but
it may be associated with significant increase in the myopic spherical
equivalent.
Pterygium surgery
The pathogenesis of pterygium is not completely known. Sun exposure
and ultraviolet light seem to play an important role in its development.
Protective sun glasses may reduce pterygium formation in sunny areas.
Surgical treatment is often indicated when the pterygium threatens vision
by encroaching on or near to the visual axis, or when it causes a
significant dellen effect.
Several methods of treatment have tried in the treatment of pterygium

with varying degrees of success. The traditional method of treatment in
vision threatening pterygium is by surgical excision. Recurrence is
common and also more aggressive in some cases after surgical excision.
The rate of recurrence varies considerably depending on the method of
treatment employed. These methods include:
Excision with bare sclera technique

Excision with mitomycin c
Excision with beta irradiation
Excision with conjunctival flaps
Excision with buccal mucosal grafts
Excision with amniotic membrane
The use of a bare sclera technique is better avoided in the treatment of

primary pterygium as the possibility of recurrence is high if no
conjunctival graft is carried out, or if Mitomycin C treatment is not applied.
Intraoperative application of Mitomycin C (0.02 mg/ml) for two to three
minutes after pterygium excision seems to be effective in reducing
recurrence rate. The midterm results of this procedure is also
encouraging. Mitomycin C may also be applied postoperatively in the
form of eye drops. A recent study showed that intraoperative
administration of 0.04% mitomycin C is more effective than irradiation as
an adjunctive treatment for pterygium surgery. Excision of pterygia with
the use of Mitomycin C or beta irradiation may, however, be associated
with some complications e.g. infectious scleritis associated with scleral
abscesses formation. Pseudomonas infection seems to be common in
this type of scleritis. Early diagnosis and prolonged treatment with topical
as well as systemic antibiotics is needed in these cases
Sliding conjunctival flaps may also be used with pterygium excision. This
technique may, however be limited in cases with repeated surgery due to
shortening of the conjunctiva in this area. The use of conjunctival free
grafts is also effective and safe. Advanced recurrent pterygia may be
treated by limbal autograft transplantation, which could be included in the
procedure of conjunctival transplantation.
When it is not possible to obtain enough conjunctiva from the superior

bulbar conjunctiva or from the other eye, the conjunctiva covering the
pterygium may be used instead. After dissecting the pterygium, the
conjunctiva is freed from the underlying tissue. It can then be used to

cover the bare scleral area after rotating the graft so that the leading apex
of the conjunctiva is facing towards the fornix. Intraoperative use of
mitomycin C with conjunctival autograft reduces the rate of recurrence of
severe pterygia compared with use of conjunctival autograft alone.
Recurrent pterygia may be aggressive and repeated conjunctival

excisions may result in conjunctiva scarring and shortening. Repeated
conjunctival grafts may therefore not be possible. In recurrent, and
aggressive cases, excision of the pterygium may be repaired by full
thickness or partial thickness buccal mucosal grafts, and postoperative
beta irradiation. The advantages of using buccal mucous membrane is
that it is often available in sufficient quantities. Mucous membrane
covering may also delay any re-growth of the pterygium. Partial thickness
mucosal grafts may have some advantages over full thickness grafts,
resulting in a better cosmetic appearance. Transplantation of human
amniotic membrane with a limbal autograft may also be used in patients
with recurrent pterygium associated with conjunctival shortening and
symblepharon.
Limbal transplants, and

amniotic membrane transplantation
Epithelial stem cells in the cornea are located in the basal layer of the
limbal epithelium. Limbal basal cells contain 4-5 folds higher levels of
epidermal growth factor receptors than the central corneal cells. This
higher level of growth factor may help to maintain the limbal basal cells in
an undifferentiated stem cell state. The stem cells are responsible for the
repopulating of the rest of the corneal cells.
Limbal transplantation is a surgical procedure used in conditions

associated with stem cell deficiency (e.g. aniridia keratopathy, chronic
contact lens epitheliopathy, chemical burns, Steven Johnson syndrome
and corneal intraepithelial dysplasia). Absence of progressive
epithelialisation, with 2 to 3 weeks of corneal lesions, should alert the
surgeon to the possibility of poor stem cell function and also to the
possibility of needing a limbal transplantation to promote corneal healing.
Limbal auto-transplantation is used in the treatment of unilateral
conditions, while allograft transplantation is used for bilateral conditions.
The procedure may be carried out either in acute or the chronic phase of
the disease, and also in preparation for penetrating keratoplasty in
severe external surface and corneal diseases. Close monitoring of the
conjunctival epithelium to ensure that it does not cross to the corneal
surface, in the immediate postoperative period, will ensure that the
corneal surface will re-epithelialise mainly from the epithelial limbal cells
which may improve the success rate of the operation.
In the reconstruction of the ocular surface disease, three factors are

considered; limbal cells restoration, basement membrane replacement,
and tear substitution. Amniotic membrane may be used if the limbal
epithelial cells are available for further repair (e.g. in persistent epithelial
defects as in aniridia). If no stem cells or conjunctival cells are available,
limbal autograft or allograft is then needed (e.g. chemical burns, and
Steven-Johnson syndrome). If tear secretion is also involved, artificial
tear drops with serum drops may also be needed. Limbal cells function
seems to depend on the extra-cellular environment. The use of Amniotic
membrane in situation of damaged or diseased stroma seems to be
rational.
Amniotic membrane have been used for the repair of skin and mucosal
wounds. They have also been used in the eye for the treatment of
persistent corneal epithelial defects, ocular surface reconstruction, and in
the treatment of pterygia. Repeated transplantation of amniotic
membrane may be associated with a hypopyon iritis. Immunological,
toxic, and hypersensitivity may be responsible for this reaction.
The Amniotic membrane is separated from the chorion and cut into the
appropriate size and then stored at -80 degrees. The membrane is often
sutured in the damaged area with 10/0 nylon sutures. The transplanted
membrane dissolves with several months of application. Transplantation

with preserved amniotic membrane when combined with limbal allograft
may be used effectively in patients with severe cicatricial diseases and
also in patients with persistent epithelial defects and ulceration. Oral
cyclosporin may be used to prevent rejection.
Advantages of using Amniotic membrane include:
1. They are non-antigenic

2. Easy to manipulate surgically
3. They have a strong and a stable connective tissue substrate
Cataract Surgery
Anaesthesia
Local anaesthesia is used in about 70% of intraocular operations in the
UK. Routine medical assessment does not appear to be necessary for
patients having cataract surgery under local anaesthesia. A recent report
indicated that preoperative medical assessment does not lead to any
significant reduction in the operative or postoperative complication and
does not increase the safety of the patients.
The majority of cataract operations are carried out under peribulbar

anaesthesia. Retrobulbar, sub-conjunctival, sub-Tenon and topical
anaesthesia are also used. Lignocaine, marcaine and prilocaine are
commonly used as anaesthetic agents. Prilocaine is the least toxic of the
commonly used local anaesthetics. The drug has a longer duration of
action than lignocaine, greater tissue diffusion, no requirement for
adrenaline and slower systemic absorption. The main disadvantage of
prilocaine is the production of methaemoglobinaemia (and falling oxygen
saturation) when used even in small volumes. Warming the local
anaesthetic solution, in peribulbar anaesthesia, to body temperature, is
associated with less pain sensation by patients. An increase in the
temperature tends to raise the pH of the solution and increase its lipid
solubility which also increase its potency. Warming the solution may also
cause a change in its pH resulting in more rapid onset blockade.
Peribulbar anaesthesia is supposed to be safer than retrobulbar

anaesthesia regarding brain stem anaesthesia, orbital haemorrhage and
scleral perforations. Serious systemic and local complications may,
however, occur with any type of anaesthesia. Some of the complications
may be life or sight threatening. The rate of local anaesthesia related
complications seems to be higher than previously thought. Retrobulbar
haemorrhage is the most common complication of retrobulbar
anaesthetic. Visual loss has been reported following retrobulbar
haemorrhage from retrobulbar and peribulbar anaesthesia. Sub-
periosteal orbital haemorrhage, following a retrobulbar injection, may also
result in permanent and severe visual loss.
Inadvertent globe penetration and dense vitreous haemorrhage may

also occur after local anaesthesia injections. In a study of 50000
injections, it was found that the only significant factor for scleral
perforation, during peribulbar or retrobulbar injection, is the presence of a
posterior staphyloma. In theses cases, prompt referral for early
vitrectomy is recommended. Early vitrectomy may lead to a good visual
outcome by preventing retinal detachment. Some other studies
documented a spontaneous improvement in visual acuity in some eyes
after this complication. In an experimental study in rabbits eyes,

Intravitreal injection of 0.2 ml of lidocaine (2% to 0.25%), bupivacaine
(0.75% to 0.25%) and a mixture of 2% lidocaine and 0.75% bupivacaine
was found to be non toxic to the animal’s retina.
Peribulbar anaesthesia may be associated with impairment of the retinal

circulation. The effects of peribulbar anaesthesia on ocular blood flow
may be caused by elevations in intraocular pressure or direct
pharmacological action on the vascular tone. Drug-induced
vasoconstriction may occur after peribulbar anaesthesia, and visual loss
may occur in patients with compromised retinal or choroidal circulation.
The effect of covering the patient’s head with the surgical drapes is
controversial. Carbon dioxide may accumulate under the surgical
drapes. Oxygen breathing via nasal intubation had been thought to
prevent increased levels of carbon dioxide in patient’s breathing air. A
recent study, however, reported that nasal intubation is beneficial in
preventing hypoxic effects but it does not seem to be effective in
preventing increased carbon dioxide levels in breathing air. Elimination of
accumulated carbon dioxide by a suction machine appears to be the only
effective method.
Monitored anaesthesia is preferred in cataract surgery, even with pure

local anaesthesia, as a high percentage of patients need some kind of
intervention during the operation. The intervention may only be verbal
reassurance or active intervention to deal with respiratory and blood
pressure problems.
Topical local anaesthesia (with or without IV sedation) is a new

technique that allows rapid visual rehabilitation and also avoids the
complications and side effects associated with peribulbar and retrobulbar
injections e.g. diplopia, amaurosis, ptosis, lid ecchymosis, and pain
associated with injection anaesthesia. Topical anaesthesia for cataract
surgery can, however, damage the ocular surface in older patients with
dry eye and blepharitis. This technique seems to be as effective as either
of these two methods in cataract surgery. However, eye movements and
lid squeezing are more common with topical anaesthesia, but do not
seem to cause major problems. Topical anaesthesia with a van Lint block
may be used in cases with severe lid squeezing. Patients selection and
preparation are the keys to using topical anaesthesia. Iris manipulations,
irrigation-aspiration, and IOL implantation may also be associated with
some discomfort. Topical anaesthetic drops are used in both eyes prior
to surgery in order to reduce the blinking reflex. Patients having topical or
retrobulbar anaesthesia may have different visual experiences during
their operation. Some patients may be able to see the surgeon’s hand
and the instruments. Some of these visual sensation may also frightening
to some patients. patients should be counselled about these visual
sensations.
Most surgeons consider supplementing the topical block during cataract

surgery with additional drops, or with intracameral lidocaine
anaesthesia, if needed. Some drops may Inadvertently enter the eye and
may cause clinically and statistically significant corneal thickening and
opacification. Intracameral injection of lidocaine 1% during surgery may
alternatively be used to increases patient’s comfort. On the other hand, a
recent double-masked, prospective, randomised, controlled trial showed
that there was no significant reduction in intraoperative pain when
intracameral 1% lidocaine was used during phacoemulsification under
topical anaesthesia.
lidocaine 1% may cause a transient endothelial cells oedema to in-vitro

perfused endothelium of human and animal corneas. Short term
exposure, however, seems to be harmless. Non-preserved bupivacaine
0.5% is as effective, clinically, as lidocaine 1.0% for intracameral
anaesthesia during surgery. However, experimental studies in rabbits
showed that perfusion of bupivacaine 0.5% can damage the corneal
endothelium except when the drug was diluted 1:1 with glutathione
bicarbonate Ringer solution. Electrophysiological studies showed that
ERG amplitudes are not significantly reduced after 0.15-ml intracameral
lidocaine half an hour after surgery.
Sub-Tenon anaesthesia may also be used. The technique is very

comfortable to administer with good pain relief and good akinesia. A
small opening is made in the conjunctiva in the inferior nasal quadrant
after injecting a small amount of anaesthetic solution in the conjunctiva. A
sub-Tenon curved cannula is then passed in the sub-Tenon space
around the eyeball and a further 2-3 ml of the anaesthetic solution is then
injected. The addition of Hyaluronidase to the anaesthetic solution
appears to increase the akinesia effect, but not the sensory effect, of the
block. The technique is reported to be superior to topical anaesthesia in
ensuring patient comfort, and better akinesia during phacoemulsification
cataract surgery. A significant number of patients experience a sever
pain at the time of acetylcholine intracameral injection with this technique.
The obvious advantages of topical anaesthesia over sub-Tenon
infiltration are time saving and shorter duration of action which allows the
patient to regain visual acuity rapidly after surgery.
Recent progress in cataract surgery technology has diminished the need

for complete ocular akinesia during phacoemulsification cataract surgery.
Rand-Stein Analgesia Protocol for Cataract Surgery is a new technique
that produces ocular analgesia while eliminating the risks and side effects
associated with general, local, topical, and intracameral anaesthesia. In
this technique a very low-dose, titrated, intravenous alfentanil (125 mcg
in 0.5 ml) is used to achieve ocular analgesia. Alfentanil is a potent
synthetic opioid that has an intense rapid-onset analgesia and a short
action. It produces a significant generalised body analgesia that is
effective in relieving chronic back and neck pain, which can induce
unwanted patient movements during surgery. Complete control of lid
squeezing and ocular and general body movements, can be achieved,

whenever necessary, by using very low-dose, titrated, intravenous
methohexital (10 mg), which is an ultra–short-acting barbiturate. The
technique allows for an immediate postoperative recovery with
instantaneous vision restoration. Midazolam (short-acting
benzodiazepine, a central nervous system depressant) may also be used
for preoperative anxiety.
Intraocular implants
• foldable implants
Foldable IOLs with small corneal section technique is gaining popularity

because of the rapid postoperative visual recovery associated with the
small incision. Foldable IOLs are thought to provide superior visual
results than rigid IOLs. However, in some studies foldable acrylic IOLs
did not provide any visual advantages than rigid PMMA IOLs in the early
postoperative period. Long term visual outcome may depend on the
degree and rate of posterior capsule opacification associated with the
IOL.
There is some controversy about the best foldable IOL that can be used.
The current popular foldable IOLs are made of the following material:
Silicon
Hydrogel
Soft acrylic
Postoperative inflammation and posterior capsule opacification depend,

among other factors, on the design and the biocompatibility of the lens
material. Heparin surface modification of the IOL seem to reduces
postoperative inflammatory features after phacoemulsification.
Posterior capsule opacification is caused by proliferation, migration and

transformation of the lens epithelial cells that remain in the capsular bag.
The hydrogel IOLs, when compared with the PMMA and the silicon
IOLs, are very bio-compatible. They are associated with reduced number
of inflammatory cells on the lens surface. They are also, on the other
hand, associated with great number of lens epithelial cells growing on the
posterior capsule, and higher rates of posterior capsule opacification. A
recent study showed that intraocular lenses made of hydrogel are
associated with a significantly higher degree of posterior capsular
opacification and more laser capsulotomies than polymethylmethacrylate
and silicone intraocular lenses over a period of two years.
Acrylic foldable IOLs seem to adhere to the posterior capsule more than
PMMA IOLs, and also seem to be associated with considerably less
proliferation of the lens epithelial cells on its surface. Silicon IOLs, on the
other hand do not seem to show any adhesiveness to the posterior
capsule. The presence of lens epithelial cells on the posterior capsule is
considerably less with polyacrylic IOLs than with PMMA or silicon IOLs.
The regression of the epithelial cells also appears to be quicker with the
polyacrylic IOLs. Silicon IOL with large positioning holes seem to be more
fixed to the capsule than IOL with small holes. The increased fixation is
due to regeneration and fibrous tissue in-growth through the holes. IOL
with large holes may be useful in preventing IOL de-centration.
Foldable silicon IOLs are now recognised to be associated with these

main complications:
1. Lens de-centration
2. Moisture condensation during fluid gas exchange in vitreoretinal
surgery. Heating the anterior segment by warmed irrigation fluid is a
cheap, non-invasive, and safe means to prevent condensation on IOL
materials.
3. Silicon oil-silicon IOL interaction
4. Accumulation of pigmented cellular membrane on the anterior surface
of the IOL
5. Intraoperative deposition of crystalline materials have also been
reported with some implants, mainly silicon implants. The crystalline
deposits are thought to be due to the use of BSS +, as a source of the
calcium deposits. Exchange of the implant, and anterior chamber wash
out with simple BSS may be needed.
6. There is also some reports that, the use of three piece foldable silicon
polypropylene IOL may be associated with an increased risk of
postoperative endophthalmitis.
7. Discoloration of silicon IOL have been described before. Recent report
described similar complication in acrylic IOLs during surgery and also
several months afterwards. Some cases may improve spontaneously
while others may need explantation. The cause of this phenomena is
not completely understood. It is thought that temperature change (e.g.
warming of the IOL prior to implantation) may play a role in the
development of these transient changes.
8. Adherence of S. epidermidis to IOLs may play a role in the
pathogenesis of some forms of endophthalmitis after cataract surgery.
A recent study showed that S. epidermidis can adhere, in vitro, to
Acrysof IOLs more readily than PMMA IOLs.
Silicon material has been used in ocular and other surgeries for some
time. It has been suggested that patients receiving silicon implants or
prosthesis might have a specific anti-polymer immune response which
might lead to severe immunological symptoms, as in patient who receive
breast silicon implants. In a study of 49 patients who had retinal and
cataract surgery using silicon material, the frequency of enhanced serum
Ig G binding to silicon was very low, making the correlation to surgical
complications difficult. The results of the study did not suggest any
change in the clinical use of this material in eye surgery.
In-the-bag implantation of the IOL which achieve a strong contact

between the posterior capsule and the IOLs may play a role in preventing
posterior capsule opacification and wrinkling, by acting as a barrier
against the migration of the proliferating lens epithelium along the surface
of the IOL.
• multifocal lenses
Multifocal IOLs are relatively new. They are mainly used to provide less
spectacle dependency than with the monofocal lenses. The overall
patients satisfaction with these lenses is generally good. Most patients
suffer from mild haloes due to the blurring effect of the near vision rings.
Mild reduction in the contrast sensitivity is also common. Patient’s
selection is very important in the indications of these lenses. patient’s
motivation, lack of other macular diseases, less than 1 D of astigmatism,
are important factors that should be considered in selecting patients.
There are two main types of multifocal implants:
1. Diffractive lenses
2. Refractive lenses
Both types of lenses provide patients with sufficient unaided distance and
near vision. The diffractive lenses have 20-30 concentric rings
superimposed on its posterior surface providing a theoretical power add.
The main multifocal intraocular lenses currently in practice are:
• The AMO ARRAY silicon IOL.

• The tripod M F4 multifocal hydrophilic IOL.
The lens, in the ARRAY IOL, has a concentric zones of progressive

aspheric power on its anterior surfaces to provide a repeatable power
distribution for near and distance. Some loss of contrast sensitivity may
occur. Some patients also complain of seeing haloes. Night haloes and
glare disabilities may occur after monofocal as well as multifocal IOL
implantation. Patient’s age, corneal surface abnormalities, and the design
of the IOL may all play part in the pathogenesis of these symptoms. It has
been thought that mono-focal IOLs achieve a better functional
performance than multifocal IOLs outside standard conditions of vision
(e.g. low contrast and illuminations). A recent study showed that there is
high patient satisfaction with the ARRAY multifocal IOL. It also showed
a greater functional independence from spectacle wear, by objective and
subjective patient measures, than with the monofocal IOL. The ARRAY
multifocal IOL has also been shown to produced distance visual
outcomes comparable to monofocal IOL in patients with concurrent eye
disease. Management of associated eye disease does not seem to be
compromised by the nature of the IOL.
The M F4 multifocal IOL has 4 refractive zones with a + 4 add in the

central zone for reading (unlike the ARRAY lens which has a distance
refraction in the central zone). Patients may notice some reduction in the
visual acuity in bright light due to pupil constriction. The lens has a tripod
shape and needs a 3.7 mm incision.
Bilateral implantation of asymmetrical diffractive IOLs may be used for

restoring simultaneous distance and near vision with a potential for
improved contrast sensitivity compared with conventional multifocal IOLs.

Distance vision would be better for distant-dominant IOL while near vision
would be better for the near-dominant lens. This regime leads to
improved binocular visual performance, and more spectacle
independence.
• the Artisan IOL
The artisan IOL is an anterior chamber IOL that can be used for the
correction of myopia or hyperopia. It can also be used as piggy back IOL
for high myopia and hyperopia. The lens is fixated to the iris tissue by a
pair of claws. A new Toric Artisan IOL has also been recently described
for the correction of high astigmatism. Two types have been described, in
the first type the cylinder axis is in the same direction as the axis
connecting the claws haptics. In the second type the cylinder axis is at a
right angle to the axis connecting the claws. Preliminary results indicate
that these lenses may be useful in correcting high astigmatism in aphakic
or phakic eyes.
Biometry
Biometry has traditionally been carried out by ultrasound A scan for
measuring the axial length of the eye. Partial coherence interferometry
biometry is a new non-invasive method for measuring the axial length.
The method does not need any contact with the eye, and no local
anaesthesia is required. A recent study compared this method to
standard A-ultrasound axial length measurement in the evaluation of
biometry with the SRK II formula. Precision of the partial coherence
interferometry was estimated to be ten times more accurate than the
ultrasound. This could result in a 27% improvement in the mean absolute
error for postoperative refraction.
IOL power measurement and biometry is not often accurate in eyes with
high myopia or high hyperopia. The use of third generation formulae
e.g. Holladay I, SRK/T and Hoffer may provide more accurate results.
IOL power measurement in eyes that had undergone corneal refractive
surgery is also inaccurate and may result in postoperative refractive
surprises. Standard calculations in these eye may result in
underestimation of the IOL power with a postoperative hyperopia. The
use of automated corneal topography to measure the corneal power may
be useful in achieving better results. The measured corneal power must
be corrected. The modified corneal power can be calculated by
subtracting the spherical equivalent change in the corneal plane induced
by the PRK from the average corneal power measured before the PRK.
The use of pre-refractive surgery readings about corneal power and axial
length, as well as over refraction with a hard gas permeable contact lens
may also be used.
Axial length measurement may decrease after a successful

trabeculectomy operation. Biometry in phakic eyes with a history of
trabeculectomy may result in unexpected postoperative refractive results
(they tend to be more myopic). Measurement of axial length before the
trabeculectomy operations is recommended, as many of these patients
may need to have cataract surgery following the trabeculectomy
operation. Many patients with a history of vitreoretinal surgery and
silicon oil develop postoperative cataract. Combined removal of the
silicon oil and phacoemulsification surgery may be carried out in the
same operation. The speed of sound is different in silicon oil compared
with vitreous. Echography of an oil-filled eye may overestimate the axial
length of the eye. Unexpected postoperative refractive errors may occur if
biometry is calculated using the same formula as in eyes with no silicon
oil. A conversion factor (0.71 with a range of 0.70-0.73) has been
developed to allow for this difference in the sped of sound. The factor will
allow an accurate IOL power calculation, when used with the SRK / T
formula, in patients undergoing a combined phacoemulsification and
silicon oil removal.
Phacoemulsification surgery
Phacoemulsification surgery is gaining popularity world-wide. One of the
main advantages of phacoemulsification surgery is that it allows surgery
through a small incision. Recovery and visual rehabilitation is often
quicker in small incision surgery. Routine ocular examination on the first
postoperative day does not seem to be necessary after uncomplicated
phacoemulsification surgery. Current data indicates that 80% of patients,
in the UK, achieve visual acuity of 6/12 or better after phacoemulsification
surgery. Patients with macular degeneration also benefit from cataract
surgery, regardless of the technique of cataract extraction. Second eye
cataract extraction is often associated with better visual acuity, contrast
sensitivity, stereo-acuity, and also better binocular visual field. Second
eye cataract surgery improve the visual outcome more than single eye
surgery. Patients who opt for second eye surgery are often relatively
younger and have poor visual acuity in the second eye.
Phacoemulsification surgery has many advantages over ECCE surgery.

It gives much better control of the anterior chamber depth throughout
cataract operation, as well as the benefits of the small wound
postoperatively. Phacoemulsification technique is thought to be more
beneficial in reducing postoperative astigmatism and achieving a better
visual outcome in the early postoperative period than ECCE. However,
no difference in the outcome or in the rate of postoperative complications
is found between ECCE and phacoemulsification surgery four months
after cataract surgery.
The incision can be fashioned either by scleral tunnel or by clear corneal

approach. Temporal clear corneal incision is particularly useful in eyes
with against the rule astigmatism. In the immediate postoperative period,
clear corneal incision is associated with less disruption of blood-aqueous
barriers than scleral tunnel incisions. Corneal wound burns are serious
complication that may result in wound leak and high postoperative
astigmatism. Ultrasound energy is created by the forward and backward
vibration of the hand piece needle. There are two sources of heat
generation: heat transmitted from the machine to the needle tip, and heat
produced from friction between the needle and the sleeve. Corneal
wound burns occur mainly when the wound compresses down on the
phacoemulsification tip sleeve creating contact with the needle. Risk
factors of wound burn:
1. Hard nucleus
2. Tight incision
3. Irrigating tube occlusion
4. High power phacoemulsification for a long time
5. it may also occurs in the absence of all these factors.
6. Blockage of the incision by viscoelastics in the anterior chamber.
Phacoemulsification tips with dual sleeves seem to be very effective in

protecting the corneal wound from the needle tip heat. The position of the
phacoemulsification tip, in relation to the incision, seems to be important.
Determination of lens hardness is important in evaluating patients for

phacoemulsification surgery. Previous studies demonstrated a
relationship between the lens hardness and the degree of nuclear
sclerosis as measured by lens colouration. Age of the patients was also
significantly related to hardness.
There are several techniques for phacoemulsification depending on the

degree of hardness of the cataract. these techniques include:
Divide and conquer

Chip and flip
Crack and flip
Phaco-chop
Phacoemulsification is often carried out in the capsular bag. In previous

techniques the emulsification of the lens was carried out in the anterior
chamber, this was associated with higher rates of corneal de-
compensation. Recently a supra-capsular technique has been
described, in which the emulsification of the lens is done at the iris plane.
It is thought that this technique is more suitable to soft lenses.
Phacoemulsification surgery can safely be carried out in white mature

cataract. The procedure is thought to be more difficult in cases with
intumescent cataract with cortical liquefaction and high ultrasound
internal acoustic reflections, due to high rate of capsulorhexis failure.
Capsulorhexis is not often successful in these eyes due to a sudden leak
of milky cortex and poor visibility as well as irregular opening of the
capsulorhexis and tendency to extend outward. Cases with fibrosed
anterior capsule and low ultrasound internal acoustic reflection are also
thought to carry higher risks for failure of capsulorhexis. It may be
advisable to avoid the phacoemulsification technique in white cataract if
the endothelium is not very healthy.
instrumentation
Phacoemulsification of the lens is produced by the movements of the

ultrasound instrument tip. Most machines use piezo electric crystals.
Increasing the power increases the ultrasound frequency as well as the
distance travelled by the tip. The emulsification power of the machine is
due to a combination of mechanical, ultrasound acoustic wave shock,
and cavitation effect.
Phacoemulsification pumps are either of the peristaltic (most common),

venturi, or concenterix type. In the venturi and the concenterix types
occlusion of the tip is needed to build up vacuum. In the peristaltic type,

on the other hand, vacuum may be build without occluding the tip.
Laser phacoemulsification machine have been emerging on the market.

(YAG laser Photolysis). Erbium: YAG laser machine have been
developed. YAG laser has recently been used for the removal of cataract
in animal and human studies. The laser energy can be transmitted to a
titanium target within the probe tip. The laser pulsating energy impact the
target leading to the formation of a shock wave and disruption of the
cataract. Recent multicentre prospective study in human eyes showed
that this method is safe and effective. It also offers the advantage of
lower intraocular energy and heat release as well as using a 1.5 mm
corneal incision. The phacoemulsification effect of the Erbium: YAG laser
seems to occur only at the tip of the hand piece which enable
emulsification of the lens in a very small area within the bag. Erbium laser
phacoemulsification may be effective for mild to moderate nuclear
sclerosis, but not for severer nuclear sclerosis lenses.
capsulorhexis
Capsulorhexis is an important part in modern phacoemulsification

surgery. The procedure has many advantages e.g. less traction on the
zonule, more secure border preventing radial tears extending to the
posterior capsule, safer hydrodissection and also better placement of the
IOL. The disadvantages of capsulorhexis include the capsule block
syndrome, disruption of blood-aqueous barriers, and phymosis of the
capsular opening. A new complication (The Liquefied After Cataract) has
recently been described. The after cataract, in this condition is
characterised by the presence of milky white substance between the lens
optic and the posterior capsule when the anterior capsule opening
becomes occluded by the lens optic.
For the creation of a safe capsulorhexis, it is important to maintain a

deep anterior chamber throughout the procedure. The size of the
capsular opening is also crucial. Large capsulorhexis enables outside the
bag, posterior chamber phacoemulsification technique. A contact
between the capsulorhexis ring and the posterior capsule, beyond the
lens optic, is also thought to form a barrier against the migration of lens
epithelial cells and may reduce the incidence of posterior capsule
opacification. It has recently been demonstrated that large capsulorhexis
(one that lie completely off the lens optic) are associated with significantly
more wrinkling of the posterior capsule and worse posterior capsular
opacification, and visual acuity than small capsulorhexis (one that lie
completely on the intraocular lens optic).
When performing capsulorhexis, It is important to stay within the central

6.86 mm of the anterior capsule as this area is often zonule-free zone
(the position of the zonule fibre insertion in the crystalline lens seems to
be influenced by many factors e.g. age).
Capsulorhexis is often difficult to perform in eyes with mature white

cataract because of the absence of a good red reflex. A new effective
and safe method of performing capsulorhexis in eyes with white cataract
has been described. A few drops of indocyanine green or vision blue
dye can be instilled in the anterior chamber to stain the anterior chamber
to improve visualisation of the anterior capsule edge. The use of air
bubble in the anterior chamber is also thought to improve visibility in
these cases. Capsulorhexis can also be carried out by the Kloti diathermy
instrument. Diathermy capsulorhexis has the advantage of that it does
not rely on the presence of red reflex, can be done in children when the
capsule is too tough to tear manually. The mean capsulorhexis elasticity
is however significantly greater with the manual technique than with the
diathermy technique due to the difference in the morphology of the cut
edge of the capsulorhexis. The diathermy capsulorhexis also has a more
unpredictable behaviour if it tears under stress which make it less
suitable for extra-capsular cataract extraction operations.
Some surgeons advocate performing a posterior capsulorhexis in

cataract surgery routinely. The theoretical advantage of this technique is
that it removes the support for lens epithelial cell migration and
proliferation, in the central visual axis, and reduce posterior capsule
opacification. The incidence of retinal detachment also appears to be less
with primary posterior capsulorhexis than with postoperative YAG laser
capsulotomy. Loss of control of the posterior capsulorhexis has a low
incidence but can lead to serious problems during surgery.
hydrodissection
Hydrodissection enhances the general safety and efficiency of cortical

cleanup, especially at 12 o'clock. Thorough cortical cleanup and to the
cortical cleaving hydrodissection step are important for significant
reduction in incidence or the elimination of posterior capsule
opacification. The barrier effect of the IOL optic also appears to be of
critical importance in retarding in-growth of cells, functioning as a second
line of defence when cortical cleanup is incomplete.
The complications of hydrodissection is not well documented. During

vigorous hydrodissection posterior capsule rupture may occur and may
be associated with a sudden marked pupillary constriction (The pupil
snap sign). This complication may be related to strong equatorial cortical
adhesions in the lens which causes a build up of fluid and pressure until
such time when the adhesion break or the posterior capsule breaks. It
has rarely been reported that the lens nucleus may be dislocated
during the hydrodissection procedure. This complications appears to be
related to eyes with longer axial length or eyes with pseudo-exfoliation
syndrome mainly in elderly patients. It is thought that this complications
may be due to weakness in the posterior capsule. Hydrodissection
should be carried out with care in these situations.
The use of Mitomycin C in the solution used for hydrodissection, may be

effective in preventing posterior capsule opacification in rabbits eyes.
Heparin does not seem to have this effect
intraoperative vitreous loss and loss of nuclear fragments
It is estimated that the incidence of posterior capsule rupture during

phacoemulsification surgery ranges from 0.4% to 3.9%. Posterior
dislocation of nuclear fragments is a serious complication in cataract
surgery. All eyes with posteriorly dislocated nuclear fragment or cortical
material will have raised intraocular pressure; 63% will have corneal
oedema; 67% will have marked uveitis and 26% will have retinal tear or
detachment. The main reason for poor visual outcome in these cases is
retinal detachment.
If the nucleus is dropped in the vitreous during the operation,

surgeons should be discouraged from attempting to retrieve it from the
vitreous. The surgeon should, on the other hand, clear the vitreous from
the wound, implant PC or AC IOL (or leave the eye aphakic), close the
wound and then refer the patient to a vitreoretinal surgeon for pars plana
vitrectomy (or conservative treatment if the nucleus fragment is small
enough). Aggressive attempts at intravitreal lens fragment retrieval from a
cataract section should be avoided because this may result in serious
retinal complications, such as giant retinal tear.
Vitrectomy and removal of the nuclear fragments can achieve good visual
results in about 61% of patients. The timing of vitrectomy is, however still
controversial with most ophthalmologists advising early intervention,
while other reports showed that a better outcome is not statistically
significant with early intervention. The rationale from waiting include the
possible development of spontaneous posterior vitreous detachment, and
softening of the nuclear fragment.
Some studies showed that early removal of retained lens fragments

(within one week) is associated with significantly less inflammation and
less IOP elevation, while other studies showed no statistically significant
differences between early (less than 7 days) and delayed (8 days or
more) vitrectomy when increased IOP, corneal oedema, choroidal
effusions, cystoid macular oedema and visual acuity are considered.
Perfluorocarbon liquid may be used as an aid during pars plana
vitrectomy to remove dislocated lens fragments from the vitreous cavity.
Perfluorocarbon liquid allows easier and safer removal of dislocated lens
fragments, it also provide protection to the macula during the procedure.
Postoperative Complications
• endophthalmitis
Endophthalmitis may have drastic effects on the visual prognosis.

Postoperative streptococcal pneumonia endophthalmitis may also be
complicated with meningitis. Awareness of this complication and
aggressive treatment is needed to reduce mortality. The incidence of
endophthalmitis seems to depend on the type of surgery.
Endophthalmitis is estimated to occur in 0.07% to 0.12% after
phacoemulsification or ECCE, and in about 0.3% after secondary IOL
implantation. 93% of bacterial endophthalmitis are due to gram positive,
and 7% are due to gram negative organisms.
The endophthalmitis-vitrectomy study demonstrated that gram positive,

coagulase negative micrococci are the main causative organisms in
post-cataract extraction endophthalmitis. The visual prognosis seems to
be strongly associated with the type of infecting organism. Gram positive
coagulase negative cocci is associated with the best prognosis while
streptococci and enterococci seem to be associated with the worst
prognosis. Presenting visual acuity is, however, a more powerful
predictor of visual outcome than the microbiological factors.
Microbiological investigation may fail in demonstrating infecting

organisms in cases of suspected endophthalmitis. The polymerase
chain reaction may be useful in the diagnosis of endophthalmitis when
applied to the aqueous and vitreous. PCR technique seems to have a
higher rate of positive identification of the causative organism than
microscopy or diagnostic culture.
It is widely believed that endophthalmitis is often due to entry of micro-

organisms, that are present on the ocular surface, into the eye during
surgery. The application of povidone–iodine on the conjunctival surface
appears to significantly reduced the relative risk of postoperative
endophthalmitis. IOLs may also attract micro-organisms from the ocular
surface. IOLs are normally electrically charged, they are therefore able of
attracting any particulate matter form the air or from the external surface
of the eye. Washing the IOL before its implantation is likely to reduce its
surface charge and contamination. Washing the IOL leads to the
removal, or neutralisation of the electrical charge on the IOL surface.
It has been thought that phacoemulsification surgery may be associated

with less risk of postoperative endophthalmitis due to the small incision
and also the high IOP during surgery. Some reports show that
phacoemulsification surgery is associated with less anterior chamber
contamination than with ECCE but the difference does not appear to be
significant. It is also believed that superior incisions may invite infection
more readily than temporal incisions due to the rubbing action of the eye
lids especially in sutureless incisions. Patients with retained lens
fragments after cataract operations may develop severe endophthalmitis

without evidence of infection. Concomitant infection may also be present
in some of these patients.
The classic presentation of postoperative endophthalmitis includes

reduced vision, conjunctival hyperaemia, pain, hypopyon, and lid swelling
within days after cataract surgery. Physicians should be aware that pain
and hypopyon may not always present. There is commonly an
asymptomatic latent period after cataract surgery before patients
develop postoperative endophthalmitis. This period is often about 7 days,
however certain percentage of patients develop endophthalmitis one
month after the operation. 10% of these patients do not suffer with pain.
Ophthalmologists should be aware of the concept of delayed onset
chronic and often painless endophthalmitis in which the coagulase
negative Staphylococci also plays a prominent role, delayed onset
endophthalmitis may also be caused by indolent organisms e.g.
Propionibacterium acne, Candida and other organisms.
Chronic endophthalmitis often present by recurrent low grade uveitis with

partial response to topical antibiotics. Chronic pseudophakic
endophthalmitis is likely to be caused by pathogens of low virulence e.g.
Propionobacterium acne, staphylococci epidermidis, and candida
organisms. Fungal infection is typically associated with chronic indolent
inflammation associated with relatively mild symptoms and vitreous
snowballs opacities. Single dose administration of intra-vitreous
amphotericin B is inadequate in the treatment of some fungal
endophthalmitis. Vitrectomy with repeated intraocular injection of anti-
fungal drugs may be necessary to eradicate the infection.
Propionibacterium infection is also associated with low grade chronic,

delayed and recurrent infection. Propionibacterium acne is an anaerobic,
gram positive bacillus with very low growth characteristics on culture
media. Postoperative Propionibacterium endophthalmitis is characterised
by:
• The presence of white intracapsular plaque (which is a sequestrated

organism inside the capsular bag).
• Low grade iritis .
• High rate of recurrence after topical steroids treatment.
In some studies half of all patients with Propionibacterium acne

endophthalmitis have been successfully treated initially with non-surgical
or limited surgical intervention. Definite treatment of Propionibacterium
infection is often achieved with pars plana vitrectomy, total or partial
capsulotomy with removal of the capsular bag, and intraocular antibiotics
injection (vancomycin). IOL removal or exchange may be needed in
resistant or recurrent cases.
anti-microbial treatment
Gram positive organisms are often sensitive to vancomycin while gram

negative ones are sensitive to gentamicin, amikacin or ceftazidime.
Macular retinal toxicity has been reported after the injection of 0.4 mg of
intraocular gentamicin. A toxic effect from the drugs can occur even
with smaller doses. Gravitational effects and positioning seem to
contribute to the location of gentamicin induced retinal toxicity in
vitrectomised eyes. It would be advisable to position patients in such a
way to make their maculae not dependent in the immediate period
following intraocular gentamicin injection. The interval between repeated
intravitreal injection should be considered to avoid this complication.
Vancomycin and aminoglycosides (including amikacin) are the drugs

of choice in gram positive and gram negative infection respectively.
Amikacin and ceftazidime are thought to be better in gram negative
infections than gentamicin. However, some reports described retinal
toxicity with amikacin. Many surgeons, therefore, prefer to use
ceftazidime instead of amikacin for gram negative infection. It must be
remembered, however, that due to the pharmacological properties of
both drugs that vancomycin and ceftazidime are incompatible and
should not be mixed together or given at the same time in the same eye.
Mixing the two drugs often results in the formation of micro-precipitates in
the vitreous. These micro-precipitates often disappear within a period of
two months.
Studies have shown that Amikacin, when combined with a beta-lactam,

acts synergistically against many clinically important micro organisms. In
inflamed aphakic eyes and aphakic vitrectomised eyes; the vitreous drug
level is equal to or below the minimal drug inhibitory concentration for
most organisms considered sensitive to the Amikacin after 24 hours of
administration. Supplementation of the intravitreal antibiotic is therefore
required in clinical practice.
The effect of adding antibiotics in the infusion fluid, on preventing

postoperative endophthalmitis, in cataract surgery is controversial. Some
studies demonstrated a very low incidence of postoperative
endophthalmitis when either gentamycin or vancomycin was added to the
irrigating solution, and no incidence of endophthalmitis when both added
to the solution. Most studies showed, however, that the addition of
antibiotics (e.g. vancomycin or gentamicin) to the infusion fluid during
cataract surgery does not seem to have significant effects on the
organism commonly responsible for postoperative endophthalmitis. It
seems that longer periods of exposure of these organisms to the
antibiotics is needed for the antibiotics to have a significant effect. A
higher incidence of postoperative cystoid macular oedema and lower
final visual acuity may, however, be associated with intracameral
vancomycin. Care and restrain should be taken in using vancomycin as a
prophylactic antibiotics in the infusion fluid in order to avoid developing
resistant strains.
Oral ciprofloxacin may have a role in the treatment and prevention of

postoperative endophthalmitis. Some reports demonstrated good
intraocular level of ciprofloxacin after oral and IV administration.
Ciprofloxacin levels in the aqueous humour seems to be the same after
oral or topical application. The vitreous level of the drug is, on the other
hand, significantly higher after oral administration. Vitreous level of
Ciprofloxacin (750 mg orally 17.5 and 5.5 hours before the operation)
exceeds the minimal inhibitory concentration of Staphylococcus
epidermidis, Propionibacterium, Pseudomonas aeruginosa, Proteus
organisms, and Haemophilus influenza as well as Staphylococcus
aureus and Bacillus.
Ofloxacin has also been reported to have a high bio-availability and high
tissue penetration to the aqueous, vitreous and subretinal fluid. Ofloxacin
levels in the aqueous humour reaches four time higher levels than
ciprofloxacin levels after topical application. Its bio-availability to the
subretinal fluid appears to be increased after combined oral and topical
administration compared with topical administration alone.
Levofloxacin is a new fluoroquinolone. The drug can be administered

orally and also intravenously. It is reported to be more potent and to have
a lower inhibitory concentration to most of the ocular pathogens, in the
aqueous and in the vitreous, than ofloxacin. Trovafloxacin is another new
antibiotic that may have a potential role, when given orally, in the
treatment of endophthalmitis. The drug has a great activity against gram
positive cocci, and also gram negative organisms.
The role of oral or intravitreal steroids in the treatment is controversial. In

a recent study, oral and intravitreal dexamethasone was reported to
produce less inflammation in postoperative and post-traumatic
endophthalmitis. Reduction of inflammation might help reducing the
elimination of intravitreal antibiotics and might, therefore, enhance its
effect. A recent report, however, showed that visual results in eyes that
have intravitreal steroid injection are worse than eyes that does not have
steroids.
The endophthalmitis-vitrectomy study showed that there is no difference

in the final visual acuity or in media clarity with or without the use of
systemic antibiotics (ceftazidime + amikacin). A recent study showed
that vitreous vancomycin concentrations after intravenous administration
does not reach therapeutic levels. Therapeutic level are, on the other
hand, achieved after intravitreal administration. The endophthalmitis-
vitrectomy study also showed that, in patients with initial visual acuity of
HM or better, there is no difference in the final outcome whether or not
immediate vitrectomy is performed. However, vitrectomy is associated
with a better visual prognosis, in patients with initial visual acuity of PL,
than vitreous tap only.
This is a recommended regime

for treatment of post-cataract endophthalmitis:
1. Aqueous and vitreous tap if the visual acuity is better than hand
movements or by aqueous tap and vitrectomy if the vision is less than
hand movements. Vitrectomy may be carried out if vitreous tap was not
enough and repeat intravitreal injection may also be carried out.
2. Intravitreal antibiotics (vancomycin 1.0 mg + ceftazidime 2.25 mg or
amikacin 0.4 mg). A single intravitreal antibiotic injection may not be
sufficient to cure some cases of bacterial endophthalmitis. Resistant
organism may include Staphylococcal, Streptococcal,
Propionobacterium and fungal species. A second injection of amikacin
may produce more retinal toxicity than a second injection of
vancomycin. Teicoplanin is a new antibiotic that has the same
spectrum of activity to vancomycin. Animal studies showed that the
drug can penetrate ocular tissues after IV, and topical administration.
The drug does not seem to penetrate readily into the vitreous in human
eyes when applied systemically, and not detected in the vitreous at all
when given topically. Vancomycin (50 mg/ml) may also be applied
locally to the eye either in the conjunctival sac or into the medial
canthus with closed lids with good therapeutic concentrations in the
aqueous.
3. Topical hourly Ofloxacin
4. Systemic Ofloxacin (200 mg twice a day and imipenem 500 mg three
times a day).
5. The antibiotics may be adjusted according to the culture and sensitivity
results.
6. The use of preoperative Povidone iodine has also been proved to
reduced the incidence of endophthalmitis. The value of sub-
conjunctival antibiotics injection at the end of surgery is controversial.
• posterior capsule opacification
The most common complication after cataract surgery is opacification of

the posterior capsule. Posterior capsule opacification is the second most
common cause of reversible visual loss in the world. Visually significant
posterior capsule opacification develops in more than 25% of patients
undergoing standard extracapsular cataract extraction or
phacoemulsification with posterior chamber intraocular lens implantation
over the first 5 years after surgery. It has been thought, therefore, that
implantation of anterior chamber IOLs after intracapsular cataract
extraction may be a valid alternative option in poor developing countries
where resources are not readily available.
The opacification of the posterior capsule can be quantified by using the

technique of densitometry with the Scheimpflug photography system.
Densitometry measures appears to be correlated with patients symptoms
and visual acuity.
The design and the material of the IOL have an important effect on the
degree of opacification. IOLs made of polyacrylic material are associated
with less posterior capsule opacification than PMMA, and silicon IOL. The
cause of reduced posterior capsule opacification with the polyacrylic IOLs
is not known but it thought that it might be due to stronger adhesions
between the IOL and the posterior capsule. Heparin surface-modified
IOLs does not seem to provide any significant advantages regarding the
amount of cellular deposits in patients with previous uveitis or diabetes.
The use of Mitomycin C in the solution used for hydrodissection, has
also been shown to be effective in preventing posterior capsule
opacification in rabbits eyes.
It has also been shown, in animal experiments that, transforming

growth factor-beta plays an important factor in the genesis of posterior
capsule opacification. Regulation of Transforming growth factor-beta may
be useful in inhibiting the opacification. In patients with postoperative
fibrinous uveitis the fibrinous reaction may lead to posterior synechiae
formation, and posterior capsule opacification. The use of intracameral
plasminogen activator may be associated with less posterior capsule
opacification. This technique does not seem to be associated with
significant ocular side effects.
Tranilast is an anti-allergic drug that also has an effect on wound healing

and granulation tissue formation. Tranilast eye drops also appears to be
effective in preventing fibrous posterior capsule opacification in the early
postoperative stage. The possible mechanism of this drug’s action may
be prevention of collagen synthesis by minimising transforming growth
factor type â released during lens epithelial cell metaplasia.
• anterior capsule opacification and phymosis of the capsular

opening
Anterior capsule opacification and fibrosis often occurs much earlier than
posterior capsule opacification. The rate of anterior capsule opacification
depends on the IOL material and design being relatively higher with
plate-haptic silicon IOL than with three piece acrylic optic-PMMA haptic
IOL. Contraction of the capsule opening (phymosis), and IOL tilt is a
known complications of capsulorhexis in some conditions associated with
zonule weakness e.g.:
Diabetes.
Old age.
Retinitis pigmentosa.
Pseudoexfoliation syndrome.
The maximum rate of capsule contraction seems to occur in the first 6

weeks after surgery. Silicon IOLs seem to be associated with more
phymosis of the capsulotomy than PMMA IOL. Phymosis may be
complete leading to a complete occlusion of the capsular opening. It may
also be complicated with traction ciliary detachment, choroidal effusion

and ocular hypotony. Capsule contraction may be caused by excessive
shrinkage of the capsule by actin filaments in the residual epithelial cells,
as well as proliferation of the lens epithelial cells. Weakness of lens
zonule may also play a part in its development. Implantation of a
capsular tension ring might help in preventing this complication in high
risk patients. Clinically significant phymosis may be divided by YAG laser
treatment. Caution should be taken as delayed dislocation of silicon
implants may occur after this treatment.
• capsular bag distension syndrome
Capsular bag distension syndrome is a newly described complication of

capsulorhexis that may present with:
Shallowing of the anterior chamber.

Anterior displacement of the IOL.
Unexpected postoperative high myopia.
In this syndrome, the capsule opening is occluded by the IOL optic,

distension of the capsular bag then occurs due to the high osmotic
pressure of its contents (e.g. viscoelastics, soft lens matter or epithelial
cells). Capsular bag distension syndrome often occur 1 to 2 days after
surgery. It has also been reported about 5 years after uncomplicated
cataract surgery. The syndrome has often been reported with PC IOL
implantation in the capsular bag. Rarely it may also occur with IOL
implantation in the ciliary sulcus.
YAG laser peripheral anterior capsulotomy has been successfully

performed in cases of slowly resolving myopia. Surgical removal of the
viscoelastics from behind the IOL may be needed if the condition
persists and if laser treatment is not possible. Care should be taken in
making the capsulorhexis opening adequate and in ensuring that the
viscoelastic is removed from behind the implant at the end of surgery.
Entrapment of the viscoelastic material may also result in unexpected
myopic shift, without increase in the IOP, due to the forward displacement
of the IOL. Removal of the viscoelastic material at the end of surgery is,
there, very important.
• retinal detachment
The risk of developing postoperative retinal detachment 2 years after

cataract surgery is 0.18%. About 75% of post-cataract surgery retinal
detachments occur within the first year. Some studies shows no
difference in the incidence rate of retinal detachment between
phacoemulsification and ECCE.
YAG laser capsulotomy seems to be associated with a significantly

raised risk of retinal detachment. The relative risk of developing retinal
detachment after YAG laser capsulotomy is 4.9, this risk is changed by a

factor of 1.3 with an increase of axial length of 1 millimetre and by a factor
of 0.94 for each added year of the patients age. The time between
cataract surgery and YAG laser capsulotomy does not seem to affect the
risk of retinal detachment development.
Atrophic retinal holes may play a role in the pathogenesis of post-YAG

laser retinal detachment. Identification and prophylactic treatment may
reduce the incidence of retinal detachment after YAG laser capsulotomy.
Pseudophakic retinal detachment may be treated with conventional
scleral buckling surgery, pneumatic retinopexy or by pars plana
vitrectomy without scleral buckling. Primary pars plana vitrectomy with
fluid–gas exchange and laser appears to be safe, and effective in
repairing primary pseudophakic retinal detachments.
• retinal phototoxicity
The incidence rate of induced retinal injury by the use of the surgical
microscope varies considerably among ophthalmologists. Retinal lesions
caused by the operating microscope are often found in the lower part of
the macula, they typically have a horizontal oval shape or a round shape.
Prevention of retinal lesion during surgery may be achieved by reducing
the light power, using filters, avoiding foveal exposure by tilting the
microscope towards the surgeon, and also by using an air bubble if
possible to defocus the light. Decreasing the temperature of the irrigation
fluids, and decreasing the oxygen tension of inspired air may also reduce
the risk of light injury. Surgeons should also be aware of the agents that
cause photo-sensitisation (phenothiazine, allopurinol,
haematoporphyrin, and hydroxychloroquine.
• cystoid macular oedema (CMO)
Macular oedema is a major complication after cataract surgery. The

disease may occur as a result of vitreo-macular traction or due to
liberation of prostaglandins from the anterior segment. The incidence of
CMO after routine phacoemulsification is 19%. A recent study showed
that patients with CMO at day 60, after surgery, had significantly worse
visual acuity, than those who did not. The study also showed that more
postoperative inflammation may be associated with more CMO at day 60.
Treatment is often possible with topical, peribulbar, sub-conjunctival

injection, orbital floor injections or systemic steroids, with or without
carbonic anhydrase inhibitors. It must be remembered that Peribulbar
steroids injection may result in serum steroids levels comparable to
those achieved by a high oral dose. After a peribulbar injection of 5 mg of
dexamethasone, an average intravitreal dexamethasone concentration is
reached with a 75 times greater anti-inflammatory potency than
physiological levels. Dexamethasone concentration in the serum is also
several times higher than physiological levels. Sub-conjunctival injection
of 1 mg of dexamethasone results in a higher vitreous concentration than

after peribulbar injection of 5 mg or after oral administration of 7.5 mg of
dexamethasone. Systemic absorption after sub-conjunctival injection
may also be high.
A new method of an intraocular biodegradable polymer

dexamethasone drug delivery system has been described in the
treatment of postoperative inflammation after uncomplicated cataract
surgery. The system appears to be safe and effective in suppressing
postoperative inflammation with no additional topical anti-inflammatory
drops needed for most patients.
A meta-analysis of previous published reports about medical prophylaxis

for cystoid macular oedema indicated that medical prophylaxis with
cyclo-oxygenase inhibitors and steroids are effective in aphakic and
pseudophakic angiographic and clinical cystoid macular oedema.
Treatment with topical non-steroidal anti-inflammatory drugs (e.g.
ketorolac) may also be effective in chronic cases identified more than 24
months after cataract surgery. The treatment may be needed for a long
time. It has also been suggested that treatment with no-steroidal
medications may only ask the CMO, and that the oedema may recur after
cessation of the treatment. The commonly used anti-inflammatory
ophthalmic drops currently available are:
• Flurbiprofen (Ocufen)
• Diclofenac (Voltarol)
• Ketorolac (Acular)
Some cases are, however, resistant to these traditional methods of

treatment. Macular grid laser photocoagulation (yellow dye, and
medium intensity burns) may be beneficial in the treatment of macular
oedema caused by Irvine-Gas syndrome or uveitis. The treatment may
be associated with angiographic as well as clinical improvement. Pars
plana vitrectomy may also be needed in resistant cases of CMO. The
technique may improve visual acuity, in patients with chronic CMO, that is
not responding to medical treatment especially when there is vitreous
adhesions to the anterior segment structures. Improvement in the
macular oedema and visual acuity may also occur even in eyes with no
apparent vitreous abnormalities.
• other complications
Retained nuclear fragments in the anterior chamber may cause

postoperative iritis, raised IOP and mechanical damage to the corneal
endothelium, and corneal oedema. Gonioscopic examination may be
needed to exclude the presence of such fragments in resistant iritis and
corneal oedema. Surgical removal of the nuclear fragment may be
needed. Iris bubbles in the anterior chamber is a common occurrence
during phacoemulsification surgery. Air bubbles in the intraocular fluids
with a high surface tension may cause a ring shaped damage to the
corneal endothelium. Severe damage to the corneal endothelium may
occur after a contact with the air bubbles for as little as 20 seconds. The
mechanism that cause this damage seems to be due to surface tension
of the bubbles.
Operative suprachoroidal haemorrhage may be associated with

devastating visual results. Longer axial length, old age, and higher
preoperative IOP are associated with increased risk of acute operative
suprachoroidal haemorrhage. Poor visual results often occur in the
following conditions:
• Retinal detachment,
• Four quadrant haemorrhage,
• Eyes with spontaneous nuclear expression,
• ECCE “rather than phacoemulsification surgery”,
• Visual acuity of perception of light or worse on the first postoperative
day.
Cataract surgery in the future

It is thought that cataract surgery in the future will be carried out by
removing the lens via a small capsular opening and then filling the
capsular bag by injecting a polymer that solidifies and offers some
degree of accommodation range. Re-filling of the lens capsule after
endocapsular phacoemulsification through a mini capsular opening and
sealing the opening with a silicone plug has been shown to provide a
small degree of accommodation in monkey’s eye [1]. An inflatable
endocapsular balloon has also been used to fill the lens capsular bag in
animals eyes. A mixture of two silicon oils polymers which can
polymerise in about two hours is then injected in the balloon to refill the
capsular bag.
Glaucoma
Basic science
Glaucoma is the second leading cause of visual loss in the world. It is
estimated that there is about 66.8 million people with primary glaucoma in
the world, 6.7 million of them are suffering from bilateral blindness.
The pathogenesis and aetiology of primary open angle glaucoma is

unknown. Raised IOP is the main risk factor in the development of
glaucoma. A recent study showed that some cells exhibit morphological and
cytoskeletal changes as well as alteration in their intracellular adenylyl
cyclase activity when exposed to increased levels of hydrostatic pressure.
Myopic individuals have a twofold to threefold increased risk of developing
glaucoma compared with that of non-myopic subjects.
Sleep apnoea syndrome is a disease characterised by recurrent complete

or partial upper airway obstructions during sleep. These obstructive
respiratory disturbances may last from 10 seconds up to 2 minutes, leading
to severe hypoxia and hypercapnia. Other ophthalmologic findings in
patients with Sleep apnoea syndrome include:
1. Floppy eyelid syndrome.

2. Keratoconus.
3. Optic disc oedema.
4. Recently, Hayreh described patients with anterior ischaemic optic
neuropathy with a high prevalence of Sleep apnoea syndrome.
5. Sleep apnea syndrome has also, recently, been described as a risk factor
for open angle glaucoma (7.2% of patients with the syndrome are
reported to have glaucoma). The syndrome is characterised by episodes
of upper airway obstruction during sleep, causing hypoxia with risks of
cardiovascular and neurological disorders.
Hereditary factors also play an important role in the pathogenesis of

glaucoma, and a positive family history is a major risk of developing the
disease. Glaucoma may be inherited as autosomal dominant, recessive, or
X-linked disorder. The disease has been mapped to the chromosomes 2
cen-2q 13 region, 3q 21-q 24 region, 8q 23 region, and also to the 10p15-
p14 region. Juvenile open angle glaucoma, on the other hand, has been
located to chromosome 1q 21-q 31. The Gln368stop mutation has recently
been found in several cases of late-onset primary open-angle glaucoma.
The penetrance of glaucoma increases with age in Gln368stop carriers. The
myocilin Gln368stop mutation shows a good genotype-phenotype
1
correlation and should be investigated in all familiar cases of chronic primary

open angle glaucoma . This may be important for early diagnosis and
periodical check-ups of pre-symptomatic individuals belonging to these
families.
Abnormal blood perfusion of the optic nerve head appears to play an

important part in the pathogenesis of glaucomatous optic neuropathy.
Vasospasm and cardiovascular disease have been identified as risk factors
for some patients with glaucoma irrespective of the level of IOP. Vasospasm
appears to be more prevalent in patients with focal ischaemic discs, while
patients with senile sclerotic discs have a higher prevalence of
cardiovascular diseases. There is also a positive correlation between
systemic blood pressure and IOP. Lower diastolic perfusion pressure
appears to be associated with a marked increase in the frequency of
hypertensive glaucoma.
There are conflicting reports about the state of ocular blood flow in patients
with glaucoma or ocular hypertension. Some studies found no significant
difference between normal eyes and eyes with ocular hypertensive, while
other studies demonstrated impaired circulation and ocular blood flow in
eyes with ocular hypertension and glaucoma. It is not known whether these
changes in the blood flow are a cause or a consequence to the raised IOP,
the vascular insufficiency may be primary or secondary to raised IOP.
Abnormalities in the enzymatic activities in the red blood cells walls are
common in patients with primary open angle glaucoma compared with
normal subjects. These enzymatic abnormalities may interfere with blood
flow and oxygen transport in retinal and disc micro-circulation. It is not known
if these abnormalities play any significant role in the optic nerve head blood
perfusion.
There is also some evidence that some patients with normal tension
glaucoma may have an autoimmune component to the disease that is not
related to the level of IOP. HLA-DR3, HLA-B8, HLA-DRB and HLA-DQB and
HLA-DQA1 have all been associated with glaucoma in different populations.
A subgroup of normal tension glaucoma patients have a high level of serum
immune reactivity to bacterial heat shock protein 60. Immune responses to
heat shock protein are implicated in the development of human autoimmune
diseases. A recent study showed an increased immuno-staining of heat
shock proteins in the retina and optic head of normal and glaucomatous
eyes suggesting that immune-regulation plays an important part in the
pathogenesis of glaucomatous optic neuropathy. High levels of serum
immune-reactivity may also be associated with anti-Sjogren’s Syndrome A
and B antigen which are non-organ specific auto-antibodies. Some
glaucoma patients also have increased levels of auto-antibodies to
glycosaminoglycans of the optic nerve head. These auto-antibodies play
important part in immune mediated diseases. They may increase the
2
susceptibility of the optic nerve head to damage by changing the functional

structure of the lamina cribrosa.
A recent study described some patients with normal tension glaucoma who
have increased serum immuno-reactivity to retinal protein. In some of these
patients the immuno-reactivity regress and visual field improves after a
course of methotrexate treatment.
Optic nerve damage in glaucoma may be caused by direct traumatic effect

of the increased IOP or by IOP rise-mediated optic nerve head ischaemia.
Nitric oxide (NO) and endothelin are cellular mediators that act as
hormones or neuro-transmitter. Nitric oxide produces relaxation of the
smooth muscle cells, by stimulating the production of cGMP. Endothelin, on
the other hand, is a potent vasoconstrictor. Vascular endothelial cells can
produce Nitric oxide. Nitric oxide synthase enzyme has also been identified
in the lamina cribrosa of normal eyes. Eyes with ocular hypertension and
eyes with primary open angle glaucoma seem to have more cells which
stain positive for the enzyme. It has recently been shown that higher levels
of hydraulic pressure enhanced basal production of nitric oxide in human
trabecular cells. Nitric oxide may be a physiological mediator in the
regulation of intraocular pressure.
It has been shown that Nitric oxide and endothelin are involved in the
regulation of IOP and ocular blood flow. Trabecular meshwork has
contractile elements that can be relaxed or contracted by Nitric oxide or
endothelin respectively. Nitric oxide and endothelin can thus play an
important part in controlling the IOP by changing the resistance of the
trabecular meshwork.
Nitric oxide is also involved in the control of retinal ganglion cell apoptosis by
interacting with glutamate. Experimental studies in animal models showed
that reduction of nitric oxide by nitric oxide synthase inhibitors provide
significant protection against the effect of anoxia and excitatory amino acids
on the animal ganglion cells.
The amino acid glutamate has been found in large quantities in the vitreous
body of glaucoma patients. Increased glutamate production may be initiated
by an increase in the IOP. Glutamate can produce apoptosis and ganglion
cell death by activating some enzymes with simultaneous production of
Nitric oxide in larger quantities than its physiological levels. This process
also results in the production of the free radicals super-oxide which reacts
with Nitric oxide resulting in the formation of toxic the agent peroxynitrite that
can trigger apoptosis. Pharmacological inhibition of the Nitric oxide system,
and blocking the excito-toxic effect of glutamate may protect against cell
death and may prove useful in the treatment of glaucoma.
3
Glaucoma is associated with morphological as well as metabolic and

structural changes in the lamina cribrosa. The lamina cribrosa is normally
consisted of a lattice-like structure composed of connective tissue sheets
and channels through which the retinal ganglion cell fibres pass. The
lamina’s structure consists of various collagen types e.g. elastin,
proteoglycan, fibronectin and glycoproteins. The changes associated with
glaucoma include compression of the cribriform plates, posterior rotation of
the peripheral lamina, and elongation of its pores. An increase in the total
collagen content of the lamina cribrosa and a decrease in the percentage
of type III collagen to type I collagen have also been previously described.
The elastin component of the lamina seems to decrease with age. it’s
mechanical compliance and the resilience also decrease with age. Such
metabolic and physical changes may be implicated in the pathogenesis of
optic nerve head changes in raised IOP and glaucoma.
4
Clinical science
IOP Measurement
Goldman contact tonometry is the most common method of measuring the

IOP. Variation in corneal thickness is a significant source of variation in IOP
measurements between individuals. Corneal thickness is significantly
reduced in patients with normal pressure glaucoma as compared with
patient with primary open angle glaucoma and healthy controls. The
reduced corneal thickness may lead to underestimation of IOP readings.
Measurement of corneal thickness should be considered when assessing
IOP. Goldman tonometry overestimates the IOP in cases with thick cornea,
and underestimates the IOP in cases with thinner cornea. Measuring the
central corneal thickness may be useful in determining the accuracy and the
importance of elevated IOP in glaucoma suspect or the normal IOP in
patients diagnosed as low tension glaucoma. A single measurement of
central corneal thickness is sufficient when assessing patients with
suspected glaucoma.
The role of Tono-pen in measuring the IOP, in corneas with abnormal

thickness, is not known. In some studies the IOP measured by the Tono-
Pen was significantly correlated to the central corneal thickness. The
instrument seems to overestimate IOP readings in individuals with thicker
central corneal. In other studies, it was suggested that the use of Tono-pen
tonometer may be more accurate than Goldman tonometer, the instrument
appeared to be less affected by changes in the corneal thickness than
Goldman tonometry. Pneumotonometry is also thought to be more reliable,
than Goldman applanation tonometry, in measuring the IOP after PRK in the
peripheral as well the central cornea. The use of Goldman applanation
tonometry, in these eyes, in the central cornea may underestimate the IOP.
IOP measurement may vary with age. Applanation tonometry markedly

underestimates IOP readings in young patients eyes. The
pneumotonometer method seems to be the best method for measuring the
IOP clinically in all ages. It is thought that applanation tonometry is better
reserved for patient of 10 years of age or older. Changes in blood circulation,
(e.g. increase in the venous pressure in the Valsalva technique) may affect
the IOP. These changes can be observed in measuring the IOP in very
obese patients, due to the difficulty they encounter in positioning their
heads on the slit lamp. Perkins tonometry in these situation may be more
accurate than Goldman tonometry.
The sensation of light elicited by a non-photic stimulus is an entoptic

phenomena called phosphene. Application of pressure on a closed eyelid
gives rise to a phosphene sensation described as a glow, and perceived
opposite to where the pressure is applied. The source of pressure
phosphene is supposed to be the bipolar cells in the retina. A new
5
tonometer (The Pressure Phosphene Tonometer) has been described.

The tonometer is applied with the eye close and the patient is instructed to
indicate when the pressure phosphene is perceived, the IOP is then
determined by reading the pressure on the dial. The IOP measured by the
new instrument seems to be comparable to Goldmann tonometry results
and may be used for home IOP self measurement.
6
The optic nerve head

Instrumentation
In glaucoma patients progressive optic nerve cupping may occur without

causing recordable visual field loss. Evaluation of the optic nerve head is,
therefore, an important part of glaucoma evaluation. The optic nerve head
can be examined by direct and indirect ophthalmoscopy, slit lamp
biomicroscopy and also by photography. These methods are, however,
subjective and may not be reproducible.
Objective computerised image analysis methods with digital videographic

image storage and processing techniques have recently bee used to avoid
this problem. It is generally thought that none of these instruments is suitable
for routine use in clinical diagnosis of glaucoma. The main computerise
image analysers used at present are:
• The Rodenstock optic nerve head analyser.

• The Confocal Scanning laser Tomograph (The Heidelberg retina
tomograph).
• The scanning laser polarimetry for the nerve fibre layer.
• Optical Coherence tomography.
The Rodenstock optic nerve head analyser uses a stereoscopic video

camera to produce digitised image of the optic nerve head. The instrument
is, however, technically difficult to operate, it also needs pupil dilatation and
clear media.
The Heidelberg retina tomograph projects a diode laser beam on the retinal
via a confocal system. The instrument has a high spatial resolution due to its
confocal system. The depth of scanning ranges from 0.5 to 4.0 mm with a
0.5 mm increments. The instrument performs 32 scans within this depth.
The computer then forms a three-dimensional image of the disc. The
instrument has a better axial resolution than the Rodenstock optic nerve
head analyser. The instruments also uses a low light intensity, and images
can be obtained through undilated pupil. The main disadvantage of the
instrument is that it needs a reference plane.
The Optical Coherence tomography operates by the same principle as

ultrasound but by using optical, rather than, ultrasound beam. The
instrument provides a very high resolution images without contact with the
eye. It is not affected by the refractive status of the eye. Media opacities
may, however, affect its results. Testing with this instrument also need pupil
dilatation. Optical coherence tomography may be able to differentiate
between normal, ocular hypertensive and glaucomatous eyes. A
considerable overlap may, however, occur between all these three groups.
7
Measurements taken by the optical coherence tomography seem to

correlate with scanning laser polarimetry measurements.
Morphological features
Normal optic nerve heads in the general population may vary significantly in
the disc and neuro-retinal rim area. Age related changes may affect several
parameters in the eye. However, age does not appear to be associated with
significant disc characteristics.
Different patterns of disc damage have been described in glaucoma

patients. Optic disc damage may be diffuse (in the majority of patients),
localised, or undetectable. Patients with different disc appearances show
differences in their demographic characteristics, prevalence of certain
systemic risk factors, IOP levels and the patterns of their visual field loss.
The presence of various disc appearances may represent different patients
population with different mechanisms for the glaucoma. The 4 different
patterns of glaucomatous discs are:
1. Focal ischaemic disc.

2. Myopic glaucomatous disc.
3. Senile sclerotic disc.
4. Generalised enlargement of the optic cup disc.
Disc and retinal imaging can be carried out by different imaging systems
(e.g. fundus camera, infra-red scanning laser ophthalmoscope, and the
Heidelberg retina tomograph). The size of the disc parameters depends on
the magnification by the camera and by the eye. The use of a single
magnification correction value for all these methods is not accurate, this may
have significant implication in the calculation of disc and retinal lesions sizes.
The topography of the optic nerve head seem to be dependant of the level
of the IOP. Increases in the IOP are associated with significant enlargement
of the optic disc cupping in both emmetropic and myopic eyes. Lowering of
the IOP, e.g. after trabeculectomy surgery, may be associated with improved
optic nerve morphology (as demonstrated with Heidelberg retinal
tomograph). The amount of improvement in the morphology of the optic
nerve head seems to be correlated to the degree of IOP reduction. Recent
studies, however, showed that there are no apparent differences between
high tension and low tension glaucoma in the morphometric parameters as
measured by scanning laser ophthalmoscopy.
Vertical cup/disc ratio has been used in the evaluation of disc cup in
glaucoma patients. There is, however, a wide variation in the cup/disc ratio
in normal population. The cup/disc ratio relative to the disc size is a new
parameter that can be a useful in the evaluation of glaucomatous discs,
especially in small discs.
8
The neuro-retinal rim is one of the main features in the diagnosis of

glaucomatous optic neuropathy. Analysing the relation between the disc size
and the neuro-retinal rim by the Laser scanning ophthalmoscope is a
specific and sensitive method to differentiate between normal and
glaucomatous discs. The system provides a high degree of reproducibility
and can be used in the evaluation of the optic disc in glaucoma patients.
Glaucomatous neuro-retinal rim loss generally begins in the inferior temporal

region and progresses to the superior temporal to temporal, inferior nasal,
and finally the superior nasal region. Abnormally low inferior / temporal and
superior / temporal ratio can be used to detect glaucomatous disc damage
in some eyes with raised IOP. These ratios offer a method of neuro-retinal
evaluation independent of disc size and magnification problems.
Measurement of the absolute rim area and the rim / disc area, is significantly
larger with confocal laser ophthalmoscope than with planimetry or disc
photos. This difference may be due to the fact that confocal laser
ophthalmoscope measures the retinal vessel as a part of the retinal rim. It
should be taken in consideration when comparing data.
Disc haemorrhage appears to be strongly associated with glaucoma

(especially low tension glaucoma). The presence of disc haemorrhage is
associated with localised damage of the nerve fibre layer in both NTG and
primary open angle glaucoma and seems to increase the risk of further
visual field deterioration. Most disc haemorrhages are present in patients
with no other signs of glaucoma. They seems to be associated with larger
vertical cupping and also with a history of migraine.
Acquired optic nerve head pits are known to be associated with the
development of glaucoma, specially low tension glaucoma. They are often
associated with an increased risk of developing progressive disc and visual
field damage. The field changes associated with disc pits are deep and have
a sharp margins scotoma which approaches or even involve fixation. Visual
field loss within 1-3 degrees from fixation occurs in about 96.7% of cases.
The presence of these pits constitutes a threat to central fixation vision
specially if it is located in the inferior pole of the optic disc. 76% of the
acquired optic nerve head pits occur in the inferior part while only 11% occur
in the upper part.
The value of measuring the peripapillary atrophy in the diagnosis of

glaucoma is uncertain. 38% of eyes with primary angle closure glaucoma
and 68% of eyes with primary open angle glaucoma have peripapillary
atrophy. The peripapillary atrophy in primary angle closure glaucoma has a
different relationship to the structural and functional optic disc changes than
that in primary open angle glaucoma. Different mechanisms seem to be
involved in the development of the optic disc damage in the two types of
9
glaucoma. Beta zone (central peripapillary atrophy), and alpha zones

(peripheral peripapillary atrophy) are found in 49% and 100% eyes with
primary open angle glaucoma, respectively. It must also be remembered
that the prevalence of zone beta seems to be higher in high myopic eyes.
Both areas, especially beta zone, are associated with glaucomatous visual
field loss when tested by standard automated perimetry and short-
wavelength automated perimetry. It is suggested that clinical decision should
not be based only on the presence or absence of these zones.
10
Nerve fibre layer polarimetry

Nerve fibre layer damage in glaucoma may be either diffuse or localised.
The Nerve fibre layer can be visualised by direct ophthalmoscopy, slit-lamp
biomicroscopy, high-resolution monochromatic photography, or by the more
recent technique of scanning laser polarimetry.
The changes in the state of polarisation (retardation) of a light beam falling

on the nerve fibre layer can be measured and quantified by the confocal
laser ophthalmoscopy, a technique called Scanning Laser Polarimetry.
The scanning laser polarimetry utilises the birefringent properties of the
nerve fibre layer, and the principle of polarisation. The instrument measures
the degree of retardation of the nerve fibre layer which is positively related to
the degree of nerve fibre layer thickness. This method has the advantages
of being independent of a reference plane, quick, sensitive, does not need
pupil dilatation, and also independent of patient’s refractive errors. Other
polarising structures in the eye e.g. the cornea and the lens may, however,
affect its readings.
The thickness of the retinal nerve fibre layer, as measured by polarimetry,

seems to be correlated to its thickness as measured by histological
methods. A quantitative differences, in retinal nerve fibre layer thickness,
between age-matched ocular hypertensive, normal, and glaucomatous eyes
has been recently reported. It should also be noted that there is asymmetry
of the retinal nerve fibre layer thickness with respect to the horizontal midline
and the vertical meridian between the two eyes in normal individuals. These
findings should be taken in consideration when interpreting the results of
polarimetry.
The value of retinal nerve fibre layer retardation seems to be less in black
than in white subjects. Nerve fibre thickness also appears to decreases with
age and in myopic individuals. The nerve fibre layer thickness, in myopic
individuals, also seem to decrease with increasing myopia. Retardation
values are greater in the superior and inferior quadrants of the peripapillary
retinal nerve fibre layer compared with the nasal and temporal quadrants.
The variation of retardation around the optic disk appears to be less than
expected from the histological variation seen around the peripapillary area.
The effect of age, optic disc size and neuro-retinal rim area should be
considered when interpreting the results of polarimetry. It should be noticed
that the cross section area of retinal nerve fibre layer increases significantly
with an increase in the optic disc size. In using the Nerve Fibre Analyser,
the superior-nasal and inferior-nasal ratios of the retardation values appear
to be more useful indices than individual values in discriminating patients
with glaucoma. The results of scanning laser polarimetry measurement may
also depend on the corneal refractive status. A new base measurement is
recommended after Laser in situ keratomileusis (LASIK) surgery.
11
Optic nerve head measurements, as measured by the confocal scanning

ophthalmoscope, correlate well with the optic nerve fibre layer
measurements, and also with perimetry. The correlation of the two
measurements around the disc margin, however, seems to be variable.
Assessment of the nerve fibre layer, by polarimetry can differentiate between

patients with glaucomatous optic neuropathy from controls. Glaucoma
suspects can also be differentiated from normal individuals by this method.
The system might, however, fail in detecting a substantial number of
subjects with severe damage, and it is not recommended for glaucoma
screening at present. The use of a combination of more than one
measurement by the instrument, improves the ability to differentiate between
healthy eyes and eyes with early and moderate visual field loss. Retinal
nerve fibre layer blood vessels may affect the results and the reproducibility
of polarimetry measurements. The use of blood vessels removal algorithm
seems to increase the reproducibility of scanning laser polarimetry, and
enables an improvement in the ability of polarimeter to differentiate between
normal and glaucomatous eyes.
Peripapillary retinal nerve fibre layer volume can be measured by various

optic nerve head imaging techniques (e.g. confocal scanning polarimetry,
optical coherent tomography and retinal thickness analyser) by using a
special soft ware. Nerve fibre layer volume appears to be useful in the
differentiation between normal individuals, patients with open angle
glaucoma, patients with ocular hypertension or patients with normal tension
glaucoma.
12
Perimetry
Large ganglion cells are more susceptible to damage in glaucoma patients.
These cells project to the magnocellular layer and the lateral geniculate
body. Damage to both the magnocellular and the parvocellular layers
occurs in glaucoma patients. Ocular hypertension patients, on the other
hand, have significant damage only in the magnocellular layer and only
marginal damage in the parvocellular layers.
Few white patients become completely blind from glaucoma. The rate of
visual field progression, in white patients, is not dependent on the level of
IOP. Visual field progression seems to be similar in normal tension
glaucoma and in primary open angle glaucoma. Visual field progression
may continue despite a good IOP control. White patients with severe visual
field loss in one eye are not at a high risk of having severe loss in the fellow
eyes. The Advanced Glaucoma Intervention Study showed, on the other
hand, that visual field defects are more severe in black patients than whites.
Black patients also have fewer disc haemorrhages than whites.
Baseline perimetry should consists of more than one test. The learning
effect of repeated perimetry should be taken in consideration in the
evaluation of the progress of the disease. Wearing the proper refractive
correction during perimetric testing is essential, refractive errors can produce
refraction scotomas, spurious test results and increased variability. If
patient's pupils are less than 3 mm in diameter, they should be dilated during
the test.
Visual field testing should provide maximum amount of information with the
least effort to the patients. Fast Pac, SITA standard, SITA fast have been
compared against a full threshold Humphrey’s test in a recent study. Both
SITA programmes seem to provide a greater visual field defects than the
Fast Pac, with a reduction in the test time to 53% in SITA standard, and 50%
in SITA fast tests compared to full threshold Humphrey’s test.
There are three statistical algorithms programmes commercially available to

use with the Humphrey’s visual field analyser to determine true
progression of visual field loss :
1. The Linear Regression Analyser.

2. Glaucoma Change Probability Programme.
3. The Progressor Programme.
There is a high index of variability between the three programmes in

determining visual field progression and non of them seem to correlate well
with the clinical judgement. Glaucoma change probability test seems to be
the most useful single test.
13
the FAST PAC programme
The standard threshold programme of the Humphrey visual field analyser

uses steps of 4-2 dB and crosses the threshold twice when measuring
retinal sensitivity in glaucoma patients. This programme often takes a long
time to perform and might be tiring to some patients. Two time-saving visual
field test strategies are being used. The FASTPAC and the supra-threshold
screening programmes. The standard full threshold algorithm uses staircase
bracketing logic. In contrast the FASTPAC uses 3 dB steps in bracketing the
test points. It tests half of the test points with 1 dB higher than the test
location and the other half with 2 dB below the test location threshold. The
supra-threshold, on the other hand, uses 6 dB in bracketing the test points.
In healthy subjects and in patients with early glaucoma FASTPAC strategy
saves 40% of test time without significant deterioration in field defect
detection.
blue on yellow perimetry
Visual damage in glaucoma affects either the parvocellular pathways (as

detected by short-wavelength automated perimetry) or magnocellular
pathways (as detected by motion automated perimetry). There might be an
individual variation in which type of pathway is glaucoma damage first
shown. Blue on yellow perimetry can isolate and measure the sensitivity of
the short wavelength-sensitive S-cone pathway mechanism which seems to
be affected centrally and peripherally early in glaucoma. This method is
useful in detecting visual field defects in early glaucoma and also in
glaucoma suspects with large disc cupping. Visual field defects detected by
this method is highly associated with nerve fibre layer assessments, and
may precede visual field defects detected by the Humphrey visual field
analyser or the detection of nerve fibre layer defects by polarimetry.
Clinically detectable structural abnormalities frequently coexist with blue-
yellow visual field defects, in patients with ocular hypertension, are
frequently associated with clinically detectable glaucomatous structural
abnormalities. However, long and short term fluctuation and variability of
blue-on yellow perimetry is greater than of that with white perimetry.
the oculo-kinetic perimeter test (OKP)
The Oculo-kinetic Perimeter test (OKP) is a simple, inexpensive and self-

administered visual field screening test designed to make visual field
screening possible. The test relies on eye movements to project a dark
stimulus onto different areas of the visual field. The test is designed for
screening purposes and lacks some sensitivity. The size and contrast of the
target make this method effectively a supra-threshold method which make it
less sensitive than humph perimetry.
14
dark stimuli on a bright background
Fields tests using dark stimuli on a bright background allows the

differentiation between glaucomatous field loss and normal regions in central
visual fields. Dark stimuli of lower contrast provided higher abnormal points
detection rates. Visual field defects to the low contrast dark stimuli are more
extensive than those to the luminous stimuli. These findings suggest that in
glaucoma suspect eyes dark stimuli may diagnose visual fields
abnormalities before they become evident equal sized deterioration on
conventional positive contrast stimuli .
whole field scotopic sensitivity test
Whole field scotopic sensitivity test provide a high level of sensitivity and
specificity in distinguishing patients with glaucoma from controls. The test
assess the scotopic vision which is a function of the magnocellular retinal
ganglion cells.
15
Miscellaneous
• Frequency Doubling Tests
Frequency doubling test is a new test that is based on detecting

abnormalities in the magnocellular ganglion cells layer (other tests include
Motion sensitivity testing, scotopic sensitivity). In this test, alternating light
and black bars, that are rapidly reversed between white and dark, appear to
have twice the actual number of bars. There is a theoretical and clinical
evidence that the use of this phenomena may be useful in the diagnosis of
early glaucoma.
The technique provides high sensitivity and specificity for detecting early,
moderate and advanced glaucoma. Grading of glaucomatous visual field
defects, in a clinically significant manner similar to that obtained by
conventional visual field testing, is possible with this new psycho-
physiological test. There is also a significant correlation between frequency
doubling technique results and visual field defects. The test seems to be a
promising method in screening for glaucoma. The test may be more
sensitive than threshold perimetry in screening for glaucoma. visual field
loss. It is simple, rapid and not affected by the patients refractive errors.
Motion impairment may be used as a predictor for visual field loss in
glaucoma patients. The period between motion impairment and visual field
loss in not known.
• The Retinal thickness analyser
The Retinal Analyser test is useful in detecting retinal thickness alteration in

macular diseases, and may provide multiple optical cross sections of the
retina. The ganglion cell layer forms a significant part of the retinal thickness.
Mapping the retinal thickness with the retinal thickness analyser may be
helpful in the detection of ganglion cell layer abnormalities and may be
useful in the diagnosis and follow up of glaucoma.
• Fundus perimetry
Fundus perimetry with scanning laser ophthalmoscope is new promising

technique that allows correlation between the appearance of the fundus and
visual field measurements. Visual fields obtained with this technique appear
to be correlated with those obtained by computerised static perimetry.
Increasing age may be associated with decrease in the light sensitivity and
greater losses of fixation during the test.
• Confocal tomographic angiography
Blood supply to the optic nerve head is thought to play an important part in
the pathogenesis of glaucomatous optic neuropathy. A new technique
16
(Confocal tomographic angiography) is developed to study the optic nerve

head superficial and deep circulation by using both the scanning laser
ophthalmoscope and indocyanine green angiography technique. Vascular
filling abnormalities in the nerve head are noticed in patients with visual field
loss.
17
Normal Tension Glaucoma

It is not known if the pathogenesis of low tension glaucoma is similar to that
of the primary open angle glaucoma. Systemic cardiovascular and
rheological factors have been implicated in the pathogenesis of this type of
glaucoma. Pulsatile ocular blood flow is significantly lower in eyes with NTG
than in normal eyes. Eyes with NTG, with visual field loss, are also
associated with lower pulsatile blood flow indicating that blood flow
difference may play an important role in the pathogenesis of this type of
glaucoma.
A histopathological study of an eye with low tension glaucoma

demonstrated optic nerve changes similar to that in eyes with raised tension
glaucoma. The study also demonstrated deposition of serum
immunoglobulin G and A in the ganglion cell and in the inner and outer
retinal layers. Serum antibodies to retinal protein may play a role in the
pathogenesis of low tension glaucoma.
In making the diagnosis of low tension glaucoma, the clinical differentiation

between glaucomatous optic disc cupping and non-glaucomatous
(compressive, traumatic, hereditary, or demyelinating) optic disc cupping is
difficult. Pallor of the neuro-retinal rim is thought to be 94% specific for
predicting a non-glaucomatous disc cupping, and focal or diffuse obliteration
of the rim is thought to be 87% specific in predicting glaucomatous cupping.
Imaging studies are often undertaken in patients with optic nerve head
cupping with visual field loss and normal IOP. Imaging of the visual pathway
rarely reveal compressive lesions in the evaluation of these patients. It is
thought that the following factors may increase the likelihood of identifying
intracranial mass lesion in this group of patients:
younger age.
lower levels of visual acuity.
vertically aligned visual field defects.
pallor of the neuro-retinal rim.
A recent study showed that chronic high-pressure glaucoma and normal-

pressure glaucoma show morphologic similarities in the appearance of
the optic nerve head. The study indicated that the lower frequencies of
detected disc haemorrhages and rim notches in high-pressure glaucoma
may be due to a smaller size of haemorrhages and localised retinal nerve
fibre layer defects in high-pressure glaucoma. it seems that both glaucoma
types have morphologic features in common, suggesting that they may
possibly belong a spectrum of the same pathologic process.
Patients with normal tension glaucoma and visual field loss in one eye are
at increasing risk of loosing visual field in the fellow eyes. The risk is
increased if the visual field loss in the first eye is great and/or if the neuro-
18
retinal rim in the fellow eye is reduced. High IOP in normal pressure
glaucoma, is associated with more damage to the optic nerve head and the
neuro-retinal rim. Lowering the IOP may be useful in these eyes.
A multicentre randomised study in patients with low tension glaucoma

demonstrated that a 30% reduction in the IOP is associated with less
progression of visual field loss. Some patients with low tension glaucoma do
not progress whether IOP is reduced or not. Methods of treatment in low
tension glaucoma is controversial. Medical treatment has always been
disappointing. Recently it has been demonstrated that once a day
latanoprost may be effective in lowering the IOP and increasing pulsatile
ocular blood flow in these patients. Filtration surgery may also be needed in
many patients to lower the IOP to very low levels. Trabeculectomy with
adjunctive per-operative 5-FU should maintain a suitable target IOP without
the additional sight threatening complications seen with adjunctive
Mitomycin C. Filtration surgery may, however, be associated with an
increase in lens opacities. The benefit of filtration surgery, on the visual
function, is only significant after the effect of the increased cataract on the
visual field is removed by cataract surgery.
19
Medical treatment
glaucoma, in the majority of patients, can be controlled by medical treatment
only. However, about one third of white population with glaucomatous
damage, at the time of diagnosis, needs filtration surgery. At present,
reducing the IOP is still the main objective of the treatment. Some studies
showed that reducing the IOP by 30% may be effective in reducing visual
field loss progression even in normal tension glaucoma. A recent study, on
the other hand, showed that there is no correlation between IOP and visual
field loss progression.
The chronic use of glaucoma medications may be associated with drug-

induced conjunctival scarring and ocular cicatricial pemphigoid which
might affect the outcome of surgical treatment.. The clinical features of drug-
induced and idiopathic ocular cicatricial pemphigoid seem to be very similar.
Both conditions may respond to immunosuppression treatment. Conjunctiva
biopsy may reveal a similar histopathological features in both conditions.
Stopping the medication early in the disease may result in resolution of the
conjunctival scarring.
Topical steroid drops are known to increase the IOP and cause glaucoma in
susceptible patients. Physicians should be aware that systemic and inhaled
steroids may also increase the IOP in susceptible patients and patients with
a positive glaucoma family history.
Beta blockers
Beta blockers have been the most commonly prescribed medical treatment
for open angle glaucoma. The main side effects of oral and topical beta
antagonists medications are:
heart failure
hypotension
bronchospasm
Topical beta antagonist drugs have also been implicated as a major risk
factor for falls in elderly glaucoma patients. Timolol also seems to adversely
affects the high-density lipoprotein and total cholesterol / high-density
lipoprotein ratio in women age 60 years and older with ocular hypertension
or primary open-angle glaucoma, this may be due to its effect on the
lipoprotein lipase enzyme. Carteolol, on the other hand, appears to be
neutral in its effect on serum lipid levels.
Beta blockers medications should be used with caution in African black

glaucoma patients. Recent studies showed that the IOP lowering effect of
beta blocker drops, in this group of patients, is less than its effect in white
Caucasian individuals. Rebound rise in the IOP may also occur in some
20
black individual after stopping the drops. A recent paper also showed that
beta blockers may be less effective when used at night than during the day.
The authors of the report suggested that this difference in action may be due
to the circadian variation of the IOP, it is known that aqueous formation is
less during the night.
Efficacy of topical timolol may also be reduced with the concurrent

administration of systemic ß-blockers. Systemic side effects may also be
increased. Ocular hypotensive agents other than ß-blockers, may be a more
appropriate first-line therapy for ocular hypertension and glaucoma in
patients concurrently taking systemic ß-blockers.
Beta blocker drops should be avoided in elderly patients because as many

as 41% of elderly people have airways disease, most of these diseases are
undiagnosed and unsuspected. Topical timolol application may be
associated with mild bronchial obstruction even in patients with no pre-
existing respiratory diseases. If there are no suitable alternatives
cardioselective preparations are usually chosen. Spirometry studies (or at
least a peak flow recording) should be performed before commencing beta
antagonist therapy and should also be repeated at each outpatient visit.
Most patients at risk of using beta blockers can be detected by performing
spirometry at the start and then one month after starting the treatment.
Timolol gellan is a new preparation of Timolol 0.5% that is suspended in a

polysaccharide derived from a gellan gum which forms a gel on application
to the conjunctival surface. Once a day application of Timolol gellan is as
effective as twice a day application of the aqueous solution with the added
advantage of lesser systemic absorption. Both Timolol preparations reduce
resting and peak heart rate but the reduction produced by the Timolol gellan
is significantly less than with the aqueous solution even in peak exercise
performance.
Topical Metipranolol may be associated with adverse reactions e.g.

granulomatous anterior uveitis and blepharoconjunctivitis. Uveitis is often
associated with large KPs, cells and flare and secondary glaucoma, when
the drops are discontinued and topical steroids are started the uveitis often
subside within 4 to 6 weeks. Beta blockers, with benzalkonium chloride, may
also cause reduction in the mean basal tear turnover when compared with
healthy controls. Non-preserved drug achieve better stability of the tear film
which may be relevant when prescribing these drops for elderly patients with
corneal surface diseases.
• Beta blockers and the ocular blood flow
The effect of systemic hypertension, and its treatment, and nocturnal

hypotension on glaucoma patient is controversial. Some studies showed
that glaucoma patients without systemic hypertension have lower optic
21
nerve blood flow than those with hypertension. It is thought that treatment of
systemic hypertension may further decrease optic nerve blood flow in some
glaucoma patients. Increase in nocturnal hypotension may be a potential
risk for visual field deterioration in susceptible glaucomatous optic disc and
anterior ischaemic optic neuropathy.
There has been some controversy about the role of beta blockers drugs on
ocular and optic disc blood flow, (and consequently on visual fields),
because beta adrenergic receptors have previously been identified in the
human ciliary body, and in the anterior optic nerve and the optic nerve head
in human eyes. The majority of these receptors seem to belong to the beta-2
subtype. Some beta blockers drops may be associated with significant drop
in the nocturnal blood pressure and heart rate, and may thus increase the
risk of further visual field loss in vulnerable discs. Previous studies, in
glaucoma and ocular hypertensive patients, showed evidence that
betaxolol as well as metipranolol might have a better protective effect than
timolol, on the visual field, even if the IOP control with the two drug was
similar, or even better with the timolol.
In a double masked, randomised, placebo-controlled study, the effect of

betaxolol and timolol on the retinal blood flow was measured by laser
Doppler velocimetry. Betaxolol was associated with a long term increase in
the retinal blood flow, while timolol was associated with a short as well as
long term decrease in the blood flow. It was concluded that betaxolol may
have an additional vasodilator action to its IOP lowering effect. This action
may be due to a calcium channel blocking action similar to that achieved by
Verapamil.
22
Topical carbonic anhydrase inhibitors
Dorzolamide (Trusopt) is a topical carbonic anhydrase inhibitor that has

been proved effective and safe as a monotherapy and also in combination
with other glaucoma medications. Treatment with dorzolamide reduces
aqueous humour secretion by about 13% during the day time, and by 9%
during the night time. The drug also increases ocular pulse pressure in
glaucoma patients and normal subjects, an action which may have a
protective effects on the visual field in patients with high IOP.
The reduction in aqueous secretion seems to be less with dorzolamide than

with the maximum dose of oral acetazolamide. The smaller effect of
dorzolamide is due to insufficient inhibition of some of carbonic anhydrase
inhibitors. Topical dorzolamide and oral acetazolamide (250 mg four times a
day) do not seem to have an additive effect in lowering the IOP. Small doses
of oral acetazolamide, when added to the dorzolamide does not reduce
aqueous secretion any more. The use of both drugs in patients with
glaucoma is not rational.
Dorzolamide has an additive hypotensive effect when added to timolol.

When dorzolamide is combined with timolol eye drops, in a single drop, the
IOP lowering effect of the combination, when used twice a day, is
comparable to timolol twice a day and dorzolamide three time a day. The
IOP lowering effect of the combination drops is greater than either of the
timolol twice a day or of the dorzolamide three time a day.
The most common local adverse effects associated with dorzolamide use
are burning, blurred vision, itching, tearing, foreign body sensation, stinging,
eyelid discomfort, and non-specific conjunctival hyperaemia. Severe sterile
purulent conjunctivitis may also occur in patient s taking the drug.
Cessation of the drops leads to immediate resolution of the conjunctivitis.
Concern about the adverse effect of topical application of dorzolamide on

the corneal carbonic anhydrase has been raised because the corneal
endothelium contains carbonic anhydrase enzymes types I and II, which
play a role in the water pumping action of the endothelium. In a double
masked randomised one year study comparing the corneal effects of timolol
and dorzolamide, no significant changes in the central endothelial density
were noticed between the two drugs. Other retrospective studies suggested
that dorzolamide can cause irreversible corneal endothelium de-
compensation and corneal oedema in some patients with compromised
corneal endothelium.
Dorzolamide treatment may be associated with some systemic side effects.

The use of the drug has been associated with the development of renal
stones in some patients. Cessation of the treatment may lead to clinical
improvement and disappearance of the stones.
23
Other topical carbonic anhydrase inhibitors include Cosopt and

Brinzolamide (Azopt). Cosopt is a drug combination that consists of timolol
and Trusopt. The us of this combination, in glaucoma patients, seems to be
equivalent in its effect and safety to the concomitant administration of timolol
and Trusopt, both twice a day. The use of the fixed combination drug might
be useful in cases of poor compliance. Brinzolamide (Azopt) has a high
inhibitory action against carbonic anhydrase type II which is the main iso-
enzyme responsible for aqueous production. Topical application of
brinzolamide 1.0%, twice daily, produces IOP lowering effect similar to that
of dorzolamide 2.0% with less ocular discomfort.
24
Latanoprost
Latanoprost is a potent prostaglandin F 2-alpha analogue. Treatment with

latanoprost reduces the IOP, in primary open angle glaucoma, chronic
narrow angle glaucoma, and also in some cases of secondary glaucoma,
mainly by increasing the uveoscleral aqueous flow. Some animal studies
showed reduced collagen types I, III, and IV immuno-reactivity in the ciliary
muscle and adjacent sclera following topical prostaglandin F2 isopropyl
ester treatment. These changes may explain the increased uveoscleral
outflow observed with topical prostaglandin treatment.
The drug appears to be more effective than timolol eye drops in primary
open angle glaucoma and also in pigmentary glaucoma. Unlike beta
blockers medications, latanoprost can be used in patients with glaucoma
and concomitant bronchial asthma. Airway function and asthma symptoms
do not appear to be affected by the drug. The initial IOP reducing effect of
latanoprost declines to some extent during the first two weeks of treatment
and then remains at the same level reducing the IOP with about 20%. A two
years study of Latanoprost (0.005%) showed that the drug is effective and
tolerable for the long term treatment od glaucoma and ocular hypertension.
The drug may have an additive effect, in lowering the IOP, to timolol,
dorzolamide and Propine. When timolol is added to latanoprost, once a day
treatment in the morning may be effective in reducing the IOP.
Latanoprost treatment is not without side effects. The drug has been
associated with the following side effects:
Increased iris pigmentation

Darkening of the eye lashes
Anterior uveitis
Cystoid macular oedema in pseudophakic eyes
Optic disc swelling
Increased risk of recurrent herpes simplex virus
keratitis
The most significant side effect of latanoprost is increased iris

pigmentation, which may occur as early as 4 weeks after starting the
treatment. The colour change is mainly found in green-brown, grey-brown,
and blue-brown iridis. These eyes become progressively more brown with
the use of latanoprost. The mechanism of iris darkening is not known.
Sympathetic innervation is needed for age related darkening of the iris in
rabbits. Prostaglandins may play a part in compensating for sympathetic
denervation to produce the darkening effect. A recent morphologic and
histological study, on an iris of patient who had latanoprost treatment with
change in his iris colour, showed that, there is little indication that
proliferation or any pre-cancerous changes of melanocytes occurred.
25
Growth of eyelashes, in a patient with total loss of eyelashes for 5 years

secondary to alopecia, has also been reported after treatment with
latanoprost.
Latanoprost therapy also increases the breakdown of the blood-aqueous

barrier. A significant incidence of anterior uveitis (6.4%) and angiographic, as
well as, clinical cystoid macular oedema (2.1%) has been reported with the
use of latanoprost in the early postoperative period after cataract surgery.
Cystoid macular oedema has also been described in phakic patients. The
cystoid oedema often resolves after stopping the treatment. The use of
latanoprost in patients with active, or with a history of uveitis or cystoid
macular oedema should be with great caution. The administration of non-
steroidal eye drops such (e.g. diclofenac) seems to prevent the adverse
effects of latanoprost therapy while maintaining its effect to lower intraocular
pressure. It is suggested that the concurrent use of these drops with
latanoprost may be useful in preventing the macular oedema. Bilateral optic
disc swelling has also been reported after the use of latanoprost. The
swelling appears to resolve after cessation of the treatment.
Prostaglandins are known to have effect on the multiplication of herpes

simplex virus. Animal studies, in rabbits eyes, showed that latanoprost may
worsen acute herpetic keratitis, and increase the risk of recurrences in
latent infection. Some case reports, in human eyes, also indicate that the
drug may be associated with the development of herpes simplex virus
infection.
26
Brimonidine and Apraclonidine
Brimonidine is a highly effective Alpha-2 adrenergic receptor agonist. It is

estimated to be 1000 more selective to Alpha-2 receptors than to Alpha-1
receptors. It is also a more potent Alpha agonist than either Apraclonidine or
Clonidine. Brimonidine has been shown to be safe and effective in lowering
the IOP when topically applied twice a day for 12 months. The efficacy of
Brimonidine is comparable to that of timolol but without a significant effect on
the heart. Some studies showed no statistically significant difference in the
IOP lowering effect of Brimonidine and apraclonidine.
Brimonidine, unlike clonidine, does not have a significant CNS action (e.g.
sedation and hypotension). Topical Brimonidine in infants may, however,
result in CNS depression (hypotension, bradycardia, hypotonia and
apnoea). The drug should not be used in this subgroup of patients.
Brimonidine lowers the IOP, initially, by decreasing the aqueous flow. After
chronic treatment, the drug lowers the IOP by increasing the uveoscleral
outflow. The drug is known to have a vasoconstrictor effect on the blood
vessels in the anterior segment of the eye. However, the haemodynamics of
the posterior segment of the eye and the optic nerve head, do not appear
to be affected by the drug even after long term use. The drug does not
appear to alter the retinal capillary blood flow in patients with ocular
hypertension.
The incidence of ocular allergy, dry mouth and conjunctival follicles seem to
be higher in patients receiving Brimonidine when compared to timolol, while
the incidence of burning and heart rate is higher in patients taking timolol.
The drug may have an additive IOP lowering action when added to timolol.
Brimonidine and apraclonidine reduce intraocular pressure in timolol-treated
eyes, by further suppressing aqueous flow. The chronic use of Apraclonidine
may be associated with allergic manifestation in many patients. It is
generally safe as well as efficacious to administer Brimonidine to patients
with apraclonidine allergy.
27
Calcium channel blockers
Vasospasm has been suggested to play a role in the pathogenesis of low

tension glaucoma. Calcium channel blockers block membrane-bound
calcium channels and inhibit calcium influx causing a relaxation of smooth
muscle cells in the vascular wall and a decrease in the vascular tone and an
improvement in the blood flow. Systemic administration of Calcium channel
blockers is associated with a mild or no reduction in the IOP while topical
administration of Verapamil eye drops is associated with a sustained
reduction in the IOP and the episcleral venous pressure. The mechanism of
action is not completely understood but it may be partially due to increase in
the outflow facility. After two weeks administration of the topical drops the
reduction of the IOP is estimated to be about 12% in the treated eye and by
about 7% in the untreated eye.
28
Others
Marijuana, Ticrynafen, and Citicoline are new drugs that may have a
potential in the treatment of glaucoma. Drugs containing cannabis and
marijuana have been shown to cause a reduction in the IOP. Continuos use
of marijuana, at high enough levels to control the IOP, may be associated
with psychological problems. Ticrynafen (a drug similar to Ethacrynic acid) is
another drug that has also been shown to increase the aqueous outflow and
decrease the IOP in monkeys. The hypotensive effect is believed to be due
to the sulphhydryl group. Ticrynafen and Ethacrynic acid may have potential
for clinical use in humans. Citicoline is an intermediate substance for the
synthesises of phosphatidyl-choline which is a major phospholipids in the
neural cell membranes. The substance is thought to increase the neural
metabolism and also inhibits phospholipids degradation. In randomised
clinical study Citicoline produced a significant improvement in the VEP and
PERG in patients with primary open angle glaucoma. The drug may have a
potential in the treatment of glaucomatous optic neuropathy as a neuro-
protective agent.
29
Laser treatment
Laser Peripheral Iridotomy
The initial treatment of acute closed angle glaucoma is often by medical

treatment, followed by laser or surgical peripheral iridotomy. There does not
seem to be any significant difference in visual acuity or intraocular pressure
control 3 years after treatment of acute angle closure glaucoma with
surgical or YAG peripheral iridotomy. Peripheral iridotomy is also beneficial
in chronic narrow angle, or angle closure glaucoma. A recent study showed
that laser peripheral iridotomy is successful in opening the anterior chamber
angle in 73.4% of eyes with angle closure glaucoma.
Different types of lasers have been used in the treatment. Picosecond

lasers use lower energy than nanosecond YAG laser, which result in
considerably less disruptive effects in the treated eye. Picosecond lasers
seem to be more suitable for peripheral iridotomy procedures, unlike
nanosecond YAG laser which seem to be more suitable to capsulotomy
procedures. When pilocarpine or Apraclonidine eye drops are applied peri-
operatively significant IOP rise after the peripheral iridotomy is very
uncommon. Routine post-peripheral iridotomy check of the IOP may,
therefore, not be necessary.
Argon Laser Peripheral Iridoplasty
When systemic and topical anti-glaucoma treatment fail to control the high
IOP, and when peripheral iridotomy is not possible (e.g. in cases of severe
corneal oedema), the technique of Argon Laser Peripheral Iridoplasty may
be effective in controlling the IOP and clearing the corneal oedema. The aim
of this procedure is to, mechanically, open the appositional closed angle.
In this technique a ring of low power, long duration, and a large size burns is
applied to the iris periphery to contract the iris stroma and open the angle.
This technique is often applied after controlling the IOP medically. Argon
laser iridoplasty without medical treatment may also be used in cases with
primary angle closure of duration less than 48 hours. A full 360 degree ring
is often applied, but a more limited area of treatment may also be effective.
Laser Trabeculoplasty (ALT)
Argon, krypton, diode, and YAG laser trabeculoplasty, have all been used in
the treatment of primary open angle glaucoma, pseudoexfoliation glaucoma,
and pigmentary glaucoma. The mechanism by which Argon laser
trabeculoplasty lower IOP is not completely understood. It is thought to be
due to either displacement of the inner part of the trabecular meshwork
pulling it from the outer wall and thus opening the Schlemm’s canal or due to
liberation of mediators released by the inflammatory response following the
laser treatment that activate trabecular endothelial cells causing them to
30
multiply and thus improving the trabecular outflow. Failure of argon laser
trabeculoplasty, in some patients, is often caused by a membrane
formation in the anterior chamber angle.
Postoperative rise in the IOP may be reduced by preoperative use of

apraclonidine or Brimonidine 0.2% drops. Pilocarpine 4% appears to be as
effective as apraclonidine in preventing IOP rise. Apraclonidine does not
seem to be very effective in patients on long term apraclonidine use.
Pilocarpine may be more effective in these patients.
The Advanced Glaucoma Intervention Study examined 7 years result of two

different surgical intervention sequences for black and white patients with
advanced glaucoma. The two different sequences were:
1. Argon laser trabeculoplasty-Trabeculectomy-Trabeculectomy

2. Trabeculectomy- Argon laser trabeculoplasty-Trabeculectomy
The second and third intervention procedure were carried out after the
failure of the preceding one. The mean decrease in the IOP was greater in
second sequence more than in the first in both black and white patients.
However, black patients were less likely to lose visual acuity and visual field
if laser trabeculoplasty was carried out as a first intervention. In white
patients visual acuity and visual field were more preserved when the first
intervention was trabeculectomy rather than trabeculoplasty. The data from
this study suggest that in advanced glaucoma the first surgical intervention
should be trabeculectomy in white patients and trabeculoplasty in black
patients.
Current methods of laser trabeculoplasty causes thermal scarring and

damage to the trabecular meshwork. Some studies indicated that prior
argon laser trabeculoplasty may lead to a higher rate of encapsulated
trabeculectomy bleb afterwards. This may be due to damage of trabecular
meshwork caused by the thermal coagulation of the argon laser.
Selective laser trabeculoplasty is a new technique in which the laser

power is aimed at the pigmented trabecular meshwork without damage to
the other structures in the meshwork. A prospective randomised clinical trial
showed that selective laser trabeculoplasty with Q-switched 532 nm wave
length YAG laser appears to be equivalent to ALT in lowering IOP during the
first 6 months after treatment. In this technique about 50 non-overlapping
400 micron spots are used to treat an entire 180 degrees of the trabecular
meshwork. Laser power is adjusted to level just below that level which
causes cavitation bubbles. The technique is associated with a greater
anterior chamber reaction 1 hour after treatment. Patients with previous
failed ALT may have a significantly greater drop in IOP when treated with the
selective technique. The lack of coagulation damage to the trabecular
meshwork with this procedure makes it potentially a repeatable operation.
31
Some authorities believe that this technique can be used in association with,
rather than instead of, argon laser trabeculoplasty.
32
Trabeculectomy
Trabeculectomy is the main surgical operation to control the IOP in patients
with primary or secondary glaucoma. Reduction of IOP after trabeculectomy
surgery may be associated with reversal of cup / disc ratio. A steady long-
term decline in visual acuity and visual field have also been reported in
some patients after surgery. The decline in visual acuity may lead to
blindness. Estimated probability of retaining useful vision 15 years after
surgery, is about 0.6. Eyes that have good preoperative visual acuity have a
significantly better chance of retaining useful vision.
Success of trabeculectomy appears to be related to the type of glaucoma.

Patients with neovascular, traumatic, paediatric or uveitic glaucoma often
have the worst outcome after surgery. Trabeculectomy with adjunct
chemotherapy is probably most needed in these patients. There is a high
risk of surgical failure and complications after trabeculectomy for acute
primary angle closure glaucoma.
Certain other conditions (e.g. previous conjunctival surgery, laser

trabeculoplasty, and anti-glaucoma medications) are known to have a
negative effect on the success rate of the operation. This may be due to an
increase in the fibroblasts and inflammatory cells in the conjunctiva. Anti-
glaucoma drugs may be associated with histological changes in the
conjunctiva and in the trabecular meshwork. The conjunctival changes is
believed to be mainly due to benzalkonium chloride preservative toxicity.
Some authorities think that the use of anti-metabolites may be indicated in
these situations. A high rate of uric acid in the aqueous in the anterior
chamber has also been associated with increased risk of trabeculectomy
failure, and thought to be a prognostic indicator for the success of surgery.
Episcleral, and Tenon capsule fibrosis are the most common cause of failure
after trabeculectomy. Tenon capsule is inserted about 2 mm posterior to the
limbus. Micro-trabeculectomy is a new technique that is reported to be
safe and effectively in reducing the IOP, and also reducing the postoperative
fibrosis rate. In micro-trabeculectomy a 2 by 2 mm scleral flap is fashioned
and a 0.75 mm internal ostium is created using the Kelly Descemet’s
membrane punch. The procedure achieves a good IOP control in low risk
eyes. This technique is also associated with smaller changes in the
topographic and keratometric astigmatism than the conventional technique.
Nasally sited micro-trabeculectomies seem to work better than temporally
sited ones.
Shallow anterior chamber from excessive drainage is a main complication

after trabeculectomy operations especially in chronic and acute narrow
angle glaucoma. Releasable scleral flap technique reduces the incidence
of shallow and flat anterior chamber without affecting the long-term result of
the operation. The use of releasable sutures minimises the incidence of
33
postoperative hypotony and shallow anterior chamber and also maximises

long term bleb formation and IOP control..
34
Complications
• bleb failure
Postoperative flattening of the bleb is often associated with failure of the

trabeculectomy. Bleb failure in primary open angle glaucoma ranges from
67% to 94% of cases. Bleb encapsulation is a frequent cause of failure that
is reported to occur in 13% of patients. It often occurs in the early
postoperative period, due to adhesions and scar formation between the
episcleral tissue and the Tenon capsule. Several factors have been
associated with bleb encapsulation. These factors include glove powder,
prior conjunctival surgery, prior treatment with sympathomimetic drugs, or
prior argon laser treatment. Several methods have been used to reform the
bleb and prevent failure. These methods include:
Early needling
Laser suture lysis
YAG laser opening of fistula
Sub-conjunctival Perfluoropropane gas bubble
Medical anti-glaucoma treatment
Ocular massage
Topical steroids
Surgical revision of the bleb
Early needling of the capsulated bleb is a relatively new method of

treatment. A 30 gauge needle attached to an insulin syringe can be used.
The needle is passed in the sub-conjunctival space, few centimetres away
from the encapsulated bleb. Repeated punctures of the cyst is then tried till
the bleb is inflated. Another needle with 5 FU (25 mg / ml), is then passes
and the 5 FU is injected. This procedure seems to be safe and effective in
treating encapsulated blebs. Sub-conjunctival injection of 5 FU may also be
used in delayed bleb failure. Delayed sub-conjunctival injection of 5 FU
reduces the IOP if ocular massage reduces the IOP prior to the injection.
Injection of air bubbles under the conjunctiva may give only a transient
formation of the bleb.
Laser treatment may be useful in failing blebs. The use of tight scleral flap
sutures during trabeculectomy in conjunction with postoperative laser suture
lysis has been reported to minimise hypotony and its associated
complications. Suture lysis may be performed using either argon or YAG
laser and Hoskin’s lens The best results are obtained when lysis is done
within the first two week after the operation. No benefit is expected if the
suture lysis is done 4 weeks after the operation. When anti-metabolite is
used with the trabeculectomy wound healing can be delayed so much that
suture lysis can be beneficial even after as long as 21 weeks after the
operation.
35
YAG laser may also be used to open failing filtering blebs, either by an
internal gonioscopic approach or by an external approach. In the external
approach, laser beam is focused on the bleb sub-conjunctival scar tissue.
Multiple applications of medium power laser burns is then carried out till
disruption of the scar tissue is achieved and the aqueous appears to
percolate through the scar tissue. A new method to reform the bleb by sub-
conjunctival injection of Perfluoropropane gas bubble has been described.
The Perfluoropropane gas acts as a spacer in the sub-conjunctival space
and may last for up to 2-4 weeks.
• hypotony and bleb leak
Hypotony may be caused by either decrease in the production of aqueous

(due to inflammation, choroidal detachment, or medications), or due
excessive filtration of aqueous (due to bleb leak, or cyclodialysis cleft).
Postoperative bleb leak, and hypotony is a major problem after successful
trabeculectomy surgery. Postoperative hypotony often resolves
spontaneously within few days. Conservative treatment is, therefore,
indicated in eyes with deep anterior chamber. Immediate anterior chamber
re-formation is, however, needed in cases with flat anterior chamber (stage
3 shallow anterior chamber) to prevent rapid development of cataract and
endothelial de-compensation. Chronic hypotony may cause poor visual
acuity caused by cataract, choroidal effusion, supra-choroidal haemorrhage
or maculopathy. Various methods has been used to treat leaking blebs.
These methods include:
Intrableb autologous blood injection

Autologous fibrin tissue glue
Nd: YAG laser
Large contact lens wear
Autologous blood injection may be used to reduce filtration in an over-

filtering bleb and hypotony. Under topical anaesthesia, about 0.1 or 0.2 ml of
venous blood in injected with a 27 gauge needle about 6 mm away from the
bleb. Inflammatory cells and serum protein from the injected blood
accelerate the inflammatory and healing process. Laser-cured fibrinogen
glue has also been used to close a leaking bleb in rabbit eyes. Fibrinogen
may be taken from the patient own blood to prevent any blood transmitted
diseases. The fibrinogen glue can be coagulated on the ocular surface by
the diode laser.
The continuous wave Nd: YAG laser may also be effective in repairing bleb-
related problems while maintaining successful filtration. The laser is applied
to the large leaking bleb, after being painted with methylene blue dye, in a
grid fashion. The laser beam is defocused so that the internal surface of the
bleb is treated. The IOP may rise in the immediate postoperative period, but
36
it often drops again with time. Cataract formation, and pupillary abnormalities
may also result after treatment. It has also been reported that
phacoemulsification surgery may be associated with a statistically
significant elevation in IOP in previously filtered eyes with hypotony.
• blebitis, and endophthalmitis
Bleb infection and late onset bleb infection are serious complications after
trabeculectomy. The risk of bleb related infection is increased in inferior
blebs, with the use of anti-metabolites, in younger age, and also in patients
with late bleb leak. Blebitis may represent a limited form of endophthalmitis.
Other risk factors that have been previously identified include blepharitis,
ocular trauma, and nasolacrimal duct obstruction. Streptococcus,
Haemophilus influenzae and Staphylococci organisms are currently
recognised to be the most frequent organisms in bleb-related late
endophthalmitis. The infection may also be recurrent.
Aggressive treatment is often needed by intravenous antibiotics (e.g.

Cefazolin), and frequent topical antibiotics (e.g. Cefazolin and gentamicin).
The incidence of post-trabeculectomy endophthalmitis, with or without anti-
metabolites has been reported to range from 0.061% to 13.2%.
Endophthalmitis after trabeculectomy operation is likely to result from
infected thin avascular bleb especially if Mitomycin C has been used.
Delayed-onset endophthalmitis is caused by a different spectrum of
organisms than those in acute-onset, post-cataract surgery endophthalmitis.
37
Trabeculectomy with adjunct therapy
Adjunct therapy that has been used, with trabeculectomy, in the treatment of
glaucoma include:
5 FU
Mitomycin C
Idarubicin
Suramin
Perfluoropropane
Beta irradiation
Photo-dynamic therapy
Electroporation
The use of cytotoxic drugs in glaucoma filtration surgery to prevent

proliferation of fibroblasts of the human Tenon capsule has been
established. Mitomycin C and 5 FU are currently the most commonly used
drugs. The route of administration of 5 FU in glaucoma surgery has changed
several times over the years. The exact amount of 5 FU applied to the sclera
during trabeculectomy surgery is not often well determined. Application time,
type of the sponge used, and the concentration of the drug are important
factors that can significantly affect the amount of the drug applied. The effect
of the drug appears to reach its maximum in about three minutes. There
does not seem to any rationale in applying the drug for longer than three
minutes. The intraoperative application of a single dose of 5 FU in high risk
eye may not be enough to prevent trabeculectomy failure. Postoperative
needling, with 5 FU, of failed blebs may be used in some cases.
Primary trabeculectomy may be carried out with Mitomycin C in high risk

patients. When Mitomycin C is used the IOP is estimated to fall by about
30% in about 86% of eyes by the first year. Endophthalmitis has also been
reported in about 2.2%, and hypotony in about 4.5% of eyes after Mitomycin
C with primary trabeculectomy. Late leak after trabeculectomy is increases
with the use of Mitomycin C, this complication is difficult to treat and may
lead to sight threatening complications.
The optimum dose and duration of application of Mitomycin C with

trabeculectomy in phakic eyes is not known. Mitomycin C is often applied to
the sclera for few minutes during surgery, this may be associated with
spread of the drug to the cornea and the conjunctiva. In a study of phakic
eyes the application of Mitomycin C (0.5 mg/ml) for 0.5 to 1 minute was
optimal for successful IOP control of primary trabeculectomy when
compared with longer application and also with no Mitomycin C application.
Mitomycin C is often applied to the scleral surface before fashioning the

scleral flap. It can also be applied under the scleral flap in high risk eyes.
This method of application appears to be associated with a higher success
38
rate and lower complications rate than if the Mitomycin C is applied under
the Tenon capsule. Simultaneous application of Mitomycin C to the scleral
bed as well as to the conjunctiva may result in an additional IOP lowering
effect. Mitomycin C application under the scleral flap, without sub-
conjunctival application, may result in less avascular and healthier
trabeculectomy blebs.
Idarubicin is a new drug that has the property of rapid entry into the cells.
The drug has been shown to reduce cellular proliferation of human Tenon
capsule after incubation for 0.5 minutes at a concentration of 0.3-1.00
microgram/ml. The short duration of application may be useful in reducing
spread of the drug to neighbouring tissues.
The use of anti-metabolites in trabeculectomy surgery may be associated

with serious side effects. Other techniques have been used to increase
success rate in high risk eyes. Suramin is an anti-parasitic drug that can
bind to growth factor receptors and inhibits binding of the growth factor to its
target cells. It has been shown to delay wound healing in previous animal
studies. In animal studies, Suramin was shown to be effective in preventing
scarring after glaucoma filtration surgery with fewer side effects than other
anti-metabolites. The drug may have a beneficial effect in glaucoma surgery
in humans. Beta irradiation has also been used to reduce postoperative
cellular proliferation. A single application of beta irradiation significantly
inhibits Tenon capsule fibroblasts proliferation in vitro for a period of 28 days.
This method may be beneficial in the management of eyes with high risk
glaucoma. Perfluoropropane gas bubble may also be used in high risk
eyes to reduce postoperative sub-conjunctival scarring. The gas bubble,
with its long action, acts as a tamponade spacer between the conjunctiva
and the episclera.
Photo-dynamic therapy has been described for the treatment of some

ophthalmic and skin tumours as well as for the treatment of choroidal
neovascular membrane. The technique may also be used to prevent or
reduce postoperative fibrosis after glaucoma filtration surgery. Photo-
ablation of the tissue cells has been achieved in animal eyes by using the
fluorescent substance BCECF-AM. This substance can penetrate cellular
membrane, and cause fluorescence upon cleavage by the intra-cellular
enzymes. In an experimental study rabbits eyes were injected with the
substance and then illuminated with a blue light for few minutes. Post-
treatment histological studies confirmed the anti-fibrotic effect of the
treatment. This treatment technique may be useful as an adjunct for
drainage surgery in the future.
Electroporation is a promising new technique to increases the efficacy and

safety of using anti-metabolites with trabeculectomy surgery. In this
technique, application of short electrical pulses is made to increase cell
membrane permeability in the area where the Mitomycin C applied.
39
Electroporation allows the use of smaller doses of anti-metabolites, and also

minimise its local and systemic side effects.
40
Phacotrabeculectomy; one stage or two stage surgery?
There is controversy about whether patients with cataract and glaucoma

should have a combined cataract and trabeculectomy operation or should
have two separate operations. A recent study compared the intraocular
pressure lowering effects of single-incision combined phacoemulsification
and trabeculectomy with phacoemulsification done after previous
trabeculectomy, both with an intraoperative dose of 5-fluorouracil. The study
conclusion was that combined cataract and glaucoma surgery with
intraoperative 5-FU is associated with good long-term IOP control similar to
that after phacoemulsification with intraoperative 5-FU in eyes with previous
trabeculectomy. In patients who had had filtration surgery, IOP appears
to be better controlled by phacoemulsification than by ECCE.
Simple cataract extraction may be associated with a better IOP control in

eyes with narrow angle glaucoma. The width and depth of the anterior
chamber angle in eyes with Angle Closure Glaucoma increase significantly
after cataract extraction and IOL implantation. This may lead to a better IOP
control in the postoperative period.
Opinions vary regarding the benefit of a one stage phacoemulsification-

trabeculectomy operation or a two stages procedure. The success rate of
combined phacoemulsification-trabeculectomy surgery with or without anti-
metabolite varies considerably. Phacoemulsification procedures with
foldable IOLs seem to have better postoperative IOP results than with
ECCE. Combined surgery may be carried out either by two sites or one site
technique. Two sites technique seems to be associated with a slightly
better IOP control.
Fornix-based and limbal-based conjunctival incision may be used. Both

techniques appear to give the same IOP results. In a prospective, non-
randomised comparative (fellow eyes) study, both, limbal and fornix based
conjunctival flap techniques, were found equally effective in improving visual
acuity and in lowering IOP. The fornix based is safe and effective with the
use of Mitomycin C and may offer more advantages regarding the
phacoemulsification surgery. In patients with no risk factors, the use of
Mitomycin C does not seem to be justified.
The indication of a triple phacoemulsification with IOL implantation and

trabeculectomy surgery with Mitomycin C should be based on the presence
of major risk factors for glaucoma surgery failure (e.g. in black patients, high
preoperative IOP, multiple drugs medical treatment). African American race,
more than 2 preoperative medications, and intraocular pressure greater than
14 mm Hg in the first postoperative week are major independent risk factors
for initial filtration failure during the first month after primary glaucoma triple
procedure.
41
Previous failed trabeculectomy appears to be risk factor for failure of a

combined trabeculectomy-cataract extraction surgery. The use of anti-
metabolites may be associated with improved results in these cases.
Intraoperative sub-conjunctival Mitomycin C application (0.5 mg/ml for 3
minutes) during combined glaucoma and cataract surgery has a beneficial
effect of inhibiting posterior capsule opacification after combined surgery in
patients with Primary open angle glaucoma. This observation indicates that
aqueous Mitomycin C must reach great enough levels to inhibit the lens
epithelial cell proliferation to result in a long-term decrease in posterior
capsule opacification.
Cataract surgery after a previous trabeculectomy may result in failure of the

bleb, and about 10-38% of eyes may need further medical or surgical
treatment to control the IOP. Most bleb failure occur soon after cataract
surgery. When cataract extraction is performed after trabeculectomy the
following factors may be considered as risk factors for failure of the
trabeculectomy bleb:
Age of 50 years or younger.

Preoperative IOP greater than 10 mm hg.
Intraoperative iris manipulation.
Early postoperative IOP greater than 25 mm Hg.
42
Other Surgical procedures

Deep sclerostomy with collagen implants
Deep sclerotomy with collagen implants is a non-penetrating glaucoma

surgery which has recently been described for the treatment of open angle
glaucoma. The operation controls the IOP by allowing aqueous filtration
through a thin trabeculo-corneal membrane to the sub-conjunctival and
supra-choroidal space. After opening the conjunctiva, a scleral flap is
created, the thickness of the flap should be about 40%. A deep sclerotomy is
then performed leaving a thin scleral layer over the choroid and the ciliary
body. This sclerotomy can be created by using the excimer laser. Care
should be taken to keep the sclerotomy site dry during laser application. The
canal of Schlemm is then de-roofed and the corneal stroma is removed
anteriorly down to the Descemet’s membrane. A collagen implant is then
secured to the deep sclera by 10/0 nylon suture. The implant prevent re-
attachment of the scleral flap to the deeper scleral tissue (complete
resorption of the collagen implants takes about 6 to 9 months). The scleral
flap is then closed and sutured. Long term ultrasound studies showed
filtration through the thin trabecular membrane to the area under the scleral
flap, sub-conjunctival apace and then to the suprachoroidal space.
Trabecular aspiration
Trabecular aspiration is a new non-penetrating surgical procedure based

on the hypothesis that removing fibrillar flake-like material, in patients with
pseudoexfoliation glaucoma, from the trabecular meshwork may lead to
lowering of the IOP. In this procedure an aspirator instrument is introduced in
the anterior chamber via a paracentesis incision and directed to the
trabecular meshwork. Another paracentesis incision is used to introduce an
irrigating cannula to keep the anterior chamber formed. Suction pressure
between 100-200 mm Hg is then applied to the anterior chamber angle. The
aspirating and the irrigating cannula are then changed over, and more
suction pressure is applied to another part of the trabecular meshwork.
The procedure appears to be safe and effective in decreasing IOP, in

patients with pseudoexfoliation glaucoma, both with and without cataract
extraction. There is, however some regression in its effect over time due to
further liberation of pseudoexfoliation debris in the meshwork. Argon-laser
trabeculoplasty before trabecular aspiration may reduce the IOP lowering
effect of this procedure.
Trabecular aspiration in the glaucoma triple procedure could also be

considered as a possible first-line treatment for pseudoexfoliative eyes with
coexisting cataract and glaucoma. Although trabecular aspiration in the triple
procedure does not achieve good pressure control in all patients, the risks
43
appear to be more favourable in the trabecular aspiration–treated eyes than

in the filtering glaucoma triple procedure group.
Eyes with pigment dispersion syndrome and with pigmentary glaucoma also
respond to trabecular aspiration but not as well as eyes with
pseudoexfoliation syndrome. The response in these is better in eyes with
pigment dispersion syndrome than eyes with pigmentary glaucoma. The
response in these eyes, however, seems to be of short duration.
Gonioscopic curettage
It is proved that the main resistance to the aqueous humour outflow in open
angle glaucoma lies in the trabecular meshwork. Gonioscopic curettage is
an Ab interno non-fistula procedure designed to remove the trabecular
meshwork and open a communication between the anterior chamber and
the canal of Schlemm's. The procedure is carried out under the microscope
by using a gonio lens and a micro-curette similar to that used in chalazion
surgery. The micro-curette is used to scrape away the trabecular tissue
without causing any damage to surrounding tissues. Morphological analysis
of treated post-mortem eyes confirmed that gonioscopic curettage
completely remove the trabecular meshwork and open Schlemm's canal,
ensuring direct access into the anterior chamber. The main advantages of
the operation is that the conjunctiva is not disturbed. The procedure should
be more attractive in cases with severely damaged conjunctiva from
previous surgery or previous medications or diseases. The reduction in the
IOP is not, however, great. Level of IOP in the high teens is considered
success. This might not be appropriate in some patients with severe disease
when IOP in the low teens is required. Minimal to moderate and, rarely,
severe hyphaema may also occur in some cases. Injury to the Descemet’s
membrane may also occur in some cases. Gonioscopic curettage in the
presence of opaque cornea is difficult. The use of ophthalmic micro-
endoscope is safe and effective in these situations.
Viscocanalostomy
Viscocanalostomy started in South Africa where black patients often have

poor results after conventional trabeculectomy operations. In this procedure
a parabola-shaped superficial and a deep sclerostomy flaps are fashioned.
The deep flap in then dissected to the plan of Schlemm's canal. An window
in the Descemet’s membrane is then created by a gentle pressure. This
window enables the aqueous to flow out to the space under the deep scleral
flap. The Schlemm's canal is then un-roofed and high viscosity viscoelastics
is passed to the right and to the left in the two ends of the canal. The deeper
scleral flap is then excised and the superficial flap sutured. More high
viscosity viscoelastics is injected under the flap to prevent fibrinogen
migration and to keep the sub-scleral lake formed. The earlier results of this
procedure is encouraging.
44
Enzymatic Sclerotomy
Proteolytic enzymes and bacterial extracts have been used for tissue
modifications. Clostridium histolyticum is a bacterial enzyme that hydrolyses
collagen under physiological conditions. Clostridial collagenase enzyme has
been used in animal model to produce a localised thinning and an increase
in the scleral permeability which result in a significant decrease in the IOP.
this technique may prove useful in the treatment of human eyes with
glaucoma.
45
Neuroprotection in glaucoma
Visual damage in glaucoma is mainly due to damage of the retinal ganglion
cells layer. Neuroprotection means treating the disease by preventing
neuronal death. Factors that are important for the neuronal survival are
called neurotrophins. Several neurotrophins have been identified e.g. brain
derived neurotrophins factor (BDNF) and ciliary neurotrophins factor (CNTF).
Different mechanisms may be involved in the process on neuroprotection.

These include the delivery of neurotrophins, blockage of receptors mediating
excitotoxins (one example of these toxins is glutamate), and scavenging of
reactive oxygen species. Injection of BDNF in the vitreous is known to
protect retinal ganglion cells from death as result of severing the cell axon.
Blocking the receptors may be achieved by pharmacological antagonists to
the excitotoxins. Examples of scavengers that can be delivered to reduce
the levels of reactive oxygen species include super-oxide dismutases,
catalases, glutathione peroxidase. The drug betaxolol has a calcium
channel blocking function as well as an IOP lowering effect. By blocking
calcium transport, the drug may be able to prevent retinal ganglion cell death
and thus it may have a neuroprotective function.
46
Gene therapy in glaucoma

It has been shown that herpes simplex virus may be used in the transfer of
foreign genes to the ciliary muscles and the trabecular meshwork system in
the living cats. The transfer of genes may enable us to regulate the aqueous
outflow thorough the trabecular meshwork and uveoscleral outflow. It may
also affect the outflow by modulating prostaglandins secretion. Gene
transfer in the retinal ganglion cells may also facilitate investigation of the
process of apoptosis.
47
Treatment of intractable glaucoma

The two main techniques used in treating intractable glaucoma are:
1. Glaucoma implants
2. Cyclodestructive procedure
Cyclodestructive procedures need to be repeated more often than glaucoma

implants. Glaucoma implants are often associated with a better IOP control
but they are also 3.8 times more likely to develop postoperative
complications. Some reports demonstrated superior results with
trabeculectomy with Mitomycin C in some cases of intractable glaucoma.
Cyclodestructive procedures
Transscleral cyclophotocoagulation, with diode or YAG lasers, has been

used for the treatment of refractory glaucoma. The semiconductor Diode
laser wavelength is transmitted through the sclera less effectively, but they
are better absorbed by the melanin than the YAG laser. Diode laser appears
to have the same IOP lowering effect as the YAG laser. The hypotensive
response varies among patients because the ciliary process can not be
visualised directly during treatment. During trans-scleral cyclo-
photocoagulation, about 3-5% of the laser energy reaches the posterior
pole. The clinical significance of this finding is not known. Contact diode
laser cyclo-photocoagulation may be associated with the development of
neurotrophic corneal ulceration especially in eyes with external surface
diseases. This may be due to the effect of the laser treatment on the limbal
corneal innervation.
Glaucoma implants
The material of the glaucoma implants is very important in reducing

adherence of fibroblasts and macrophages and increasing the rate of
aqueous flow through them. New material for coating the implants may offer
promise in improving drainage. The main types of glaucoma implants are:
Valved implants Non-valved implants

1. Ahmed implant 1. Optimed
2. Krupin
3. Molteno implants
4. Baerveldt
The optimed and the Krupin implants offer resistance to aqueous outflow
which stays relatively stable independent on the IOP, thus increasing the
IOP when the outflow increases. The Ahmed implant, on the other hand,
functions as a true valve that regulate the pressure with a certain range by
48
decreasing or increasing the level of resistance in the valve depending on

the aqueous outflow, thus avoiding hypotony and increases in the IOP. The
majority of patients show increases in the IOP after valved implants (e.g.
Ahmed implants) that peaks after one month of surgery, with gradual
stabilisation over a six months period. One third of patients, however needs
a second surgical operation to better the IOP. The incidence of hypotony
and flat anterior chamber appears to be low after the implantation of these
implants. Occlusion of Ahmed valved implant may occur in the early or in
the late postoperative period. Early occlusion is mainly due to blood, vitreous
or due to Tenon capsule thickenings. The cause of late occlusion is not
completely understood. treatment of early occlusion can be achieved by
irrigation of the tube. Late occlusion, on the other hand, is better treated by
exchanging the tube with particular attention to careful handling of the no
touch zone over the valve area.
Previous In vitro testing showed that non of the implants manage to maintain
the advertised pressure level while being perfused at a rate close to the rate
expected in human eyes. In vivo, however, it seems that the surrounding
conjunctiva contribute to the measurable resistance to aqueous humour
outflow.
Shunt failure is a common problem. The main cause of shunt failure is

fibrosis and tube encapsulation. When the tube fails, as additional tube may
offer a better IOP control than revision of the failed tube. All of the major
complications of non-valved tubes drainage operations is due to hypotony.
Postoperative hypotony is associated with suprachoroidal haemorrhage and
visual deterioration. Older patients with hypertension and atherosclerosis are
more likely to develop suprachoroidal haemorrhage after the insertion of
non-valved tubes (e.g. Baerveldt implants 350-mm2 and 500 mm2). A
number of techniques has been developed to reduce the aqueous outflow in
the immediate postoperative period to avoid hypotony after the insertion of
non-valved implants. The placement of a an absorbable suture just anterior
to the implant plate followed by a through-and-through penetration of the
tube by anterior to the ligature suture is a new technique that is reported to
provide an adequate IOP control after non-valved implants.
Extraocular motility disturbances also commonly occur after double-plate

Molteno surgery. Muscle palsies, acquired Brown syndromes, and
generalised restrictions occurred in similar proportions. Patients should be
counselled before Molteno surgery concerning the risk of strabismus and
diplopia.
Corneal endothelial touch by the implant anterior chamber tube may also
lead to endothelial injury especially in eyes with shallow anterior chamber,
pars plana insertion of the tube following a pars plana vitrectomy can be
considered as an alternative technique for tube implantation in some eyes.
49
Secondary glaucoma
Malignant glaucoma
The exact cause and mechanism of malignant glaucoma is not well
understood. It is widely believed that the rise in the IOP is mainly due to
misdirection of the aqueous. In a study of six eyes with postoperative
malignant glaucoma, high resolution ultrasound examination showed
annular ciliary body detachment in all of them. Resolution of the condition
and deepening of the anterior chamber was also associated with the
spontaneous resolution of the detachment, or with the surgical drainage of
the fluid. Malignant glaucoma may be due to either aqueous misdirection, or
in some patients, may be due to ciliary body detachment. High resolution
ultrasound examination may be very useful tool in examining these eyes.
Pseudoexfoliation syndrome
Pseudoexfoliation is a specific lens epithelium disorder that may be
associated with secondary open angle (or rarely closed angle) glaucoma. A
distinct type of corneal endothelial cells changes may also occur in these
eyes. This endothelium changes may lead to an early corneal endothelial
de-compensation after cataract surgery.
There are certain difference in the clinical features, and in the prognosis
between primary open angle glaucoma and pseudoexfoliation glaucoma.
The optic discs seem to be more vulnerable to IOP rise in the
pseudoexfoliation syndrome than in primary open angle glaucoma. The
correlation between IOP rise and visual field defects also seem to be
stronger in the pseudoexfoliation glaucoma than in primary open angle
glaucoma.
Cataract surgery is often associated with a higher rate of complications in

pseudoexfoliation syndrome due to zonular weakness. A recent study
showed that a shallow anterior chamber, as shown by an A ultrasound scan,
may indicate zonule weakness and should alert surgeons to the possibility of
complications.
It has been thought that the disease may be associated with higher risks of
cardiovascular abnormalities and early death. Recent reports, however,
showed that, there is no increased risk of mortality or cardiovascular
morbidity associated with the disease.
Pigmentary glaucoma
It has recently been shown that the number of melanin granules in the
anterior chamber is strongly correlated to with the level of IOP and also with
50
the visual field loss. quantification of aqueous melanin by the flare-cell metre
may be useful in the evaluation of cases with pigmentary glaucoma.
Raised IOP in pigmentary glaucoma is thought to be due to a reversed

pupil block mechanism. 60% of patients with pigmentary glaucoma have
posterior iris bowing, and irido-lenticular contact. Factors that have been
shown to increase the IOP gradient between the anterior and the posterior
chamber are accommodation and blinking. The iris-lens diaphragm has
been shown by the micro-bubble ultrasound technique to act as a one way
valve, allowing the aqueous to pass from the posterior chamber to the
anterior chamber. An increases in the IOP in the anterior chamber may
result in increasing the concavity of the iris. Laser iridotomy can restore the
normal iris shape and decrease the irido-lenticular contact in these patients.
Eyes with pigmentary glaucoma do not show any differences in the

appearance of the optic disc from eyes with primary open angle glaucoma.
Aqueous melanin granules are essential in the mechanism of raised IOP in
this condition. Quantification of the granules by the laser flare-cell meter is
possible and reproducible, it shows increased number of granules in the
anterior chamber especially after pupillary dilatation. This method may be
useful in the assessment and treatment of this condition.
Neovascular Glaucoma
IOP rise in neovascular glaucoma may be due to increased permeability of
newly formed vessels or angle closure by PAS formation. Another factor
which may be responsible for IOP elevation is neovascular tissues which
can be found in the trabecular spaces in some eyes. Patients with
neovascular glaucoma have increased levels of vascular endothelial growth
factor VEGF in the aqueous humour. VEGF may play a role in the
development of neovascularisation in these patients. it thought that the
ciliary body as well as the retina may take part in the production of this
factor.
51
Medical Diseases Of The Retina
Central and branch retinal vein occlusion

pathogenesis
The pathogenesis of central retinal vein occlusion is not completely

understood. Venous thrombus formation, venous stasis and inflammation
play varying roles in the development of central and branch retinal vein
occlusion. Local as well as systemic factors play parts in the
pathogenesis of the disease, local factors are considered to be more
important than systemic factors. Different pathogenic mechanism may be
involved in first and second order branch retinal vein occlusion.
Anatomical factors appear to be more crucial in second order branch
retinal vein occlusion than in more peripheral occlusions. Narrowing of
retinal veins at the A/V crossing may induce haemodynamics changes
that lead to thrombus formation and venous occlusion. Among the other
anatomical factors that play a role in the mechanism of the disease, is the
axial length of the eye. The axial length in eyes with central or branch
retinal vein occlusion appear to be shorter than controls.
Chemical mediators also play important roles in the pathogenesis of the

disease. Vascular endothelial growth factor (VEGF) has been detected
in higher levels in animal eyes with central retinal vein occlusion.
Hypoxia-induced VEGF in human eyes is also likely to be the linking
factor between retinal ischaemia and iris and retinal neovascularisation.
Plasma endothelin-1 (a vaso-active peptide that is released by
endothelial cells) has also been shown to be raised in patients with retinal
vein occlusion. The plasma levels seem to be higher in cases with
ischaemic type of the disease. The exact role played by this peptide in
the pathogenesis of the disease is not yet known.
aetiology
Retinal vein occlusions is a major cause of unilateral visual loss. The

prevalence of this condition is estimated to be 0.7% in patients younger
than 60 years of age and, 4.6% in patients older than 80 years. Central
and branch retinal vein occlusion are multifactorial conditions. Patients
presenting with branch, hemispheric or central retinal vein occlusion
should be evaluated for:
• diabetes
• glaucoma
• cardiovascular diseases
1
In young patients, the disease may also occur secondary to retinal

congenital arteriovenous communication. It is proposed that a
turbulent flow, high intra-vascular volume and arteriolar pressure in the
venous side of the malformation may lead to vessel wall damage,
thrombosis and occlusion of the blood vessel. Recent reports indicate
that the incidence of retinal vascular diseases may also be slightly
increased in recent contraceptive pills users.
Antiphospholipid antibodies syndrome is a rare syndrome

characterised by:
1. Recurrent venous and / or arterial thrombosis.

2. Recurrent spontaneous abortion.
3. Thrombocytopenia.
The main Antiphospholipid antibodies are the lupus anticoagulant and the
anticardiolipin antibodies. Antiphospholipid antibodies may be primary, or
secondary to other disease (e.g. SLE, lymphoma, dysglobulinaemia and
some infections such as Q-fever). Patients with occlusive retinal diseases
have a significantly high prevalence of antiphospholipids antibodies.
Screening of these antibodies is indicated in patients who do not have
any of the common risk factors e.g. hypertension, cardiovascular
diseases or diabetes.
A recent study of 39 patients with primary antiphospholipids syndrome

demonstrated that permanent pathological ocular features are rare. The
study also demonstrated that, there is a high prevalence of visual
disturbances among patients. Most of these disturbances are transient
and mainly caused by central nervous system ischaemia.
Recurrent thrombosis appears to be significantly reduced with treatment

with warfarin as compared with systemic prednisolone or with no
treatment at all. A prothrombin ratio of 1.5 / 2.0 is recommend. It is also
recommended that treatment should be continued for at least 6 months
after the disappearance of the antibodies. Recurrent branch artery
occlusion has, however, been reported in some patients after the
disappearance of the antibodies, despite treatment with aspirin and
steroids.
Retinal vein occlusion may also be associated with abnormalities in the

coagulation system. Resistance to activated protein C has been
associated with retinal vein occlusion in some younger patients. More
than 90% of resistance to protein C is caused by a mutation in factor V (R
506Q), which renders activated factor V relatively resistant to its
degradation by activated protein C. The prevalence of this mutation is
high in white patients but very rare in blacks. Mutation of factor V has
been identified in many patients with retinal vein occlusions as well as
deep venous thrombosis. Screening for this mutation, in patients with
2
retinal vein occlusion, is recommended by some authorities in order to

identify patients at risk of developing deep vein thrombosis.
Patients with central retinal vein occlusion and family history of

thrombotic diseases should be investigated for a possible
hypercoagulability conditions. Hyper-homocysteinemia is a risk factor
for central retinal vein occlusion and may suggest a poor prognosis in
patients with central retinal vein occlusion. Thrombophilia,
hypofibrinolysis and raised thrombin-anti-thrombin III complex are
other abnormalities with the coagulation system that have been reported
with retinal vein occlusion. These abnormalities may be more important in
retinal vein occlusion near the main vein trunk rather than in the retinal
periphery.
management
The clinical course of the disease is determined by the location of the

venous occlusion with relation to the fovea and the formation of collateral
blood vessels. The prognosis of central retinal vein occlusion is highly
unpredictable because non-ischaemic types may become ischaemic.
About 54% of initially non-ischaemic eyes progress to ischaemia over
one year period.
Neovascular glaucoma is a major complication after central retinal vein

occlusion. Eyes with a large amounts of retinal haemorrhage obscuring
capillary details of fluorescein angiography need to be monitored closely
for iris, or / and angle neovascularisation. Angle neovascularisation may
occur in the absence of pupil margin rubeosis. Gonioscopic examination
should be a routine examination procedure in these patients.
• medical treatment
Medical treatment, in this disease, seems to be limited. Intravenous

thrombolysis by streptokinase infusion has rarely been reported to
produce dramatic improvement in the visual and angiographic features of
acute central retinal vein occlusion. Treatment is, however, associated
with increased risk of life threatening bleeding elsewhere (e.g. cerebral
bleeding) and patients should be properly counselled about this risk. The
risk of such life threatening bleeding is high enough to make this method
of treatment unacceptable in a such non-life threatening condition as
retinal vein occlusion. In a recent experimental animal study, smaller
dose of streptokinase was successful in opening all the retinal vessels,
which had laser-induced thrombosis, when associated with low energy
ultrasound application to the animal eye. This approach may be useful in
using lower safer doses of the drug.
Central retinal vein occlusion may also be associated with thrombosis at

the level of the lamina cribrosa. Experimental studies showed that, by
inserting a cannula in the blocked vein and injecting tissue plasminogen
3
activator, visual and angiographic improvement may be achieved. The

effects of intravitreal tissue plasminogen activator in recent onset
central retinal vein occlusion has recently been studied. Intravitreal tPA
treatment (75-100 µg)for central retinal vein occlusion appears to be
simple and safe, but did not significantly modify the course of the
occlusion in our patients immediately after treatment.
• laser treatment
Laser photocoagulation in retinal vein occlusion is indicated for

proliferative changes as well as for macular oedema in cases of branch
retinal vein occlusion. In branch retinal vein occlusion with macular
oedema, improved central visual function in treated eyes seems to be
due to the movement of scotoma away from fixation. Scotoma size does
not appear to be correlated to the improvement in the visual acuity.
Laser photocoagulation to the Bruch’s membrane may also stimulate

anastomosis between the choroidal and the retinal circulation and may
be helpful in the treatment of non-ischaemic central retinal vein occlusion
and in preventing ischaemic complications. The mechanism of action of
this method of treatment in not completely known. The laser anastomosis
seems to work by diverting part of the venous drainage away from the
compromised area. Visual improvement of 6 or more lines has been
reported in some patients. However the general results of this procedure
are still very guarded.
Laser applications are often placed about three disc diameters nasal to
the optic disc head in eyes with central retinal vein occlusion and, within
one disc diameter peripheral to the occlusion site in branch vein
occlusion. Avoiding the posterior ciliary artery and staying about three
disc diameters away from the disc is recommended to avoid, but not
guaranteed to prevent, complications. Successful cases may not be
associated with any special signs. Asymmetry of the venous diameter at
the disc margin and a hyper-fluorescent spindle sign one week after
treatment are observed in many successful cases.
One of the major complication of this procedure is retinal

neovascularisation at the site of treatment due to retinal ischaemia. Laser
treatment to the ischaemic retina may reduce the risk of this complication.
This procedure may also result in severe vitreous haemorrhage and
macular scarring which might affect the final visual outcome even when
the procedure is successful. Vitreous haemorrhage may need vitrectomy
in some patients. Anterior segment neovascularisation may also occur
after a successful treatment.
• surgical treatment
4
Retinal vascular surgery in eyes with retinal vein occlusion has become
more feasible and is gaining popularity. A recent paper described a new
technique for surgical decompression of the arteriovenous sheath via a
pars plana approach. The technique appears to improve the retinal
perfusion and may improve vision in some patients.
Surgical chorioretinal anastomosis has also been tried in ischaemic

central retinal vein occlusion. In a recent study five eyes with ischaemic
disease had pars plana vitrectomy, a slit like incision in the retinal veins in
each quadrant of the retina, and insertion of a Mersilene suture to
promote vascularisation and then pan retinal photocoagulation. the
results of the study was fairly encouraging regarding a low incidence of
iris neovascularisation in the treated eyes.
Branch retinal vein occlusion is occasionally complicated by retinal holes

without vitreous traction or retinal traction tears, that may lead to a
rhegmatogenous retinal detachment. In eyes with traction retinal
detachment, following central retinal vein occlusion, better surgical results
can be achieved in eyes without disc new vessels than in eyes with disc
new vessels. The degree of retinal perfusion, the presence of
angiographic factors and the distance of the site of occlusion may affect
the visual and the surgical outcome.
Retinal vein occlusion in young patients
Central retinal vein occlusion in young patients is rare. The disease is

rarely associated with systemic disease. It often undergoes a slow
spontaneous resolution over a period of 4-6 months. Good visual
recovery often occurs in most patients. Some studies on the other hand
demonstrated poor visual outcome. The final visual results largely
depend on the degree of retinal ischaemia as well as the presence of
complications e.g. cystoid macular oedema.
The cause and pathogenesis of the disease is unknown. It is thought that

the disease, in most cases, is caused by a mild non-specific vasculitis of
the retinal or disc capillary vessels. Other investigators believe that
vitreous traction may play an important role in the pathogenesis of the
disease.
Routine examination should be directed at excluding possible causes.

The following systemic and local conditions have previously been
described in association with central retinal vein occlusion in young
adults:
Systemic causes Local causes

1. Hypertension 1. Glaucoma
5
2. Diabetes 2. Congenital arteriovenous

3. Hyperlipidaemia malformation
4. Hypercoagulability conditions 3. Anterior and posterior uveitis
(e.g. smoking, abnormal 4. Optic nerve disease (e.g. drusen
platelets function and blood and papilloedema)
diseases associated with 5. Trauma
increased viscosity)
5. Migraine
6. Mitral valve prolapse (it is
thought to be due to abnormal
platelets function)
7. Collagen vascular diseases
8. AIDS
9. Carotid artery disease
(possibly due to the presence
of atherosclerotic vascular
changes in both the carotid and
the retinal vessels)
10.Medications (e.g. oral
contraceptives, diuretics)
treatment
Systemic steroids may be used in cases with other local or systemic

features of inflammation. Anticoagulants have also been suggested by
some clinician in order to promote collateral development.
Plasmapheresis and haemodilution may also be effective in causing
regression in the clinical findings and improvement in the visual acuity in
some patients with mixed connective tissue diseases. Vitrectomy may
also be indicated to relieve vitreous traction or to treat vitreous
haemorrhage or traction retinal detachment.
There is a controversy about the role played by contraceptive pills in

the risk of developing cardiovascular diseases. Case control and cohort
studies suggest that taking norethisterone or levonorgestrel-containing
pills (second generation pills) increases risk of developing venous
thromboembolism from 5 cases per 100,000 per year to about 15 cases
per 100,000 per year. Taking pills containing a desogestrel or gestodene
(third generation pills) increases the risk, on the other hand, from 5 to 25
cases per 100,000 per year. There does not appear to be any data to
show that the risk of having myocardial infarction is increased with any of
these medications.
It is thought that the use of HRT is not associated with any significant
cardiovascular risks, or retinal vascular occlusion. However, there are
recent reports and case presentations, that highlights the possibility of an
association between retinal vein occlusion and the use of HRT. Central
retinal vein occlusion may be associated with celioretinal artery occlusion.
6
The mechanism of this condition is not completely understood. a recent

case report documented this condition in a patients who had started
hormone replacement therapy 6 weeks previously. The authors believe
that the celioretinal artery occlusion followed the central retinal vein
occlusion.
7
Central and Branch Retinal Artery Occlusion

aetiology
Significant carotid artery stenosis is a major cause for transient

monocular blindness, retinal artery occlusion and ocular ischaemic
syndrome. The presence of emboli does not appear to be necessary for
the pathogenesis of these conditions. Embolic acute retinal artery
occlusion has, however, a higher mortality rate than non-embolic disease.
The presence of a retinal embolus does not necessarily indicate the
presence of a significant carotid stenosis, but their presence has a 39%
sensitivity and 68% specificity for the presence of a significant carotid
artery stenosis. Patients with retinal emboli, even if asymptomatic, are at
increased risk of having strokes, hypertension, and cardiovascular
disease. Medical referral for assessment may be beneficial.
Patient with retinal artery disease, at any age, should have carotid
ultrasound examination to investigate the status of the carotid artery.
Selection for treatment should be based on the morphology of the lesion
as well as the degree of stenosis. Complex heterogeneous carotid
lesions are known to be associated with more vascular lesions than
simple heterogeneous or homogenous lesions. In patients with severe
carotid artery stenosis (70-99% reduction in carotid artery diameter),
associated with symptoms (e.g. amaurosis fugax, transient ischaemic
attacks, or minor ischaemic strokes), carotid endarterectomy appears to
be beneficial in reducing subsequent stroke rate. Carotid endarterectomy
may also change the haemodynamics in the circulation of the ophthalmic
artery, central retinal artery, and some posterior ciliary vessels.
Amaurosis fugax is typically associated with carotid artery diseases.

Abnormal haematological factors may also cause occlusive retinal
vascular diseases, and amaurosis fugax. Amaurosis fugax may also be
associated with intra-orbital mass lesions in young patients. Gazed
evoked amaurosis has been previously described in patients with
cavernous haemangiomas, optic nerve sheath meningiomas, osteoma,
and neurofibroma.
Central retinal artery occlusion is rare in young adults. Systemic

evaluation is necessary to rule out any life threatening conditions.
Cardiac valve diseases are the most commonly diagnosed cause in this
age group. The prevalence of cardiac valve diseases in patients
presenting with occlusive vascular retinal diseases is about 25%.
Investigations to rule out the presence of emboli (e.g. by trans-thoracic or
by, the even better, approach of trans-oesophageal
echocardiography) is recommended for the evaluation of the heart
condition in these patients, even in the absence of retinal emboli.
Tailoring the investigations according to the type of emboli (calcific,
cholesterol, or platelets) does not seem to be reliable as there is inter-
8
and intra-observer disagreement in the diagnosis of the type of the

embolus.
Other diseases causing hyper-coagulation or systemic emboli (e.g.

atrial myxoma, subacute bacterial endocarditis, smoking, internal carotid
artery disease, oral contraceptives and leukaemia) may also cause the
disease. Trauma, sickle cell haemoglobinopathy (even if not associated
with any contributing factors), intravenous drug abuse, SLE, varicella-
zoster infection and T cell lymphoma may also cause retinal artery
occlusion in children. Activated protein C resistance should also be
considered in patients with retinal arterial occlusion when the usual
embolic or thrombotic diseases are ruled out.
Hyper-homocysteinaemia has been identified as a general vascular risk

factor. Homocysteinaemia, has a toxic effect on the vascular endothelium
which may result in arteriosclerosis and arterial and venous thrombo-
embolism at a younger age. Patients with Hyper- homocysteinaemia
have increased risk of vascular occlusive diseases, strokes and
myocardial infarction. The disease may also lead to the development of
retinal artery and retinal vein occlusion and also non-arteritic anterior
ischaemic optic neuropathy in young patients. This condition should be
excluded in these patients who are otherwise healthy, or patients with
bilateral or recurrent disease. Diagnosis is important as the high serum
level of homocysteine can be lowered by high doses of vitamin B6, folic
acid or betaine.
management
Patient with central retinal artery occlusion, central retinal vein occlusion,
or anterior ischaemic optic neuropathy are at increased risk of developing
macro-vascular diseases (e.g. myocardial infarction and
cerebrovascular accidents). Hypertension, hypercholesterolaemia and
hypertriglyceridaemia appear to be associated with vascular retinal
diseases e.g. central and branch retinal artery occlusion and anterior
ischaemic optic neuropathy.
Many studies demonstrated clinical benefit from treating blood pressure,

higher than 160 systolic and 95 diastolic, in patients under the age of 65
with vascular retinal diseases, other studies proved this benefit in older
patients as well. It is suggested that the combined treatment of
hypertension, hypercholesterolaemia and the use of anti-platelets drugs
would reduce recurrence in the fellow eyes. In high risk patients it has
also been shown that anti-platelets therapy (aspirin 75-325 mg daily)
reduces the risk of vascular death, myocardial infarction and stroke. In
view of the increased mortality noticed in patient with central retinal vein
or artery occlusion it seems appropriate to treat patients with anti-
platelets drugs.
9
It is also recommended that patient taking combined oral contraceptive

pills should discontinue the treatment if they develop retinal artery or
retinal vein occlusion to avoid recurrence in the fellow eye. Patients with
retinal artery or retinal vein occlusion, on the other hand, should continue
treatment with HRT to avoid macro-vascular diseases.
Re-breathing into a bag produces hypercapnea (which increases the

retinal blood flow) and hypoxia (which causes vasodilatation). Both
hypercapnea and hypoxia increases the cardiac output, systemic blood
pressure and also increases the ocular perfusion pressure and produce a
large increase in the macular leukocyte velocity. Re-breathing into a bag
might be useful in the immediate treatment of retinal arterial obstructive
diseases, but they should be used with caution in elderly patients with
cardiovascular diseases.
10
Age related maculopathy

Age related maculopathy is the leading cause of legal blindness among
older people in the Western countries. Blind and partially sighted
registration rates, in the UK, because of cataract, glaucoma and optic
atrophy have decreased during the past 50 years. However, the
incidence of registration due to age related maculopathy seems to be
increasing in the order of 30-40%.
Age related maculopathy patients have greater difficulties with daily

activities than patients with cataract who have the same visual acuity.
The visual difficulties of these patients are better assessed using either
the DLTV (Daily Living Tasks Dependant On Vision) index or the NEIVFQ
(National Eye Institute Visual Function Questionnaire) index. These
systems are based on several questions asked to patients about routine
daily activities.
26% of eyes with age related macular degeneration (with unilateral extra-
foveal choroidal neovascular membrane) develop choroidal neovascular
membrane in the fellow eyes 5 years after presentation and are
associated with poor visual acuity at the end of the 5 years period. In
patients with a unilateral visual loss, the risk of visual loss in the second
eye is between 7-10%. Significant risk factors for the development of
exudative or non-exudative lesions include the degree of confluence of
drusen within 1600 mm of the centre of the fovea, focal hyper-
pigmentation, slow choroidal filling, and focal extra foveal areas of
atrophy of the retina pigment epithelium.
risk factors
Some of the risk factors that has been associated with age related
maculopathy include:
Drusen
Hyperopia
High body mass index in men
Decreased stromal iris pigmentation
Serum high density lipoprotein
Alcohol consumption
Tobacco smoking
Drusen are subretinal pigment epithelium hyaline deposits that may be

associated with age related maculopathy. Choroidal neovascular
membrane may develop in eyes with drusen and good visual acuity. Up
to 40% of patients with drusen and good visual acuity, and up to 87% of
fellow eyes may develop choroidal neovascular membrane in a period of
5 years. The risk of developing choroidal neovascular membrane in eyes
11
with drusen depends on the health status of the macula as well as on the
presence or absence of hypertension. Drusen may be classified
depending on their morphology into:
• Hard drusen
• Soft drusen
• Drusen of the basal lamina
Large and confluent soft drusen are thought to be clinical marker and
predisposing factor for choroidal neovascular membrane. Drusen may
gradually disappear spontaneously. Its disappearance may be
associated with retinal pigment epithelium atrophy. The pathogenesis of
drusen is not known. There are three main theories to explain the
pathogenesis of the disease:
1. Transformation theory of Donders

2. Deposition theory of Muller
3. Vascular theory of Friedman
Donders proposed that drusen are directly transformed from unhealthy

pigment epithelium. Muller, on the other hand, thought that drusen are
deposited by an intact retinal pigment epithelium. Friedman proposed that
drusen originate from blood constituents. Other workers also postulated
that certain genetic mutation may result in drusen formation e.g. in
Malattia Leventinese and Best disease.
Alcohol consumption (with the exception of beer), does not seem to be a

risk factor for the incidence of age related maculopathy. Beer
consumption, especially in men, appears to be associated with a slightly
higher incidence of age related maculopathy and soft drusen
development. Tobacco smoking also seems to have adverse effect on
age related maculopathy. Previous smokers appear to remain at higher
risk. A slower recovery from glare and more extensive fundus changes in
the affected eye also appear to be risk factors for the fellow eyes
involvement. A slower foveal ERG implicit time may also be an indicator
of early stage choroidal neovascular membrane development because of
outer retina ischaemia.
clinical features
Patients with good visual acuity may have symptoms of poor vision in dim
light, and central scotoma in the dark. These symptoms reflect changes
in the scotopic sensitivity and alteration in the dark adaptation
mechanism. Visual loss in geographic age related maculopathy is nearly
always perceived by patients as slow and gradual even when
considerable decrease in visual acuity occur. This can be explained by
having a transitional period during which patients switch between foveal
and extra-foveal site for fixation. The complaint of sudden loss of vision
12
should raise the suspicion of choroidal neovascularisation which may be

occult and difficult to detect.
Macular perimetry, with the scanning laser microscope, provides

considerable information on the functional status of the macula. Patients
with central scotoma usually develop a single preferred retinal locus
(PRL) for fixation and reading. The preferred locus is often located in the
lower and left part of the visual field. It has recently been shown that the
number of preferred loci may be more than one depending on the size
and the degree of illumination of the target. Patient may also use certain
eye movements to maintain fixation.
The natural history of sub-foveal choroidal neovascular membrane does

not necessarily lead to profound visual loss. 95% of patients have stable
or improved visual acuity over a median follow up period of 87 months.
The size of the choroidal neovascular membrane seems to be the only
variable associated with long term visual acuity.
In age related macular degeneration, choroidal neovascular membrane

can be classified, according to fluorescein angiography, into two types,
classic and occult:
Classic Occult
The typical features of classic Occult choroidal neovascular membrane, on
choroidal neovascular membrane the other hand, include lesions with the
are: following characteristics:
• Areas of bright hyper- • A fibrovascular pigment epithelium
fluorescence, detachment with hyper-fluorescence, (not as
• Well demarcated bright as with the classic choroidal
• Identified in the early stages of neovascular membrane), within 1 to 2
fluorescein angiography minutes after the fluorescein injection with
• Progressive pooling of the dye in staining or leaking of the dye later on, or
the later stages of the angiogram. • The presence of areas of late leaking of
• The fibrovascular tissue grows in undetermined origin, or
subretinal space in classic • The presence of both features.
membranes. • The location and the extent of occult
subretinal membrane is difficult to delineate
with fluorescein angiography.
• The fibrovascular tissue grows on the
choroidal side of the retinal pigment
epithelium in occult membranes.
Peripapillary membranes accounts for less than 10% of choroidal

neovascular membranes. Their rate of growth is very unpredictable and
treatment is only recommended if the fovea is threatened. Small
symptomatic peripapillary choroidal neovascular membrane can be
completely treated by laser, but massive lesions (3.5 disc diameter or
bigger) only need partial laser treatment. In these massive lesions,
treatment is often applied to the active edge of the membrane that
13
threatens the fovea. Patients under 40 years of age often have a

unilateral disease and seem to have a better prognosis. Early and
aggressive laser treatment is recommended in older patients, while
conservative treatment is needed in younger patients. Aggressive
treatment may result in ischaemic optic neuropathy.
retinal angiography
Fluorescein angiography is the main diagnostic tool used in age related

maculopathy. Indocyanine Green is, however, considered more superior
when used with confocal scanning laser ophthalmoscopy, because of its
biophysical properties:
1. Indocyanine dye has a better penetration through blood and overlying

pigments.
2. It is also highly protein bound (98%), which account for its relatively
slow and limited leakage through fenestrated blood vessels compared
with fluorescein. About 11% of patients, however, demonstrate
intraretinal leakage of the dye between 14 and 34 minutes after
injection.
Fluorescein angiography should be performed in all patients with

suspected choroidal neovascular membrane membranes as it is more
useful in identifying classic membranes than the Indocyanine Green
angiography technique. It might not be possible to administer fluorescein
intravenously in some patients (e.g. children). Oral fluorescein, when
used with confocal scanning laser ophthalmoscopy, appears to produce
good enough images to enable diagnosis of most retinal disease. Oral
fluorescein angiography might also be associated with less side effects
than intravenous administration.
Indocyanine green angiography is beneficial in demonstrating

choroidal neovascular membrane under haemorrhagic retinal pigment
epithelium detachment. The angiographic features of Indocyanine green
angiography in age related maculopathy varies in the size of the changes
as well as in the degree of fluorescence and the presence or absence of
late leak. Choroidal neovascular membrane can be classified into three
types, based on the size of their Indocyanine green angiographic
features:
Plaques (commonest, poor visual outcome).

Focal spots.
Combined type(rare).
Plaque choroidal neovascular membrane tends to become larger with

time. The resulting loss of visual acuity, however, is not significant, and is
slightly correlated with the extension of the lesion. Patients with the
plaque type choroidal neovascular membrane are generally considered
untreatable, whereas patients with the spot type may benefit from laser
14
treatment. Eyes with the focal spot on the edge of the plaque (marginal
spot) may also benefit from laser treatment and may show improvement
in the visual acuity after treatment.
Indocyanine Green angiography is useful in demonstrating well

demarcated choroidal neovascular membrane in about 50% of eyes
diagnosed of having occult choroidal neovascular membrane and in
about 80% of eyes diagnosed of having pigment epithelium detachment.
Indocyanine green angiography may be useful in predicting the visual
outcome in eyes with choroidal neovascular membrane. In a study of 89
eyes, the angiograms were classified into 4 types based on the whether
the choroidal neovascular membrane is well or poorly demarcated and
also on the presence or absence of late leak. Well demarcated choroidal
neovascular membranes with late indocyanine green leak were
associated with the highest risk of visual loss.
Indocyanine Green angiography can also delineate occult choroidal

neovascular membrane, choroidal neovascular membrane with overlying
subretinal fluid or haemorrhage and also choroidal neovascular
membrane with retinal pigment epithelium detachment. Although ICG
angiography may enhance visualisation of choroidal neovascular
membrane associated with serous retinal pigment epithelium detachment
in age related maculopathy, ICG-directed laser treatment does not
appear to improve visual acuity when compared with no treatment.
Indocyanine green angiography-guided laser photocoagulation may
temporarily stabilise visual acuity in some eyes with occult choroidal
neovascular membrane, and choroidal neovascularisation associated
with pigment epithelial detachments. Final visual acuity, however, seems
to decrease with time.
Retinal-choroidal anastomosis can present as a primary manifestation

of the exudative process in age-related macular degeneration. Specific
clinical and angiographic features have been identified that can aid in the
diagnosis of these vascular anomalies. Their presence represents a poor
prognostic sign for successful ICG-guided laser treatment. Clinical
evidence of pre-retinal and intraretinal haemorrhage and cystic oedema
coupled with angiographic evidence of intraretinal dye leakage were key
features of retinal choroidal anastomosis.
The prevalence rate of serious side effects after fluorescein angiography

is estimated to be about 0.7%. Photo-toxic or photo-allergic reactions to
fluorescein in humans have been reported only rarely. Patients may
experience marked cutaneous erythema, oedema and pain to sun-
exposed areas within 1 hour of exposure. Drug incompatibility has been
noticed when promethazine and fluorescein are mixed together in the
syringe because of the formation of microscopic precipitates. This
precipitation reaction may result in delayed and ineffective treatment of
the allergic response as well as causing more complications if the
precipitates are injected.
15
Indocyanine green angiography seems to be as safe as fluorescein

angiography. Adverse reactions are reported in only 0.34%, most of
these are mild reactions (e.g. nausea, rash, urticaria and urgency to
defecate). Treatment for shock may be needed for patients with severe
hypotension.
optical coherence tomography
Optical coherence tomography is a new non-contact, non-invasive

imaging technique that is similar to ultrasound but with using light rays,
instead of acoustic waves, to provide a cross-sectional image of the
posterior segment with micrometer scale resolution. It has a high depth of
resolution (10 micro-meter), compared to (150 micro-meter) with the
standard ultrasound technique and (20 to 40 micro-meter) with the high
frequency ultrasound and (300 micro-meter) with the scanning laser
tomography. The technique is useful in the quantitative evaluating of
subretinal and intraretinal fluid, assessing subfoveal involvement and
also in monitoring response to laser treatment. Optical coherence
tomography does not seem to be able to detect choroidal neovascular
membrane beneath serous detachment.
scanning laser ophthalmoscopy
The Heidelberg confocal laser ophthalmoscopy can be used to study

retinal and macular diseases. It provides non-invasive quantitative
measurements of the neuro-sensory retinal detachment. It is also useful
in the examination of the vitreoretinal interface for conditions e.g.
epiretinal membranes. The technique has a good reproducibility for
measuring the height of retinal lesions especially when used with dilated
pupils. In scanning laser tomography the Z profile signal width analysis
offer a non-invasive objective topographic index of macular retinal
thickness. The peak intensity of this signal is assumed to indicate the
depth of the vitreous internal limiting membrane interface.
Treatment of choroidal neovascular membrane
Idiopathic choroidal neovascular membrane is an uncommon condition

that affect patients younger than 50 years of age with no other ocular
pathology. It is an important cause of visual loss in young Japanese
patients. The prognosis of this condition is thought to be better than age
related choroidal neovascular membrane, with many eyes retaining
useful vision many years after presentation. Conventional fluorescein
angiography is often unhelpful in the evaluation of these eyes. Choroidal
vascular anomalies, as shown by Indocyanine Green Angiography
appear to predispose to the formation of these membranes. Regression
may be indicated by the finding of a dark rim surrounding the choroidal
neovascular membrane in Indocyanine Green Angiography. Laser
photocoagulation of these idiopathic membranes has been
16
recommended by previous studies. Current opinion, on the other hand,

recommends conservative treatment based on the often good prognosis
of the condition.
• laser photocoagulation
About 87% of primary choroidal neovascular membrane, in age related

maculopathy, are ill-defined by fluorescein angiography and can not be
treated adequately by laser. Persistence and recurrence of age related
choroidal neovascular membrane is another big problem that may lead to
further visual loss. Recurrent membranes are often poorly defined by the
fluorescein angiography. Indocyanine green angiography can achieve a
better imaging in about 30-40% of ill-defined membranes, and can also
achieve a better definition of recurrent and persistent membranes. It does
not however seems to be beneficial in well defined recurrent membranes,
or in cases where fluorescein angiography does not reveal any recurrent
choroidal neovascular membrane.
In age related subfoveal choroidal neovascular membrane, direct laser

photocoagulation is often associated with a sudden and a dramatic
decreases in visual acuity. Photocoagulation of the feeder vessels, as
detected by fluorescein angiography, has been successfully tried in these
cases. Some studies demonstrated 70% reduction in macular exudate,
and 68% stabilisation or improvement in visual acuity. Good prognostic
factors for the treatment include small vessels, larger distance of laser
burns from the fovea, and the absence of fibrous tissue. Dynamic
indocyanine green angiography can detect smaller feeder vessels and
can also detect incomplete treatment in some cases. The success or
failure of treatment seems to be related to the width, length, and number
of the feeder vessels.
Soft confluent drusen are major risk factor in the development of

choroidal neovascular membrane especially in fellow eyes with age
related maculopathy. There are conflicting reports regarding whether
laser photocoagulation might prevent neovascular complications and
blindness in these cases. Some studies showed evidence of decreased
risk of exudative age related maculopathy development and improvement
in the visual acuity after treatment. Other studies, on the other hand,
showed that laser treatment in high risk fellow eyes may increase the
short term incidence of choroidal neovascular membrane. Choroidal
neovascular membrane associated with laser photocoagulation to soft
drusen often develop at the site of treatment, and are often occult.
Surgical excision of these choroidal neovascular membrane may be
associated with good visual prognosis because the membranes are often
extra-foveal, and the degree of cell damage is often focal.
More than 50% of treated eyes with choroidal neovascular membrane

develop resistant or recurrent choroidal neovascular membrane within 3
years after treatment. Additional damage to the visual function may result
17
from the persistence or the recurrence of neovascularisation. Clinical

examination probably cannot replace fluorescein angiography in
detecting all recurrent choroidal neovascular membrane after laser
treatment. The protocol used in the macular photocoagulation study to
detect recurrent lesions recommend repeat fluorescein angiography at 3
and 6 weeks and then at 3, 6, 9 and 12 months after treatment. A definite
recurrence is indicated by the leaking of fluorescein dye at the periphery
of the treated areas at late stages of fluorescein angiography, the area of
leakage is often preceded by intense hyper-fluorescence early in the
course of the angiogram. Other features of recurrence are Focal staining
along the edges of the laser lesions, blocked fluorescence from
subretinal haemorrhage that was not documented previously, and
speckled hyper-fluorescence noted beyond the edges of the laser
lesions.
• Sub-threshold laser retinal photocoagulation
Sub-threshold laser retinal photocoagulation is a new technique that uses

Nd:YLF non-visible retinal laser photocoagulation to reduce the side
effects of the conventional laser photocoagulation methods. The
technique involves using short laser pulses that remains confined to the
retinal pigment epithelium layer, with little or no thermal effect on the
photo-receptors layer. Recent experimental studies showed that this
technique is useful in many retinal conditions e.g. diabetes, drusen, and
central serous retinopathy. A recent multicentre randomised study also
showed that infra-red diode laser photocoagulation, with sub-threshold
laser burns, to macular drusen in non-exudative age related maculopathy
reduces macular drusen and improve visual acuity. Long term effects in
the fellow eyes is not known.
• teletherapy
Laser photocoagulation of subfoveal choroidal neovascular membrane

results in the destruction of the overlying retina with sudden and dramatic
visual loss. The rationale of radiation therapy is based on the fact that
growing blood vessels are more sensitive to radiation damage than
mature vessels. Ionising radiation, unlike laser photocoagulation, has
been shown to induce regression of choroidal haemangioma and
choroidal neovascular membrane without thermal damage to the
overlying retina. Radiotherapy also appears to have a favourable
treatment effect in eyes with subfoveal neovascular membranes and
haemorrhage associated with pathological myopia.
Low dose of radiation has been reported to cause regression of the

subretinal vessels and maintain the central vision in a significant number
of patients. In some studies low dose of radiation (1000 c Gy in 5
fractions) has been reported to cause significant regression of the
choroidal neovascular membrane, and maintained the central vision in
about 77% of eyes after 12 months. Some other studies, on the other
18
hand, showed that external beam radiotherapy, when using this dose, is
not effective. The long term benefit of radiotherapy on the anatomical and
visual outcome has been described in a recent study. The visual acuity,
in this study, improved by 2 or more lines in 34% of patients after 12
months, in 31% of cases after 18 months, and in 32% of cases in two
years. Long term complications may include radiation neuropathy,
retinopathy, branch retinal vein occlusion and choroidal vasculitis.
After radiotherapy for age related maculopathy, a subgroup of patients

may experience extensive growth of choroidal neovascular membrane
after radiation, causing greater functional damage than occurs
spontaneously. The crystalline lens may also shows pre-cataractous
changes, in some patients, six months following radiotherapy. Most of
these changes disappear after 12 months. A recent report also showed
that radiation therapy to subfoveal choroidal neovascular membrane may
be associated with an unusual pattern of choroidal neovascular
membrane, characterised by the presence of round vascular blebs at the
end on the neovascular membrane. This unusual pattern appears to be
associated with a poor prognosis for vision.
The usual method of treatment often require a CAT scan and a face
mask for the delivery of the radiation. A new method of delivery that does
not require a CAT scanning has been described in a pilot study. This
technique would significantly reduce the cost of treatment.
Ophthalmic plaque radiotherapy can also be used to treat neovascular

age-related macular degeneration. The advantage of this technique is
that it is a unilateral treatment, which allows a larger dose to be delivered
to the macula with less irradiation of normal ocular structures. The
technique does not seem to be associated with sight threatening
complications e.g. radiation retinopathy, optic neuropathy, or cataract.
VEGF and other growth factors play a role in the pathogenesis of the
disease and the development of choroidal neovascular membrane. Anti-
angiogenic medications have been tried for the treatment of the disease
with varying results. These medications include:
Steroids
Interferon-alpha
Thalidomide (in non-pregnant patients!)
Pentoxifylline
Isotretinoin
Choroidal neovascular membrane may develop in young patients with

posterior segment inflammatory conditions (e.g. punctate inner
choroidopathy, and multifocal inner choroidopathy). In these conditions
when no other cause for the choroidal neovascular membrane is found, a
19
course of oral steroids (60-80 mg per day for about 3,5 days, then
reduced gradually over a period of 6-8 weeks) may reduce leakage and
stabilise vision.
Interferon has an anti-proliferative effect on the vascular endothelium. In

clinical studies, Interferon provided no benefit as a treatment for choroidal
neovascularisation secondary to age-related macular degeneration. It
may also associated with marked side effects which include flu-like
symptoms, leucopaenia, thrombocytopenia, increase liver enzymes,
alopecia, nausea, fever and suicidal depression. Treatment with
interferon alpha may also be associated with Interferon-associated
retinopathy. Two weeks to three months after the start of interferon
therapy retinal haemorrhage and cotton wool spots appear. The
incidence of retinopathy depends on the initial dose of the drug.
Pentoxifylline is a methyl xanthine derivative that has been used in the

treatment of vascular insufficiency diseases because of it’s ability to
improve the blood flow. The drug can produce a vasodilatation effect in
rats muscles. It can also increase the blood flow because of its
vasodilatation effect, decreasing the blood viscosity and also because of
its ability to improve the deformability of the red and white blood cells.
Oral administration of Pentoxifylline in healthy volunteers produces a
significant improvement in the retinal capillary blood flow velocity and
viscosity but not in the filterability of the whole blood. Pentoxifylline might
be useful in the treatment of age related maculopathy. A three months
course of Pentoxifylline increases the choroidal, but not the retinal, blood
flow in patients with age related maculopathy.
• surgical excision of the choroidal neovascular membrane
About 80% of choroidal neovascular membrane are not treatable with

laser photocoagulation because they lie under the fovea, and laser
photocoagulation is associated with dramatic visual loss after the
treatment. Surgical excision of the choroidal neovascular membrane is a
relatively new method of treating subfoveal choroidal neovascular
membrane.
It is now known that choroidal neovascular membrane may be

classified into two types, type 1 and type 2. Age of the patient, and
clinical features of the fundus may help in the differentiation of the two
types. Older patients seem to be more prone to type 1, while younger
patients are to type 2. Type 2 is characteristically associated with
subretinal pigmented halo or plaque in the area of the membrane, and
also with a well defined border of the membrane.
Type 1 Type 2
located beneath the retinal pigment located between the sensory retinal
epithelium, some portion of the and the retinal pigment epithelium.
membrane enters the subretinal
20
space.
occurs mainly in older patients. occurs mainly in younger patients
e.g. POH and myopia and
idiopathic.
can not be excised with removing Can be excised surgically.
the retinal pigment epithelium at the
fovea.
Surgical removal of type 1 choroidal neovascular membrane is often

associated with damage to RPE and disruption of the function of
overlying retina. During surgical excision of age related choroidal
neovascular membrane, the Bruch’s membrane and the retinal pigment
epithelial cells are damaged to varying degrees, resulting in poor visual
outcome. The extent of the damage of the Bruch’s membrane affect a the
future growth of transplanted RPE cells. Injured Bruch’s membrane does
not allow growth or differentiation of the host or the transplanted RPE
cells. Recurrence of choroidal neovascular membrane after surgical
excision is often due to incomplete excision of an occult membrane. Re-
surfacing of the membrane with by RPE and fibroblasts may play a part in
limiting visual improvement after the surgical excision.
When there is subretinal haemorrhage affecting the macular region, the

final visual acuity depends on the underlying cause and the duration of
the haemorrhage. Sub-macular haemorrhage secondary to age related
macular degeneration have a poor visual prognosis after surgical
treatment. The addition of tissue plasminogen activator can assist clot
lysis but it does not appear to improve the visual outcome from surgery.
In sub-retinal haemorrhage, from different causes (e.g. trauma), pars
plana vitrectomy with subretinal tissue plasminogen injections is possible
and may be associated with improved visual acuity. It has been shown, in
an animal experimental studies, that intravitreal injection of commercial
tissue plasminogen activator solution results in dose-dependent retinal
toxicity in cat eyes. Intravitreal injections of commercial tissue
plasminogen activator in concentrations greater than 25 µg/0.1 mL may
be potentially unsafe in human eyes.
non-age related choroidal neovascular membrane
The results of surgical excision of non-age related choroidal neovascular

membrane are promising. It is controversial whether laser
photocoagulation is useful in the treatment of myopic choroidal
neovascular membrane. A recent study shoed that surgical excision of
choroidal neovascular membrane in myopic patients may result in visual
improvement in some patients.
Selected eyes of children with choroidal neovascular membrane may

also benefit from surgical excision. Postoperative visual loss may be
noticed in eyes with good preoperative visual acuity. The assessment of
vision on the basis of Snellen visual acuity alone is misleading. Reduction
21
of visual distortion may be achieved even in the presence of the same

visual acuity after surgery. Recurrences of the choroidal neovascular
membrane may occur after surgery, especially in eyes with subfoveal
haemorrhage. Repeat surgery does not seem to be associated with
worsening of the visual acuity. RPE atrophy and older age may be
associated with poorer outcome.
• retinal pigment epithelium transplantation, and foveal trans-

location
Current experimental therapies, such as photoreceptor transplantation

and implantation of a visual prosthesis, are based on the fact that some
inner retinal neurones are preserved after death of photoreceptors as
shown in patients with retinitis pigmentosa. Despite a statistically
significant loss of cells in all retinal layers, a large percentage of the inner
retinal neurones appear to remain histologically intact. A healthy Bruch’s
membrane appears to be important for the success of RPE
transplantation. Macular trans-location in patients with subfoveal
choroidal neovascularisation, from age-related macular degeneration,
offers a potential for improving visual function. It may be associated with
less loss of vision than the disease itself, if allowed to progress.
The technique of foveal translocation involves vitrectomy with or without

lensectomy, creation of retinal detachment by a retinotomy, removal of
the subfoveal membrane and retinal re-attachment with trans-location of
the fovea. Trans-location of the fovea may also be achieved after
performing scleral resection in the superior temporal or inferior temporal
equatorial sclera, suturing the edges of the resected scleral will,
subsequently, result in scleral shortening and foveal trans-location. Laser
photocoagulation of the subfoveal choroidal neovascular membrane
(which is now not subfoveal) would be possible. Surgical shortening of
the sclera is useful in the management of several retinal disorders, but
causes significant changes in axial length.
Foveal translocation may also be achieved by redistribution and

mobilisation of the neuro-sensory retina. Relocation of the fovea is
achieved by utilising the natural redundancy of the neuro-sensory retina.
Stabilisation of the retina is then achieved by using perfluorocarbon
liquid, intra-operatively, and silicon oil postoperatively. Vascular
occlusion, RPE changes, macular hole formation, and epiretinal
membrane formation are all possible complication after surgery.
This technique has also been used in choroidal neovascular membrane

in myopic eyes. Visual acuity have been reported to improve from
20/200 pre-operatively to 20/20 postoperatively in some patients after this
technique. The postoperative results of this technique, however, do not
appear to be predictable. Oblique astigmatism, transient diplopia,
torsional and micropsia may occur after surgery. These side effects may
resolve with time due to the development of suppression. Other
22
complications may include development of epimacular proliferation,

retinal detachment and neovascular glaucoma.
• photodynamic therapy
Photo-dynamic treatment is a new method for selective treatment of

subfoveal choroidal neovascularisation secondary to age related
maculopathy and also in selected cases with choroidal neovascular
membrane secondary to pathologic myopia, ocular histoplasmosis
syndrome, angioid streaks and idiopathic causes. The technique causes
occlusion of the neovascular tissue with minimal damage to the healthy
surrounding structures. This mode of treatment involves intravenous
injection of a photosensitiser dye, followed by irradiation of the
photosensitised tissue by a suitable light.
Photodynamic therapy has been applied successfully for experimental

treatment of tumours as well as for photo-thrombosis therapy for normal
and abnormal blood vessels. It is generally accepted that the dye binds to
the endothelium lining of the choroidal neovascular membrane. Light
induced activation of the dye generates oxygen radicals which would
then starts a clotting mechanism inside these abnormal vessels. Release
of free radicals from the sensitised tissue also leads to structural damage
of cells membranes and cell death.
A liposomal preparation of benzoporphyrin derivative (Verteporfin) have

been shown to be safe and effective for use in the treatment of choroidal
neovascular membrane since the dye can easily be taken by the growing
vessels. Effective occlusion of normal choroidal vessels can also be
achieved by using the new photosensitiser NPe6, with minimal injury to
overlying neuro-sensory retina. Both NPe6 and the benzoporphyrin have
a strong far-red absorption and rapid skin clearance, but NPe6 differs
from the benzoporphyrin in that it is hydrophilic and can be available in
aqueous preparation. Lutetium texaphyrin (Lu-Tex) is a new agent that
may be used in the treatment. Lutetium texaphyrin (Lu-Tex) is a water
soluble agent that has the advantage of being used as a dye for
diagnostic angiography, as well as for therapeutic causes in
photodynamic therapy.
ATX-S10(Na) is a new Photosensitiser that has recently been shown to

induces selective occlusion of choroidal neovascular membrane in non-
human primate eyes. Occlusion of choroidal neovascular membrane
without direct damage to the sensory retina is useful to preserve visual
acuity The dye might have a therapeutic application in the clinical
practice.
A new hypothesis has been put forward to explain few of the clinical and
angiographic features of treatment that can not be explained by the
traditional hypothesis. It is thought that light activation of the dye would
lead to liberation of oxygen radicals, which act on the red blood cells, first
23
of all, to liberate haemoglobin which has a vasoconstriction effect. Flow

reduction to the treated area may, thus be due to vasoconstriction of the
vessels, followed by clotting of the slowed down blood.
Post-treatment fluorescein angiography shows significant reduction in

the filling of the choroidal neovascular membrane and also reduction
of the late phase leaking. An area of choroidal hypo-fluorescence is also
noticed for about one week after treatment. A recent non-randomised,
multicentre, open-label, clinical trial showed that photo-dynamic therapy
achieves short-term cessation of fluorescein leakage from choroidal
neovascular membrane without loss of vision or growth of classic
choroidal neovascular membrane in some patients after a single
treatment. Non-perfusion of neuro-sensory retinal vessels at high light
dose (150 J/cm²) may occur in some patients. Fluorescein leakage from
at least a portion of the membrane reappears by 4 to 12 weeks after
treatment in almost all cases.
Multiple laser treatments appears to achieve repetitive, short-term

cessation of fluorescein leakage without loss of visual acuity. There is
concern, however, that re-treatment may result in progressive thinning of the
neuro-sensory retina with loss of photoreceptor outer segments and nuclei in the
rabbit eye. Animal studies showed that repeated applications is associated
with limited damage to the retina when using 6 mg/ m² Verteporfin. High
doses of the dye may, however, be associated with significant damage to
the retina, choroid and the optic nerve.
The 12 months results of this treatment were recently reported in a

multicentre, double-masked, placebo-controlled, randomised clinical trial.
61% of treated eyes, lost fewer than 15 letters of visual acuity, from
baseline, compared with 46% of untreated at the end of a 12 months
period examination. The visual results of the study were strikingly better
in eyes with predominantly classic choroidal neovascular membrane
(classic choroidal neovascular membrane was defined as a membrane
with a classic component that is equal to or greater than 50% of the area
of the entire lesion). There was no difference in visual outcome in
patients demonstrating less than 50% classic choroidal neovascular
membrane at the initial visit. Other reports showed that results may vary
depending on intraocular pressure, region of fundus treated, ocular
pigmentation, and the total time of exposure to the photosensitizer.
The protocol of treatment that was used in the recent trial includes:
1. Injection of 6 mg / square meter of body surface area of Verteporfin.

2. Fifteen minutes after the start of the infusion, a laser light at 689 nm
delivered 50 J/cm2 at an intensity of 600 mw/ cm2 over 83 seconds.
3. A spot size with a diameter 1000 µm larger than the greatest linear
dimension of the choroidal neovascular membrane lesion was used.
4. At follow-up examinations every 3 months, re-treatment with the same
regimen was applied if angiography showed fluorescein leakage.
24
Possible adverse effects of the treatment include:
1. Transient visual disturbances

2. Injection-site adverse events
3. Infusion-related low back pain.
4. Transient photosensitivity reactions
• trans-pupillary thermotherapy
Trans-pupillary thermotherapy may provide an alternative method of

treatment for subfoveal choroidal neovascular membrane. The technique
has been used successfully in treating choroidal malignant melanoma. In
this technique, heat is delivered to the choroid and retinal pigment
epithelium with a modified diode laser. Near infrared radiation is ideal for
this technique as tissue penetration is high and absorption by the ocular
media is minimal. Thermal treatment for choroidal neovascular
membrane needs less choroidal tumours, and damage to the surrounding
retina is, thus, expected to be small. Earlier studies showed no significant
side effects from this method of treatment.
• optical methods
The Implantable Miniaturised Telescope (IMT) is a new approach to

aide vision in patients with dry age related maculopathy. The telescope
consists of a 3X telescope that is contained in carrying device made of
PMMA that can be implanted in the capsule bag under local anaesthesia.
The IMP provide improvement of the central visual acuity in the implanted
eye for reading, while the other eye cam be used for peripheral
navigational vision. The implant has a universal power, fine adjustment of
vision can be achieved by wearing low power plus or minus spectacles.
91% of patients tried with this device reported improvement in viewing
television, and 66% reported improvement in reading vision. The
advantages of the implant is that it provides magnification of vision
without the need to hold the device by hand, which avoid the relative
movements between the eye and the hand. Transient postoperative
difficulty in orientation may be noticed by some patients.
• genetics
Determining the genetic locus of the disease and targeting it may provide
an effective way of treatment. Studies are currently underway to
investigate the relationship of age related maculopathy and the ABCR
gene which code for the retinal photoreceptors, and which has been
found to be altered in patients with Stargardt’s disease.
25
Diabetic retinopathy
epidemiology and natural course
Diabetic retinopathy is an important cause of visual loss in relatively

younger patients. The presence of severe diabetic retinopathy and poor
vision is also considered as a risk factor for the development of ischaemic
heart disease and death. The prevalence of diabetic retinopathy in newly
diagnosed non-insulin dependant diabetics is estimated to be 39% in
men and 35% in women. In a population based incidence study, of 634
insulin dependant diabetics, 14 years rate of progression of diabetic
retinopathy was estimated to be 86%, regression 17%, and progression
to proliferative diabetic retinopathy was 37%. The incidence of macular
oedema was estimated to be 26%.
Male sex, higher glycosylated haemoglobin, higher diastolic blood

pressure, and proteinuria are factors that may be associated with
progression of diabetic retinopathy. A 10 mm Hg or more increase in the
systolic blood pressure is associated with an increased incidence of
diabetic retinopathy in younger onset diabetic patients. Reduction of
hyperglycaemia and blood pressure may be associated with a decreases
in the progression of diabetic retinopathy to proliferative diabetic
retinopathy. The presence of gross proteinuria is associated with
Increased risk of developing macular oedema. The risk of proliferative
diabetic retinopathy in patients with gross proteinuria is also higher than
in patients without proteinuria. Micro-albuminuria (between 0.03 and 0.29
g/l) is also associated with greater risk of developing retinopathy in
diabetic patients and also with the presence of proliferative diabetic
retinopathy in younger onset patients.
basic science
The pathogenesis of diabetic retinopathy is not completely understood.

Hyperglycaemia, retinal blood flow, retinal capillary occlusion and non-
perfusion, growth factors, hormonal factors, and dietary factors play
important role in the pathogenesis of the disease. High concentrations of
glucose can stimulate the transcription of genes coding for growth factors
which may influence the glucose regulatory mechanisms of the retina,
and consecutively, affect progression of diabetic retinopathy. Retinal
blood flow and oxygen consumption appear to be increased during
periods of acute hyperglycaemia. It has been suggested that increased
retinal blood flow, and increased ocular perfusion pressure may play a
role in the development of diabetic retinopathy and also a role in the
progression of the disease to proliferative diabetic retinopathy in the
younger onset groups.
Retinal capillary occlusion and non-perfusion is a common feature of

diabetic retinopathy. Haemodynamics factors, increased blood viscosity
and decreased red blood cells deformability are believed to be important
26
factors in causing capillary occlusion and retinal non-perfusion. Both

increased and decreased blood flow have been described. In a recent
study it was found that pulsatile choroidal blood flow, but not the retinal
blood flow, increases with the progression of diabetic retinopathy.
Micro-displacement of the RBC cell membrane indicates the

deformability of the cells, which is directly related to its ability to pass
through small retinal blood vessels and retinal capillaries. The RBC cell
membrane micro-displacement is reduced in eyes with advanced diabetic
retinopathy. This indicates that the RBC are unable to pass through small
vessels causing capillary occlusion and areas of retinal non-perfusion.
Renin is a major vaso-active agent that is thought to play an important

role in diabetic retinopathy. There are evidences that there is an
intraocular Renin-Angiotensin system independent of that in the
circulation. Vitreous levels of pro-renin in diabetic patients is higher than
that in non-diabetic patients suggesting an activation of the Renin
Angiotensin system in diabetics. Intraocular synthesis of angiotensin II
may be involved in the blood supply and also in the pathogenesis of
vascular processes e.g. neovascularisation in diabetic retinopathy.
Serum total renin concentration is elevated in patients with active diabetic
retinopathy, irrespective of the renal and the autonomic system functions.
Diabetic retinopathy appears to be the most important determinant of
serum renin in patients with insulin dependent diabetes. It is possible that
serum total renin concentration could be used as a marker for activity in
diabetic retinopathy in patients with insulin dependent diabetes.
Growth factors are likely to be involved in the pathogenesis of

Proliferative diabetic retinopathy. Vascular endothelial growth factor
(VEGF) is a glycoprotein that is secreted by the endothelial cells and
pericytes in the retinal blood vessels. It plays an important role in the
regulation of Angiogenesis in the developing eye and also in many
pathological conditions (e.g. diabetic retinopathy, central retinal vein
occlusion, choroidal neovascular membrane, ROP, corneal
neovascularisation and wound healing, and iris neovascularisation).
Vascular endothelial growth factor is also believed to be the most likely
factor responsible for the development of diabetic retinopathy, and
proliferative diabetic retinopathy.
Hypoxia increases VEGF levels in the retina, and vitreous. The vitreous
levels of vascular endothelial growth factors is significantly higher in
patient with proliferative diabetic retinopathy than in eyes without
proliferative diabetic retinopathy. Systemic hyperoxia can lower retinal
VEGF gene expression and re-oxygenate ischaemic retina. Other growth
factors (e.g. Insulin-like growth factor 1 and fibroblast growth factor), and
chemical mediators, (e.g. Interleukin 8, and interferon-induced protein)
are present in the vitreous in eyes with active proliferative diabetic
retinopathy more than controls, and may also play an important part in
the pathogenesis of the disease.
27
High levels of serum Laminin (a glycoprotein) have been reported in

patients with proliferative diabetic retinopathy. It is thought that a
substantial amount of this chemical is secreted by the retinal basement
membrane. Laminin levels reflect changes in the basement membrane in
diabetic retinopathy. It has also been proposed that Laminin may be
considered as an indicator for diabetic retinopathy. It is not however an
early indicator of the disease. It should be mentioned that this chemical
may be reduced after panretinal laser photocoagulation.
Diabetic retinopathy rarely occurs before puberty suggesting that sex

hormones may play a role in its pathogenesis. The blood retinal barrier
appears to remain stable until puberty and then progressively declines
afterwards. There seems to be an association between puberty, decline
of the blood retinal barrier and the development of diabetic retinopathy.
Increased androgen activity may also be associated with progression of
retinopathy in male subjects with type 1 diabetes.
The effects of dietary factors on diabetic retinopathy are not completely

known. In one study of 387 patients with type 2 diabetes, antioxidants
nutrients (vitamin C, E and beta-carotene) had no protective effects on
diabetic retinopathy. It also appears that these nutrients may be
associated with worsening of the diabetic retinopathy in some patients
depending on their insulin use.
screening for diabetic retinopathy
Screening programs for diabetic retinopathy are proved to be cost

effective. Screening reduces the risk of blindness in diabetic patients by
50%. There is no agreement, however, on the best method of screening
for diabetic retinopathy. The prevalence of diabetic retinopathy seems to
be higher when screening is carried out by photos and clinical
examination than by either method alone. When screening sensitivity is
high (e.g. by expert Ophthalmologists) the frequency of screening makes
little difference to the years of sight saved, but when sensitivities are
close to 50% the frequency of examination seems to be an important
factor. Biannual, (rather than annual) screening may be considered when
the screening sensitivity is high.
clinical features
Patients with diabetes, with or without diabetic retinopathy, may suffer

from visual loss, loss of contrast sensitivity, and abnormalities in colour
perception ((tritan-like defect). Visual pathway dysfunction may also
occur in the absence of obvious diabetic retinopathy or hyperglycaemia.
The mechanism underlying this abnormality is unknown. The visual loss
may be caused by reversible changes in retinal function at the ganglion
cell layer. Reduced retinal oxygenation seems to be contributing factor.
28
Senile cataract is commoner in diabetic patients. Diabetic patients are

also more likely to develop cataract at an early age. Cataract surgery in
patients with diabetic retinopathy is often associated with good visual
results, especially if the retinopathy is well controlled by laser
photocoagulation before hand. Patients with severe non-proliferative
diabetic retinopathy or more advanced retinopathy have poor results.
There are several advantages of ECCE in cataract surgery in diabetics;
the technique allows a can opener capsulotomy technique which will
avoid postoperative capsule phymosis and opacification of the anterior
capsule, it also allows implantation of a large 7 mm IOL to make further
fundus examination and laser photocoagulation easier. A recent study,
however, showed that phacoemulsification surgery may be associated
with a better visual acuity and less postoperative inflammation than
ECCE. The visual results and rate of retinopathy progression after
phacoemulsification surgery does not seem to differ significantly from
those reported with other techniques.
The main causes of poor results in these patients are macular oedema
or proliferative diabetic retinopathy. It is thought that clinically significant
macular oedema found at the time of surgery is unlikely to resolve
spontaneously and laser treatment should be carried out without delay.
Macular oedema appearing after surgery may however regress
spontaneously, and conservative treatment may be taken.
Diabetic retinopathy is occasionally very asymmetrical between the two

eyes. Asymmetry of bilateral diabetic retinopathy may be related o the
presence of carotid artery disease or to posterior vitreous detachment.
Complete posterior vitreous detachment, optic atrophy, and high myopia
are considered to be protective factors against the development of
severe proliferative diabetic retinopathy.
Macular oedema is estimated to develop in 20.1 % of the younger onset

diabetics, 25.4% in the older onset patient taking insulin, and 13.9% in
non-insulin patient over a 10 years period. Macular oedema is an
important cause of visual loss in diabetic retinopathy. Light sensitivity is
reduced in oedematous areas. Recent studies showed that the
correlation between the amount of oedema and visual function is not
significant. Reduction in hyperglycaemia may result in reduction in the
incidence of the macular oedema. Vitreous abnormalities and vitreo-
macular adhesion may play a role in the pathogenesis of diabetic
macular oedema in some eyes. Eyes with diabetic retinopathy are more
likely to develop macular oedema if the posterior hyaloid membrane is
attached to the macula. Vitreo-macular separation either spontaneously
or by vitrectomy may result in reduced macular oedema and improved
visual acuity after laser photocoagulation.
The assessment of retinal and macular thickness by slit lamp

biomicroscopy is difficult and also subjective. Retinal thickness
analyser, scanning laser ophthalmoscope and optical coherence
29
tomography are new tools that may be used in the diagnosis and
evaluation of treatment of macular and retinal thickness in diabetic
patients. Fundus perimetry with scanning laser ophthalmoscope allows
the creation of exact maps of retinal dysfunction before and after laser
treatment. It may help in making management decisions in diabetic and
non-diabetic patients by offering a sensitive parameter in addition to
visual acuity. Retinal Thickness Analyser gives quantitative, and objective
measurement of the retinal thickness. The technique is based on angular
delivery of a narrow green helium laser beam to the retina and detection
of the intersection of the beam with the retinal structures. Evaluation of
the macula by the scanning laser ophthalmoscope is also accurate,
reliable and reproducible.
Optical coherence tomography has been shown to be more sensitive

than scanning laser ophthalmoscopy in detecting early diabetic
retinopathy. Recent optical coherence tomography studies shows three
patterns of structural changes in diabetic macular oedema; a sponge-like
retinal swelling (88%), cystoid macular oedema (47%), or serous retinal
detachment (15%). Visual acuity with best correction moderately
correlated with retinal thickness regardless of the different tomographic
features.
Proliferative diabetic retinopathy is often associated with poorer visual

prognosis, due to recurrent vitreous haemorrhage and also due to the
higher incidence of thrombotic glaucoma. Spontaneous regression of
new vessels in proliferative diabetic retinopathy may rarely occur.
Spontaneous regression does not seem to be related to any
improvement in the diabetic control, but it seems to be associated with
improvement in the blood-retinal barrier. Iris new vessels occasionally
develop in the anterior chamber angle before the pupil margin. Screening
gonioscopy is valuable and important for the early detection of iris
neovascularisation. Rubeosis iridis may develop rapidly in eyes with non-
proliferative diabetic retinopathy in patients with IDDM or non-IDDM after
ECCE with posterior camber IOL despite good diabetes control.
diabetic papillopathy
Diabetic papillopathy is a syndrome of a relatively benign optic disc

swelling that occurs not only in young diabetics, but also in older patients
with type 2 diabetes. Affected eyes often have macular oedema and
retinal vascular changes that commonly affect the final visual outcome.
Small physiological cup may represent an anatomical predisposition to
this condition. The condition may be associated with rapid progression of
the diabetic retinopathy and the development of disc neovascularisation.
Patients with diabetic papillopathy should be monitored closely.
diabetic retinopathy in pregnancy
30
There is a significant decrease in the retinal venous diameter and blood

flow in diabetic Pregnant women. This fall in retinal blood flow may
exacerbate retinal ischaemia and hypoxia and thus may be associated
with the progression of diabetic retinopathy. Pregnant women with
moderate to severe retinopathy at conception are at greater risk of
retinopathy progression. Retinopathy progression is increased in patients
with poor diabetic control and higher systolic blood pressure. Women with
diabetic retinopathy should have their diabetes and blood pressure well
controlled when they consider conception. In those patients with
moderate background retinopathy, fundus examination should be
performed at each obstetric visit and if progression is detected the patient
should be examined at 2 week intervals to detect any high risk
characteristics. If high risk characteristics develop photocoagulation
should be carried out.
Treatment
Poor glycaemic control seems to be a cause of clinically significant

macular oedema. The risk of developing clinically significant macular
oedema, in patients with type 1 diabetes, increases with poorer blood
glycaemic control. Some patients show progression of their diabetic
retinopathy shortly after establishing a strict diabetic control, which may
be due to the increase in blood flow of the retinal circulation, or to an
increase in serum insulin-like growth factor. Metabolic control in the
elderly diabetic patients with established diabetic retinopathy should be
instituted gradually. Insulin appears to have a more marked effect on the
choroidal blood flow more than on the retinal flow. Increased level of
insulin significantly increase choroidal blood flow and mean blood flow
velocity in the ophthalmic artery, but not the retinal blood flow.
Hypertension is now established as a major risk factor for the

development and the progression of diabetic retinopathy. Increased
retinal capillary perfusion is a major part in the pathogenesis of diabetic
retinopathy. Factors that increases the retinal perfusion (e.g.
hypertension, hyperglycaemia, and pregnancy), may worsen the
retinopathy, while other factors that decreases it, (e.g. carotid stenosis
and increased IOP), may protect the retina. Tight control on the blood
pressure (less than 150/85) has been shown to reduce the risk of
developing complications in diabetic retinopathy. In type 2 disease. In the
UK prospective diabetic study, a 10 mm Hg reduction in systolic and a
5 mm Hg reduction in the diastolic blood pressure was associated with a
47% fall in the risk of doubling the visual angle in 9 years.
The UK prospective diabetic study also showed that reducing the

pressure is the main factor, no matter what medications are used in
achieving that. Anti-hypertension drugs, mainly the ACE inhibitor group,
have a primary role in reducing retinal capillary leak and hypo-perfusion.
31
Reducing the blood pressure also appears to be associated with further

benefits to the cardiovascular system and the kidneys. The evidence that
tight blood pressure control is beneficial in type 1 diabetes is not as
strong as in type 2 disease. The target blood pressure for patient with
diabetic retinopathy is systolic and diastolic blood pressure equal or less
than 130/80.
In patients with diabetic retinopathy elevated serum lipid levels seems to

be associated with increased risk of having retinal hard exudate.
Lowering serum lipids may be associated with decreased risk of hard
exudate development and visual loss. The association of lipid lowering
agents with improvement of diabetic retinopathy, on the other hand, is not
known. Some recent reports indicate that lowering serum lipids and
cholesterol does not seem to affect the progression of retinopathy.
Pentoxifylline (a methyl xanthine derivative) that has been used in the

treatment of vascular insufficiency diseases because of it’s ability to
improve the blood flow. Oral administration of Pentoxifylline in healthy
volunteers produce a significant improvement in the retinal capillary blood
flow velocity and viscosity. It may be useful in the treatment of diabetic
retinopathy, and other vascular eye diseases.
• laser treatment
Laser photocoagulation is the main method of treatment of clinically

significant diabetic macular oedema. It is not exactly known how laser
photocoagulation works in reducing macular oedema. Reduction in
macular oedema may result from post-laser vasoconstriction, which occur
secondary to the improved retinal oxygenation caused by the laser
treatment. Pre-treatment fluorescein angiography may improve the
accuracy of laser treatment. Quantitative retinal thickness measurement
provide an objective method of assessing and monitoring laser treatment
in macula oedema.
Krypton, argon, and micro-pulsed diode lasers can be used in the

treatment of diabetic macula oedema. The main advantage of krypton red
over argon blue-green laser in diabetic retinopathy is the better
penetration of the red light through red blood or yellow lens nuclear
sclerosis. Diode laser has the advantage of being compact, portable,
easy to connect the main electrical supply and easier to cool than Argon
laser. Transscleral contact diode laser photocoagulation seems to induce
less disruption of the blood-retinal barrier than the conventional
cryotherapy in rabbits eyes.
Retinal laser photocoagulation is often carried out under topical

anaesthesia. Occasionally peribulbar injection may be needed in
extensive or very peripheral treatment. The use of topical sodium
diclofenac 0.1% eye drops may help in relieving pain during the
treatment.
32
Laser pulse of very short duration seems to affect the retinal pigment
epithelium mainly with no or little damage to the neuro-sensory retina or
the choriocapillaris due to the reduced thermal effect produced by this
type of laser. The Iris Ocullight Micro-Pulse 810 nm diode laser is a new
laser that has the advantage of a greater retinal pigment epithelium
specificity and less damage to the inner retinal layers. Visual field, and
colour vision loss appear to be reduced with this type of laser treatment.
Recent studies showed that this laser is useful in the treatment of
macular oedema in patients with diabetic retinopathy and vascular retinal
occlusive diseases.
Diabetic patients with proliferative diabetic retinopathy should be treated

aggressively with panretinal photocoagulation or cryotherapy or both.
The mechanism of action is not completely understood. It has been
suggested that panretinal photocoagulation is associated with a local
increase in the retinal and the pre-retinal oxygen tension, in the treated
areas, which causes vasoconstriction of the new vessels. Panretinal
photocoagulation is also thought to be associated by vascular narrowing
which might lead to the regression of the new vessels.
Regression of the proliferative diabetic retinopathy is known to occur in

about 93% of all treated patients. Regression of proliferative diabetic
retinopathy appears to be significantly related to the cumulative total
number of laser burns applied to the retina. Renal disease and age (<50
years) are risk factors for non-regression of retinopathy after panretinal
photocoagulation. Patients with diabetic nephropathy requires
considerably more aggressive treatment than patients with no
nephropathy. Hypertension, neuropathy, duration of disease and insulin
dependence seem to have no significant effect on outcome.
Poor prognostic factors after panretinal photocoagulation include the

presence of disc neovascularisation at base line, short interval between
the diagnosis of diabetes and the need for panretinal photocoagulation,
and earlier onset of diabetes. Patient with good visual acuity at
presentation seem to maintain a good visual acuity after one year, while
patients with poor visual acuity at onset seem to have poor visual
outcome. Vitreous haemorrhage, traction retinal detachment may still
occur after panretinal photocoagulation. Panretinal laser
photocoagulation may be associated with loss of the visual field of vision.
It may be possible to reduce the amount of visual field loss by altering the
pattern of laser photocoagulation.
Premacular haemorrhage is common in patients with proliferative

diabetic retinopathy. Most of these haemorrhages occur in association
with partial posterior vitreous detachment. The haemorrhages are often
slow to clear and may result in epimacular membrane or macular traction
retinal detachment. Division of the posterior cortical face by the YAG
laser has been used to achieve rapid intravitreal drainage of the
premacular haemorrhage. Laser application allows the trapped blood to
33
enter the vitreous where it quickly gets absorbed. Complete intravitreal

dispersion of the blood can be achieved in most eyes within one week.
The technique can be used instead of vitrectomy to allows an early
identification and treatment of any existing significant macular oedema.
• vitrectomy
Vitrectomy in diabetic patients has a valuable role in improving the

patient’s overall visual function, especially in patients with vitreous
haemorrhage, and traction retinal detachment, and some eyes with
intractable macular oedema. In eyes with diffuse diabetic macular
oedema and no posterior vitreous detachment, vitrectomy and induction
of posterior vitreous detachment may be effective in resolving the
macular oedema with improvement of visual acuity for up to twelve
months. Diabetic patients with fibrovascular proliferation affecting the
macular (without macular detachment) suffer from visual loss even after
full laser pan-photocoagulation. Pars plana vitrectomy in these cases
may preserve useful vision in most of the patient.
Pars plana vitrectomy for proliferative diabetic retinopathy may be

followed by vitreous haemorrhage. Intraoperative fluorescein
angiography may be useful in disclosing unusual findings in the extreme
peripheral retina and pars plana which might lead to vitreous
haemorrhage. The technique may aid intraoperative evaluation and
treatment of proliferative diabetic retinopathy. In eyes with persistent
vitreous haemorrhage, peripheral retinal cryotherapy stabilises the
peripheral retina and vitreous and also of the visual acuity in most
patients. Trans-scleral cryotherapy is often possible even in eyes with
opaque media.
34
Retina infection
and AIDS related disorders
CMV retinitis
CMV retinitis is the most frequent opportunistic eye infection in patients
with HIV infection. Low CD 4+ T lymphocytes (less than 50 x 106 / L), is
the most significant predictor for the development of CMV retinitis in AIDS
patients. Patients with low CD 4 counts and positive urine cultures have a
sevenfold increased risk of developing retinitis than patients who have
negative urine cultures. Patients with CMV retinitis and positive blood or
urine culture, during treatment, have greater mortality rates, and greater
risk of involvement of the second eye. The diagnosis of CMV retinitis
should also be considered in patients with immunosuppression (due to
disease or drugs) as well as patients with low T-lymphocytes count due to
HIV infection, cancer, or organ transplantation. The disease has also
been reported in 14.6% of patients after cardiac transplantation.
CMV retinitis patient often present with painless loss of vision in one or
both eyes. The diagnosis of CMV retinitis relies on the retinal
appearance. The typical retinal features of the disease include the
following:
1. The most common lesions are: micro-aneurysm (100% of patients),

followed by cotton-wool patches (70-92% of patients) and retinal
haemorrhages (12-40% of patients).
2. The eye is often white and quiet with little or no anterior chamber or
vitreous cells.
3. The disease is characterised by multiple distinct areas of retinal
opacification with irregular feathered borders.
4. The necrotic retinal areas often starts along the major vascular arcades
and enlarge with time.
The retinitis may also be associated with serous retinal detachment, CMV
papillitis, cystoid macular oedema and visual loss, and retinal
detachment. In the early stages of disease and in patients with atypical
features, it is difficult to differentiate between retinitis caused by CMV,
and retinitis associated with the other herpes viruses. Polymerase chain
reaction tests for CMV DNA in ocular fluids (e.g. aqueous humour) is a
sensitive method to use in doubtful cases. Cystoid macular oedema
and epiretinal membranes formation are major causes of poor visual
acuity in patients with AIDS even in the absence of active retinitis. This
maculopathy is often associated with mild vitritis. These macular changes
and the associated vitritis may be caused by the methods of treatment of
CMV retinitis.
Various changes in visual function have also been reported in the

absence of retinopathy in HIV-positive patients. A significant
35
percentage of HIV-positive patients with visual acuity of 20/20 or better

and no ophthalmologic evidence of retinitis have abnormal psycho-
physical tests.
A newly described syndrome characterised by a stable or slowly

progressive multifocal peripheral retinal infiltrates with mild uveitis and
vitritis has recently been described in HIV patients. The retinal lesion are
typically grey white, or yellow in colour, irregular in shape, and measure
less than 200 micron in diameter. They are often located in the mid
periphery or the anterior retina. The lesions may respond to treatment
with zidovudine. The visual prognosis of this syndrome is often good.
Uveitis in AIDS patients is often caused by opportunistic infection, e.g.

CMV, herpes simplex virus, herpes zoster virus, fungus or Toxoplasma
infection. It must be remembered that HIV patients may present with
vitritis as the only and initial manifestation of syphilis. Syphilis in these
patients should be treated as neuro-syphilis with IV penicillin G. Transient
intraocular inflammation may also be associated with anti-retroviral
medications. The inflammatory response, in these cases, may be due to
improvement in the immune mechanism. The inflammation seems to
subside spontaneously in most patients, but topical steroid treatment may
be needed in some cases. It should also be remembered that HIV
infection may also be associated with uveitis in the absence of any other
opportunistic infection. A trial of anti-retroviral treatment may be needed
in the uveitis does not respond to steroids treatment.
CMV retinitis may be associated with corneal endothelial deposits,

which are likely to represent a mild form of anterior uveitis rather than
direct infection of the corneal endothelium with the virus. IOP is lower
than normal in patients with HIV infection, with or without CMV retinitis,
which is important in evaluating and treating HIV patients for glaucoma.
the decrease in the IOP may be due to decreased aqueous production or
increased outflow.
CMV retinitis may be associated with other extraocular infections. In

patients with CMV retinitis, rising levels of CMV DNA in the blood may be
an indication of extraocular extension of the disease. Reactivation of the
infection may also occur in the absence of high CMV DNA levels. CMV
encephalitis may be associated with retinitis, particularly when the
retinitis involves the peripapillary region. In cases of suspected CMV
encephalitis, a retinal examination may support the diagnosis if retinitis is
present, if retinitis is absent other causes of encephalitis should be
considered. CMV infection can also cause colitis, oesophagitis,
encephalitis and pneumonia. The retinitis may follow extraocular
infections in AIDS patients. Maintenance treatment with protease inhibitor
drugs prolong the time interval between extraocular infection and ocular
involvement. Maintenance treatment with protease inhibitor drugs is
recommended in non-ocular infection.
36
The presence of a positive blood culture at the time of diagnosis of

retinitis is associated with a greater mortality rate, and the occurrence of
a positive blood or urine culture during follow-up is associated with the
development of cytomegalovirus retinitis in the second eye of patients
who initially had unilateral disease. Elevated CMV DNA blood levels may
indicate the development of CMV disease, the reactivation of an already
present disease, or the spread of CMV retinitis to extraocular sites.
Reactivation of CMV retinitis may also occur without changes in the DNA
blood levels.
treatment
The use of anti-retroviral agents (e.g. ganciclovir, foscarnet, and

cidofovir), in AIDS patient has lead to increased patient survival. At
present the main drugs available for the treatment of CMV retinitis are:
Anti-retroviral drugs HAART therapy

The main anti-retroviral drugs are: HAART therapy includes:
• ganciclovir (causes myelo- • Protease inhibitors e.g.
suppression and may result in ◊ saquinavir
neutropenia and ◊ retonavir
thrombocytopenia). ◊ nelfinavir
• foscarnet (nephrotoxic and may ◊ indinavir
result in electrolyte imbalance). • Reverse transcriptase inhibitors
• cidofovir (causes nephrotoxicity e.g.
and uveitis). ◊ zidovudine
◊ didanosine
◊ zalcitabine
Ganciclovir and foscarnet are often given intravenously with an induction

dose for 2 to 3 weeks followed by a lower daily maintenance dose.
Ganciclovir causes myelosuppression and may result in neutropenia and
thrombocytopenia, while Foscarnet is nephrotoxic and may result in
electrolyte imbalance.
Intraocular administration either by Intravitreal injection or by Ganciclovir

ocular implants may also be used as an alternative to intravenous
treatment in patients who cannot receive systemic treatment either due to
intolerance or due to the development of side effects to the drug or to
indwelling catheter. Intravenous treatment with ganciclovir or foscarnet
is associated with a relatively short period of remission. It may also be
associated with systemic complications, and complications related to the
presence of indwelling catheter.
Ganciclovir ocular implants, on the other hand, are associated with

longer remission periods (221 days compared to 71 days with IV
treatment). Treatment with the ganciclovir implants may, however, be
associated with involvement of the other eye, or with systemic
dissemination of the disease. Ganciclovir implants may be associated
37
with posterior segment complications (e.g. rhegmatogenous retinal,

vitreous haemorrhage, endophthalmitis, cystoid macular oedema) These
complications occur in 12% of the ganciclovir implant procedures and
may be associated with irreversible loss of vision. Ganciclovir implants is
less successful in the treatment of cases that recur after or despite IV
treatment. Longer treatment of preoperative IV ganciclovir or larger areas
of CMV retinitis is associated with lower success rate of ganciclovir
implants in recurrent cases. Treatment with potent anti-retroviral appears
to be effective in those patients with recurrent disease when ganciclovir
implants are used.
Cidofovir (HPMPC) is most potent and selective inhibitor of CMV in vitro.

The drug has excellent anti-CMV activity when administered
intravenously every 2 weeks. Nephrotoxicity, however, limits its dose.
There is also a potential for haematological toxic effects. Treatment and
maintenance with repeated intravitreal 20 microgram injection of Cidofovir
every 5-6 weeks appears to be highly effective with only rare episodes of
reactivation and progression of the disease. Acute intraocular
inflammation may occur with or without hypotony after intravenous and
intravitreal cidofovir therapy. The uveitis may be due to improvement in
the immune state of the patient. It often respond to treatment and should
not preclude the continuation of cidofovir treatment. Monitoring the IOP is
important after starting treatment with cidofovir. Continued treatment with
the drug is possible with the use of topical steroids and cycloplegic.
Concomitant use of probenecid appears to decrease the frequency of the
iritis from 71% to 18% after the first intravitreal injection. Probenecid
inhibits anion transport across the epithelial barriers and reduce renal
toxicity by decreasing renal tubular secretion of the cidofovir. Triple
therapy with, foscarnet and cidofovir, seems to be associated with
increase in the survival, decrease in relapses, and changes in the ocular
features.
CMV resistance to Ganciclovir or Foscarnet at the time of diagnosis of

CMV retinitis is uncommon. About 4% of patients, however, become
resistance to Foscarnet, and about 2% are resistant to Ganciclovir.
Clinical failure of intravitreal treatment with cidofovir for CMV retinitis may
be related to cidofovir resistance caused by prior ganciclovir or cidofovir
treatment. CMV isolates cultured from the blood and urine, may not
represent the CMV population in the eye.
HAART (Highly Active Anti-Retroviral Therapy), is a relatively new

approach for the treatment of CMV retinitis. It is characterised by using a
combination of nucleoside reverse transcriptase inhibitor as well as a
protease inhibitor. The current main protease inhibitors are saquinavir,
retonavir, nelfinavir and indinavir. The protease inhibitors inhibit cleavage
of the viral poly-proteins preventing HIV replication. HAART therapy
improves patient’s immune mechanism and is often associated with
reconstitution of CD 4+ cells and dramatic fall in HIV serum virus load.
38
A new syndrome called (immune recovery vitritis) has been described

in patients with CMV retinitis associated with the recovery of their
immunity after anti-viral treatment with protease inhibitors. The syndrome
consists of: vitritis, papillitis and cystoid macular oedema or epiretinal
membrane. Optic nerve head neovascularisation may also occur. The
syndrome is associated with visual morbidity and may respond to
steroids treatment.
Zidovudine is a member of the nucleoside reverse transcriptase

inhibitors drug that is used in the treatment of advanced AIDS disease.
Different side effects have been reported with the anti AIDS drug
Zidovudine e.g. anaemia, neutropenia, nausea, vomiting, myalgia, and
abnormal liver function tests. Temporary colour vision abnormalities have
also been reported with this drug. Tritan colour vision deficit is the main
colour vision abnormality associated with the drug. Didanosine is a purine
analogue drug. It may be associated with the drug include pancreatitis,
peripheral neuropathy, and retinopathy characterised by multiple well
circumscribed depigmented lesions in the mid retinal periphery.
The use of an HIV-1 protease inhibitors in the treatment of AIDS may

lead to complete regression of cytomegalovirus retinitis. HAART therapy
also increase the efficacy of anti-retroviral drug and delay the emergence
of resistance of CMV isolates. The routine use of protease inhibitors has
resulted in longer survival, higher CD +4 T lymphocytes, and improved
immune status in a large number of AIDS patients. AIDS patients with
advanced CMV retinitis may be started on treatment with potent anti-
retroviral drugs as well as intravenous anti-CMV drugs or ganciclovir
implants. The role of the anti-CMV drugs is to control the disease till the
potent drugs produce a sufficient improvement in the patient immune
status. Anti-CMV drugs may also be used in patients taking HAART
therapy if CMV retinitis develops or relapse or if there are signs of
decreased immune status.
discontinuation of the treatment
After starting treatment with combination therapy, it might be possible, in

some patients, to discontinue treatment for short periods of time.
Discontinuation of maintenance therapy may be considered in the
following patients:
• Patients with HAART-induced elevated CD 4+ counts above 100

cells/ul.
• Prolonged relapse-free intervals during the reconstitution period before
CD 4+ counts rise above 100 cells/ul.
• Completely quiescent retinitis characterised by RPE scarring only.
• HIV-positive patients with CMV retinitis, who demonstrate a sustained
HAART-induced elevation of CD 4 cell count on two consecutive
counts 3 months apart and whose retinitis remains healed on anti-CMV
39
therapy for greater than 4 months, are likely to remain healed if the
anti-CMV therapy is withdrawn.
Reduced risks of drug toxicity and drug-resistant organisms are potential

benefits. Close observation for evidence of recurrent retinitis is indicated.
It is important to monitor these patients with indirect ophthalmoscopy
because HAART failure may occur and allow CMV retinitis reactivation.
retinal detachment in CMV retinitis
The incidence of retinal detachment in CMV retinitis is between 17% to

34% with a high frequency of bilateral involvement. Most of retinal
detachments in theses eyes are of the rhegmatogenous type. The life
time risk of developing retinal detachment in patients treated for CMV
retinitis has been estimated to up to 50%. Eyes with peripheral retinal
involvement greater than 25% have a five fold risk of retinal detachment
compared to eyes with 10% involvement. If there is retinitis activity with
more than 25% involvement the risk of retinal detachment is 24 fold.
Vision is stabilised or improved in the majority of patient s after surgery.
Cataract and optic atrophy may develop in 29% and 22% of cases after
surgery.
Retinal detachment surgery in eyes with CMV retinitis is difficult because

retinal breaks, in these eyes, are often multiple, posterior, and difficult to
locate, through hazy vitreous, preoperatively as they are often present in
areas of necrotic and atrophic retina. Posterior vitreous separation may
also be incomplete and significant epiretinal membrane formation may be
present. These features have made vitrectomy and silicone oil
tamponade the treatment of choice for the majority of patients. Scleral
buckling, alone, often fails to treat the detachment in these cases.
Elimination of the scleral buckling procedure may reduce the time of
surgery and also reduce possible morbidity associated with this
procedure. The use of silicon oil in the retinal detachment repair in these
patients is effective, safe and delays or prevents loss of vision. The use
of silicone oil, rather than intraocular gas, as the retinal tamponade
agents has the advantage that prolonged face down positioning is not
required and visual rehabilitation is relatively rapid. Although the majority
of patients recover macular vision in the first 1-2 months after vitrectomy,
there is a gradual decline in acuity thereafter, sometimes without obvious
cause. It may be reasonable to postpone surgery until the macula
detaches and that patients whose fellow eye is free of retinitis with normal
vision are unlikely to have their quality of life improved significantly by the
surgery.
The use of laser photocoagulation alone may result in an excellent visual

outcome in some cases with peripheral localised detachments. Localised
retinal detachments involving less than quarter of the retina with less than
50% of the retina affected by the CMV retinopathy with macula sparing
may benefit from laser photocoagulation treatment. Laser
40
photocoagulation (demarcation) is useful in delaying or avoiding

vitrectomy with silicon oil surgery in some patients with CMV related
retinal detachment. Laser treatment may ultimately fail in many patients
but delaying vitreous surgery may be beneficial.
41
Progressive outer retinal necrosis (PORN)

Progressive outer retinal necrosis syndrome (PORN) is a recently
recognised variant of necrotising herpetic retinopathy. The disease is
characterised by the appearance of progressively enlarging multifocal
deep white grey retinal opacities scattered throughout the periphery of
the retina, with subsequent retinal vascular attenuation. Macular lesions
may also be present in about 32% of patients at presentation.
A history of cutaneous Zoster may be documented in 67% of patients.

Although the etiologic agent is reported to be VZV, HSV-1 can be an
etiologic agent in PORN. Patients often have less uveitis, vitritis, and
vasculitis than is seen in typical acute retinal necrosis. There is also a
tendency for the earliest visible lesions to occur in the posterior pole
rather than in the periphery. Involvement of the fellow eye even with anti-
viral treatment is over 70%. Patients with progressive outer retinal
necrosis also have a higher risk of developing encephalitis. Progressive
outer retinal necrosis can also affect immunocompromised patients due
to other causes. This condition has also been describe in immune-
competent patients with uniocular involvement. Treatment of progressive
outer retinal necrosis syndrome by acyclovir or ganciclovir has been
disappointed. Sorivudine is a new anti-viral with activity against varicella-
zoster. The drug my represent an effective alternative treatment for this
condition. The ability of sorivudine to inhibit VZV is about 1000 greater
than acyclovir
42
Acute Retinal Necrosis

Acute retinal neurosis is characterised by diffuse uveitis, occlusive retinal
arteritic, necrotising retinitis and vitritis. Acute retinal necrosis syndrome
may also present with orbital inflammation, proptosis and optic nerve
involvement. Some clinicians have restricted the use of the term acute
retinal necrosis syndrome to otherwise healthy patients. Others believe
that this restriction is unnecessarily. It is thought that if a patient has
clinical findings consistent with the syndrome, that the diagnosis should
be made regardless of the patient’s systemic health.
Although most reported cases have been caused by varicella-zoster

virus, others appear to be associated with herpes simplex virus, either
types I or II. A recent report showed that Varicella-Zoster virus and
herpes simplex virus type 1 cause acute retinal necrosis in patients older
than 25 years of age, while herpes simplex virus type 2 causes the
syndrome in patients younger than 25 years of age. Herpes simplex virus
is also likely to be the causative agent if there is an associated CNS
infection. ARN may also, rarly, occur in primary VZV infection
(chickenpox). The mode of retinal infection is unclear. Possible routes
include haematogenous or trans-neural spread to the retina.
The use of polymerase chain reaction based assay on vitreous specimen

is proved to be a useful tool in making the diagnosis. Several previous
reports have documented the association between acute retinal necrosis
and chicken box in healthy or mildly immune compromised patients and
also in patients with AIDS. The disease has been reported in pregnancy
during the second trimester. Treatment with acyclovir and interferon lead
to partial recovery of vision and no foetus abnormalities.
43
Miscellaneous retinal diseases
• Central serous retinopathy
Pathogenesis
The mechanism of central serous retinopathy is not completely known.

Recent indocyanine green angiography and scanning laser
ophthalmoscopy studies indicate that central serous retinopathy probably
originates primarily in the choroid. Hyper-permeability of the
choriocapillaris characterises all the stages of the disease and seem to
be the primary alteration of he disease. Localised choroidal ischaemia
can also be observed in other areas of the involved eye or in the other
fellow eye in some patients with central serous retinopathy. Capillary or
venous congestion after choroidal ischaemia may explain the choroidal
hyper-permeability observed in central serous retinopathy patients. A new
study suggested that some cases of presumed idiopathic CSR may be
due to a thrombosis of the choroidal circulation secondary to the primary
Antiphospholipid antibody syndrome.
A variety of risk factors have been associated with the development of

central serous retinopathy. These include psychological stress, type A
personality, hypochondria or hysteria, pregnancy, haemodialysis,
Cushing syndrome and systemic or intra-muscular corticosteroid use.
Clinical features and Treatment
Central serous retinopathy typically affects patients between 30 to 50

years old. It is now believed that there is greater range of ages of the
patients affected than previously though with a much lower male / female
ratio. Older patients who have a lower visual acuity are more likely to
have a diffuse retinal pigment epitheliopathy, have bilateral involvement
and secondary choroidal neovascular membrane than young patients.
Central serous retinopathy have the same features in women as in men.

it tends to develop in women in later age than in men. A significant
number of women who develop central serous retinopathy take
exogenous steroids, an observation which support the theory that
steroids may play a role in the development of this condition. In women
who take exogenous steroid, the central serous retinopathy is likely to be
bilateral and associated with subretinal fibrin. Central serous retinopathy
in pregnant women typically appear in the third trimester and
spontaneously resolve 1-2 months after delivery.
Serous pigment epithelium detachment have been reported in neonates

and also in premature babies. It is thought that the mechanism of his
condition is a dysfunction of the retinal pigment epithelium cells due to an
unknown lesion in the choriocapillaris. It is thought that the use of dilating
44
drops (e.g. phenylephrine) in premature neonates may induce changes in

the choriocapillaris causing secondary retinal pigment detachment.
Fluorescein angiography, indocyanine green angiography and Ocular

coherent tomography can be useful in the qualitative and quantitative
evaluation of patients with central serous retinopathy. Central serous
retinopathy may be associated with a plaque of sub-retinal hard exudate
without any choroidal neovascular membrane. The sub-retinal plaque
often overly an area of retinal pigment epithelium leak and often
disappear before or with the resolution of the sensory retinal detachment.
These exudates are believed to be fibrin in nature. When sub-retinal fibrin
is present, early laser treatment is encouraged if the leak is not sub-
foveal. The disease may also be followed by retinal vascular leak and
cystoid macular oedema This may be due to accumulation of sub-retinal
fluid leading to toxic breakdown of the retinal vessels or due to retinal
vascular leak caused by the hypoxic detached retina.
The disease often resolves spontaneously, however recurrence may

occur in up to 40% of patients. The disease may also become chronic
with extensive lesions and a poor final visual acuity, visual field defects
and sub-normal EOG. Central serous retinopathy may also present by a
bullous serous retinal detachment with subretinal exudate. The
detachment often resolves spontaneously with restoration of the visual
acuity. It is important to recognise this variant of the disease to avoid
unnecessary investigations and treatment. Central Serous
Chorioretinopathy with persistent and / or recurrent exudation may also
be difficult to differentiate from idiopathic polypoidal choroidopathy. In
these cases ICG angiography is useful in differentiating between the two
conditions.
The treatment of choice in patients with chronic central serous

retinopathy is by laser photocoagulation. Direct laser photocoagulation
of the leakage site(s) for CSR that persists for 4 months is safe and
effective to shorten the duration of the serous detachment to improve
final visual acuity and to decrease the incidence of recurrence. The
duration of the disease and the recurrence rate may be reduced by laser
photocoagulation. The lower recurrence rate associated with laser
treatment appear to be maintained for up 10 years or more. Systemic
steroids treatment is ineffective and dangerous as it may cause severe
exacerbation of retinal detachment associated with lasting visual loss.
Central serous retinopathy and steroids
Early morning, late morning and 24 hours urine endogenous cortisone

levels are increased in patients with central serous retinopathy when
compared to controls. Diffuse retinal pigment epitheliopathy may develop
in patients taking large doses of systemic steroids. The high levels of
cortisone may be responsible for the RPE barrier damage and
choriocapillaris changes that lead to this disease. In patients who are
45
susceptible, the periocular or systemic absorption of inhaled

corticosteroid may be sufficient to produce central serous retinopathy.
Patients in whom CSR develops while using corticosteroid inhalers or
nasal sprays should be alerted to the possible relationship between CSR
and these agents.
Central serous retinopathy has been associated with several other

conditions characterised by increased exposure to and / or enhanced
secretion of steroids. A high % of patients with endogenous Cushing’s
syndrome have one or more episodes of central serous retinopathy, in all
cases the episodes occur during a period when there is an increase
cortisone blood level.
Central serous retinopathy and beta blockers
Lesions similar to central serous retinopathy have been caused by

epinephrine injection in monkeys and beta-blockers have been
suggested as treatment. A prospective, randomised double-masked trial
compared the beta blocker nadolol to placebo in 16 patients with central
serous retinopathy. The data of the study suggested that nadolol may
have an adverse effect on the rate of resolution of central serous
retinopathy.
Central serous retinopathy and systemic disease
It is thought that choroidal vascular abnormality and secondary RPE

dysfunction may be the common mechanism for a group of diseases (e.g.
accelerated hypertension, pregnancy, haemodialysis, organ
transplantation and hyper-secretion of corticosteroid) that may present
with serous retinal detachment similar to central serous retinopathy. Most
patients do well but chronic central serous retinopathy and visual loss
may occur in some patients.
Systemic lupus erythematosus may rarely present with choroidopathy

with serous detachment. Central serous retinopathy has also been
described in patients with membrane-proliferative glomerulonephritis type
2.
46
• idiopathic polypoidal choroidal vasculopathy

Idiopathic polypoidal choroidal vasculopathy IPCV (also called posterior
uveal bleeding syndrome), is a rare condition characterised by:
1. A juxta-papillary (macular or peripheral) branching choroidal vascular

network with surrounding polypoidal aneurysmal dilatation.
2. Recurrent, multiple, and bilateral serous and haemorrhagic detachment
of the neuro-sensory retina and the RPE.
3. No macular drusen or intraocular inflammation.
There is a high incidence (85%) of polypoidal choroidal lesions, on

indocyanine green angiography, in white patients presenting with
haemorrhagic or exudative PED. Diagnosis of this condition and
differentiation from age related maculopathy is important as laser
treatment in this condition is often associated with good results.
The condition is commoner in females and may be associated with

systemic hypertension. Optical coherence tomographic images show that
some of the polypoidal structures are anteriorly protruding lesions in the
inner choroid. These lesions may cause detachment of the retinal
pigment epithelium. Sub-macular haemorrhage may also occur in some
patients. The differential diagnosis of this condition include various
causes of choroidal neovascular membrane.
The macular variant of this disease is characterised by recurrent

subretinal haemorrhage and exudates. It can be distinguished from other
causes of macular choroidal neovascular membrane by indocyanine
green or fluorescein angiography. Fluorescein and indocyanine
angiography often show the choroidal vascular network and RPE
detachment.
Laser photocoagulation may be used in cases with subretinal exudate

or fluid. Surgical excision of the subretinal membrane may be beneficial
in eyes with sub-macular haemorrhage associated with idiopathic
polypoidal choroidal vasculopathy.
The orange-red lesions in eyes with idiopathic polypoidal choroidal

vasculopathy have a more sharply peaked shape than serous retinal
pigment epithelium detachment, suggesting polypoidal vascular lesions in
eyes with idiopathic polypoidal choroidal vasculopathy are situated
beneath the Bruch’s membrane and covered anteriorly with both the
retinal pigment epithelium and the Bruch’s membrane.
Histological studies of removed tissues demonstrated fibrovascular

tissue between the retina and retinal pigment epithelium (type 2 pattern).
Visual prognosis is good, but vitreous haemorrhage and choroidal
neovascular membrane may lead to visual deterioration in some patients.
47
• retinal macro-aneurysm
Retinal macro-aneurysm are commoner in women in their sixth to eighth
decade. They are often located at the arteriovenous crossing or at
arteriolar bifurcation. Systemic hypertension, and arteriosclerosis have
been associated with the disease. Visual acuity may be compromised
due to the presence of macular or sub-macular haemorrhage, macular
oedema, or vitreous haemorrhage. The macro-aneurysm may be
associated with bleeding at the pre-retinal, intra-retinal, sub-retinal space
or in the vitreous. Indocyanine green angiography is useful in the
diagnosis when fluorescein angiography is inconclusive because of pre-
retinal, intraretinal, or subretinal haemorrhage.
The pathogenesis of retinal macro-aneurysm is not completely known. It

is thought that weakening of the retinal arterioles by a micro-emboli may
play a role in its pathogenesis. About 61% of patients with macro-
aneurysm are associated with atheromatous plaques in the ipsilateral
carotid artery. Carotid ultrasonography, and medical examination may be
important in patients with retinal macro-aneurysm.
The treatment of this condition is controversial. Some authorities advise

conservative treatment while others recommend laser photocoagulation
in cases with macular oedema. The treatment of associated sub-macular
haemorrhage may be difficult as the haemorrhage usually obscure the
aneurysm. Disruption of the internal limiting membrane by the YAG laser
may be useful in dispersing pre-retinal haemorrhage to the vitreous
cavity. Vitrectomy may be used in cases with thick pre-retinal
haemorrhage that may obscure a hidden intra-retinal or sub-retinal
haemorrhage. The use of plasminogen activator-associated thrombolysis,
and removal of the liquefied blood, in eyes with recent onset may achieve
better visual results. Pneumatic displacement of the subretinal
haemorrhage by injecting Perfluoropropane gas in the vitreous cavity
may also be used to displace the subretinal haemorrhage. Macular
haemorrhage secondary to retinal artery macro-aneurysms may also be
managed by observation alone, good visual acuity outcomes can often
be achieved.
48
• retinal vasculitis
Retinal vasculitis may occur as a manifestation of systemic disease (e.g.
Behcet’s disease, systemic lupus erythematosus syndrome, Wegener’s
granulomatosis, Ig A nephritis and sarcoidosis). It may also be a part of
ocular inflammatory process (e.g. bird-shot choroidopathy or pars
planitis). Infections (e.g. CMV retinitis, Lyme disease, syphilis and
toxoplasmosis) may also be associated with retinal vasculitis. Less
commonly retinal vasculitis may occur as an isolated primary condition.
In the absence of a medical history or systemic manifestation to suggest

an underlying disease, few diagnostic tests should be ordered as full
routine tests are likely to be costly and unrewarding and also because the
positive predictive value of some of the most commonly ordered test is
low. Potential false-positive results are also likely to cause confusion.
Idiopathic retinal vasculitis is an inflammatory condition of the retinal

vessels which predominantly affects young adults and which can lead to
blindness. Patients with primary retinal vasculitis represent a distinct
entity and are unlikely to manifest a systemic disease.
Retinal vasculitis may be Ischaemic type, or Non-ischaemic (leaky).

There is a high prevalence of thrombophilic abnormalities in retinal
vasculitis patients. Smoking may play a role in the aetiology of the
ischaemic type. Visual loss in retinal vasculitis is mainly due to CMO or
vitreous haemorrhage secondary to neovascularisation.
Ischaemic retinal vasculitis is associated with a worse visual outcome

than non-ischaemic cases (34% of patients compared to 6%). The
ischaemic type is often due to localised thrombosis. Fluorescein
angiography, full blood count and ESR, urine analysis, FTA-ABS test,
rapid plasma reagent and chest X ray are indicated in patients with
unremarkable medical history.
The significance of anticardiolipin antibodies in patients with isolated

retinal vasculitis is not known, increased prevalence of raised
anticardiolipin antibodies in patients with retinal vasculitis associated with
other diseases have been previously reported. Measurements of
anticardiolipin antibodies, in isolated retinal vasculitis, has no clinical or
pathological importance and is generally of limited value in the
management of these cases. Positive ANCA serology is found in a
spectrum of vasculitis disease including polyarteritis nodosa, microscopic
polyarteritis and Wegener's granulomatosis. Two main types are
recognised: c-ANCA, which has a high positive predictive value for
Wegener's granulomatosis, and p-ANCA, which is less specific but does
suggest a vasculitis condition.
Systemic steroids, with or without cyclosporin A are the main treatment of

retinal vasculitis. Azathioprine may also be used in combination with
49
systemic steroid. The drug seems to be useful in reducing relapses rate,

but it does not seem to be useful in reducing the dose of systemic
steroids. The drug does not appear to be associated with significant side
effects
50
• paraneoplastic syndromes
Three autoimmune paraneoplastic syndromes have recently been
described:
1. Carcinoma-associated retinopathy.
2. Melanoma-associated retinopathy.
3. Bilateral diffuse uveal melanocytic proliferation
BDUMP (rare).
Cancer associated retinopathy is an uncommon paraneoplastic

syndrome that often presents with visual loss, ring like scotoma, and
night blindness as well as retinal phlebitis and vitritis. In carcinoma
associated retinopathy there is degeneration of the retinal photo-receptor
cells and antibodies to the retinal protein recoverin. The highest reported
incidence of carcinoma associated retinopathy has been reported with
small cell carcinoma of the lung. In epithelial cancers associated
retinopathy (e.g. lung cancer) the onset is often gradual with progressive
retinal degeneration which may lead to extinguished ERG similar to
retinitis pigmentosa. Lung cancer associated retinopathy may present
before the diagnosis of cancer is made, unlike melanoma associated
retinopathy which often occur in already diagnosed patients.
Melanoma associated retinopathy MAR is a rare condition, distinct from

lung cancer associated retinopathy. The disease has been described in
cutaneous melanoma. Biological differences between the skin and the
uvea may explain its rare occurrence with uveal melanomas. The disease
is characterised by a sudden onset of night blindness and a central visual
field loss, rather than ring scotoma. Patients may also present with
bilateral central scotomas. ERG studies typically show dysfunction of the
rods system and normal cones system. Circulating antibodies to the
retinal bipolar cells are also often present. The disease occurs in patients
with metastatic melanoma. It is often acute and non progressive.
Treatment of this condition may be carried out by systemic steroids,
plasmapheresis, or intravenous immunoglobulin.
51
• ophthalmic side effects of sildenafil (viagra)

Viagra is a new medication that is prescribed to stimulate and enhance
penile erection. The drug acts by inhibiting phosphodiesterase-5 (PDE-5)
in the corpus cavernosum. The drug also inhibits PDE-6, in the retinal
photo-receptors, which controls the level of cyclic guanosine mono-
phosphate in the retina and control the process of transduction. The drug
may also have some vascular effects on the choroid and the retina.
Animal studies showed that viagra changes ERG only when used in very
high doses. Some patients receiving the drug may suffer from perception
of bluish haze and increased light sensitivity.
Recent reports showed that, patients with micro-vascular disease, may

develop third nerve palsy with pupil sparing with the use of the drug. The
mechanism of this side effect is not known, but it is thought that the
transient systemic hypotension associated with the use of the drug may
cause hypo-perfusion of the third nerve. Anterior ischaemic optic
neuropathy and transient changes in colour perception have also been
described in association with viagra. No persistent visual abnormalities
have been reported with using the drug. Patients should be counselled
about these side effects of the drug, especially patients with pre-existing
retinal or vascular diseases should be cautious in using the drug.
52
• congenital hypertrophy of the retinal pigment

epithelium (CHRPE)
Congenital hypertrophy of the retinal pigment epithelium (CHRPE) is
characterised by dark grey or black, flat round lesions at the level of
retinal pigment epithelium. The lesions are typically surrounded by halo of
de-pigmentation areas. CHRPE may rarely occur in the papillo-macular
area. Lesions in this area may undergo progression and affect the visual
acuity The retinal lesions may undergo progressive hypo-pigmentation,
enlargement of the lesions or new pigmented areas or linear streak of
pigment epithelium may appear adjacent to the old pigmented lesions.
Congenital hypertrophy of the retinal pigment epithelium can also spawn
a nodular growth that slowly enlarges, attains a retinal blood supply,
and causes exudative retinopathy and chronic cystoid macular oedema.
It is believed that the tumour probably represents either an acquired
adenoma or a reactive proliferation of the retinal pigment epithelium.
Multiple patches of CHRPE have been described in association with

familial adenomatous polyposis (Gardner’s syndrome). Familial
adenomatous polyposis is an autosomal dominant condition
characterised by the presence of thousands of polyps in the colon. The
adenomas in this condition is typically pre-malignant. CHRPE is identified
as a sensitive and useful marker of the disease. The CHRPE lesions in
this disease are typically oval pigmented lesions with pale halos in the
centre. Bilateral multiple patches of CHRPE is considered to be an early
marker of the familial adenomatous polyposis coli gene (chromosome 5q
21). A positive criterion for identifying the syndrome include:
• At least four lesions whatever their size, or

• At least two lesions one of which is large.
By using this new positive diagnostic criterion, fundus examination allows

early detection of children carrying the gene responsible for familial
adenomatous polyposis.
53
Vitreoretinal Surgery
posterior vitreous detachment

Posterior vitreous detachment can be classified into four types:
1. Complete PVD with vitreous collapse (with age related changes and
myopia).
2. Complete PVD without vitreous collapse (uveitis and central retinal
vein occlusion).
3. Partial PVD with thickened posterior vitreous cortex (proliferative
diabetic retinopathy).
4. Partial PVD without thickened posterior vitreous cortex (age related).
Posterior vitreous detachment is not limited to elderly patients only. In a

study of 861 patients under the age of 30 years, a complete posterior
vitreous detachment was found in 11%, and partial detachment in 17%.
In the first and second decades of life, the detachment was associated
with retinitis pigmentosa, non-diabetic retinal vascular diseases and
history of trauma or surgery. In the third decade of life, the detachment
was commonly associated with proliferative diabetic retinopathy. In high
myopia the risk of developing posterior vitreous detachment increases
with age and with the degree of myopia.
Detecting the posterior vitreous face by biomicroscopy is essential in

making the diagnosis of posterior vitreous detachment regardless of the
presence of Weiss ring or floaters. The presence of a Weiss ring or a
detached posterior vitreous face (regardless of the presence of Weiss
ring) is a definite sign of posterior vitreous detachment. Some eyes may
have posterior vitreous detachment without the presence of a Weiss ring
or floaters.
Prompt vitreoretinal examinations of patients presenting with floaters and

/ or light flashes is needed. The presence of both floater and flashing
lights represent a higher risk of developing posterior vitreous
detachment with retina breaks than patients presenting with either
floaters alone or flashes alone. Patients with posterior vitreous
detachment with vitreous pigments or haemorrhage are, also, at a
higher risk of have a retinal tear compared with those who have normal
vitreous examination. Aphakic eyes also have a higher risk of retinal
tears associated with posterior vitreous detachment and also a greater
risk of retinal detachments from such tears. Asymptomatic retinal
breaks detected in phakic primary eyes do not often show significant
tendency to develop retinal detachment. Posterior vitreous detachment,
in phakic eyes, may occur in the presence of a pre-existing retinal break
without provoking any further complications. Only a few of those cases
progress to sub-clinical retinal detachment. About 1% to 2% of all

asymptomatic tears, may need treatment.
The need for follow up of phakic patients with posterior vitreous

detachment is controversial. A recent study showed that in the absence
of retinal breaks, on initial examination and retinal indentation, further
follow up may not be necessary.
vitreo-macular traction syndrome

Vitreo-macular traction syndrome is characterised by incomplete
posterior vitreous detachment associated with persisting vitreous traction
on the macula. The syndrome represents a wide spectrum of vitreoretinal
anatomical configuration that may cause visual symptoms.
Macular traction frequently causes cystoid macular oedema and

decreased visual acuity, metamorphopsia, photopsia and micropsia.
Spontaneous complete vitreo-macular separation may be followed by
resolution of cystoid macular oedema and improvement in visual acuity.
Vitreo-macular traction may also be associated with macular pucker,
retinal blood vessels avulsion, retinal hole formation, and also traction
macular detachment. Vitreous surgery to release the macular traction
may result in an improvement of 2 or more lines of visual acuity in up to
75% of patients with about 40% of patients achieving a postoperative
visual acuity of about 20/50 or better.
Vitreo-papillary traction may also cause trauma to the disc vessels

causing intra-papillary and subretinal peripapillary haemorrhage, and
elevation of the optic disc. Evaluation of the posterior hyaloid face should
be an important part in the examination of patients with elevated optic
nerve head. The optic nerve function is often preserved. Myopic discs
may be particularly predisposed to this condition.
optic disc pit maculopathy

Optic nerve head pits are rare congenital anomalies that may be
associated with serous macular detachment in many patients in the
second or third decades of life. It has been thought that the origin of the
subretinal fluid is either liquefied vitreous or CSF passing through the pit
to the subretinal space. Recent indocyanine green angiography studies
suggests that the fluid comes from the vitreous cavity.
Genetic defect may play a role in the pathogenesis of this condition.

Congenital pits are often isolated, generally non-familial and unilateral
malformations. Unilateral optic pits may also be inherited in an autosomal
dominant fashion separate from mutations in the PAX2 gene which is
responsible for the renal-optic coloboma syndrome.
Optic disc pits may be associated with macular detachment in about 30%
to 45% of patients, especially if the pit is located at the temporal region of
the optic disc. Optical coherence tomography studies showed that retinal
detachment, that communicate with an optic disc pit, is most probably a
schisis-like separation of the internal layer of the retina with
detachment of the outer layers that occur later and is considered as a
secondary phenomena. The outer layer detachment start in the macula
without apparent communication with the pit. This explains the frequent
failure of laser photocoagulation to create a barrier between the disc pit
and the sub-retinal fluid. The dense central scotoma in optic nerve head
maculopathy relates to the outer layer detachment.
Treatment of the macular detachment either by pneumatic

displacement of the outer layer detachment from the posterior pole, or
by macular buckling procedure results in an improvement in the visual
acuity and may be associated with improvement in the central and
peripheral visual field. The scotoma related to the inner layer separation
may remain but it is often mild and consistent with relatively good visual
acuity.
stickler syndrome
Stickler Syndrome is an autosomal dominant disease characterised by
ocular, articular, facial, auditory and oral abnormalities. Ocular
features of the syndrome include myopia (about -5 D) with vitreous
degeneration and retinal detachment often with giant tears. Clinical
overlap with Marshall syndrome (Marshall syndrome is similar to Stickler
syndrome but without arthropathy), Wagner’s syndrome (Patients
infrequently have rhegmatogenous retinal detachment, but they often
have traction retinal detachments, empty vitreous, choroidal atrophy,
cataract and glaucoma.) and other hereditary vitreoretinal syndromes
exists. Refractive errors, cataract and vitreoretinal abnormalities can be
detected early in life in affected children.
Patients with Stickler syndrome are at higher risk of developing retinal

detachment. Retinal detachment in these patients often have poor
surgical prognosis. The reason for frequent "retinal detachments" in
these patients is thought to be related to the vulnerability of the retina and
the presence of lattice degeneration and retinal pigment epithelial
thinning. Almost all the vitreous cavity in these patients is congenitally
absent but a sheet of vitreous cortex exists and is often firmly attached to
the weak retinal areas. If the vitreous cortex sheet remains intact, retinal
tears might not lead to progressive retinal detachments, but if the vitreous
cortex is broken, progressive bulbous retinal detachments will occur.
Prophylactic laser photocoagulation has been used in patients with
Stickler Syndrome in a 360 degree fashion between the pathological and
the normal retinal or in a localised fashion to surround isolated lesions. It
is reported, however, that the incidence of retinal detachment is
significantly higher in the non-treated eyes than in the treated eyes. The
disease can be classified into two sub-types depending on the

vitreoretinal phenotype:
• Type I denotes all patients with congenital vitreous anomalies.

• Type II are patients without the congenital vitreous anomaly.
The disease has been linked to the gene coding for type II procollagen
(COL2A1) in about 2/3 of families. Type I patients show complete linkage
to (COL 2A1). Type II patients are not necessarily linked to (COL 2A1).
Type II disease is likely to be associated with other genes encoding other
collagen. Mutation at (COL 11A2) and (COL 11A1) have also been linked
to Stickler Syndrome without ocular manifestations. Mutation in the genes
encoding collagen XI can give rise to manifestations of Stickler Syndrome
but only mutation at (COL 11A1) seems to give rise to the full picture of
the Syndrome. New data suggest that mutation involving exon 2 of the
COL2A1 gene may lead to a predominantly ocular variant of the
syndrome with a high risk of retinal detachment. these data may be
useful in counselling patients.
Retinal detachment surgery

There is a high rate of satisfaction and improvement in the visual
functions among patients who have vitreoretinal surgery even in the
presence of good vision in the other eye. Preoperative visual acuity and
the duration of retinal detachment are the most important factors
associated with the return of central vision after surgery. If the macula is
attached preoperatively, there is 82% to 87% chance of retaining a good
postoperative visual acuity, whereas eyes with preoperative macular
detachment have only a 20% to 37% chance of regaining the same
visual acuity.
Death of retinal photoreceptors, in retinal detachment, is mainly due to

retinal hypoxia caused by the separation of the outer retina from the
retinal pigment epithelium. Preoperative hyperoxia may enhance retinal
function after surgery. It may also reduce the proliferation of Muller cells
and postoperative proliferative vitreoretinopathy.
Metamorphopsia is a sensitive indicator of previous macular detachment

even in the presence of normal central vision and normal colour vision.
Rhegmatogenous retinal detachment results in rapid and almost total
loss in the blue cones. Significant loss in the rods also occur but the red-
green cones, which are responsible for visual acuity, seems to be
resistant to damage. These findings may explain the observed blue-
yellow colours abnormalities in some patients, despite having a good
visual acuity.
prophylactic treatment of retinal tears

The effect of prophylactic laser photocoagulation in fellow eyes with
retinal tears and / or lattice degeneration has not be proved. Fellow eyes
with or without posterior vitreous detachment and retinal tears may
develop retinal detachment even after prophylactic laser treatment. Some
authorities believe that laser photocoagulation might actually precipitate
the formation of new retinal tears by increasing vitreous traction.
Prophylactic laser treatment is strongly recommended in symptomatic

flap tears. There is no strong evidence, in the literature, to support
prophylactic treatment in other types of tears. Prophylactic treatment has
been carried out with laser and / or cryotherapy. Many retinal surgeons
believe that cryotherapy may be associated with a greater incidence of
macular epiretinal membrane formation than with laser photocoagulation.
Recent reports showed that the incidence of epiretinal membrane after
prophylactic treatment is 10% with laser treatment, 14% with cryotherapy
and 18% with combined treatment. Argon laser retinopexy may also be
associated with corneal complications e. g. corneal perforation. Corneal
perforation may occur when a pigmented substance is present on the
corneal surface.
The semiconductor diode laser, Erbium : YAG laser and argon fluoride
laser have also been used in vitreoretinal surgery with promising results.
The semiconductor diode laser has the following advantages:
1. It can be applied through silicon buckling material.

2. Is associated with reduced blood-ocular barriers breakdown (when
compared to cryotherapy).
3. It can be applied in the presence of media opacities.
4. It does not seem to be associated with significant weakness of the
sclera (unlike with diathermy).
Demarcation laser photocoagulation has also been shown to be useful

in the treatment of acute or chronic, primary or recurrent shallow macula-
sparing rhegmatogenous retinal detachments without proliferative
vitreoretinopathy. A triple row of confluent laser burns should be applied.
The Erbium : YAG laser and argon fluoride laser are promising new
lasers for the precise tissue cutting with minimal damage to adjacent
tissues. The Erbium laser has the advantages of efficacy and precision of
tissue cutting as well as coagulation of vascular tissues, and can be
safely used in vitreoretinal procedures. Erbium:YAG appears to minimise
intraoperative forces and movements of intraocular structures and may
provide, therefore, a safer vitrectomy.
conventional scleral buckling technique

Uncomplicated retinal detachment is often treated with the scleral
buckling technique. Scleral buckling technique involves a certain degree
of surgical dissection and may have some limitations in patients with high
myopia, patients with posterior staphyloma and in re-operations. Scleral
indentation has been produced, in cadaver eyes, by using Holmium laser
with a fibre-optic delivery system. Holmium YAG laser provides an infra-
red light that is absorbed by the scleral causing shrinking the collagen
tissues and causing a buckling effect to the sclera. The amount of the
buckling effect can be controlled by controlling the laser setting. The main
advantages of this technique is the creation of a small, localised and
precise scleral buckling with minimum surgical dissection.
The surgical sequence during retinal detachment repair varies. The

sequences CDAE involves: Cryotherapy-Drainage-Air-Explant, the
sequences CDE involves: Cryotherapy-Drainage-Explant, while the
sequence D-ACE involves: Drainage, Air injection, Cryotherapy, and
Explant. In D-ACE retinal detachment surgery, it is important to obtain a
single gas bubble in order to achieve good visualisation. This can be
achieved by inserting the needle through the highest point of the pars
plana. The speed of gas injection is very important in achieving a single
gas bubble.
The two main types of retinal explants are silicon and hydrogel (MIRA)
explants. Complications, e.g. infection or extrusion seem to be more
common with silicon explants than with the hydrogel explants. Intra-
scleral complications are, however, common with hydrogel implants too
due to their expanding nature. Hydrogel explants have the advantages of
having a smooth surface, being porous with hydrophilic properties
enabling fluids and antibiotics to penetrate them. Progressive
encapsulation may also occur with all types of materials. Some hydrogel
explants may undergo microscopic breakdown inside the capsule
associated with giant cell foreign body reaction. Long term follow up is
recommended with both types.
Scleral buckling operations are known to cause postoperative squint in

some patients (with incidence rate from 3% to 57% of patients).
Restriction of eye movements are mainly due to adhesions between the
globe and the muscles, the bulk effect of the explant under the muscle,
disinsertion and retraction of a rectus muscle, or due to a direct injury to
the muscle. Removing the explant may not lead to resolution of the
muscle restriction. Vitrectomy with internal tamponade may be a better
option in patients who are likely to develop diplopia (e.g. macula on
detachments).
Scleral buckling may also be associated with postoperative raised IOP

especially with retinal encirclement. Patients having extensive scleral
buckling surgery for retinal detachment may benefit from prophylactic
Diamox treatment. Scleral buckling, with encirclement bands, may also
be associated with reduced retinal and choroidal blood flow on the
buckle side.
Surgery may cause corneal shape changes and may lead to

postoperative astigmatism. Encircling bands may be associated with up
to 3D of myopic shift in some eyes. Vitrectomy and all types of
circumferential scleral buckling surgery produce prolonged irregular and
asymmetric corneal shape changes. The patterns of the changes differs
depending on the buckling procedures used. Pneumatic retinopexy, on
the other hand, does not produce significant corneal shape changes.
Scleral buckles infection may occur in about 3%-5% of cases. The most
common organism identified has been staphylococci. Scleral buckling
infection may also be caused by methicillin resistant S. aureus in patients
with retinal detachment associated with atopic disease. Aggressive
treatment by removing the buckle, and vancomycin with vitrectomy, in
cases with endophthalmitis may be needed. Inadvertent scleral
perforation at the time of buckle placement may be complicated by
sympathetic ophthalmia.
Retinal detachment may be complicated with choroidal detachment.

Surgery in eyes with choroidal detachment is associated with poor results
because of the high incidence of postoperative proliferative
vitreoretinopathy. The postoperative proliferative vitreoretinopathy in

these eyes is mainly due to the breakdown of the blood-retinal barriers.
Aggressive perioperative treatment with oral steroids followed by pars
plana vitrectomy and scleral buckling may be more superior than using a
scleral buckling technique alone. Sympathetic ophthalmia may occur
after retinal detachment surgery. It is important to recognise the
significance of bilateral uveitis following surgery, since early diagnosis
and vigorous treatment of sympathetic ophthalmia can be associated with
a good visual prognosis.
pneumatic retinopexy
Pneumatic retinopexy is a relatively new technique for repairing
uncomplicated retinal detachment. The technique appears to be gaining
popularity during the last few years. Pneumatic retinopexy involves
intravitreal injection of an expansile gas in association with cryotherapy or
laser photocoagulation, without the use of scleral buckling. The classical
indications of this technique has been:
• Retinal detachment due to a tear located in the upper two thirds of the
retina.
• Retinal detachment due to several retinal breaks within one hour.
• Pneumatic retinopexy has also been described in the treatment of
progressive rhegmatogenous retinoschisis.
The success of pneumatic retinopexy depends on proper case selection.

In phakic eyes, this technique appears to be associated with higher
complications rate than the scleral buckling procedure. A high incidence
of new inferior postoperative retinal tears has been shown by some
studies. The final anatomical and visual outcome, after repeated surgery,
appears to be equal with both pneumatic retinopexy and scleral buckling
techniques. The technique may also be complicated by dehiscence of
clear corneal incisions after recent cataract surgery. Pneumatic
retinopexy technique may be more economic than scleral buckling
technique even in cases with repeated surgery.
pars plana vitrectomy

Conventional scleral buckling procedures in pseudophakic eyes are
complicated by re-detachment and proliferative vitreoretinopathy. Pars
plana vitrectomy (with or without scleral buckling) is an effective method
for treating uncomplicated rhegmatogenous retinal detachments in these
eyes. The technique is particularly useful when the retinal view is poor
and also when internal tamponade is needed to close difficult tears.
Vitrectomy in pseudophakic eyes has a better success rate (94%) than
conventional surgery. Primary vitrectomy has the advantage of better
viewing of the peripheral retina, better removal of vitreous traction and
better application of endolaser treatment.
Posterior capsule opacification is about 400% greater in eyes containing

foldable silicon IOL than in eyes containing PMMA IOL. If vitreoretinal
surgery is anticipated, PMMA IOLs should initially be considered, in
cataract surgery, instead of a silicon IOLs. When an eye contains silicon
oil as well as a silicon IOL, posterior capsulotomy should be carried out at
the end of the vitrectomy operation in anticipation of posterior capsule
thickening.
Moisture condensation during fluid gas exchange may also occur on the
posterior surface of PMMA and silicon IOL. The condensation is more
marked in the presence of a posterior capsulotomy, it may limit the view
of the retina during the operation, and may diminish the patient's visual
acuity afterwards. Heparin coated IOL does not seem to prevent IOL
adherence to silicon oil. It has been suggested that the use of a pre-
chilled balanced saline solution, for the infusion fluid, may prevent the
moisture droplets formation.
Pars plana vitrectomy may also be beneficial in other types of retinal

detachment. In children with complicated retinal detachment, lens-
sparing vitreoretinal surgery, with silicon oil tamponade, has been
proposed as a treatment of choice for vitreoretinal disease in eyes with
attached peripheral retina and non-extensive retina-lens adhesions.
Retinal detachment secondary to choroidal coloboma is difficult to treat
with conventional scleral buckle technique. Pars plana vitrectomy and
silicon oil tamponade seems to be the treatment of choice. Gas
tamponade seems to have a limited value in this condition.
surgical considerations
Poor pupillary dilatation is a major problem during vitreoretinal surgery.
The adverse effects of mydriatic agents (to maintain mydriasis peri-
operatively during prolonged vitreoretinal procedures) are well
documented. They include severe hypertension subarachnoid
haemorrhage, ventricular arrhythmia’s, and myocardial infarction. Suture
fixation of the iris, iris retractors, or the use of a trans-pupillary continuos
suture with a straight 16 millimetres needle mounted on a 10/0 Prolene
suture have been described. In the trans-pupillary continuos suture

technique, the needle enters through the pars plana and exits through the
corneal scleral limbus on the opposite side across the anterior chamber
stretching the pupil in it’s path. The needle is then passed in a similar way
about 6 times to achieve complete pupillary dilatation.
Relieving vitreous traction is an important part of vitreoretinal surgery.

Complete removal of the cortical vitreous from the retina surface is often
difficult particularly in children. Plasmin has a fibrinolytic action that can
hydrolyse a variety of glycoproteins. It can be used to produce a
cleavage at the vitreoretinal interface between the posterior vitreous
cortex and the internal limiting membrane.
At the end of pars plana vitrectomy the sclerotomy site is traditionally

closed with 8/0 sutures. Water-tight wound closure is sometimes difficult.
Maintenance of IOP during wound closure could also be difficult
especially in inferior sclerotomy during the removal of the cannula. Pars
plana vitrectomy can be performed through self-sealing sutureless
sclerotomy. This technique allows wound closure with good IOP control.
A half depth scleral tunnel incision is created for about 2 mm towards the
limbus by a sharp crescent shape knife. Pars plana sclerotomy is
considered to be a potential site for complications (e.g. peripheral traction
retinal detachment, retinal tears and traction of the ciliary body causing
hypotony and recurrent vitreous haemorrhage) in vitreoretinal surgery.
These complications may be attributed to fibrovascular proliferation at the
sclerotomy site High frequency ultrasound biomicroscopy may be used to
evaluate entry sites after pars plana vitrectomy.
Internal retinal tamponade is often carried out by:
• Gases (air, SF6, C3F8).

• Silicon oil.
• Perfluorocarbon liquids.
The use of gas tamponade after fluid-gas exchange is an important part

of modern vitreous surgery. Gases can be used in vitrectomised and non-
vitrectomised eyes (e.g. in pneumatic retinopexy and in the D-ACE
technique). Gas injection is also used with vitrectomy in order to flatten
the retina and remove any subretinal fluid with the flute needle. The most
commonly used gas is air. Air is rapidly absorbed (2-3 days). Sulphur
hexafluoride SF6, and Perfluoropropane C3F8 are the other gases
commonly used when more prolonged internal tamponade is required.
The length of time that a gas remains in the eye depends on its
concentration, and the volume injected. SF6 can last for about 10 days
inside the eye, while C3F8 can last for about 28 days.
Postoperative posturing is needed after gas injection to place the gas

bubble under the retinal tear. It has been thought that the use of nitrous
oxide anaesthesia produces an increase in the size of the intraocular
gas (C3 F8) bubble, with a subsequent rise in intraocular pressure. This
has led to the practice of discontinuing nitrous oxide at least 15 minutes
before gas-fluid exchange in vitreous surgery to allow clearance of
nitrous oxide from the body. Recent studies suggest that general
anaesthesia using nitrous oxide does not adversely affect the size of the
C3 F8 gas bubble 24 hours after surgery.
Silicone oil can also be used in retinal tamponade. The silicone oil study
confirmed the superiority of silicone oil to Sulphur hexafluoride (S F6)
gas as an intraocular tamponade for the management of retinal
detachment complicated by advanced grades of proliferative
vitreoretinopathy. Silicon oil injection may also be indicated in cases of
giant tears, when postoperative posturing can not be achieved (e.g.
children), in only eye patients as postoperative visual acuity is better with
silicon more than with gas, and in CMV retinitis. Postoperative hypotony
is also less common after silicon use.
Silicon oil may be complicated with intraoperative passage of the oil to

the subretinal space or to the anterior chamber in aphakic eyes.
Postoperative glaucoma, keratopathy, and corneal de-compensation may
also occur. Postoperative glaucoma, due to oil in the anterior chamber,
develops in 10% of patients even after several years. Postoperative
gonioscopy may be helpful in identifying eyes at risk of developing oil
related glaucoma. In vitrectomised eyes having long term retinal
tamponade with silicone oil, inferior peripheral iridotomy can reduce the
forward migration of the oil and help to prevent secondary keratopathy,
and pupillary-block glaucoma. Retinal toxicity may also develop.
Silicon oil has a refractive index of 1.4 which is higher than that of the
vitreous, and can cause a high hyperopic shift in phakic eyes which
may lead to amblyopia and esotropia when used in young children.
There have been some concern about the stability of silicon material in
the body. Some women developed immunological disorders after silicon
breast implants. Highly purified silicon oil in the eye, on the other hand,
seems to be chemically stable in cases with prolonged retinal
tamponade.
Intraocular silicone oil may migrate out of the eye, along the intracranial
portion of the optic nerve, and into the lateral ventricles of the brain. A
case of a 42-year-old man with AIDS and a rhegmatogenous retinal
detachment has recently been described. The patient developed
peripheral neuropathy and MRI features of an intracranial shifting fluid
that has the same imaging properties to the intraocular silicone oil.
It is strongly recommended that complete removal of the silicon oil

should be attempted at least 8 weeks after injection to reduce the
incidence of complications. In proliferative vitreoretinopathy re-
detachment may occur in about 33% of eyes after the removal of the oil,
often within the first 3 postoperative months. The risk of re-detachment

decreases with increasing time after oil removal. It is unlikely that the
retina will re-detach 5 months after removing the oil. Prophylactic argon
laser retinopexy 3-6 weeks before the removal of the oil seems to reduce
the incidence of the re-detachment. Silicone oil removal can be combined
with cataract surgery. Trans-pupillary drainage of silicone oil through a
planned posterior capsulotomy is an alternative method for the removal
of silicone oil to pars plana sclerotomy.
Perfluorocarbon liquids are clear fluids that have low viscosity, heavy
specific gravity, and different refractive index to water. Perfluorodecalin is
another substance used in vitreoretinal operations for giant retinal tears.
Intraocular perfluorodecalin may be tolerated by the retina for up to 6
months. It may be used in combination with silicone to achieve retinal
tamponade in retinal detachments with inferior and superior breaks. The
two substances have different densities, perfluorocarbon liquids supports
the inferior retina, while silicone oil supports the superior lesions. An
intermediate area of the retina, between the two substances, may not get
in contact with either substances and may develop proliferative
vitreoretinopathy.
Proliferative vitreoretinopathy (PVR)

The most common cause of retinal detachment surgery failure is the
development of proliferative vitreoretinopathy (it occurs in 7%-10% of
eyes). The time interval between the onset of the PVR and the onset of
the retinal disease ranges from 2 weeks to 45 months (average 2
months). Patients with proliferative vitreoretinopathy are at increased risk
of developing vision threatening conditions in the fellow eyes e.g. acute
retinal detachment, proliferative vitreoretinopathy and age related
maculopathy. Significant risk factor for the development of proliferative
vitreoretinopathy, after primary vitrectomy, are preoperative proliferative
vitreoretinopathy, aphakia, and high vitreous protein levels.
Proliferative vitreoretinopathy results from cellular activities within the

vitreous, e.g. dispersion or migration of certain cells within the vitreous
cavity, proliferation of theses cells, synthesis of extra-cellular matrix and
contraction of this matrix causing retinal detachments. MRI examination
of the blood-retinal barrier shows that barrier breakdown is an important
and early factor in the developing of proliferative vitreoretinopathy.
Cryotherapy in eyes with giant retinal breaks is likely to enhance
dispersion of retinal pigment epithelium cells in the vitreous..
Growth factors (fibroblast growth factor and platelets derived growth

factors) play a major role in the pathogenesis of the formation of
proliferative vitreoretinopathy. Growth factor blocking agents may pay a
role in the treatment. There is also some evidence that an immune
response may be involved. Adjunct treatment with steroids, and 5-FU,
has been tried. Intra-vitreous injection of Triamcinolone in rabbits eyes
reduces the barrier breakdown and proliferative vitreoretinopathy
formation. Intravitreal injection of steroids at the end of vitreoretinal
surgery may prove useful. Intravitreal 5-FU inhibits the progression of
proliferative vitreoretinopathy in animal models, with no significant drug
related corneal complications.
The herpes simplex virus thymidine kinase gene (suicide gene) is

known to cause selective cell death by inhibiting DNA synthesis. The use
of the virus gene with ganciclovir in animals with experimental
proliferative vitreoretinopathy was associated with reduction in the
proliferative vitreoretinopathy in some studies. A single short term
exposure to thiotepa or 5 FU may be useful in inhibiting collagen
contraction and RPE cells proliferation, and thus reducing proliferative
vitreoretinopathy.
Postoperative use of oral 13 cis-retinoic acid (a potent inhibitor of the

retinal pigment epithelium proliferation), appears to decrease proliferative
vitreoretinopathy and increase the rate of retinal reattachment in
vitreoretinal surgery.
Macular hole surgery

mechanism and natural course
Macular holes are often idiopathic. Other causes of macular holes include
trauma, myopia, and solar maculopathy. The development of macular
hole can be classified into 4 stages:
stage features
stage 1 central yellow spot (stage 1 A), or a yellow ring (stage 1 B)
at the fovea with loss of the foveolar depression.
stage 2 an eccentric crescent shape full thickness retinal defect
with pseudo-operculum.
stage 3 a round central retinal defect with an overlying free pseudo-
operculum.
stage 4 similar to stage 3 but with a posterior vitreous detachment.
The mechanism of macular hole formation is not completely understood.

It has been hypothesised, by Gass, that shrinkage and tangential
traction of the peri-foveal vitreous cortex induces traction detachment of
the foveola and the fovea which may result in full thickness macular hole
formation. It has therefore been thought that complete vitreous
detachment may give protection against the development of full thickness
macular holes. Tangential traction which causes macular holes appears
to originate mainly in the premacular vitreous cortex that forms the
posterior wall of a premacular liquefied pocket. Gass also hypothesised
that Muller cells may possibly play an important role in the pathogenesis
of the disease. He hypothesised that Muller cells layer is the primary
structural support for the fovea, and may be the primary site of retinal
changes causing the pathognomonic features of foveomacular schisis.
Recent optical coherence studies, on the other hand, showed that in

fellow eyes posterior hyaloid detachment begins around the macula, but
the hyaloid remains adherent to the foveolar centre, producing an
anteroposterior traction forces. This anteroposterior traction forces
results in an intraretinal split evolving into a cystic space, and then to the
disruption of the outer retinal layer and the opening of the foveal floor,
thus constituting a full-thickness macular hole.
Full thickness macular holes seem to be associated with few systemic

risk factors. Some studies demonstrated some relationship of macular
hole formation and changes in hormonal balance around the menopause
period, and also relationship to previous hysterectomy and
oophorectomy, and the use of oestrogen as HRT.
A recent study showed that approximately 34% of all eyes with macular
holes have an increase in the size of the hole. During a follow up period
of 3 years 84% of stage 2, 55% of stage 3 and 16% of stage 4 macular
hole undergo enlargement. Visual acuity also decreases by 2 or more

lines in 30%, 68%, 29%, and 13% of macular hole stages 1, 2, 3, and 4
respectively. In the presence of posterior vitreous detachment, it is
unlikely that stage 1 holes will progress to stage 2. Other studies showed
that visual acuity remains stable in about 40.9% of eyes.
The rate of development of a new macular hole during follow-up in fellow

eyes that are unaffected at baseline is about 4.3% for 3 or fewer years of
follow-up, and 7.1% for 6 or more years of follow-up. Spontaneous
regression may occur in 8.6% of patients in a follow-up period of 6 or
more years. Spontaneous closure may occur due to a spontaneous
release of vitreous traction, constriction of an epiretinal membrane or due
to pigment epithelial hyperplasia. Closure or constriction of the macular
hole may be associated with improvement of the visual acuity of the
patient. Improvement in the visual acuity is greater in eyes in which
macular holes disappear within 24 months.
Epiretinal membrane occur in about 65% of patients with macular hole.

The prevalence is greater in pseudophakic than in phakic eyes. It also
increases with increasing severity of the hole. The presence of
membrane does not seem to be correlated with visual acuity.
The true nature of macular hole operculae is not completely understood.

Analysing the vitreous in most patients after surgery does not show any
evidence of cellular or fibro-cellular elements in the vitreous. This
suggests that operculae rarely if ever contain retinal elements. Many
investigators believe that operculae, in this disease, is better called
pseudo-operculae. On the other hand, a recent study of stage 3 macular
hole identified two distinct types of macular hole operculum:
1. Operculum containing only glial tissue (pseudo-operculum), that is

thought to results from a failed attempt at macular hole formation. The
presence of pseudo-operculum indicates evidence of vitreo-foveal
separation and is considered a favourable prognostic sign with low risk
of developing a macula hole.
2. Operculum containing glial and foveal cones, neurites and synaptic
complexes (true operculum). Successful anatomical and functional
results may occur in both type. Loss of macular tissue in the true
operculum eyes may explain the worst success rate and the more
modest visual improvement in these eyes even after complete
anatomical success.
In another histopathological study of vitreous samples removed during

macular hole surgery retinal and cellular membrane fragments were very
rarely found. The absence of cellular membrane fragments in the majority
of cases suggests that mechanisms, other than cellular proliferation, are
important in the pathogenesis of macular holes. The study also found that
operculae rarely contain retinal fragments, and the authors suggested
that the term pseudo-operculum is better used.
fellow eyes
2% of the normal fellow eyes develop full thickness macular holes, and
25% of the eyes that have pre-macular holes changes develops full
thickness macular hole. The macular hole in the fellow eyes often
develop within 24 months. Fellow eyes with separation of the posterior
hyaloid membrane in the foveal region appears to be protected from
future macular hole development. Patients with attached hyaloid
membrane in both eyes are at higher risk of developing macular hole in
the fellow eyes. Patient with separated hyaloid membrane in the macular
hole eyes only with attached membrane in the fellow eyes are at
intermediate risks.
Ultrasound examination can be helpful in determining which of the fellow

eyes is at higher risk. When the posterior hyaloid membrane is
completely attached to the retina surface, it can not be seen
ultrasonically, it becomes visible when it is separated from the retina
surface by more than 500 micrometer. Electrodiagnostic and psycho-
physical tests do not seem to be able to predict the outcome in the fellow
eyes. A tritan colour contrast sensitivity loss at base line, in apparently
normal eyes, may indicate sub-clinical foveal dysfunction.
management
The differentiation between true full thickness macular holes and pseudo-
macular holes may be difficult. Fundus auto-fluorescence is known to
arise from the retinal pigment epithelium. Auto-fluorescence imaging with
confocal scanning laser ophthalmoscope is a non-invasive and rapid
technique which can be used for the evaluation, staging, and the
differential diagnosis of macular hole.
Idiopathic macular holes may be treated by vitrectomy with fluid gas

exchange with or without the use of transforming growth factor-beta-2. In
the absence of posterior vitreous detachment, as in traumatic macular
holes in children, posterior vitreous detachment can be induced by the
injection of autologous Plasmin. Surgical treatment may result is
anatomical closure and improvement in the visual acuity even in long-
standing macular holes.
The use of recombinant TGF beta-2 does not seem to be necessary,

similar results have been reported in patients who had TGF beta-2 and
patients who received placebo. Injection of an autologous platelet
concentrate over the macula during surgery for stage 3 and 4 macular
holes of less than 3 years duration improve the anatomic success rate.
The final visual acuity is, however, not better than without platelet.
Postoperative positioning of patients is very important in achieving good

results. Peeling of the internal-limiting membrane is traditionally carried
out in cases of macular pucker. A recent retrospective study showed that

routine peeling of the membrane in all cases may achieve good result
with short postoperative periods of posturing. Air tamponade may also be
enough in cases with internal-limiting membrane peeling. Silicon oil
tamponade may be used with good anatomical results in patients who
can not properly position after the surgery.
Surgery for longstanding macular hole may be beneficial in some

patients even after 12 months of onset. The rate of anatomical success
seems to be the same but visual acuity improvement is more likely in the
recent onset holes. After surgery, complete closure of full thickness
macular holes seems to result from proliferation of the Muller cell and
fibrous astrocytes. This seems to occur whether adjuvant treatment is
used or not. Histopathological studies show that the edges of the hole
approximate after treatment and the remaining gap seems to be sealed
with Muller cells.
Although overall anatomical closure success rates of macular holes is

reported to be between 56% and 100%, a significant number of holes
remain open after initial vitrectomy. Re-treatment with rigorous
membranectomy and autologous serum administration is beneficial in
most eyes in which initial macular hole surgery has failed. Final visual
acuity improvement seems to be less than after successful primary
closure, due to the longer duration of holes with failed primary surgery.
Re-opening of a successfully repaired macular hole may occur in about

5% of cases. In a recent study macular hole reopening occurred in 9.5%
of cases. In most of the cases, no definite cause was evident. This
phenomena does not appear to be related to cataract surgery. Re-
operation in these cases results in good visual results similar to those
obtained before the re-opening. Laser photocoagulation to the macular
hole bed has also been described. Stimulation of the RPE is thought to
release different cytokines that may promote healing. Persistent and re-
opened macular hole after surgical treatment may also be treated with
argon laser photocoagulation to the hole bed, and fluid-gas exchange.
Anatomical closure of macular holes can be achieved in a high

percentage of patients. Smaller number of patients, on the other hand,
demonstrate improvement in the Snellen visual acuity, as a high
percentage of patients develop postoperative cataract and visual field
loss. Visual loss in macular holes are thought to be due to loss of the
retinal function in the area of neuro-sensory defect as well as reduction in
the retinal function in the surrounding area. After surgery, patient may
have some visual distortion and metamorphopsia without any evidence
of a subjective scotoma .
The use of Snellen visual acuity chart alone to measure functional

success may underestimate patient satisfaction. Other methods of
assessment include:
• Biomicroscopic examination of the fundus.

• Scanning laser ophthalmoscope examination.
• Micro-perimetry.
• Optical coherence tomography.
• ERG.
Micro-perimetry performed preoperatively show an area of absolute

scotoma that correspond to the size of the neuro-sensory defect
surrounded by an area of relative scotoma. After surgery, areas with
absolute scotoma disappear, and most eyes show partial or complete
resolution of the surrounding relative scotoma.
Optical coherence tomography can be used in the postoperative

evaluation of macular holes repair. Patients can be classified into one of
three pattern: U type, associated with normal foveal contour and best
visual acuity, V type, associated with steep foveal contour and
intermediate visual acuity results, and W type, associated with foveal
depression of the neuro-sensory retina and the worst visual acuity.
Greater foveal thickness appears to be associated with better
postoperative visual acuity.
Focal macular ERG significantly improves after surgery. The

preoperative b-wave implicit time measured with 5 degree spot,
correlates significantly with the postoperative improved visual acuity. A
new method of differential perimetry that involves objective study of the
retinal photoreceptors displacement and metamorphopsia has also been
described. Patients with full thickness macular holes shoe evidence of
centrifugal photoreceptors displacement.
complications
1. Nuclear cataract formation is common after pars plana vitrectomy.
Phacoemulsification and posterior chamber IOL is a safe and effective
technique of removing the cataract in these patients. A posterior
capsule plaque is often present. It is sometimes difficult to remove the
plaque safely. Postoperative thickening of posterior capsule is also
common in these patients.
2. About 36% of patients with macular hole develop increase in the IOP
after vitrectomy. There are several causes of IOP rise; these include;
pupil block, migration of the oil to the anterior chamber, inflammation,
and pre-existing glaucoma. The IOP rise may also be due to
expansion of the gas bubble, reduction of the aqueous humour
outflow, or due to reduction of the uveoscleral outflow caused by the
scleral band. Anterior chamber angle closure may also be responsible
in some eyes. Glaucoma often occur in the first postoperative week.
IOP rise and treatment seem to occur only for a short period. The use
of topical aqueous suppressant seems to be useful in preventing IOP
rise after pars plana vitrectomy with long acting gas tamponade.
extended therapy may be needed in some patients. Aggressive
treatment is often needed by oil removal, trabeculectomy, glaucoma
shunts, or cyclodestructive procedures. All these methods may,
however fail in controlling the IOP.
3. Visual field abnormalities may occur after vitrectomy and gas-fluid

exchange. The most common visual field defect is a dense, wedge
shaped temporal defect. The mechanism of visual field defects is not
completely known. They may be caused by manipulation and trauma
to the peripapillary blood vessels or the nerve fibre layer during
elevation of the posterior vitreous face or aspiration during the gas-fluid
exchange process. Occlusion of the peripapillary blood vessels by
compression, and dehydration injury to the nerve fibre layer during
fluid-air exchange may also play significant role in the mechanism of
visual field loss. The field defects that occur after room air is used may
result from desiccation of the retina by the room air. Some studies
showed that passing air, used for fluid–air exchange, through
water seems to prevent the development of visual field defects in
these eyes. It has also been suggested that confining peeling of the
posterior hyaloid face to the macular area, and avoiding membrane
peeling in the peripapillary area may reduce the risk of inducing visual
field defects.
4. Retinal detachment is a recognised complication after vitrectomy for

macular hole (the rate of postoperative detachment varies from 1-14%
in different reports). Prophylactic scleral buckling may reduce the rate
of postoperative detachment.
5. Ulnar nerve neuropathy may occur with patient’s positioning after

macular hole surgery. Patients and surgeons should be caution in
minimising the amount of time the elbow is bent, and also the pressure
exerted on the bent elbow.
Paediatric Ophthalmology
Amblyopia and screening

Amblyopia may be due to strabismus, anisometropia or due to visual
deprivation. Previous studies showed that abnormal level of hyperopia
(more than 3.5D in one or more meridian) is frequent in children.
Anisometropia, larger or equal to 3.00 D at one year of age persists till
the age of ten years in 90% of cases and will be associated with
significant risk of amblyopia.
It is not known if pre-school screening results in a better visual outcome

than screening children at school. Recent studies indicate that pre-school
orthoptic screening does not seem to have an influence on the age of
detection of squint or squint amblyopia but may achieve a significant
reduction in the age at which amblyopic eyes and refractive errors are
diagnosed. The overall prevalence of amblyopia at age 7 seems to be
similar in the children who were screened at 3 years old and controls. On
the other hand, a significant number of children, without amblyopia, but
with reduced vision due to uncorrected refractive error may be detected
by pre-school screening.
The majority of amblyopic children detected by pre-school screening

seem to achieve good visual outcome by hospital treatment. Poor
compliance of patients follow up has been a problem in many studies. A
family history of visual defect seems to have a protective effect on
individual infants, most probably because more of these infants are
brought in for a check-up at an early age on the parents initiative.
Amblyopic eyes, when compared with normal eye, have more

widespread VEP abnormalities. The fellow eyes also show some
abnormalities mainly in pattern reversal P100 amplitude, the pattern-
offset P110 amplitude, and the pattern-offset n165 latency. These
abnormalities may be due to occlusion therapy. Automated perimetry
shows that all types of amblyopia are associated with a generalised
depression of light sensitivity, which is correlated with visual acuity loss.
Amblyopia is not associated with any area of focal loss of threshold light
sensitivity. If a focal defect is present in the visual field of the amblyopic
eye, organic causes of visual loss should be suspected.
refraction
Cycloplegic refraction is often needed in children, especially in children

with esodeviation. Topical administration of cyclopentolate can be
associated with CNS symptoms, e.g. confusion, psychosis, cerebellar
dysfunction and seizures. Gastrointestinal disturbances in neonates and
generalised urticaria have also been reported. The use of

proxymetacaine prior to cyclopentolate results in a less traumatic
experience for the small children. Fundus examination may be helpful in
assessing the refractive error in young children. In young children, the
finding of abnormal disc shape should alert the physician, because
abnormal disc shape may be associated with corneal astigmatism. The
direction of the longest disc diameter seems to indicate the axis of the
corneal astigmatism. Abnormal disc appearance in children warrant
refraction to avoid the possibility of amblyopia.
auto-refraction
Refraction in children may be difficult due to poor co-operation. There is

an increased acceptance of auto-refraction use in clinical practice by
patients and physicians due to its speed, accuracy, and reproducibility.
The use of advanced automatic refractors, in children and adult refraction
seems to comparable or superior to subjective retinoscopy in accuracy
and speed. Automatic cycloplegic refraction may safely be used to
prescribe glasses in children. The instrument does not have to be used
by doctors, but can safely be used by a technician. Hand held infrared
auto-refractor (e.g. Retinomax auto-refractor), is a useful and quick
method, that may be used to diagnose abnormal level of hyperopia
without the use of cycloplegia.
photo-screening
A significant limitation of traditional screening techniques for young

children is their reliance on subjective response. Photo-screening, a new
and an acceptable technique for detecting the presence of absence of
certain vision disorders from a photograph. The technique eliminates the
subjective element and allows vision screening of preverbal children. Two
types of photo-refraction systems have been used, they differ in the
placement of the flash source:
• the on-axis system (coaxial flash)

• the off-axis system (eccentric flash).
The coaxial type is more accurate but it is more complicated to use

because it needs several photos taken from different distances. The off-
axis system is cheaper but it can not detect astigmatic errors and has
less accuracy than the on-axis system.
Photo-refraction in infants 3 months of age or younger is particularly

difficult. In black infants, photo-refraction is often improved after
cycloplegic application. The technique is associated with a wide
variability in the sensitivities and specificity which may be due to
inconsistent photograph interpretation skills or deficient screening
guidelines or both. Caution should be taken in relying on photo-screening
in detecting strabismus and refractive errors in children. The technique
can also be used for screening for refractive errors in young patients with
learning disabilities is effective.
Strabismus
infantile esotropia and exotropia
Infantile esotropia occurs before the age of 6 months. Prematurity, low

birth weight, low Apgar scores, and a family history of strabismus are
significant risk factors for congenital esotropia. While monocular visual
acuity is relatively unaffected in these patients, the majority of patients fail
to achieve normal stereopsis.
Children presenting with infantile exotropia and esotropia appear to be at

risk for having other ocular or systemic disease. In a study of 70
patients diagnosed with exotropia in the first year of life, 67% of patients
had a coexisting ocular or systemic abnormality. In the same study ,
about 49% of patients diagnosed with esotropia before 1 year of age also
had coexisting abnormalities .
The association between Dissociated Vertical Deviation DVD and

infantile esotropia ranges from 50% to 90%. It is possible that infantile
esotropia may consist of two distinct subgroups: one consisting of
esotropia with DVD, latent nystagmus and asymmetrical OKN and
another group without these features. These two subgroups may have a
different pathophysiology and prognosis.
Dissociated Vertical Deviation is thought to be due to lack of stability of

fusion. Several factors are believed to be included in the pathogenesis of
DVD. These factors include disorders in the optomotor transmission
pathway, disorder in the optic chiasm or abnormal visual sensitivity.
There is no one single successful operation for the correction of the

dissociated vertical deviation. The standard operations are:
1. Large superior rectus muscular recessions,

2. Conventional superior rectus recessions combined with posterior
fixation suture (Faden procedure ).
3. Recession of the ipsilateral inferior rectus muscle with or without
superior rectus muscle recession. Large superior rectus recessions are
currently the preferred surgical method of treating DVD, with a success
rate of 72%.
4. Anterior transposition of the inferior oblique is an effective treatment for
dissociated vertical deviation with an inferior oblique over action, but it
may be less stable in the long-term when the pre-operative dissociated
vertical deviation is more than 15 prism dioptres.
5. Inferior oblique resection and anterior transposition of both muscles
may also be used in the treatment of asymmetric DVD and inferior
oblique over-activity.
Surgical treatment of infantile esotropia may be followed by amblyopia. In

some reports amblyopia was reported to be less common in untreated
patients compared to a similar group of surgically treated patients. This

low incidence of amblyopia in untreated patients may be due to the
presence of cross fixation and bilateral macular stimulation.
The risk of developing amblyopia is outweighed by the chance of

developing a better binocular vision. Postoperative follow up to avoid
amblyopia is, however, very important. When access to postoperative
follow up is not possible, it is advisable that surgical treatment for infantile
esotropia with alternating deviation, and no anisometropia should be
postponed till later years. Psychological difficulties resulting from squint,
may occur in school children, teenagers and adults. Correction of squint,
even in adult age, may offer an improvement in the psychological
functions of patients.
There is a potential for the development of some form of binocularity if

appropriate ocular alignment is achieved early in life. It has been thought
that amblyopia must be treated and reversed before surgical treatment of
esodeviation. Recently it has been suggested that surgical alignment of
the esotropia within the first 6 months of life may improve the
development of binocularity. Surgical treatment for esotropia in children
before full resolution of amblyopia is, now, thought to be safe and
effective if the amblyopia therapy is continued after the operation.
In a study of 103 treated patients with infantile esotropia, the outcome of

treatment was classified into the following groups:
1. Subnormal binocular vision.

2. Microtropia.
3. Small, cosmetically acceptable angle.
4. Large cosmetically unacceptable angle.
In this study, all eyes in group 1 remained aligned after a follow up period
of 8 years. 20% of the eyes with microtropia and 26% of eyes with small
angle squint lost the stability of ocular alignment during the follow up
period. After surgery to infantile esotropia, the best result that can be
expected is a mono-fixation syndrome with a residual small angle of
esotropia and peripheral fusion.
Failure to align the eye and treat amblyopia in young age may result in
poor vision for the rest of the patient life. Surgery in adults age not only
eliminates ocular alignment deformity but can also improve fusion and
increased field of binocular vision. Binocular field expansion occur in the
great majority of adults with esotropia after squint surgery, even if the
squint is long-standing. The expansion appears to be consistent with the
degree of straightening the eye and not related to the type (infantile or
acquired), duration of squint, visual acuity or history of squint surgery in
childhood.
accommodative esotropia
Most children with refractive accommodative esotropia have an excellent

outcome in terms of visual acuity and binocular single vision. In most
patients the degree of hyperopia remains unchanged with poor prospects
for discontinuing glasses wear. In accommodative esotropia, the classic
teaching indicates that surgery should be used to correct only the part of
esodeviation that is not corrected by full cycloplegic glasses. Some
reports suggested that correcting the whole angle of squint (when
measured without glasses) or an average angle (an average angle when
measured with and without glasses) may lead to reduction of the
hyperopia afterwards.
The prism adaptation test can be used to determine the potential for
binocularity before surgical alignment of the squint. Patients with
esodeviation are fitted with a base out prism to correct the angle of
squint. Testing for binocularity is then carried out after sometimes of
wearing the prism. Full surgical correction is then planned if there is
evidence of binocularity. The test can also be used to determine the
target angle that should be corrected. Prism responders show a better
motor outcome as well as better fusion after surgery than eyes operated
on before wearing prism.
exodeviation and Intermittent exotropia
Intermittent exotropia typically occurs late in childhood. This type of

squint may be difficult to treat. High rates of recurrences may follow
surgical treatment and repeated surgeries may be needed.
Patients ability to control intermittent exotropia deviation is often

assessed by subjective means e.g. observation of eyes control in the
clinic, questioning the patients or the family, and reports of mono-ocular
eye closure in the bright light. Patients with intermittent exotropia
demonstrate significantly worse distance stereo-acuity than the normal
subjects. Diminished distance stereo-acuity seems to be an objective
measure of poor control of the deviation. This test may provide important
objective criteria for deciding when to perform surgery in patients with
intermittent exotropia. Most of the patients with poor distance stereo-
acuity preoperatively have dramatic improvement, after the operation, in
their distance stereo-acuity.
In the treatment of intermittent exotropia, the conventional teaching is to

correct refractive errors (e.g. anisometropia, astigmatism and myopia) to
improve the retinal image and promote fusion and also to stimulate
accommodative convergence. Hyperopia is not usually corrected on the
assumption that, without correction, children are forced to accommodate
and that the associated accommodative convergence might be
beneficial. A trial of spectacle correction may be warranted in exotropic
children (between 2-10 year old) with severe hyperopia (more than 5.D)
and also in those patients with moderate hyperopia and a low

accommodative convergence / accommodation ratio.
The angle of squint in patients with intermittent exotropia undergoing

surgery should be measured for an outdoor target and after one hour of
monocular occlusion. Surgery should be carried out for the largest angle
measured.
surgical treatment
• recession-resection surgery
Surgical alignment of congenital esotropia can be achieved with either

bilateral medial rectus recession, or by medial rectus recession/lateral
rectus resection surgery. At least one additional surgical procedure is
required on average to maintain alignment in the first 10 years after initial
successful surgery.
The degree of change of ocular alignment per millimetre of rectus muscle

recession seems to correlate to the degree of preoperative esodeviation
or exodeviation. The degree of changes also correlate significantly and
inversely with axial length of the eye (larger eyes have smaller
responses). This correlation does not appear to be clinically significant.
8 millimetres medial recti recession can correct up to 80-90 prism

dioptres of esodeviation with no clinically significant limitation in
adduction. However, muscle recession beyond the tangential point may
result in mechanical restriction of ocular movements.
Most ophthalmologists prefer augmented medial rectus muscles

recession than operating on three or four muscles for large angle
esodeviation. It is easier and safer to perform large recessions by using
(hang back) sutures whereby the muscle is re-attached to the sclera at
the original muscle insertion and not at the new recession site. Mersilene
and Teflon material have also been tried as muscle implants. In animal
studies the Mersilene implants seem to induces a severe fibroblastic
reaction, while the result of the Teflon implants appear to be more
promising and, suggest that this material may be used as a spacer in
squint surgery.
A and V patterns esotropia have often been treated by recession of the

medial rectus muscle with vertical transposition of the new insertion.
Slanting muscle insertion technique can also be used as an alternative in
A or V esotropia without over-action of the vertical muscle. In A pattern
the upper margin of the recessed medial rectus muscle is recessed more
than the lower margin and vice versa in V pattern esotropia.
Squint surgery may be followed with the following complications:

• Endophthalmitis. Endophthalmitis after paediatric strabismus surgery is

rare. Children may not show symptoms. Lethargy, asymmetric eye
redness, eyelid swelling, or fever in the postoperative period, even if
initial postoperative examination results are normal, should prompt
urgent ocular examination.
• Postoperative pain.
• Permanent diplopia.
• Anterior segment ischaemia.
• Anisocoria.
• Lower eyelid retraction.
• Postoperative nausea and vomiting.
Postoperative pain after squint surgery can be managed by the

administration of topical anaesthesia drops at the beginning and at the
end of the operation or by sub-conjunctival bupivacaine (0.5%).
Intractable diplopia may occur after over-correction of exotropia. It may

also occur if the inferior oblique muscle has accidentally been included
into the lateral rectus muscle during surgery to the lateral rectus muscle.
A vertical deviation or a deficiency of vertical rotation are significant
indicators of the involvement of the inferior oblique muscle into the lateral
rectus muscle insertion. Careful dissection during surgery is important as
re-operation to free the inferior oblique muscle often fails.
Anisocoria May occur after routine squint surgery. A significant mydriasis

May be observed in the operated eyes in some patients. It is thought that
these changes in the pupillary diameter result from the release of neuro-
transmitters from the tissue damage during the surgery. Other possible
causes May be iris ischaemia. The pupillary changes seem to be
independent of the number or the type of extra-ocular muscles surgery.
Lower eyelid retraction may occur after inferior rectus muscle recession
because of the intimate anatomic correction between the inferior rectus
muscle and the lower eyelid retractors. Wide dissection around the
inferior rectus muscle or advancement of the Capsulo-palpebral head to
counter the forces created by the recession of inferior rectus are new
techniques to avoid this complication. Primary infra-tarsal eyelid
retractors lysis is also an effective technique to prevent lid retraction. This
procedure seems to be effective in large inferior rectus muscle
recessions (up to 10 mm).
Postoperative nausea and vomiting is a major problem in paediatric

patients undergoing strabismus surgery, and can prolong hospitalisation.
It is thought that the oculo-cardiac reflex is a major cause for this
complication. Orbital infiltration of anaesthetic solutions may reduce the
incidence of postoperative vomiting by blocking the afferent limb of the
reflex. It is possible that and sub-Tenon injection may also has the same
effect. The prophylactic fentanyl-droperidol prolongs recovery time and
provides no benefit over acetaminophen alone in children. Cost-
effectiveness analysis strongly favours the use of acetaminophen over

fentanyl-droperidol prophylaxis in children undergoing primary strabismus
surgery. Many authors also recommend routine intraoperative opiate
analgesia and prophylactic anti-emetics
• adjustable suture surgery
The adjustable sutures technique has many advantages. This technique

is thought to be more suitable in cases when traditional surgery has
unpredictable results e.g. paralytic squint, previous surgery, dysthyroid
eye disease, and squint surgery in eyes with scleral buckles. Adjustable
sutures surgery is generally considered to carry no greater risks than
standard squint surgery. The technique may also be successfully used in
children with horizontal squint, especially in re-operation cases.
The adjustment is often carried out to the recessed muscle. Accurate

adjustment may be difficult in eyes where performing a cover test might
be difficult due to poor fixation. Suture adjustment is often carried out
about 5 to 24 hours after surgery when the patient has recovered
completely from the anaesthesia, the results of suture adjustment at both
times seem to be similar. The adjustment may be made difficult by the
vasovagal effects of extraocular manipulations and the patient feeling of
nausea. In adult patient, the use of intravenous anaesthesia using an
infusion of propofol and mivacurium may enable the surgeon to carry out
suture adjustment immediately after surgery in the operating room.
Ocular alignment may drift with time following adjustable sutures surgery.
Delayed adjustment may be needed. Interseed is an absorbable
cellulose material that is designed as a surgical adjunct to reduce
postoperative adhesions. It may be useful in delaying the time of
adjustment after adjustable suture surgery for up to one week. Interseed
shows a promise as a method of delaying the formation of postoperative
adhesions and delaying the time of adjusting the sutures for up to one
week
• botulinum toxin in squint surgery
Botulinum toxin injection induces muscle palsy without causing damage

to the rectus muscle or the peripheral nerve. The toxin has a long
duration of action of 2 to 4 months. A localised injection to a specific
extraocular muscle could achieve paralysis of the muscle without
inducing unwanted side effects.
There is controversy concerning the efficacy of Botulinum treatment in

establishing satisfactory motor alignment in patients with infantile
esotropia. Botulinum toxin is believed, by most ophthalmologists, to be
very helpful in treating small under-corrections and over-corrections
following conventional strabismus surgery. It is also believed to be more
effective when given within 3 months after surgery.
in intermittent and constant exodeviation, botulinum toxin injections to the

lateral rectus muscles appears to be as effective as surgical treatment in
children 2 to 4 years old. Toxin treatment is effective irrespective of the
squint angle, it does not seems to be associated with complications or
secondary abnormalities of the muscles.
Botulinum toxin injection may also be used in paralytic squint.. Toxin

injection of the medial rectus muscle with full temporal tendon
transposition of the ipsilateral superior and inferior rectus muscles seems
to be the most effective treatment for chronic sixth nerve palsy.
Other promising indications for Botulinum toxin therapy include its use in
adults exhibiting a small angle intermittent esotropia and exotropia with
symptomatic diplopia. Temporary partial ptosis and unwanted vertical
deviations may sometimes occur.
Miscellaneous
acute acquired concomitant esotropia
Acute acquired concomitant esotropia is a rare condition characterised by

the sudden onset of a large angle concomitant esotropia and diplopia in
association with good binocularity and no or minimal refractive errors,
and no evidence of lateral rectus weakness. The condition has been
previously classified into three subgroups:
1. Group 1 (swan type): characterised by acute onset of diplopia after

occlusion
2. Group 2 (Franceschetti type): associated with minimal hyperopia with
no accommodative element.
3. Group 3 (Bielschowsky): in which the esotropia is associated with
myopia.
It has been thought that this condition is often benign and harmless.
Recent reports however showed that this condition may be associated
with CNS tumours and hydrocephalus. De-compensation of a pre-
existing phoria or a mono-fixation syndrome are also commonly
associated with this disease.
The management of this condition is controversial. It has been thought

that the presence of abducting nystagmus, a V pattern of deviation, or
failure to re-establish binocularity after alignment, should be considered
as risk signs of a possible CNS disease. A recent report, on the other
hand, showed that no clinical sign is reliable in the differentiation between
benign and CNS related disease. Investigation of a possible CNS
disease is essential in the absence of significant refractive error or in the
presence of any CNS manifestations. Binocular function is also expected
to be present in CNS related conditions.
Surgery has always been considered as the treatment of choice in these

cases. Botulinum toxin therapy may also be used in the treatment of this
condition. It may obviate the need for squint surgery.
microtropia
Microtropia or mono-fixation syndrome indicates the presence of a

macular scotoma with binocular vision. Patients may or may not have a
small angle of deviation. The condition may be classified into:
• primary, with no history of strabismus.

• secondary, following the treatment of a larger angle strabismus.
It has been believed that microtropia is always a static condition, with

visual acuity of about 6/9 as the optimum results that can be achieved. It
has been shown, recently, that treatment may result in improvement in
the visual acuity to levels of 6/5 with high grades of stereo-acuity.

Elimination of the condition is also possible in some cases.
Treatment may include maximum refractive correction with occlusion

therapy. It is thought that for patients who recover good visual acuity a
period of normal development must have preceded the onset of the
disease during which normal retinal correspondence was established.
strabismus with myopia
In adult patients with unilateral or bilateral high axial myopia, esotropia

and hypotropia may develop. The cause of this restrictive type of
strabismus is not understood. Numerous theories about the cause of
acquired esotropia and hypotropia in high myopia have been published.
Progressive neurogenic palsy, structural extra-ocular muscles changes
and myositis have all been suggested. Another hypothesis assumes that
the large globe compresses on the lateral rectus muscle leading to its
atrophy (which also results in medial rectus muscle fibrosis in long
standing cases). Atrophy of the orbital wall may also contribute in
decreasing the protective effect to the lateral rectus muscle.
Surgical treatment of this restrictive motility is often problematic. Magnetic

resonance imaging study in high myopia may give additional information
on orbital anatomy and bio-mechanical mechanisms of strabismus, and
may be useful before strabismus surgery in these patients. The path of
the lateral rectus, in the anterior and mid-orbital regions, was shown, in
some patients with typical esotropia and hypotropia, to be displaced
downward an average of 3.4 mm. If this misalignment of the lateral rectus
is detected by MRI, a common high dosage recess-resect procedure for
esotropia may even aggravate the deviation. Fixing the lateral rectus in
the physiological meridian at the equator with a silicone loop (guide
pulley) or a non-absorbable suture seems to be successful. This results
in a better alignment and improves abduction and elevation.
Retinopathy Of Prematurity
(ROP)
introduction
There is a slight trend to improvement in the survival of premature

neonates who are treated with prophylactic surfactant. The increased
survival rate does not appear to be associated with any significant
difference in the incidence of acute ROP in the long surviving treated
patients. The increased survival of premature infants with and without
retinopathy of prematurity causes a long term problem in terms of
increased incidence of ocular complications. Many of these babies have
other impairments and place considerable demands on health and
educational services in the community. The onset of involution of acute
retinopathy of prematurity correlates better with postmenstrual rather than
with chronological age. Retinopathy begins to involute at a mean of 38.6
weeks postmenstrual age. Retinopathy of prematurity that is present only
in zone III during a child's serial retinal examinations is never associated
with the development of a partial or total retinal detachment.
basic science
A new hypothesis for the development of ROP has been described. In

eyes with ROP. The vascular endothelium growth factor (VEGF) is
produced in the part of the retina anterior to the developing blood
vessels. Exposure of neonatal animals to hyperoxia is associated with a
loss of VEGF production and this leads to cessation of the growth of
developing blood vessels. The decrease in VEGF expression by
hyperoxia is also associated with hyperoxia-induced vasoconstriction
which can be inhibited by supplemental VEGF. As the retinal
development proceeds, the metabolic demands of the avascular retina
increases and the retina becomes more hypoxic. In response to hypoxia,
VEGF production is increased and this stimulates abnormal
neovascularisation from the retina. If VEGF production persists, the ROP
progresses and if it decreases, regression of ROP can occur. It seems
that VEGF does not only cause abnormal vascularisation, but it is also
important for normal development of the blood vessels. Appropriate
timing of intervention to increase or decrease VEGF production by the
retina might prevent blinding complications in ROP.
Many risk factors have been associated with the development of ROP.
The following risk factors have all been associated with a higher risk for
the development of ROP:
• Lower birth weight (birth weight of less than or equal to 1500 grams).
• Younger gestation age (gestational age of 28 weeks or under).
• White race,
• Oxygen toxicity,
• Exchange blood transfusion during the neonatal period.
• Patent ductus arteriosus.
A relationship between light exposure and the development of ROP has

been suggested. Some reports showed that a reduction in light intensity
reduces the incidence of ROP in infants with birth weight less than 1000
grams by about 25%. Some reports, on the other hand, showed that
patching of eyes from birth to 35 weeks of post-conception age does not
seem to decrease the risk of ROP in pre-term infants when compared
with controls. Advanced ROP has also been reported in patients with
congenital cataract severe enough to greatly reduce the amount of light
exposure of the retina. It seems that the role played by light exposure is
probably not as important as prematurity, low birth weight and oxygen
treatment.
The effect of multiple gestation pregnancy on the severity of ROP is not

well defined. Recent report showed no difference between single and
multiple gestation pregnancy on the severity of the disease. Antenatal
steroid treatment has been shown to decrease the neonatal mortality
and decrease the incidence of respiratory distress syndrome. It also
appears to reduce the severity of intra-ventricular haemorrhage, and also
the incidence of stage 2 or higher ROP.
clinical features
The disease can be divided into five stages:
Stage 1: Flat retina with a white demarcation line separating

vascular from non-vascular retina
Stage 2: A ridge
Stage 3: A ridge + extra-retinal fibro-vascular proliferation
Stage 4: Exudative or traction retinal detachment with or without
macular detachment
Stage 5: Funnel shaped total retinal detachment
Each stage can also be either a (+) disease or not. A (+) disease indicate
a more advanced disease and poorer prognosis. The features of a (+)
disease are:
1. Vitreous haze
2. Marked vascular shunting
3. Dilated veins and arteries seen in the posterior pole
4. Iris vascular engorgement
5. Poor pupillary dilatation
The retinal changes can also be located into 3 zones. The more posterior
the zone of ROP and the greater the extent of disease, the greater the
unfavourable outcome will be. The 3 zones are:
Zone I :A circle centred at the optic disc with a radius twice the disc-
macula distance (8 mm)
Zone II: From zone I to the nasal ora serrata nasally and to an equal
distance temporally.
Zone III: Anterior to zone II temporally.
Premature birth is also associated with abnormal refractive errors

(anisometropia, myopia and astigmatism). There is a linear growth in
axial length during the neonatal period in premature infants. Premature
infants with ROP have shorter axial length. Higher degrees of ROP seem
to be associated with shorter axial length and higher risk of myopia and
anisometropia. Myopia in these infants often occurs at a early age (as
early as 3 months after birth). The occurrence and the degree of myopia
appear to be related to the degree of retinal cicatrisation, depth of the
anterior chamber, thickness of the lens, and axial length changes, rather
than to the degree of cryotherapy treatment. Axial length alone does not
appear to explain all the myopia found in ROP infants.
The distribution of refractive errors in preterm infants from age 3 months

to 5.5 years varies with severity of acute-phase ROP and cicatricial
disease. Changes in refractive error distribution occur primarily between
3 months and 1 years and involve a decrease in the proportion of eyes
with hyperopia and an increase in the proportion with high degrees of
myopia. Pre-term children should be followed up and screened for errors
of refraction.
Premature children may develop subtle visual impairment irrespective

of the presence of refractive errors, retinal changes, manifest squint or
cerebral damages. These visual defects include decreased contrast
sensitivity and colour vision even in the presence of normal visual acuity
and stereopsis.
The diameter of the foveal avascular zone appears to be correlated with

the gestation age of the child. It is thought that the FAZ is densely
vascularised early in gestational period during the formation of the
vasculature of the retina. The blood vessels in the FAZ undergoes
regression by the process of apoptosis in all infants after the age of 36
weeks. Apoptosis does not occur in premature infants before the age of
30 weeks. A small or absent FAZ may be considered as a marker of
prematurity.
screening and management
The timing of screening for ROP is controversial. The American academy

of paediatrics and the American academy of Ophthalmology have
recommended that screening should be carried out between 4 or 6

weeks of chronological age or between 31 and 33 weeks of post-
conception age. The royal college of British Ophthalmologists, on the
other hand, recommend screening between 6 and 7 weeks of
chronological age. Screening of children at risk at 7 weeks of
chronological age or 34 weeks of post-conception age has shown that it
can reliably detect the onset of threshold disease while reducing the
number of unnecessary examinations. A recent paper suggested that
screening can be carried out by non-ophthalmologists, by examining the
retinal blood vessels, if there are no ophthalmologists available.
ROP screening is uncomfortable and painful for the infant. The distress
caused by screening appears to be significantly reduced by good nursing
care during the examination (infants may be placed on soft padded
surface with boundaries that help to support them but still allow some
body and arms movements). Follow up examinations depends on the
findings:
• If the retinal vasculature is immature in Zone II but no disease is

present, follow up examination should be planned at approximately
2 to 4 week intervals until vascularization proceeds into Zone III.
• Infants with ROP or immature vessels detected in Zone I should be
seen at least every 1 to 2 weeks until normal vascularization
proceeds to Zone III or the risk of attaining threshold conditions is
passed.
• Infants with threshold disease (Stage III ROP, Zone I or II in 5 or
more continuous clock hours or 8 cumulative clock hours with the
presence of plus disease) should be considered candidates for
ablative therapy of at least one eye within 72 hours of diagnosis.
Treatment of ROP may be carried out by:
Cryotherapy
Indirect argon (532 nm) laser
Indirect diode (810 nm) laser
Transscleral diode laser
Treatment of pre-threshold ROP by laser photocoagulation does not

seem to lead to more favourable outcome than holding the treatment till
the threshold stage develops. In threshold stage III ROP, Long term
follow up (3, 5 years) shows that treatment with either cryotherapy, argon
or diode laser photocoagulation is associated with the development of
visual acuity of 6/12 or better. Treatment with either method does not
seem to reduce vision. Cryotherapy may, however be associated with a
higher incidence of myopia. In the ROP Cryotherapy study, cryotherapy
of the peripheral avascular retinal reduced the incidence of unfavourable
outcome by 49% in infants with threshold ROP. The eye that benefited
the most were the eyes with Zone II disease, in Zone I disease the
benefit appears to be marginal. It is thought that cryotherapy might not be
an appropriate method for treatment in zone I. Cryotherapy can be

carried out under sedation with nasal ketamine and midazolam. A
significant number of patients, however, progress to Stage IV and V
(retinal detachment).
Argon and diode laser peripheral retinal oblation seem to be equally

efficient and associated with fewer systemic complications than
cryotherapy. Retinal lesions produced by the diode lasers are deeper
than Argon laser lesions. Persistence of the tunica vasculosa lentis is
often found in severe posterior ROP and the absorption of argon laser by
haemoglobin may lead to a lens burn. The longer wave lengths of the
diode makes this more unlikely.
The diode laser is more convenient, technically easier to administer and

better tolerated by patients. One of the main advantages of the diode
laser is that it can easily be transported to special babies units. Diode
laser peripheral retinal photocoagulation is a safe and effective procedure
for treating threshold retinopathy of prematurity. 85.4% of patients have
bilateral favourable outcomes. A dense pattern of diode laser
photocoagulation for threshold ROP significantly reduces the rate of
progression of the disease in zone 2. The outcome appears to be similar
between fellow eyes in 94.2% of patients.
Serious complications related to treatment are uncommon. Diode laser

treatment for ROP is associated with significantly less myopia than
cryotherapy up to three years after treatment. There is no trend of
increasing myopia after diode laser treatment and refraction seems to
stabilise after one year, unlike after cryotherapy where myopia
significantly increases between 1-3 years after treatment. Diode laser
photocoagulation treatment may also be complicated with the onset of
hyphaema. Hyphaema is thought to be due iris clipping which is caused
by the relatively large cone angle of some diode lasers. A dense
cataract may occasionally develop after laser photoablation for threshold
retinopathy of prematurity. The cataract may be due to anterior segment
ischaemia. Dense cataract development after laser photocoagulation
appears to be associated with a poor visual prognosis. Post-laser
cataract may be prevented by light laser application at the 3 and 9
O’clock positions to prevent anterior segment ischaemia.
Transscleral diode laser coagulation appears to be as effective in the

treatment of threshold ROP as trans-pupillary diode laser
photocoagulation. Transscleral diode laser photocoagulation seems to be
an advantageous treatment method if trans-pupillary treatment bears an
increased risk of cataract formation. A recent study showed that 48% of
eyes have 20/50 or better visual acuity three years after diode laser
photocoagulation for threshold retinopathy of prematurity. Eyes with 4 or
more D of myopia are less likely to achieve 20/50 or better visual acuity
than eyes with less than 4 D of myopia.
Stage IV in ROP indicates the presence of retinal detachment. It is

subdivided into IV-A (macula on), and IV-B (macula off) retinal
detachment. Stage IV usually progresses very quickly and results in
severe visual loss.
Localised retinal detachments may occur after the acute phase of ROP.
The detachment may progress to total detachment, may involve the
macula and cause macular fold, stay stable, or regress. Cryotherapy
does not seem to affect the outcome but it is known to reduce the risk of
developing complete retinal detachment. Scleral buckling repair of the
retinal detachment in stage IV-A has been shown to be an effective way
of preventing further progression of the detachment. The visual results
after vitrectomy for stage V ROP are often disappointing. Vitrectomised
eyes seem to function better than non-vitrectomised eyes. There is also
evidence that visual function, however poor it might be, is still useful to
these children and probably better than previously thought. Timely
surgical intervention and appropriate postoperative care can result in
useful vision in stages IV and V ROP.
Paediatric Cataract
Childhood cataract is a major cause of preventable blindness and severe
visually impairment in many developing countries. The prevalence of
paediatric cataract varies from one report to another. It is estimated that
the prevalence of the disease is between 2.3 to 7.7 per 10000 of total
births. The incidence of paediatric cataracts in developing countries is
relatively high due to inter-family marriages.
Children with cataract should be evaluated by ophthalmologists,

paediatricians and also possibly be geneticists. The role of
ophthalmologists is to exclude any other ocular condition that may be
associated with the cataract e.g. PHPV. All investigations should be
arranged by the paediatricians depending on the systemic findings.
Some investigations are however useful for routine screening e.g. urine
amino acids, reducing substances, and organic acids and blood. Blood
electrolytes, amino acids, lipids, and sugar and calcium and galactose
enzymes.
The indications for surgery are mainly to improve vision, prevent

complications (e.g. glaucoma and hypotony), and also for cosmetic
reasons in disfiguring mature white cataract. It is suggested that in
unilateral cases surgery should be carried out before 2 months of age,
with early and aggressive occlusion and optical correction.
The currently available surgical technique for paediatric cataract include:
1. Lens aspiration
2. Extra-capsular cataract extraction with or without IOL implantation,
3. Extra-capsular cataract extraction with primary posterior
capsulotomy, anterior vitrectomy and IOL implantation.
4. Lensectomy with anterior vitrectomy.
High incidence of posterior capsule opacification is a major concern in

paediatrics cataract and IOL surgery. In extra-capsular cataract
extraction technique about 44% to 100% of patients develop significant
opacification of the posterior capsule which need laser treatment which
might have to be repeated.
Lensectomy with anterior vitrectomy provides a long lasting clear visual

axis but needs certain types of aphakic correction e.g. contact lenses
wear which can have serious financial and clinical problems in children.
Lensectomy with scleral approach is associated with a high incidence of
retinal detachment. To avoid this complication, it is advised that the entry
site for the lensectomy / vitrectomy instruments should be about 1.5 to
2.5 mm behind the limbus (not 4 mm behind as in adults). One of the
advantages of lensectomy-vitrectomy operation is that a second
procedure for the capsulotomy and a second general anaesthesia are
avoided, however it has been reported that a membrane can form
posterior to the iris despite lensectomy-vitrectomy operation, and this

membrane may require another intraocular operation for treatment.
The benefits of extracapsular cataract extraction without vitrectomy may

outweigh the risks of a second general anaesthesia for non-invasive
laser capsulotomy. The technique of extra-capsular cataract extraction
with primary posterior capsulotomy, anterior vitrectomy and IOL
implantation seems to be the most appropriate technique since it
provides a long term clear visual axis and also enables IOL implantation
as a good method of correcting aphakia.
Primary posterior capsulorhexis with IOL optic capture is a new

technique to prevent posterior capsular opacification in paediatrics
cataract and IOL implantation. This technique involves capturing of the
IOL optics through a posterior capsulorhexis opening. This technique
seems to be promising in preventing secondary membrane formation. It
also ensures centration of the posterior chamber IOL while eliminating
the need for an anterior vitrectomy. Apposition of the anterior and
posterior capsule leaflet anterior to the optic would limit the migration of
Elschning pearls, reducing the incidence of secondary membrane
formation and the need for additional procedures.
IOLs have been used in paediatrics cataract surgery with increasing

frequency. In a study of more than 300 children between 2 and 16 years
of age, the use of IOL was reported to be favourable even in patients with
traumatic cataract. Visual acuity better than 20/80 was reported in 71% of
patients. Major complications were rare. Unilateral or bilateral IOL
implantation can provide a good visual outcome in very small children.
The foveal function, rather than the age of the child, appears to be the
determining factor of the visual outcome. Surgery before the
development of abnormal foveal function can therefore be beneficial. IOL
implantation in children’s eyes with uveitis may be beneficial. In children
with JRA-associated uveitis, the final visual results remain guarded
because of irreversible amblyopia and a more complicated postoperative
course. Children with JRA-associated uveitis demonstrate an active
intraocular inflammation for an extended period after surgery, and tended
to have secondary membranes, necessitating a second surgical
procedure. Implantation of a heparin surface modified PMMA IOL may
be used to correct aphakia in children with uveitis.
Axial length increases in children, rapidly till the age of 2 to 3 years old,
and then slows down till the age of 8 to 10 years old. Pseudophakia in
children is predicted to lead to myopic shift after surgery specially in very
young children. The myopic shift appears to be greatest in younger age
groups and seems to persist till the age of 8 years old. Postoperative
refraction may be predicted by using SRK II formula with intraoperative
corneal curvature and axial length measurement. Planned postoperative
hyperopia is recommended to lessen the quantity of the postoperative
myopic shift. Myopic shift in pseudophakic eyes seem to be more than in
normal phakic eyes. The mean refraction shift is estimated to be - 0.99

+/- 0.22 D with a range between - 3.25 and +0.38 D. It is advised that
children should be under-corrected by about 1 D when IOL power is
considered. A rule of thumb is to use a lens 3 D. under-corrected for a
two years old baby rising to a lens to achieve emmetropia in an eight
years old baby.
Prediction of postoperative refraction course is difficult. It is thought that

removing the crystalline lens in infancy may retard the axial growth in
human and monkeys eyes. This finding may have implication on the
postoperative refraction in children. The retardation in axial growth in
monkeys appears to be age related being of small degree after the age of
7.5 months old.
postoperative complications
Stimulus deprivation amblyopia commonly occurs after unilateral

congenital cataract extraction and is a major cause of visual impairment
in these patients. Visual rehabilitation following cataract surgery in infants
is important to prevent amblyopia. The most widely used method is
contact lenses. Improvement in contact lens materials have made it
possible to successfully rehabilitate many children with monocular
aphakia. Contact lens intolerance is still a significant problem in young
children at an age when immediate aphakic correction is imperative to
prevent deprivation amblyopia.
Most surgeons are reluctant to place an intraocular lens in an eye of a

child with a monocular cataract who is younger than 1 year. Secondary
placement of an intraocular lens in the posterior chamber appears to be a
safe, effective alternative for correction of aphakia in the contact lens or
spectacles intolerant child or young adult. The risk of secondary
implantation does not seem to be greater than primary implantation.
Epikeratophakia has also been used but it may be associated with a
significant complication rate. It is not widely practised.
Glaucoma is another well recognised complications after congenital

cataract surgery. It is not possible to recognise in which eye glaucoma
will develop. It is not also known how soon glaucoma will develop after
the cataract surgery. Careful and prolonged follow up is required. Closed
angle glaucoma usually occurs early and open angle glaucoma usually
occurs late (up to 65 years) after congenital cataract surgery. All aphakic
children should have glaucoma assessment at least every year. Other
complications include endophthalmitis, vitreous strands in the wound,
hyphaema, and endothelial cell loss.
Paediatric glaucoma
Glaucoma in children may be:
• Primary
• Secondary to other ocular disease (e.g. Aniridia, Axenfield’s anomaly,
Rieger’s anomaly or syndrome or persistent hyperplastic primary
vitreous).
• Associated with systemic diseases (e.g. Lowe’s syndrome, rubella,
phakomatosis, homocystinuria).
Important advances in the field of genetics and glaucoma have been

made. The following genes have been identified is these types of
glaucoma, TIGR gene (trabecular meshwork inducible glucocorticoids
response) gene in adult and juvenile glaucoma, the CYP1B1 gene
(GLC34 locus) in congenital glaucoma, and the RIEG homebox gene (R1
locus) in developmental glaucoma. it is thought that genetics studies
might lead, in the near future, to a better understanding of the mechanism
and classification of glaucoma.
Glaucoma in children may be associated with Aniridia. Aniridia is a rare

sporadic or familiar disease that affect the iris, cornea, angle structures,
lens and macula. Goblet cell density is also increase in the conjunctiva
and the peripheral cornea of these eyes. It has been thought that there
are two chromosomes associated with aniridia, chromosome number 11
(band 13) for the sporadic type and possibly chromosome number 2 for
the inherited type. The Wilms’ tumour gene has also been located on
chromosome.
The disease should be differentiated from congenital megalocornea,

high myopia, corneal endothelial dystrophy, and birth trauma (birth
trauma is often associated with vertical or oblique Descemet’s tears,
while congenital glaucoma is often associated with horizontal or
concentric). Measuring the IOP often needs general anaesthesia.
General anaesthesia may lower the IOP except when ketamine
hydrochloride is used.
Surgical treatment is the main line of treatment, it can stabilise the IOP in
primary and secondary types. Many procedures are often needed to
achieve satisfactory results. The first line of treatment is often with
goniotomy, followed by trabeculotomy, or trabeculectomy.
The success rate of trabeculectomy in children glaucoma is low.

Trabeculectomy with Mitomycin C is effective in children with resistant
glaucoma, especially phakic children over one year old. Filtering surgery
with or without Mitomycin C seems to be the most effective surgical
treatment. Late onset bleb related complication is still a major problem as
in adult population. Some patients may continue to lose vision despite all
efforts. Primary combined trabeculotomy-trabeculectomy is safe,
effective and sufficiently predictable to be considered as the first choice

of surgical treatment in primary congenital glaucoma with corneal
oedema.
Cyclocryotherapy is also an effective option in the treatment of resistant

paediatric glaucoma. Eyes with aniridia have a high rate of phthysis, and
may be poor candidates for this procedure. Molteno type glaucoma
implants are often reserved for resistant cases. The use of these
implants may achieve a good IOP control and preservation of sight.
Some eyes may need further surgery due to implants-related
complications.
Non-Accidental Injury
(Shaken Baby Syndrome)
It is not often easy to diagnose non-accidental injury in infants. Extensive
retinal haemorrhage in an infants is suggestive of child abuse and non-
accidental injury (shaken baby syndrome). The earliest intraocular
lesions to be found in accidental or non-accidental head injuries are
peripheral sub-hyaloid haemorrhages with or without localised retinal
detachments. The haemorrhages are typically of different duration, some
may be fresh, while others are old haemorrhage. Unilateral retinal or pre-
retinal haemorrhage may also occur.
Retinal haemorrhage can result from severe angular positive or negative

acceleration forces alone, without impact or direct ocular trauma. The
mechanism of the haemorrhages may be due to the vitreous traction
forces with or without the additional rise in the intracranial and central
venous pressure. Extensive retinal haemorrhage are more likely to be
due non-accidental rather than accidental injury. The haemorrhage is
often bilateral, but it may also be unilateral. Mild flame shaped
haemorrhage may resolve in 24 hours, severe retinal and vitreous
haemorrhage may take months before it disappear.
In shaken baby syndrome retinal haemorrhages are extremely common,

but vision loss is most often the result of brain injury. The patient’s visual
reaction and pupillary response on presentation shows a high correlation
with survival. Good initial visual reaction is highly correlated with good
final vision and neurologic outcome.
There are many conditions that may be associated with retinal

haemorrhage. Neonatal retinal haemorrhage is common. The majority of
these haemorrhages disappear in about 8 days. Some sub-hyaloid
haemorrhage may, however, persists for up to 3 months. Leukaemia,
ROP, sickle cell disease, extra-corporal membrane oxygenation, and
haemorrhagic disease on the new born, are among these conditions that
cause retinal haemorrhage. Most of these diseases can be identified by
clinical examinations. An extensive investigations approach does not
seem to be appropriate.
In children under the age of 2 years, convulsions alone are unlikely to

cause retinal haemorrhage. The finding of retinal haemorrhage in a child
admitted for convulsion should raise suspicion about the possibility of
non-accidental injury. The association between retinal haemorrhage and
intracranial damage and sub-dural haemorrhage is not invariable.
Cardiopulmonary resuscitation is very unlikely to cause retinal
haemorrhage. Causes of Valsalva’s manoeuvre have not been reported
with retinal haemorrhage in children. Pertussis may be an exception.
In shaken baby syndrome the visual outcome appears to be related to

the baby’s need to assisted ventilation more than to the initial visual
acuity. Non-reactive pupil and midline shift of the brain structures, in

these babies, correlate with mortality, neuro-surgical examination is
recommended in these situations as the baby’s life is likely to be in
danger.
Neuro-ophthalmology
Congenital anomalies
optic nerve hypoplasia and dysplasia
Optic nerve hypoplasia is, now, considered to be the most common

congenital optic nerve head anomaly. Most of the reported severe cases
have been associated with major central nervous system anomalies and
other congenital malformation resulting in death shortly after birth.
Bilateral aplasia of the optic nerves, chiasm and optic tracts may also
occur in an otherwise healthy infant.
Optic nerve hypoplasia may be caused by intracranial tumours or

congenital suprasellar teratoma. It is thought that nerve hypoplasia, in
these cases, may be due to compression. Superior segmental optic disc
hypoplasia is a special type of optic disc hypoplasia known as Topless
Disc. This condition is characterised by superior disc pallor, scleral halo,
and superior nerve fibre layer loss associated with inferior visual field
defects. Female sex, low birth weight, short gestation period, maternal
diabetes are known predisposing risk factors.
MRI may be used to demonstrate associated central nervous system

abnormalities in these patients and provide specific prognostic
information regarding the development of the nervous system and
pituitary gland problems. Based on the MRI findings, patients can be
classified into the following groups:
1. Isolated optic nerve hypoplasia

2. Absence of the septum pellucidum
3. Posterior pituitary ectopia
4. Hemispheric migration anomalies
5. Intra uterine/pre-natal hemispheric injury
Groups (3), (4) and (5) are highly predictive of pituitary gland hormones
deficiency and neuro-developmental anomalies. Thinning or agenesis of
the corpus callosum is also predictive of neuro-development anomalies.
In contrast to previous reports, endocrine abnormalities are seen in only
one quarter of patients, and the full-blown deMorsier syndrome (septo-
optic dysplasia with pan-hypopituitarism) is seen in only 11.5% of
patients with Bilateral optic nerve hypoplasia. The clinical association of
septo-optic dysplasia (optic nerve hypoplasia with an absent septum
pellucidum and a thin corpus callosum) with pituitary hormone deficiency
is known. Children with septo-optic dysplasia and hypo-cortisolism are at
risk for sudden death during febrile illness. Thermo-regulatory
disturbances and dehydration from diabetes insidious may also occur.
1
Prevention of sudden death in septo-optic dysplasia requires early

recognition and treatment of these major risk factors.
Although the visual prognosis of children with Bilateral optic nerve

hypoplasia is generally poor, 10% of patients have excellent visual acuity.
Optic nerve size could predict the visual outcome in patients with optic
nerve hypoplasia. Visual acuity is related to the ratio of the horizontal
optic disc diameter to the disc-macula distance, pupillary reaction,
nystagmus and also to VER. All eyes with ratio more than 0.3 have a
good visual acuity and all eyes with ratio less than 0.3 have poor visual
acuity. No eyes with ratio less than 0.15 has a visual acuity better than
light perception. These findings should help to assess visual acuity in
young children and infants with optic nerve hypoplasia and may lead to
diagnostic criteria for the severity of the disease.
morning glory disc
Morning glory disc anomaly is a rare unilateral congenital anomaly

characterised by a congenital excavation of the peripapillary fundus,
enlargement of the optic disc, abnormal peripapillary glial tissue and a
complex pattern of retinal vascular anomalies including arteriovenous
communication on the optic disc head or on the retina. This condition
may also be associated with difficult cases of non-rhegmatogenous
retinal detachment.
Visual acuity is often poor even in uncomplicated cases. Morning glory

syndrome is generally an isolated ocular abnormality. However some
systemic abnormalities have been associated with this condition e.g.:
1. Mid line cranial facial defects.

2. Hypertelorism.
3. Cleft lip and cleft palate.
4. Basal encephalocele.
5. Renal anomalies, occasionally.
6. CHARGE syndrome.
It may also be associated with pituitary dwarfism possibly due to pituitary

compression by an encephalocele. Children with morning glory syndrome
should have a complete general examination and growth evaluation. V-
shaped or tongue-shaped infra-papillary retinochoroidal de-pigmentation
has been reported in association with this condition. In patients with optic
disc dysplasia (e.g. morning glory disc anomaly), the finding of this
retinochoroidal pigmentary anomaly should prompt neuro-imaging to look
for trans-sphenoid encephalocele.
2
Ischaemic Optic neuropathies

and Giant cell arteritis
risk factors
Risk factors which have been associated with non-arteritic anterior optic
neuropathy include: vasculitis, migraine, blood loss, diabetes,
smoking, glaucoma and cataract surgery. There is also a significant
association between non-arteritic anterior ischaemic optic neuropathy
and elevated serum cholesterol and fibrinogen levels as well as with
smoking. Appropriate medical treatment of these risk factors may prevent
recurrence in the fellow eyes. Anterior ischaemic optic neuropathy has
been reported in children with sickle cell trait (AS haemoglobinaopathy)
and migraine. It has also been hypothesised that carotid artery micro-
emboli may play a role in the pathogenesis of non-arteritic anterior
ischaemic optic neuropathy. Recent trans-cranial Doppler studies found
no evidence that emboli from the carotid arteries are common in patients
with the disease.
The anatomical features of the optic nerve head may be related to the
development of some diseases of the optic nerve. Non-arteritic anterior
ischaemic optic neuropathy, papillopathy in young diabetic patients and
optic discs in Leber’s hereditary optic neuropathy are often associated
with small optic disc, small or absent physiological disc cup, abnormal
branching of the blood vessels and heaping of the nerve fibre layer at the
edges of the optic disc. Eyes that have anterior ischaemic optic
neuropathy also tend to be less myopic than controls.
clinical features and diagnosis
In a study of 170 patients with giant cell arteritis, 50% of the patients
presented with ocular involvement. Visual loss occurred in 97.7%,
amaurosis fugax in 30%, diplopia in 5.9% and ocular pain in about 8.2%
of patients. Anterior ischaemic optic neuropathy occurred in 81.2%,
central retinal artery occlusion in 14.%, celioretinal artery occlusion in
21.8%, posterior ischaemic optic neuropathy in 7.1%, and ocular
ischaemia in about 1.2%.
The visual loss in giant cell arteritis is unilateral in 46%, sequential in 37%
and simultaneous in 17% of patients. Bilateral non-arteritic anterior
ischaemic optic neuropathy is a well recognised clinical condition. The
time interval between the first and the second eye involvement is very
variable. Amaurosis fugax is usually caused by ocular ischaemia related
to atheromatous disease of the carotid artery and is almost always
unilateral. Alternating amaurosis fugax in an elderly patient suggests
arteritis rather than atheromatous disease and temporal artery biopsy
should be considered.
3
Anterior ischaemic optic neuropathy is the commonest cause of visual

loss in patients with giant cell arteritis. Giant cell arteritis should also be
considered in the differential diagnosis of non-embolic branch retinal
artery occlusions in old patients. It is thought that involvement of the
ophthalmic or the central retinal artery may reduce the blood flow in
branches of the retinal artery predisposing them to the development of
occlusion. Cotton wool spots may precede visual loss in patients with
giant cell arteritis. Old patients with visual symptoms and at least one
cotton wool spot, even in the absence of other clinical signs, should be
suspected of having giant cell arteritis.
The detection of RAPD is an important sign in the diagnosis of anterior

ischaemic optic neuropathy. The Marcus Gun phenomenon (pupillary
re-dilation under sustained illumination), and the alternating light tests
(a flash-light passing back and forth from one eye to the other) are often
used to elicit RAPD. The alternating light test is believed to be superior to
the Marcus Gunn test for detecting relative afferent pupillary defects.
Isolated choroidal ischaemia may be a potential cause of reversible

visual loss in giant cell arteritis. Ophthalmic examination may show
scattered yellow white lesions at the level of the retinal pigment
epithelium. There may be no ophthalmic or angiographic evidence of
anterior ischaemic optic neuropathy or central retinal artery occlusion.
Fluorescein angiography shows marked delay in choroidal filling in the
macula in the affected eye. After intravenous steroid treatment patient’s
visual acuity may improves and repeat fluorescein angiography may
show normal choroidal circulation. Choroidal non-perfusion often
accompanies central retinal artery occlusion and anterior ischaemic optic
neuropathy and might also be the only manifestation of giant cell arteritis.
Fluorescein angiography may help in making the diagnosis of this
condition
Cutaneous involvement in giant cell arteritis is common. Scalp necrosis,

on the other hand is an unusual sign of the disease. It is characterised by
oedema, urticaria, erythema, vesicles, and crusting in the area of
distribution of the temporal artery. Misdiagnosis in these cases should be
avoided as this sign may represent a sever case of vasculitis, resulting in
visual loss, and possibly death.
occult GCA
Occult GCA denotes an ocular involvement without systemic features.

Almost 21% of patients with visual loss do not have systemic
manifestations. In people 55 years of age or older, with amaurosis fugax,
anterior ischaemic optic neuropathy, and abnormal C-reactive protein
with or without elevated ESR should raise a high rate of suspicion.
Anterior ischaemic optic neuropathy with cilio-retinal artery occlusion, and
chalky white optic disc head are very helpful indicators of the disease.
4
management
The clinical and laboratory features most strongly suggestive of giant cell
arteritis include the following findings in the following order:
1. Jaw claudication.
2. C-reactive protein above 2.45 mg/dl. C-reactive protein appears to be
more sensitive (100%) than erythrocyte sedimentation rate (92%) for
detection of giant cell arteritis. Erythrocyte sedimentation rate
combined with C-reactive protein have the best specificity (97%).
3. Neck pain.
4. An erythrocyte sedimentation (ESR) rate of 47 mm/hour or more.
The ESR has traditionally been measured by the Westergren method

which dates back to 1921. This methods seems to be well correlated with
the Seditainer which is currently been used in many eye departments.
Newer automated methods of measuring the ESR, within 25 minutes,
have been introduced. A new report compared the results of measuring
the ESR with the Seditainer and with the new automated methods in
patients with GCA. It was found that there is a wide scatter in the results
of ESR measuring with the new methods, which lead the authors to
advise continuing using the Seditainer method.
Bilateral simultaneous or sequential temporal artery biopsy improves

the diagnostic yield in some cases of giant cell arteritis. There is a high
probability of obtaining the correct diagnosis in patients in whom only one
artery can be biopsied. Although the improvement in diagnostic yield of
bilateral temporal artery biopsies is low, the consequences of both
delayed diagnosis and treatment of giant cell arteritis as well as the use
of systemic corticosteroid in patients who do not have giant cell arteritis
are of such potential severity that consideration should always be given
to performing bilateral temporal artery biopsies in patients suspected of
having the disease.
Patient with anterior ischaemic optic neuropathy are at increased risk of

developing macro-vascular diseases (e.g. myocardial infarction and
cerebrovascular accidents). In high risk patients it has been shown that
anti-platelets therapy (aspirin 75-325 mg daily) reduces the risk of
vascular death, myocardial infarction and stroke. In view of the increased
mortality noticed in patient with central retinal vein or artery occlusion it
seems appropriate to treat patients with anti-platelets drugs.
Systemic steroid treatment has proved effective in preventing the ocular

and systemic complications of giant cell arteritis. Temporal artery biopsy
may be indicated to confirm the clinical diagnosis and may show
granulomatous inflammation even after several month of systemic
corticosteroid therapy. Arteritic ischaemic optic neuropathy can still
develop despite using systemic steroids treatment even when the
systemic symptoms and signs of the disease have responded to the
5
treatment. The results of IV methyl-Prednisolone treatment of patients

with visual loss from GCA are similar to the results of treatment with oral
corticosteroid, with IV methyl-Prednisolone treatment being more costly
and having a small risk of sudden death.
Osteoporosis is recognised as an important problem in patients on high-

dose corticosteroid therapy. The steroid effect on bone mass may occur
early during treatment and once established the osteoporosis may be
hard to reverse. Alternate days steroids treatment does not seem to
protect against the development of the disease. The Department of
Health Advisory Group Report on Osteoporosis states that patients on
more than 5 mg of prednisolone daily for more than 3 months should
be screened. Calcium supplementation, should be given routinely to
steroid patients. There is also evidence to suggest that HRT should be
given to postmenopausal women or women who have had a
hysterectomy when put on corticosteroid treatment for a long time.
Newly published British guidelines suggest that the following are

indications for a diagnostic work-up and further investigations with bone
mass densitometry measurement:
1. Patients on more than 15 mg/day for six months

2. Previous osteoporosis fracture
3. Patients older than 65 years of age
4. Menopause before the age of 45
5. Body mass index less than 20
6. Family history of low trauma fracture
7. Smoking
Bone mass densitometry of the spine or the hip is indicated for patients
taking a dose more than 7.5 mg/day but less than 15 mg/day. Patients
with a score of less than -1.5 should have a diagnostic work up followed
by intervention, while patients with a score of 0-1.5 should have a
repeated densitometry measurement in one year.
The role of aspirin in the treatment of this condition id still controversial.

A recent study showed that aspirin (325 mg/day) may be effective in
reducing second eye involvement in patients with non-arteritic anterior
ischaemic optic neuropathy. It has also been reported that Levodopa
and carbidopa can significantly improve the visual acuity and decrease
visual loss in some patients, especially when given within the first 45
days of onset. Visual improvement in long standing cases (more than 6
months) has also been documented. The mechanism of action may be
related to the presence of dopamine receptors and mediators in the
retina.
In a 24 months follow-up study for patient with non-arteritic anterior

ischaemic optic neuropathy, optic nerve decompression surgery did not
lead to any visual benefits when compared with observation. The value of
6
optic nerve sheath decompression in the treatment of non-arteritic

anterior ischaemic optic neuropathy has been evaluated in a single
masked multicentre randomised controlled trial. This procedure does not
appear to offer any benefit on visual outcome in patients with ischaemic
optic neuropathy and should not to be recommended to patients with non
arteritic ischaemic optic neuropathy.
7
Demyelinating Optic neuritis

clinical features
Visual recovery in patients with an initial episode of optic neuritis is

typically rapid, begins within 2 weeks and may continue in some patients
for up to 12 months. Most patients retain good to excellent vision in the 5
years following an attack of optic neuritis, even if the optic neuritis
recurred. Recurrences are more frequent in patients with multiple
sclerosis and in those treated with oral prednisolone alone. In patients
with acute unilateral optic neuritis, abnormalities in the visual acuity,
contrast sensitivity, colour vision and visual field are often found in the
fellow eye. The presence of abnormal visual tests in the fellow eyes
without, prior clinical attacks, does not necessarily mean a second
demyelinating process. Ophthalmologist should be cautious in making
the diagnosis of multiple sclerosis, in patients with optic neuritis, only on
the basis of finding abnormal visual functions in the fellow eyes.
Visual field defects are common in optic neuritis. The disease does not
seem to have any predilection for any particular visual field defect.
Central visual field is affected more than peripheral visual field in most
patients. The majority of patients with visual field defects from acute optic
neuritis return to normal after the first year. Recovery of visual field
function seems to be greater around fixation than in the periphery. Many
fields show variation in the pattern and the location of the field loss.
Patients with resolved optic neuritis may also have different visual field
results on different days and different times of the same day. The
variations may affect both pattern and severity of visual field test results.
Care should be taken in interpreting visual field results in patients with
previous optic neuritis.
Brain MRI at presentation of isolated optic neuritis is predictive of

subsequent risk of developing multiple sclerosis. A normal MRI does not,
however, preclude the development of multiple sclerosis. Eyes with optic
neuritis with MRI lesions less than 17.5 mm on the optic nerve seem to
have good visual prognosis. Lesions greater than 17.5 mm on the optic
nerve or lesions involving the intra-canalicular part of the optic nerve lead
to incomplete or partial visual recovery. The presence of three or more
MS-like MRI lesions with CSF oligo-clonal bands appears to be strongly
associated with the development of multiple sclerosis. CSF oligo-clonal
bands has been reported to have a sensitivity of 96% and a specificity of
42%. MRI has s sensitivity of 85%, and specificity of 65%. The number of
MRI lesions seem to be associated with the extent of subsequent
disability. Optic neuritis in children has a low risk of recurrence and
progression to multiple sclerosis. The history of a bilateral sequential, or
recurrent episodes is, on the other hand, associated with increased risk
Diseases of the sphenoid sinuses should be considered in patients

presenting with optic nerve disease that do not look typical of
8
demyelinating disease. CAT scan may to the paranasal sinuses be

needed.
treatment
The Optic Neuritis Treatment Trial’s major conclusions regarding

treatment include the following:
1. Treatment with high-dose intravenous followed by oral corticosteroid

accelerated visual recovery but provided no long-term benefit to vision.
The recommended dose of treatment is IV methyl Prednisolone 250
mg 6 hourly for 3 days followed by 1 mg / Kg body weight for 11 days
of oral Prednisolone.
2. Treatment with ‘standard-dose’ oral Prednisolone alone does not
improve the visual outcome and is associated with an increased rate of
new attacks of optic neuritis; and treatment with intravenous followed
by oral corticosteroid regimen reduces the rate of development of
clinically definite MS during the first two years. Oral steroids alone
should not be used as it is associated with a higher rate of recurrent
optic neuritis
3. Brain MRI should be considered to assess the risk of future neurologic
events of MS.
4. Treatment with intravenous methylprednisolone should be considered,
particularly if the brain MRI demonstrates multiple signal abnormalities
consistent with MS, or if a patient has a need to recover vision rapidly.
However, a recent study showed that high dose of oral steroids (500 mg
of methyl prednisolone/day for 5 days) may be beneficial in improving
recovery at 1 and 3 weeks after the onset of the condition. The same
study also showed no effect of the oral treatment at 8 weeks, and no
effect on the number of subsequent attacks.
gene therapy
Gene transfer is a new method for treating some diseases. The process
relies on transferring a specific gene to human tissue. This is often
achieved by using a vector which may be a viral (e.g. adenovirus) or a
non-viral (e.g. DNA injection) vector. Gene transfer may used to achieve
gene replacement, addition or control. Gene therapy may be useful in the
treatment of demyelinating optic neuritis.
Reactive oxygen species e.g. nitric oxide and super-oxide are chemical
mediators in the demyelinating process. Catalase is considered as a
super-oxide scavenger. The endogenous levels of catalase are not
enough to prevent to protect the optic nerve from these mediators. The
administration of the gene coding for catalase by adenoviral increases
catalase levels in the optic nerve cells and may suppress the
demyelination process and the blood-brain barriers disruption. The
9
increased cellular levels of catalase decreases demyelination by about

30%.
10
Disorders of the pupil

horner’s syndrome
Horner’s syndrome is caused by a lesion in the sympathetic pathway to

the eye. The syndrome is characterised by the following features:
Mild ptosis.
Miosis.
Occasionally anhidrosis.
Heterochromia, in congenital cases.
Horner’s syndrome is often classified into three types depending on the

level of the lesion:
type of lesion important causes diagnostic features

First order neurone • stroke affected pupil dilates less
lesion. • tumours well than normal pupil
• osteo-arthritis of the with the cocaine test.
neck
Second order neurone • lung carcinoma same as first neurone
lesion. • thyroid tumours lesion.
• neuroblastoma
• metastases
Third order neurone • internal carotid artery can be differentiated
lesion. dissection from the other two
• cluster headache lesions by the Hydroxy-
• herpes zoster virus amphetamine test, the
infection pupil does not dilate as
much as the other pupil.
Apraclonidine may be a useful medication for the diagnosis of Horner

syndrome. The drug is an adrenergic receptor agonist. Its major site of
pharmacological action (for reduction of aqueous production) is on post-
junctional alpha 2 receptors in the ciliary body. Instillation of apraclonidine
into eyes with Horner syndrome produces mydriasis of 1.0 to 4.5 mm.
There is no significant change in the PD of normal eyes after ipsilateral
instillation of apraclonidine.
Heterochromia does not always indicate a congenital origin, the

syndrome can still be caused by a progressive acquired condition even in
the presence of heterochromia. Corneal endothelial de-compensation
has recently been reported with acute onset traumatic Horner’s syndrome
(after right jugular vein catheterization during cardiac valve surgery). It is
thought that the corneal de-compensation may be due to traumatic injury
to the sympathetic nerve supply to the cornea, which is known to have a
neurotrophic role in the cornea.
In 70% of infants with Horner’s syndrome, presenting in the first year, no

cause is identified. Routine diagnostic imaging in isolated Horner’s
11
syndrome in children is not necessary. Infants should be examined for

cervical or abdominal masses and involvement of the other cranial
nerves. Urinary vanillymandelic acid is levels is indicated to rule out
cases associated with neuroblastoma. More investigations are needed if
the Horner’s syndrome is acquired or if other signs are present.
Surgery may be needed to repair the mild ptosis if the patient is

interested. In mild cases of Horner syndrome, sympathomimetic drugs
(e.g. phenylephrine) may be used for treatment of mild ptosis if the
patient is not interested in surgical treatment.
adie’s tonic pupil
Adie’s tonic pupil is characterised by poor constriction to light sometimes

with light-near dissociation. It is often seen in patient between the ages of
20 and 40 years of age and rarely in children. Patients typically present
with anisocoria more obvious in the light than in dark.
The progression and pattern of iris denervation and re-enervation in

patients with Adie’s pupil may be observed by the technique of
videographic infrared transillumination. A miotic tonic pupil is thought to
result from rich re-enervation of the iris sphincter by accommodation
fibres. Segments that become richly enervated seem to lose their
cholinergic sensitivity.
12
Pseudotumour cerebri
Pseudotumour cerebri (idiopathic intracranial hypertension) is a condition
characterised by raised intracranial pressure (greater than 250 mm of
water), in the absence of intracranial focal lesion, with normal CSF
composition and normal or small ventricular system. Conditions that may
be associated with idiopathic intracranial hypertension include:
• infections (otitis media, viral infections, febrile illness).

• drugs (steroid withdrawal, vitamin A intoxication, nalidixic acid,
antibiotics and Cyclosporin, and minocycline).
• endocrine disorders.
Pseudotumour cerebri may be asymptomatic in some patients. Visual

field loss is the main complication of this condition, and field defects may
take different pattern. Visual field examination is the most sensitive test to
measure visual function in these patients. Humphrey’s visual field
analyser or Goldmann perimetry may be used. The final visual outcome
is often good in the majority of patients. Macular oedema is often
associated with disc oedema in patients with benign intracranial
hypertension. In the majority of cases, the macular oedema resolves and
do not cause a significant visual loss. Patients with marked and
persistent macular oedema may develop permanent visual loss. These
patients should be considered for optic nerve sheath fenestration
surgery. Choroidal folds may be the only ocular manifestation of
increased intracranial pressure. Papilloedema may not present in some
cases depending on the timing of ocular examination. Patients with
choroidal folds should have a complete work-up to exclude raise
intracranial pressure.
management
MRI is often ordered in this disease in order to exclude any other focal
intracranial lesions. The disease may, however, be associated with
characteristic MRI abnormalities, and it can be used in making the
diagnosis of this condition. Characteristic MRI findings include:
Flattening of the posterior sclera (80%),

Empty pituitary sella (70%),
Distension of the peri-optic subarachnoid space (45%),
Enhancement of the pre-laminar optic nerve (5%),
Vertical tortuosity of the orbital optic nerve (40%),
Intraocular protrusion of the pre-laminar optic nerve (30%).
The presence of two or more of these signs should indicate to raised

intracranial pressure.
13
Treatment of pseudotumour cerebri is indicated if there is an intractable

headache, or if there is a progressive visual field loss. Weight loss and
carbonic anhydrase inhibitors may be associated with the resolution of
papilloedema. Weight loss appears to be a main factor in reducing the
severity of papilloedema. Systemic steroid may also be used, but many
patients rebounds after stopping the steroids. If medical treatment fails
two surgical procedure,
Optic nerve sheath decompression, and lumboperitoneal shunts

may also be indicated. The relative advantages and disadvantages of
both Optic nerve sheath decompression and lumboperitoneal shunts
operations are not yet defined . The choice of either operation seems to
be determined by the surgeon’s choice and experience.
The mechanism by which optic nerve sheath decompression works is

unknown. It may be due to filtration of the CSF surrounding the
intraorbital optic nerve or reversal of the ischaemic process. The
procedure may be associated with many complications, most of these
complications are minor (e.g. temporary motility disorder or pupillary
dysfunction). Other significant complications include central retina or
branch retinal artery occlusions with outer retinal ischaemia with
significant visual loss may also occur. Patient should realise that there is
a higher risk of visual loss, stroke and death. Complete loss of vision may
occur after optic nerve decompression surgery. The mechanism of visual
loss after this surgery may be due to traction or ischaemic injury to the
nerve or due to vasospasm of the central retinal artery or due to orbital
oedema. Visual recovery may still occur even after a protracted
blindness. Patients with no identifiable cause for vision loss and who do
not respond to intravenous steroids should be evaluated for an urgent
lumboperitoneal shunt operation.
Optic nerve decompression may be carried out through a medial

approach with disinsertion of the medial rectus muscle, through a lateral
approach with removal of the lateral orbital rim to gain access to the
retrobulbar optic nerve, or through a lateral canthotomy incision without
the removal of bone or disinsertion of any extra-ocular muscles.
30% of optic nerve sheath decompression operations eventually fail.

Treatment options in failed cases include repeated decompression,
Diamox therapy, lumboperitoneal shunts, repeated lumbar punctures or
steroids treatment. Adjunctive Mitomycin and Molteno type tubes
offer additional options in failed cases and also in cases of refractory
pseudotumour cerebri, the application of Mitomycin C to the optic nerve
has a dose dependent toxic effect in the short term post-surgical follow
up period.
14
Miscellaneous conditions
essential blepharospasm
Essential Blepharospasm is a rare condition characterised by bilateral
spasm of the upper facial muscles. The usual cause of the facial muscles
spasm is vascular compression of the facial nerve root by a loop of the
posterior-inferior cerebellar artery. Bony compression in the facial canal
caused by ostitis deformans is an uncommon cause. The disease may
also have a psychological as well an underlying physical origin. The
disease affects women more commonly than men. It often starts in the
fourth to the sixth decades of life.
Patients often complain of increased frequency of blinking, this often

progresses to prolonged spasmodic eye lid closure, not related to any
external provocative factor. The disease may become severe enough to
render patients functionally blind. Meige syndrome is a similar condition
characterised by bilateral blepharospasm associated with involuntary
movement of the lower face and mouth muscles (oro-facial dystonia).
Symptoms of both conditions may disappear spontaneously especially
during the first five years after the onset of symptoms.
Botulinum toxin is the most effective treatment for benign essential

blepharospasm and Meige Syndrome. 55% of patients are expected to
benefit from the treatment. The mean duration of action of the toxin is
about 14.9 weeks for blepharospasm and 11 weeks for Meige Syndrome.
The duration of relieve following Botulinum toxin injection for essential
blepharospasm has been reported to increase, decrease, or not change
for repeated injections. In the long term the mean duration of relief
changes little over a period of repeated injections. Adjunct medical
treatment with minor tranquillisers and eyelid surgery (orbicularis
myectomy) may increase the effect of Botulinum toxins.
ocular neuromyotonia
Ocular neuromyotonia is a condition characterised by spontaneous
spasms of extraocular muscle contractions resulting from spontaneous
neural discharge of ocular motor nerves. Surgery and irradiation, to the
pituitary fossa, are the common causes. Prior radiation therapy is the
most common reported cause of ocular neuromyotonia. Neuromyotonia
may present with episodic diplopia many years after radiation therapy.
The length of time from radiation to neuromyotonia in these patients
ranged from 2 months to 9 years (mean 3.5 years). Dysthyroid
orbitopathy has also been described in some patients. Ocular
neuromyotonia may also occur secondary to infectious cavernous sinus
thrombosis. This condition may also occur with other intracranial space
occupying lesions e.g. tumours or aneurysms or in the absence of any
associated conditions. A careful examination, including the effect of
15
prolonged voluntary muscle action, to initiate the episode, is needed.

Neuro-imaging is also needed to exclude any intracranial lesions. A trial
of anti-convulsant treatment (e.g. Carbamazepine) should be given.
ocular side effects of vigabatrin

Vigabatrin is an anti-epileptic drug that is used in the treatment of
seizures and infantile spasms. The drug acts by inhibiting GABA
trasminase enzymes resulting in an increases in the brain GABA. The
incidence of visual field constriction and asymptomatic visual field loss, in
patients taking vigabatrin, may be higher and more common than
previously reported. A recent report postulated that Muller cell
dysfunction, in the peripheral retina, may occur in some patients. Patients
taking the drug may also show abnormal ERG, EOG, and VEP. Epileptic
patients taking the drug are at much higher risk of developing visual field
defects than similar patients not taking the drug.
The total dose of vigabatrin seems to be correlated with the severity of

the visual field defects. In a recent controlled study, in a recent study a
total dose of 1500 g of the drug was associated with risk of developing
significant visual field defect. When vigabatrin treatment is considered the
risks of developing visual field loss should weighed against any potential
improvement in the patient’s quality of life. Visual field loss may be
severe enough, in some patients, to limit patient’s ability to perform some
routine daily activities. The visual field loss may not recover after the
cessation of treatment. Patient receiving the drug should have a base line
visual field examination and also regular follow-up with peripheral visual
field examinations.
Vigabatrin (and also carbamazepine) causes acquired colour vision

defects. The abnormal colour perception seems to be associated with
constricted visual fields in the vigabatrin monotherapy patients. The best
method for detecting dyschromatopsia in patients treated with vigabatrin
or carbamazepine was the Farnsworth-Munsell 100 hue test. Vigabatrin
also seems to impair contrast sensitivity in patients who have
constricted visual fields. The drug does not seem to affect glare
sensitivity.
16
Tumours Of The Eye

And
Ocular Adnexa
Conjunctival melanomas
Pigmented conjunctival lesion may be benign, malignant, or intermediate
types of melanotic tumours. Malignant melanoma of the conjunctiva is
rare. The disease often affects middle age white individual. It is extremely
rare in black people. There is also a subset of melanocytic lesions that
cannot be reproducibly classified by pathologists as benign, malignant, or
indeterminate.
Conjunctival malignant melanoma arises from naevi in 26%, in primary

acquired melanosis in 56%, and de novo in 18% of cases. Primary
acquired melanosis lesions may show some enlargement in adolescent
age without any malignant transformation. Malignant melanoma
associated with primary acquired melanosis has a worse prognosis than
those arising de novo or from a naevus. Clinical features suggestive of
malignant transformation in primary acquired melanosis include:
• increased thickness
• change in the pigmentation
• loss of conjunctival mobility on the lesion
• the appearance of a prominent blood vessel feeding a tumour
The tumour may arise from the bulbar conjunctiva, the palpebral
conjunctiva, or from the plica. The disease may present in a superficial
spreading pattern, or in a nodular pattern. It may also be pigmented or
non-pigmented. Amelanotic conjunctival malignant melanoma my rarely
arise in association with primary acquired melanosis sine pigmento. This
rare type of conjunctival melanoma is aggressive and has a poor
prognosis and high risk of metastases. The lack of pigmentation makes
the clinical diagnosis very difficult and diagnosis is often made by
histological examination.
In conjunctival malignant melanoma, risk factors of systemic

metastases include:
1. large size.
2. fornix or caruncle involvement.
3. multicentre tumours, mixed spindle and epithelioid cell type, or
epithelioid cell type and high mitotic index.
Conjunctival melanomas may be treated with surgical excision (with or

without cryotherapy), radiotherapy, or exenteration, depending on the
size and the location of the tumour. The role of orbital exenteration in the
treatment of conjunctival malignant melanoma is controversial. A
combination of de-bulking surgery and adjunct cryotherapy or beta
irradiation seems to be more appropriate than exenteration, which is
often a very disfiguring procedure. In malignant melanomas of the eyelid
and palpebral conjunctiva Iodine125 brachytherapy can also be used as
an alternative to wide excision or exenteration with good local control,
reasonable maintenance of vision, and good cosmetic results..
Orbital exenteration should be reserved to advanced cases as a palliative

measure. It may be followed by recurrence of the tumour in the orbit and
paranasal sinuses. Eyes with recurrent conjunctival malignant
melanoma should be carefully monitored for intraocular extension of the
disease. deep excision of the tumour with sclero-keratectomy may
reduce the natural barriers against tumour extension.
Topical Mitomycin C may also be considered for the treatment of

conjunctival melanoma and PAM with atypia in patients who can not or
are not willing to have surgical or cryotherapy treatment. Topical
mitomycin chemotherapy seems to be most effective for superficial
tumours. Nodular tumours may be resistant to the treatment. The
treatment may also be complicated with the development of
keratoconjunctivitis in some patients and secondary changes in the
superficial layers of the conjunctival epithelium. These changes should
be differentiated from recurrent tumour.
carcinoma of the external eye surface

Corneal intra-epithelial neoplasia (CIN) is a slowly progressive unilateral
lesion, that has a low malignant potential. The condition is known to lead
to squamous cell carcinoma. It may be difficult to differentiate between
advanced CIN and early invasive disease. Pre-invasive (CIN ) and
invasive carcinomas of the conjunctiva and the cornea are more common
in people in the hot tropical areas, especially fair-complexion middle age
individuals. The disease may also affect younger immunosuppressed
patients (due to drugs, AIDS, or lymphomas) with no significant history of
solar exposure. It is thought that the papilloma virus plays an important
role in the pathogenesis of this tumour in these patients. When the
tumour is diagnosed in patients younger than 50 years of age, HIV
infection should be considered.
The treatment of choice, of this tumour is by surgical excision. Single

excision is followed by recurrence in about 25-35% of cases. The slow
growth of the recurrent lesions combined with the ever present malignant
potential suggest that all patients with a history of CIN warrant annual
follow-up for the remainder of their lives. The recurrence rate falls when
single excision is followed by cryotherapy, beta irradiation therapy and
also after topical application of Mitomycin C. Excimer photo-therapeutic
keratectomy and Sub-conjunctival injection of Interferon alpha-2b may
also be used in selected cases.
choroidal melanoma
The incidences of intraocular melanoma varies between 0.49 to 0.75
cases per 100,000 population per year. Uveal melanoma is rare in
children and teenagers. Oculo-dermal melanocytosis is estimated to be 9
times more common in young patients with uveal melanoma than in the
general population with uveal melanoma. Young patients with uveal
melanoma have short-term (5-year) survival better than that of adults.
The risk of uveal melanoma in black individuals is low. The reason for the
lower risk of uveal melanoma in this group of patients is not known. It
could be related to the protective effects associated with dark skin
pigmentation or may be due to cultural, environmental or socio-economic
factors. About 40% of uveal melanomas metastasise within 10 years of
diagnosis. The commonest site for metastases is to the liver via the
blood stream. Blood levels of gamma-glutamyl transpeptidase, and
alkaline phosphatase enzymes, as well as chest X ray and liver
ultrasound scan can be used for screening purposes for tumour
metastases.
Progress has been made in elucidating the genetic basis of cutaneous

melanoma with three well-defined loci (chromosomes 1, 6 and recently
chromosomes 9). A few reports have also shown abnormalities on
chromosomes 3, 6 and 8 in uveal melanomas. The p53 gene plays a
major role in inhibiting DNA synthesis after DNA damage. Mutation in the
p53 gene have been found in more than 50% of human cancers. Some
mutations have been associated with more aggressive tumours and
metastases. Mutation in the p53 gene does not seem to be common in
uveal melanomas. The exact role of mutation in the p53 gene in the
pathogenesis of uveal melanomas in not understood. It does not,
however, seem to be common.
Immunological factors may also play a role in the pathogenesis of

ocular malignant melanoma. Choroidal malignant melanoma may be
associated with ipsilateral ocular inflammation and sympathetic
ophthalmia. Choroidal melanoma may also be associated with bilateral
retinal vasculitis. The inflammatory signs may improve in the fellow eyes
in some patients after enucleation of the eye with the tumour.
Ocular ultrasound, MRI and CAT scan can be used in making the
diagnosis of ocular tumours, and their extraocular spread. Controversy
exists about the best imaging tool to detect the extension. Some reports
showed that MRI is superior to others while other reports showed that
ultrasonography is more superior to MRI.
Choroidal melanomas should be differentiated from secondary choroidal

metastases. The shape and the height of the tumour / its base ratio in B
scan ultrasound can be used in the differentiation of choroidal
metastases from choroidal melanoma. Metastases demonstrate a
significantly lower height / base ratio than melanoma. Choroidal

excavation also seems to be present only in melanomas. The reflectivity
is also significantly higher in metastases than in melanomas. Ultrasound
biomicroscopy can be useful in the management of some iris
melanomas. It is an accurate imaging technique for the assessment of
anterior tumour margins of peripheral choroidal melanomas.
Malignant melanomas exhibit different patterns on MRI testing. It has

been thought that variable melanin content and the presence of iron (as
methaemoglobin or haemosiderin) may be responsible. Contrast-
enhanced MRI (by Godopentetate dimeglumine) is useful in evaluating
intraocular tumours and in differentiating between uveal melanomas and
other similar tumours.
Bilateral primary uveal melanoma, familial uveal melanoma, diffuse

choroidal malignant melanoma, and retina-invasive melanomas are rare
types of the disease. Bilateral primary uveal melanoma is rare. The
occurrence of bilateral primary uveal melanoma may be associated with
ocular melanocytosis. There does not seem to be any clinical evidence of
inherited genetic predisposition for these tumours. There is no relation to
familial atypical mole and melanoma syndrome, cutaneous melanoma,
neurofibromatosis, or familial uveal melanoma. Unidentified germ-line
mutation may be involved in the pathogenesis of these tumours.
Although familial occurrences of uveal melanoma are rare, there may be

a hereditary basis for this tumour in certain families. Diffuse choroidal
malignant melanoma occurs in about 4% of all choroidal melanomas.
These melanomas carry a metastatic potential of 24% at five year
periods in spite of its flat appearance.
Retina-invasive melanoma is a rare but distinct type of uveal

melanoma. Retina-invasive tumours tend to arise from a ring melanoma,
they grow slowly. Frequent secondary angle closure glaucoma may
promote invasion of the tumour cells into the optic nerve.
Cutaneous malignant melanoma may, rarely metastasise to the eye.

Ocular metastases often present by pigmented or non-pigmented
vitreous cells. Metastatic malignant melanoma may also present with
heavy pigmentation of the anterior segment and trabecular meshwork
and pigmentary dispersion in the aqueous and the vitreous with visual
loss with no echographic or pathological evidence of discrete tumour
masses. The prognosis for life in these cases is often poor.
Extraocular extension of choroidal malignant melanoma may be

associated with proptosis, restriction of EOM movements and
manifestations of orbital inflammation. Uveal malignant melanomas may
also present with symptoms and signs of orbital inflammation due to
tumour necrosis and intraocular inflammation, even in the absence of
orbital extension. The possibility of intraocular tumours in patients
presenting with acute orbital inflammation should be excluded. Orbital

extension of choroidal melanoma may be treated with local excision of
the orbital lesion as well as proton beam irradiation of the ocular tumour.
prognosis
Although the diagnostic accuracy for tumours that are more than 4 mm
thick is greater than 98%, the sensitivity and specificity of clinical
examination, ultrasound and fluorescein angiography are uncertain for
pigmented tumours less than 3 mm in height. In choroidal and ciliary
body melanomas, measurement of the largest tumour dimension in
contact with the sclera (a measurement known as The Largest Tumour
Dimension) has been shown to be of great prognostic significance. Fine
needle aspiration biopsy results may also achieve a correct diagnosis
and management in 9% of cases presumed to be small uveal melanoma
by non-invasive methods. The problem of insufficient material for
cytological examination can be minimised by the use of a 22 gauge
needle.
Cytomorphometric analysis of uveal malignant melanoma may help in

predicting the prognosis in patients with malignant melanoma. The
standard deviation of nuclear area seems to be a very significant variable
correlated with the malignancy of the tumour within each Callender group
classification. The PC-10 count also appears to have a prognostic value
in uveal melanomas when adjusting for the effect of the mean of the
largest nucleoli and diverse vascular patterns.
The presence of vascular loops (defined as periodic acid-Schiff-positive

fibrovascular septa that completely surround lobules of tumour cells), and
micro-vessels density are indications of poor tumour outcome.
Quantifying cross-sectional tumour area and the percentage area
occupied by networks and parallel vessels with cross-linking micro-
circulatory patterns in ciliary body and choroidal melanomas provides
significant prognostic information. The micro-circulatory pattern of primary
choroidal melanoma also appears in the metastases regardless of its
site.
Indocyanine green angiography with confocal scanning laser

ophthalmoscopy can be used in imaging the micro-vascular structure of
choroidal melanoma. A prognostic index combining two or more
indicators may have a better prognostic value. In posterior uveal
malignant melanoma, specific chromosomal abnormalities have been
shown to correlate with the prognosis. Fine needle aspiration biopsy may
provide an opportunity for cytological analysis, and may provide an
accurate assessment of uveal tumours.
treatment
Small choroidal melanocytic tumours are often treated by observation.

Periodic follow up with photography and ultrasonography may be all is
needed in these cases to check for tumour growth. In small choroidal
melanocytic tumours, these risk actors may be predictive of tumour
growth; the presence of several factors seems to increase the risk:
1. Tumour thickness greater than 2 mm.

2. Posterior tumour margin touching the disc.
3. Visual symptoms.
4. Orange pigmentation of the tumour.
5. The presence of subretinal fluid.
Currently the efficacy of treatment in uveal malignant melanoma, in

preventing metastatic death, is uncertain. It is predicted that, within the
next 25 years, obtaining and analysing tumour samples will be possible
by using small-needle aspiration and DNA probes technology. Genetic
defects will also be determined, and treatment based on drugs designed
to inhibit molecules related to the genetic defect in the tumour may be
possible.
Recognised methods of treatment of uveal melanomas include:
Enucleation
Radiotherapy (plaque and charged particles)
Radiotherapy with Hyperthermia
Trans-pupillary Thermotherapy
Transscleral resection
Photo-dynamic therapy
The radio-surgical Leskell Gamma knife
Interferon alpha and gamma
Vaccination
Plaque and charged particles radiotherapy are the main lines of

treatment. In plaque radiotherapy treatment several isotopes have been
used e.g.:
• Iodine-125.
• Ruthenium-106.
• Iridium-192.
• Palladium-103.
Charged particles treatment has also been carried out by using:
• Proton.
• Helium ions
Both methods seem to be effective in the treatment of choroidal

melanomas. Data suggest that there is no difference in patients survival
between treatment by irradiation, by enucleation or by brachytherapy
using radioactive scleral plaques. It is not known if physical manipulation

during surgery increases the risk of developing micro-metastases.
When the tumour is judged to be too large to be treated by any

conservative method enucleation is often carried out. Mildly curved
scissors should be used for enucleation when a long optic nerve
specimen is desired. Strongly curved scissors should be avoided.
Previous studies indicated that pre-enucleation irradiation is associated
with a worse prognosis for survival when compared with no irradiation
before the enucleation, but it has been shown, recently, that pre-
enucleation irradiation does not have an effect on the survival of patients
with uveal malignant melanoma. In the absence of tumour viability,
enucleation, after primary irradiation, does not appear to affect patient’s
survival. If there is an evidence that the tumour re-grows after irradiation,
enucleation may then be associated with a higher mortality rate. More
than 40% of post-radiation mortality after choroidal melanoma is due to
causes not related to the tumour or to the metastases.
Plaque radiotherapy is, currently, the most popular form of conservative

treatment for choroidal and ciliary body melanomas. Initially, cobalt
plaques were widely used but the high incidence of radiation
complications has led to the adoption of less energetic isotopes (such as
ruthenium, iodine and recently palladium). Ruthenium plaques appear to
be associated with higher rates of local recurrences of the tumour than
proton beam irradiation or Iodine plaque treatment. The frequency of
radiation related complications after ruthenium radiotherapy for uveal
malignant melanomas are acceptable especially in small to medium sized
tumours. Localisation of the scleral plaque may be better carried out by a
three dimension ultrasound than with the conventional two dimensional
one.
Custom designed plaque radiotherapy can be used, and seems to be

effective and safe in controlling iris malignant melanoma that can not be
excised and also in localised iris metastases. Possible complications of
this technique include iris vasculopathy, posterior synechiae and
cataract.
Radiation vasculopathy and retinopathy are common finding after

plaque radiotherapy for choroidal melanoma (they occur in 42% of
patients after 5 years). Radiation vasculopathy is a leading cause to
visual acuity loss. The earliest changes observed after radiotherapy are
peri-tumour atrophy of the retinal pigment epithelium and choriocapillaris.
The susceptibility of the retinal vascular endothelium to radiation is the
main biological factor leading to vascular occlusion and retinopathy. The
main predictors of radiation retinopathy are posterior tumour location
with margin near the foveola and high radiation dose rate to the tumour
base. Patient factors, such as diabetes, may also play a determining role.
Radiation therapy may also be associated with the development of
idiopathic peri-foveal telangiectasis.
Charged particle radiotherapy of uveal melanomas is currently possible in

few centres world-wide. Proton beam irradiation for uveal malignant
melanoma is associated with excellent local control and retention of
useful vision. Proton beam irradiation administer radiation to a
circumscribed area and is thought to minimise the damaging effect on the
neighbouring tissues. External beam irradiation may, however, be
associated with ocular complications e.g. dry eye syndrome, cataract and
macular oedema. Progressive visual field loss is also common after
proton beam irradiation for peripapillary choroidal malignant melanoma
and seems to be related to the area of the retina treated. Radiation
papillopathy does not seem to associated with progressive field loss in
most patients. Dry eyes is also a main complication after treatment. The
radiation dose to the cornea appears to be a more important factor in
causing dry eye than the radiation dose to the lacrimal gland. Large
radiation dose to the cornea may be associated with severe
complications even if the lacrimal gland is well protected.
Radiation-induced macular oedema may also occur. The oedema may

be treated with focal laser photocoagulation. Short-term results are
encouraging but the long-term results are often poor. Posterior sub-
capsular cataract develops in about 41% of patients 3 years after
treatment. The incidence increases significantly with increasing the
treatment dose and tumour light. Cataract development is related to the
amount of lens in the pathway of radiation, patient age, pre-existing
cortical opacities and also tumour height.
Neovascularisation glaucoma develops mainly in the first few years

after radiation but cataract may continue to develop for much longer
period. The strongest risk indicator for radiation cataract and vitreous
haemorrhage is thought to be the height of the tumour, for neovascular
glaucoma the TNM class of the tumour, for radiation maculopathy the
posterior tumour margin within 2 mm from the fovea, and for radiation
optic neuropathy the location of the tumour margin within 1 disc diameter
from the optic disc. Recent studies indicate that fractionated radiotherapy
doses may spare the normal tissue while delivering the right dose to the
tumour tissue.
Helium ion can be used for the treatment of tumours less than 6 mm in
thickness and more than 3 mm away from the disc. This method is
associated with good local control and reasonable retention of the treated
eyes. In a 10 years follow up after helium ion therapy for uveal melanoma
the melanoma mortality rate was estimated to be 21%.
Trans-pupillary thermotherapy is a new technique that uses an infra-

red radiation at 700 to 900 nm to produce a temperature above 45
degrees but below the retinal photoreceptor damage level. Trans-
pupillary thermotherapy appears to be an effective treatment for selected
small malignant melanoma, specially those near to the fovea or the optic
disc. Some tumours may fail to respond to thermotherapy.
Hyperthermia seems to have a synergistic action with radiation. The

effect of thermotherapy is maximum at the top of the tumour while the
effect of brachytherapy is maximum at the base of the tumour (sandwich
treatment). Trans-pupillary thermotherapy may be used as a treatment
alternative for both pigmented and amelanotic small choroidal melanoma.
Treatment may be associated with nerve fibre layer defect and dense
scotomas. Juxta-papillary tumours may be at higher risk for recurrence.
Planned combined treatment of radiotherapy, thermotherapy,
photocoagulation and resection may have a significant role in the
treatment.
Transscleral resection of choroidal malignant melanoma is becoming

more popular in some centres. Tumours extending to one disc diameter
to the optic disc or the fovea is at risk of having a residual tumour, and of
recurrence after transscleral resection. Recurrence often occurs within 7
years of resection. A histological report of complete excision is not a
guarantee against recurrence. Recurrent tumours should be treated very
aggressively by plaque radiotherapy, unless they are small and flat in
which case photocoagulation may be sufficient. Survival after transscleral
resection of malignant melanoma, at 15 years, diminishes from 92% (if
there are less than two risk factors), to less than 30% in 3.5 years (if there
are more than 3 risk factors). These risk factors include:
60 years of age or older.

Mixed or Epithelioid cell type.
Superior location of mixed or Epithelioid cell type.
Basal tumour diameter of 16 mm or more.
Lack of adjunct therapy.
Secondary enucleation for bulky residual tumours.
Recurrent small tumour or extraocular extension.
Surgical resection of choroidal malignant melanomas may be used in

tumours close to the optic nerve or the fovea. Surgical resection may
help to preserve central vision and field of vision when radiotherapy is
thought to be risky in causing ischaemic optic neuropathy. The most
common complications of this method of treatment are vitreous
haemorrhage, cataract, and retinal detachment.
Photo-dynamic therapy may have an important role in the treatment of

pigmented choroidal malignant melanoma. Animals with pigmented
choroidal malignant melanoma show complete tumour regression when
treated with Benzoporphyrin derivative and light. Tumour regression is
probably due to vascular occlusion, tumour necrosis and inflammatory
cell infiltration.
The radio-surgical Leskell Gamma knife therapy is an alternative,

relatively new method to microsurgery and conventional radiation therapy
in the treatment of many skull-base lesions. In this treatment, a single-
session delivery of a high dose of ionising radiation to a localised volume
of tissue is applied. Treatment with the Leksell gamma knife may lead to
significant reduction of the blood flow in the central retinal and the short
posterior ciliary arteries. Optic neuropathy may also follow radio-surgery
to lesions near the visual pathways. Careful dose planning guided by MRI
with restriction of the maximal dose to the visual pathways to less than 8
G y will likely reduce the incidence of this complication. The pattern of
echographic reflectivity and decrease in tumour size is similar to after
treatment with brachytherapy. An increase in reflectivity and a decrease
in tumour size in the first 6-8 months can be considered as a success.
The anti-tumour activity of interferon-alpha and gamma have been

studied in some human tumour (e.g. haematological and cutaneous
malignancies). The exact mechanism of interferon alpha and gamma is
not exactly understood but it is thought that it may modulate some cell
surface molecules. The effects of interferon alpha and gamma, on human
uveal malignant melanoma in vitro, suggest that these drugs may have a
potential role in the treatment of malignant melanoma. Interferon alpha
and gamma treatment might stimulate an important anti tumour
immunological effect in vivo.
Vaccination of melanoma patients with tumour lysate-pulsed dendritic

cells may lead to partial or complete tumour regression in some patients.
Dendritic cells are antigen presenting cells involved in the induction of T
cell response. These cells have been shown to attack melanoma cells in
an HLA restricted manner. Large scale clinical trial are needed before
reaching any definite conclusions.
Retinoblastoma
Retinoblastoma typically presents with leukocoria in children between 12
and 18 months of age. The tumour may also be associated with retinal
detachment. Advanced retinoblastoma, with massive necrosis and
anterior chamber reaction, may rarely present with preseptal orbital
cellulitis which may be due an immunological mechanism. The presence
of cellulitis does not necessarily indicate extra-ocular extension. The
cellulitis may be treated by systemic steroid treatment. The tumour may
also masquerade as uveitis. In children presenting with uveitis, the
absence of pain, conjunctival redness, posterior synechiae and cataract
should raise suspicion to the possibility of a retinoblastoma
masquerading as uveitis.
The prognosis of retinoblastoma depends on whether the optic nerve is

involved or not. CAT scan is very useful in the evaluation of eyes with
retinoblastoma, because of the presence of calcium in most tumours.
High resolution scan with 1.5 mm or thinner sections is useful in
assessing optic nerve involvement. Non-visualisation of the central retinal
vein is another reliable indicator of optic nerve involvement.
Orbital involvement with the tumour has a poor prognosis for life.
Aggressive management approach with treatment with radical surgery,
chemotherapy and external beam radiotherapy may achieve longer life
survival for the patients.
treatment
In the past several years there has been a trend towards conservative
treatment of retinoblastoma. Enucleation remains the standard treatment
for advanced unilateral and for the worst eye in most bilateral cases.
Many eyes, however, can be saved by conservative treatment which
includes:
• External beam radiotherapy.

• Radiation brachytherapy (using episcleral radioactive plaques).
• Cryotherapy.
• Chemotherapy.
• Argon laser photocoagulation (for small tumours).
• Contact transscleral diode laser photocoagulation may also be a good
alternative method for treatment.
Second tumours may occur in long term survivors after radiotherapy.

Most of the tumours occurs outside the field of irradiation. Some
investigators also showed that second tumours are relatively more
common in hereditary disease even without prior radiation therapy. The
incidence of second tumours varies significantly in the literature. The
variable incidence of non-ocular tumours recorded in various reports may
be due to difference in the technique and in the dosage of irradiation. The

risk of second tumours decreases with increased patient age at the time
of treatment. The incidence of second tumours is very small if the
treatment is administered after 12 months of age. In a study of 180
children with hereditary retinoblastoma, the incidence of second non-
ocular tumours after radiotherapy was 12% after 10 years and 30% after
40 years. Radiotherapy may also result in the development of cataract.
Cataract extraction with posterior chamber IOL, in eyes with regressed
tumours, is safe and beneficial.
Chemoreduction is a treatment method designed to reduce the tumour

size to allow for more focused and less damaging other methods of
treatment. This method enhances the effect of other therapeutic
modalities (e.g. cryotherapy, laser photocoagulation, thermotherapy or
plaque radiotherapy). Chemoreduction may also be used as a primary
treatment , but different methods of treatment should also be used if there
is no tumour regression after the chemoreduction.
Chemoreduction, when used with other adjunct therapy (e.g. laser

photocoagulation, thermotherapy, and plaque radiotherapy) is particularly
useful in massive tumours involving more than half the retina with and
without vitreous seeding. This method of treatment, in these advanced
cases, may help to avoid external beam irradiation and enucleation.
Chemoreduction may be carried out by:
Vincristine.
Etoposide.
Carboplatin.
Carboplatin is often administered intravenously. Sub-conjunctival and

episcleral (by a balloon) administration of carboplatin is associated with
higher levels in the aqueous and the vitreous than after intravenous
administration. This method of administration was reported to be effective
and safe for the treatment of intraocular retinoblastoma and may prove to
be useful in young children. Vitreous disease seems to respond well but
subretinal tumour may not respond very well to this method of treatment.
In a recent report, the authors used this protocol for the treatment: 1.4–
2.0 ml of a 10-mg/ml solution, 1–7 injections per eye, at a median interval
of 21 days between injections. This method of treatment may be
associated with transient peri-orbital oedema and optic atrophy. It does
not, however, appear to be associated with systemic toxicity. Adverse
effects e.g. myelosuppression and infection are likely to complicate the
systemic treatment. These adverse effects are often treatable and do not
often lead to cessation of the treatment.
Cryotherapy, 24 hours before the administration of chemotherapy,

significantly increases the intravitreal penetration of carboplatin. The
increased vitreous level of the drug after cryotherapy may be due to the
induced retinal oedema and sub-retinal fluid. High doses of Cyclosporin,
before chemotherapy, can also result in higher vitreous levels of the

carboplatin. A combination of Etoposide-carboplatin may also be in the
treatment of extraocular and intraocular retinoblastoma. The use of
hyperthermia (by diode laser), may enhance the effect of chemotherapy,
avoid the need for enucleation or external beam radiotherapy, and thus
save many eyes. Thermotherapy, alone, may also be used for relatively
small tumours without associated vitreous or subretinal seeds.
• Retinocytoma
Retinocytoma is considered as a benign type of retinoblastoma. These

tumours are composed of well differentiated retinal cells with no mitosis
or necrosis. The mean age of diagnosis of these tumours is 15 years of
age. The tumour may be unilateral or bilateral and family history of
retinoblastoma may be present. The characteristic features of these
tumours include:
• translucent retinal mass

• calcification
• changes in retinal pigment epithelium
• chorioretinal atrophy
It is important to recognise these tumours because they often need only

observation and no active treatment. The tumour also belong to the same
gene of retinoblastoma chromosome 13q14. Members of the same family
may develop either retinoblastoma or retinocytoma. Malignant
transformation to retinoblastoma may very rarely occurs.
Choroidal haemangiomas
The diagnosis of choroidal haemangiomas may be difficult. Several
ancillary tests (fluorescein angiography, ultrasound, and MRI) are often
needed to help with making the diagnosis. Indocyanine green
angiography may show specific characteristic patterns that do not show
with fluorescein angiography. Haemangiomas, if left untreated, may
evolve to exudative retinal detachment and marked loss in the visual
acuity. Close follow-up is recommended.
Various methods of treatment have been used for the treatment of

choroidal haemangioma. These methods include laser photocoagulation,
xenon arc photocoagulation, diathermy, cryotherapy, external irradiation,
trans-pupillary thermotherapy and brachytherapy.
The treatment of macular and juxta-papillary choroidal haemangioma is

often difficult. Cobalt-60 radiotherapy is a valuable method of treatment
especially when the tumour involves the maculae or when it is associated
with bullous retinal detachment. The role of Proton beam radiotherapy in
the treatment of choroidal haemangiomas is new and not completely
known. Diffuse haemangiomas may be treated with lens sparing
irradiation, while circumscribed choroidal haemangiomas, with
symptomatic serous retinal detachment, appear to respond well to proton
irradiation therapy. Some reports, however, showed disappointing results
of proton irradiation in preventing radiation optic neuropathy, and
maculopathy.
Ocular Lymphoma
Primary intraocular-CNS lymphoma is a non-Hodgkin type lymphoma. It
has previously been called reticulum cell carcinoma. The disease often
masquerade as idiopathic vitritis in elderly patients. It may also presents
either as a subretinal pigment epithelium infiltrates or as vitreous
opacities. The tumour should be considered in old patients with vitreous
cells, floaters and also in patients with painless visual loss without
inflammatory signs. Central nervous system involvement is frequent and
associated with a high mortality rate. Early diagnosis and treatment may
improve the prognosis. A high index of suspicion in elderly patients
with uveitis is important so that a diagnostic vitrectomy can be arranged.
Vitreous cytology is a sensitive, reliable, and reproducible method of
making the diagnosing. Malignant cells (B lymphocytes) are often
present in the CSF at the time of ocular lymphoma is diagnosed, but their
finding is often difficult. Multiple vitrectomy operations and lumbar
punctures may be necessary before finding the malignant cells and
making the correct diagnosis.
Interleukin-10 is a growth and differentiating factor for B cell

lymphocytes. Concentration of Interleukin-10 in the vitreous is raised in
most patients with intraocular lymphomas and may be helpful in making
the diagnosis. An interleukin-10 / interleukin-6 ratio greater than 1.0 in
ocular fluids is a useful adjuncts in the diagnosis. The levels of the
Interleukin-10 in the vitreous also seem to correlated with the clinical
activities of the tumour. Histologically proven cases, however, have been
reported in which interleukin-10 to interleukin-6 ratio was less than 1.0.
Elevated Vitreous Interleukin-10 Level is not diagnostic of the disease,
and chorioretinal biopsy may be needed in these cases to establish the
diagnosis.
Abnormal lymphocytes may be sequestered between the retinal pigment

epithelium and the Bruch’s membrane with minimal vitreous spill over
which might lead to a false negative biopsy. A subretinal pigment
epithelium biopsy may be used in cases when deep retinal infiltration is
seen with minimal vitreous cells. Transscleral or trans-retinal approach
may be used. PCR technique is a useful method that can be used in
making the diagnosis of suspected intraocular lymphoma. It can be used
to detect B- and T-cell gene re-arrangements in the vitreous washing
specimens in patient with Intraocular Lymphoma. It is important that the
specimens are handed with care to prevent degradation of the DNA.
Appropriate handling of specimens and examination by experienced
pathologists are critical in the diagnosis. Diagnostic yields may be
improved if the specimens are obtained from patients not receiving
systemic steroids because steroids are cytotoxic for the non-Hodgkin
lymphoma cells.
Re-arrangement of the Ig H gene may also be helpful as a marker for

primary CNS lymphomas. When the suspicion of intraocular lymphoma
remains high despite previous negative vitreous biopsies, retinal biopsy

and aspiration biopsy of subretinal lesions may enhance the diagnostic
yield.
Irradiation alone or a combination of irradiation and chemotherapy

have been shown to be effective in inducing remission of the disease.
The most frequent type of ocular lymphoma has been linked to

lymphoma of mucosa-associated lymphoid tissue arising in the
gastrointestinal tract. The term mucosa-associated lymphoid tissue
(MALT) has been introduced to describe the characteristic arrangement
of lymphoid tissues found in certain mucosal tissues (e.g. the
gastrointestinal tract). MALT lymphoma is now recognised as a specific
form of tumour that is distinguished from primary, non-Hodgkin, extra-
nodal lymphoma. It has been suggested that primary conjunctival
lymphomas originates from this MALT tissue. The conjunctival MALT
lymphoma may be bilateral or unilateral, the typical histological features
include:
sub-mucosal B -cells follicles,

a surrounding mantle zone of small lymphocytes,
a region of B-cells extending from the mantle zone to the overlying
epithelium,
extension of these B-cells to the overlying epithelium.
Patients with MALT may be treated with radiation, chemotherapy,

surgical excision, cryotherapy or by intra-lesion injection of interferon
alpha-2b. Conjunctival lymphoma may recur in other mucosal associated
lymphoid tissue.
Basal cell carcinoma

Basal cell carcinoma is the most common malignant skin tumour in
humans. It accounts for approximately 75% of all malignant skin lesions.
Ultraviolet radiation exposure plays a part in the aetiology of this disease.
Most basal cell carcinomas of the conjunctiva are cutaneous in origin.
Conjunctival involvement is often secondary to skin involvement.
Conjunctival tumours may result from seeding during the excision of an
adjacent lid tumour.
The basal cell carcinomas are stroma-dependent tumours and a break in

the conjunctiva epithelium seems to be necessary for such seeding to
occur, the conjunctiva surface should be maintained and protected during
lid tumour surgery. Primary basal cell carcinoma arising from the caruncle
has also been described.
Surgery, radiation therapy and cryotherapy are the currently accepted

methods for the treatment of basal cell carcinoma. Complete tumour
excision is the treatment of choice. Recurrence in margin positive excised
tumour is high. An aggressive treatment of margin positive tumours is
necessary. Moh’s technique for excision of peri-orbital tumours provides
horizontal as well vertical tissue sections, which allows examination of
100% of the tumour margins. Excision of lids and orbital tumours by the
Moh’s technique may reveal extensive sub-clinical extension of the
tumour. The technique may also be useful in providing an evidence for
less extensive excision of tissue, and less reconstructive surgery than
otherwise would have been predicted. The technique provides the best
cure rate as well as a maximal preservation of tissue for good
reconstruction. Laser microsurgery with microscope-mounted CO2 laser
may also be used for the treatment of primary superficial tumours without
conjunctival extension.
Diseases of The Ocular Adnexa
Oculoplastic
ptosis and ptosis surgery
Ptosis is generally classified into two types congenital or acquired.
Congenital ptosis is thought to be due to dystrophic changes in the
levator muscle. Some investigators believe that it is more likely to be due
levator muscle dysgenesis. In a recent report, levator muscle fibres from
patients with congenital ptosis and normal individuals were examined and
compared microscopically. The authors of the report found no significant
difference in the muscle fibres diameters or its distribution between the
two groups. The results of this report does not, therefore, support the
assumption that this condition is due a dystrophic changes.
Patients with congenital ptosis have an increased incidence of refractive

errors and corneal astigmatism. Amblyopia in these patients may be due
to either visual deprivation, if the pupil is completely covered by the upper
lid, or due to the refractive error. Congenital ptosis may also be
associated with strabismus in about 32% of patients. The association of
congenital ptosis with weakness, or over-action of the ipsilateral superior
rectus muscle, or with double elevator palsy has been previously
reported.
In acquired ptosis the degree of ptosis is typically the same on primary

position and on down gaze. Patients with congenital ptosis, on the other
hand, demonstrate a widening of the palpebral fissure on down gaze due
to lack of elasticity of the levator muscle. This sign may be helpful in the
differentiation between congenital and acquired ptosis. Some patients
with acquired ptosis, however, may have worsening of the ptosis in down
gaze position. The increased ptosis in down gaze noted in some patients
with acquired ptosis may be a normal physiological processes. Older
patients with no ptosis tend to have a greater decrease in their upper
eyelid margin-corneal light reflex distance on down gaze.
The increase in ptosis on down gaze may interfere with some activities
e.g. reading. Many patients with acquired ptosis complain of fatigue,
headache and brow ache after prolonged periods of reading or working in
down gaze position. The continuous action of the frontalis muscle to raise
the upper lid, may explain the symptoms of fatigue and headache in this
subgroup of patients. Ptosis repair is associated with significant widening
of the palpebral fissure height in down gaze and a significant decrease in
the use of the frontalis muscle and return of the patients ability to sustain
down gaze work more comfortably.
1
Acquired ptosis may be caused by old age, cataract surgery, contact lens
wear and myasthenia gravis. Contact lens wear is reported to be the
commonest cause of ptosis in young healthy adults. Imbedding of the
contact lens in the upper lid conjunctiva may lead to inflammatory
changes causing the ptosis. Rubbing of the contact lens against the
upper lid may also cause inflammatory changes causing the lid to droop
down. The mechanism of removing the contact lens by pulling on the
upper lid and forcibly blink may be another mechanism for causing the
ptosis.
Myasthenia gravis is an important cause of acquired ptosis. Exclusion of

the disease is important as this condition is often treated medically.
Diagnosis of the disease is often established by invasive tests e.g. the
edrophonium test. The ICE test is a fairly new, safe, quick and easy test
to help with the diagnosis of the disease. The test is performed as
follows:
1. Apply an ice pack to the ptotic eye lid for two minutes.
2. Two or more millimetres of elevation of the lid after ice application is
considered positive and highly suggestive of the disease.
The test is based on the fact that increased temperature has a

detrimental effect and cooling has a beneficial effect on muscle force
generation in myasthenia gravis, presumably by inhibiting
anticholinesterases function. The specificity of the test is estimated to be
100%, while The sensitivity ranges between 80% and 100%. The results
are not affected if the patients are taking anticholinesterases at the time
of the test. It may be positive in cases with negative edrophonium test or
anti-ACh R antibodies.
management and surgical techniques
Patient’s quality of life is reduced by ptosis. Surgical repair often results in

measurable increase in patient’s health-related quality of life. In the
preoperative evaluation of ptosis there are two methods of evaluating the
levator muscle complex function: either by measuring the lid excursion, or
by measuring the levator force (as measured by a new instrument).
Diagnosing the cause of ptosis (neurogenic, myogenic, aponeurotic or
mechanical) based on the levator force measurement is significantly
more accurate than when based on the lid excursion specially when
combined with clinical examination. It is suggested that levator force
measurement should be an important component and a constant part in
the assessment of cases of ptosis.
• brow suspension
Children with severe unilateral congenital ptosis are at risk of developing

deprivation amblyopia if the lid covers the visual axis. In this situation
2
urgent repair of the ptosis is indicated. Frontalis suspension is often the

treatment of choice because it is difficult to evaluate the levator function
properly in children. Frontalis suspension is also indicated in ptosis
patients with poor or no levator function (e.g. congenital ptosis and ptosis
associated with progressive external ophthalmoplegia, third nerve palsy
or myasthenia gravis). Using autogenous fascia lata is the preferred
method of suspension. Harvesting fascia lata is reported to cause
minimal or no postoperative morbidity though complications can arise
when a large area of fascia lata is removed. The traditional method of
harvesting fascia lata has been through an incision above the lateral
knee. Problems with this method include a conspicuous scar, herniation
of the muscle belly and haematoma formation. Fascia lata can also be
harvested safely from the region of the iliac crest with an inconspicuous
scar and with fewer complications than with the more traditional site
slightly above the lateral knee.
In young children there is insufficient autogenous fascia lata to use.

Different materials have also been used to suspend the upper lid from
the eye brow including. These methods include; non-absorbable Prolene
Mono-filaments sutures, sclera, or preserved fascia lata, supramid and
temporalis fascia. Supramid sling is often associated with only temporary
correction of the ptosis. Recurrence may be noticed any time within the
first 18 months. Mersilene mesh can also be used in patients not suitable
for autogenous fascia lata. Mersilene mesh acts as a scaffold which
support fibrovascular in-growth. Complications of this technique include
extrusion of the mesh, infection and granuloma formation. Complications
can be reduced by meticulous closure of the wound. Silicon rods are also
effective and can be used in both children and adults. Silicon rods have
the advantages of being elastic and easy to adjust. Long term recurrence
of ptosis is possible and follow up is recommended. The palmaris
longus tendon can also be used as a sling material for frontalis muscle
suspension in adults and children. The loss of this tendon is not
associated with any functional deficits. The tendon often lies in a
superficial location and can be identified and isolated easily. It is also
strong, long and thin enough to be easily placed in the eyelid.
• levator surgery
Levator aponeurosis ptosis surgery is often carried out via an anterior

approach through the skin or by a posterior approach through the
conjunctiva. Controlling the height of skin crease is easier to achieve via
the anterior approach. The anterior approach may be carried out through
a small 8 mm eyelid crease incision, in some selected patients.
The technique of levator transposition may be used in unilateral cases

of ptosis and aberrant eyelid movement. Further levator resection may be
needed to achieve better elevation of the lid. Maximum function of the
muscle may not be achieved for 12 months after surgery (time for motor
enervation to establish). It is recommended that this procedure should be
3
reserved for patients with unilateral disease, and that patients should also
be warned that they might need more than one operation and the final
outcome might take about one year to establish.
The most common complication after levator muscle surgery for ptosis
are under-correction, over-correction or abnormalities of eyelid contour.
In a study of 164 cases, 40% of cases reached their final level at one
week after surgery, and 52% continued to rise by a mean of 1.1 mm.
Most lids seem to achieve their maximum height by 6 weeks. MRI may
be used in the evaluation of the upper lid contour in patients with ptosis or
lid retraction.
Revision and further adjustment of the lid height and contour can be
performed three to four days after the operation as an out-patient
procedure. Postoperative oedema or haemorrhage, which distorts the
eyelid, are contraindications to early revision as they make revision more
difficult technically and also harder to predict.
• adjustable sutures technique
Adjustable sutures surgery for ptosis, and lid retraction is a useful

technique when surgery is performed under general anaesthesia (e.g. in
children). The technique is also useful in the following conditions:
1. Traumatic ptosis.
2. Thyroid eye disease.
3. Ptosis correction after excessive upper lid lowering.
Adjustable sutures allow the lid height to be adjusted for over- and under-
correction to achieve the optimal surgical results. Suture adjustment is a
simple procedure and is recommended to be carried out within 24 hours
after the operation. Marked postoperative lid oedema may make suture
adjustment more difficult. In the anterior approach technique the sutures
pass from the levator muscle through the anterior surface of the tarsal
plate exiting through the upper and lower skin edges. The position of the
skin crease can also be adjusted. In the posterior approach the sutures
pass from the levator through the cut upper edge of the tarsal plate and
then tied and positioned at the position of the desired skin crease.
• the single stage aponeurotic tuck technique
The single stage aponeurotic tuck technique is a simple and effective

method of treating ptosis for involutional, post-cataract, traumatic and
also congenital types of ptosis (under general anaesthesia). This
procedure may be used for degrees of ptosis ranging from 1-5 mm with
levator function greater than 8 mm. The procedure involves dissection of
the aponeurosis in the usual way. A 6/0 nylon suture is then inserted 2
mm medial to the pupil in the anterior surface of the superior tarsal border
and then re-inserted at the healthy substance of the levator aponeurosis
4
higher up. Asking the patient to look down will ensure that the second
suture bite will be taken as high as possible in the levator aponeurosis. A
slip knot is then tied first to judge the crease level and the height of the lid
and then is readjusted accordingly. An over-correction of 1.0 to 1.5 mm is
aimed at the end of the operation to ensure a good postoperative level.
• upper blepharoplasty
The traditional treatment in Progressive myopathic ptosis is by levator

muscle resection or by frontalis sling. Either of these procedures may
result in lagophthalmos and exposure keratopathy. Upper blepharoplasty
(removing all excess skin and orbicularis between the eye brow and the
eyelid margin) may be used as an alternative method for ptosis correction
in these patients. The procedure leads to an improvement in the degree
of ptosis with no corneal exposure with fewer postoperative complications
and clinics visits.
5
hydroxyapatite orbital implants

Hydroxyapatite orbital implants have gained popularity in recent years
because of the excellent cosmetic results that can be achieved with the
technique. The implants are made of calcium phosphate that is derived
from coral. They become integrated into the orbit by a fibrovascular
growth. Fibrovascular growth may occur in the pores of hydroxyapatite
orbital implants as early as 4 weeks after implantation. Bone may form
within the implant if it is implanted in a direct contact with bone. Bone may
also be produced by transformation of the circulating monocytes cells or
by osseous metaplasia of the fibrocytes which migrate inside the implant.
Ossification of the implant may occur in some patients after up to 18
months. MRI can identify the progression of fibrovascular in-growth into
hydroxyapatite implants and guide surgical planning of a successful
prosthesis attachment. It may also identify implants that failed to develop
good vascularisation and hence avoid possible complications of drilling
into avascular implants.
The presence of complete vascularisation of hydroxyapatite implants at

the time of drilling is crucial for the epithelialisation of the wall of the hole.
The technetium bone scan is sensitive to the vascularisation of the
hydroxyapatite implant and indicates when complete vascularisation is
approached. At least a 4-week interval between the time the bone scan
showing complete vascularisation and peg drilling is recommended.
Pegging of the implant is often carried out as a secondary procedure. it

may also be, reliably and safely, fitted during the primary procedure. The
main advantages of these implants are good motility results. The
postoperative results after Hydroxyapatite implants, without pegging, are
similar to those obtained after other types of orbital implants. Motility of
the of the artificial eye is, however, enhanced by pegging the prosthesis
to the implants by means of drilling a hole in the implants and then fixing
the prosthesis to the peg. Pegging the implant seems to increases the
motility and stability of the prosthesis. Inserting a begging system in the
Hydroxyapatite results in a better motility of the prosthesis. Some
authorities believe that non-pegged implants are not superior to other
spherical orbital implants at all.
Hydroxyapatite implants can be used after enucleation as a primary or

secondary procedure for many different reasons (e.g. malignant
melanoma, retinoblastoma and blind painful eyes). Prior radiotherapy
treatment does not seem to increase the complication rate.
Hydroxyapatite orbital implants are also well tolerated, and provide good
cosmetic results in the paediatric age group. In this age group it is critical
to fit the implant comfortably to avoid conjunctival erosions and thinning.
Drilling and peg placement may be delayed until the child is old enough.
complications
6
Problems encountered with this Hydroxyapatite implants include orbital

injection, conjunctival thinning and erosions. Evaluation of the
fibrovascular state of the implant is important before considering any
secondary procedure (e.g. drilling a peg hole) as this may also induce
exposure.
The reported incidence of implant exposure varies between 0% to 11%.

Implant exposure occurs more frequently after evisceration than after
enucleation. It is also more frequent in unwrapped implants or with
implants wrapped in preserved fascia rather than in sclera. Spontaneous
healing rarely occur, and conservative treatment is only limited to
exposures less than 4 mm2. Several techniques have been described for
the repair of implant exposure e.g. scleral or conjunctival flaps, or by
using free autogenous tissues (e.g. hard palate mucosa or dermis grafts).
A tarsoconjunctival pedicle flap may also be fashioned from the upper lid
to cover the exposed area. Division of the pedicle can be carried out later
on as a second stage procedure. Choosing the right size implant with
meticulous coverage with good vascular tissue and with minimal tension
helps to avoid the problem of exposure.
Dexon mesh wrapping is thought to be similar to scleral wrapping with

respect to complications, although more posterior implant placement may
be necessary to avoid exposure in the Dexon-wrapped implants.
Autogenous posterior auricular muscle may also be considered as
wrapping material in primary and secondary orbital implants after
enucleation.
Most of the complications associated with the pegging system are minor.
Severe infection may, however, occur and may lead to the removal of
the implants. Persistent orbital discomfort, discharge or the development
of pyogenic granuloma after implantation should warn the surgeon of
potential implant infection and abscess formation. Infection associated
with hydroxyapatite implants is rare, yet it is difficult to treat and implant
removal is often required.
Extrusion of the pegs is another problem which can be minimised by

employing a sleeved peg rather than a non-sleeved peg system. Medial
or lateral implant deviation is a rare postoperative complication. In
patients with pre-existing risk factors (e.g. strabismus, or severe trauma
to the extraocular muscles), it is recommended that, the anterior face the
implant is modified to avoid this complication. Some authorities
advocated flattening the anterior surface of the implants which may help
in the pigging procedure afterwards. Rotation of the flattened implants
may occur after surgery especially in patients with strabismus.
Some patients may experience severe pain after implantation of

Hydroxyapatite implants. Patients with primary implant may suffer more
pain than patients with secondary implantation. Patients should be
counselled, and precautions should be taken to deal with complication.
7
Superior sulcus orbital defects is a major complication after orbital

implants surgery. A new design of a conical-shaped enucleation implant
to help minimise the occurrence of superior sulcus defects and maximise
motility of the prosthesis has been described.
8
miscellaneous
• floppy eyelids
Floppy eyelid syndrome is typically associated with easily evertable

upper lid with papillary conjunctivitis of the upper palpebral conjunctiva.
Eye lashes ptosis and loss of eye lashes parallelism have also been
reported. This condition usually occurs in middle aged obese women.
Floppy eyelid syndrome may also manifest in childhood without other
contributing conditions and should be considered in the differential
diagnosis of chronic papillary conjunctivitis in patients at any age.
The syndrome has been described in association with various other

syndromes (e.g. keratoconus, sleep apnoea, meibomian gland
dysfunction and blepharochalasis). Lax eyelid may also occur due to
involutional changes in the medial or lateral canthal tendon or in the
orbital fat. Most elderly patients with lax eyelids are asymptomatic. The
term (Lax eyelid syndrome) is suggested for use with these various
conditions. The clinical features of the syndrome may be due to
decreased tarsal elastin.
• entropion and ectropion
Involutional entropion is often associated with increased lid laxity. The

definite treatment of entropion of the lower lid is by surgery. Surgical
treatment of this condition has traditionally been with lid splitting
procedures (e.g. the Weiss procedure) or by lid shortening ones (e.g.
Quickert operation). A recent report indicates that surgical success is
much higher, in involutional entropion with lid laxity, if the lid is
shortened. Reinsertion of the lower eyelid retractor aponeurosis to the
tarsal plate, without horizontal shortening or resection of the skin or
orbicularis muscle is an effective procedure for the surgical repair of
involutional entropion. The procedure has a low recurrence rate. In the
absence of horizontal laxity of the lower eyelid, a retrospective case
series comparative study showed that a successful outcome is more
likely after Jones retractor plication than after the Wies procedure.
Recurrence of the entropion may also be due to laxity of the lower lid
retractors. Shortening and tightening of the lid retractors may be needed.
A trans-conjunctival approach to advance or strengthen the lower
eyelid retractor in entropion surgery has been described. This technique
can also be associated with a lateral canthal suspension procedure to
shorten the eyelid or with trans-conjunctival blepharoplasty. In this
technique a lateral canthotomy is carried out, the inferior crus of the
lateral canthal ligament is incised. An incision is then made below the
tarsal plate through the conjunctiva and the lid retractors and a strip of
the orbicularis muscle is excised. The retractors are then separated from
the conjunctiva and then re-inserted in the inferior and anterior tarsal
palate.
9
When surgery is not possible botulinum toxin may be used. The use of
botulinum toxin is highly effective. It is also associated with few
complications and does not seem to have any adverse effects on the
results of future surgical entropion repair. The mean duration of action of
the toxin is about 12.5 weeks. The use of the drug does nor appear to be
associated with consistent changes in orbicularis oculi morphology after
injection.
• centurion syndrome
Centurion syndrome is a recently described syndrome characterised by

anterior displacement of the anterior part of the medial canthal tendon
and a prominent nasal bridge, with lid malposition away from the globe
and the lacrimal punctum outside the tear lake. Patients typically have
epiphora dating from birth which gets worse at puberty. Syringing of the
nasolacrimal duct is often patent. Treatment may be achieved by surgical
correction of the anterior limb of the medial canthus with / or without DCR
operation.
• capillary haemangioma
Capillary haemangioma of the eye lids can be treated by intra-lesion

injection of steroids. Central retinal artery occlusion (due to
embolization) leading to visual loss has been reported after this method
of treatment. Care should be taken when injecting long acting steroids.
The solution should not be mixed with local anaesthesia or epinephrine
or allowed to rest for any length of time before use as these two
conditions may cause a significant increase in the steroid particle size. If
mixing the steroid with local anaesthesia or epinephrine is necessary, it is
recommended that injection takes place immediately after mixing the
solutions. Most steroid injections show an increase in their particles size
within one hour of mixing with anaesthetic solutions. Mixing different
types of steroids does not seem to cause an increase in the solution
particles size.
10
Lacrimal Diseases
dacryocystitis
Lacrimal drainage dysfunction may be due to an anatomical obstruction,
or due to a physiological dysfunction. Anatomical block is often caused
by a post-inflammatory fibrosis, stenosis or due to the presence of a
lacrimal stone or tumour. Primary acquired nasolacrimal duct obstruction
is more prevalent in women than in men because women have
significantly smaller dimensions in the lower nasolacrimal fossa and the
middle nasolacrimal duct than men. Chronic intra-nasal cocaine abuse
may result in bony destruction of the orbit, orbital cellulitis and also
nasolacrimal duct obstruction. Dacryocystitis may also be caused by
diseases of the lateral nasal wall.
Systemic 5 FU is commonly used in the treatment of some tumours. A

high concentration of the drug is secreted in the tears. The systemic use
of 5 FU may be associated with ocular side effects e.g. lacrimal
canalicular fibrosis and epiphora, and ectropion. The canalicular fibrosis
in these cases may be localised or diffuse. Treatment is often difficult. If
the drug can not be stopped, prophylactic silicon intubation should be
used.
The most frequently cultured bacterial species from cases of

dacryocystitis is Staphylococcus epidermidis. Chronic dacryocystitis in
adults is also associated with an increased proportion of Gram negative
bacteria which may be a reservoir for postoperative intraocular infection.
It is recommended that specimen should always be sent for culture and
sensitivity in cases of dacryocystitis since infection may be caused by
aerobic as well as anaerobic organisms.
Herpetic canaliculitis has been recognised as a distinct entity recently.

Primary herpes simplex virus infection may result in canalicular
obstruction or stenosis. Lester Jones tube has been the traditional
method of treatment in the absence of enough patent canaliculus. DCR
operation with retrograde or antegrade intubation may also be used in the
treatment of these cases. It is also suggested that all patients with ocular
primary herpes simplex infection should be prophylactically intubated with
silicone lacrimal stents in order to prevent herpetic cicatricial canalicular
stenosis.
11
investigative procedures
Jones test I and II, syringing, probing, the micro-Reflux test and
dacryocystography may all be used in the evaluation of patency of the
nasolacrimal system.
Jones tests can be carried out and interpreted as follows:
Jones I test Jones II test

How is it done? A drop of fluorescein is • If, 5 minuets after the primary test, no
instilled in the conjunctival fluorescein is seen in the inferior meatus,
sac. Jones II test is carried out.
• Flush all the fluorescein remaining in the
conjunctival sac.
• Irrigate the lacrimal system with clear
saline solution.
Positive test If fluorescein spontaneously • If fluorescein-stained saline is retrieved
appears in the inferior meatus from the nose the test is considered
of the nose within 1-5 minutes positive.
(can be demonstrated by • This can be checked by tilting the
using a cotton bud) the test is patient’s head forward to retrieve the
considered positive. saline coming out of the nose.
Negative test No fluorescein appears in the If clear saline, or partially stained saline
nose comes out of the nose, the test is
considered negative
Interpretation Positive Jones I indicates A positive Jones II test establishes that the
normal drainage system. upper part of the drainage system is patent,
since some saline must have entered and
stayed in the lacrimal sac.
Fluorescein dye disappearance test is another useful test that can be

used. in this test, a drop of fluorescein is instilled in the conjunctival sac.
The amount of fluorescein in the conjunctival sac is then observed 5
minutes after instilling the drops. The intensity of discoloration of the tear
meniscus can be used as an indication of the amount of fluorescein
remaining in the sac.
When Jones I and II tests are carried out in association with the
fluorescein disappearance test, the results can be interpreted according
to the following table:
Test
Fluorescein dye No residual dye Residual dye Residual Residual
disappearance dye dye
Jones I Positive Negative Negative Negative
Jones II Not done Positive Negative Negative
Diagnosis Normal system Functional Upper Upper
block system and lower
block system
block
12
The Micro-Reflux test is a new test that can be reliably used for the
diagnosis of complete nasolacrimal duct obstruction. A recent study
demonstrated that the test has a specificity of 95% and sensitivity of 97%.
The test can be carried out and interpreted as follows:
Two drops of fluorescein are instilled in the lower fornix.

The patient is then asked to blink 5 times to activate the lacrimal pump.
The inferior punctum is examined under the slit lamp.
The lacrimal sac in then massaged in a counter clockwise direction to
empty the inferior canaliculus.
The test is considered positive if there was a continued reflux of the dye-
stained tears from the lower punctum after the massage.
Dacryocystography is useful in demonstrating areas of obstruction

around the common canaliculus and the nasolacrimal duct. The test
successfully shows the area of obstruction in about 98% of common
canaliculus obstruction, and in 100% of cases of nasolacrimal
obstruction. The procedure can also predict multiple, congenital and,
physiological blocks. Syringing and probing alone does not seem to be
enough for the diagnosis and localisation of these cases.
Syringing and dacryocystography may show normal drainage system in

functional lacrimal obstruction. Lacrimal scintigraphy and
dacryocystography can be used to diagnose this condition even in the
presence of normal tear duct syringing. Lacrimal scintigraphy appears
to be slightly more sensitive than dacryocystography in showing the
drainage system abnormalities in this condition. The test might be useful
in patients with epiphora in whom dacryocystography is normal.
Lacrimal endoscopy is a new technique that may be used to visualise

the lacrimal drainage system. Small calibre endoscope can be especially
designed to be coupled to a lacrimal probe and a camera. The technique
may be useful in localisation of lacrimal obstruction and in aiding decision
making regarding choosing the right surgical procedure.
13
surgical techniques
• dacryocystorhinostomy
External DCR operations are highly successful for treating nasolacrimal

duct obstruction. DCR operations can safely be carried out on a day-case
surgery basis, with local or general anaesthesia. Careful selection of
patients is important. Narrowing of the osteotomy size is the most
common cause of failure of DCR and recurrence of the symptoms.
Narrowing of the rhinostomy occurs mainly due to fibrosis. New bone
formation may also occur. Large size osteotomy is, therefore, an
important part for the success of this operation. The size and patency of
the osteotomy may be assessed by the Jones test, dacryocystography,
and also be nasal endoscopy. B mode ultrasound examination may also
be used for evaluating the size of the osteotomy. Intraoperative
Mitomycin C may be used during the surgery to maintain a larger
osteotomy size. It has also been suggested that laser-DCR surgery may
be a useful approach for the revision of failed DCR cases.
Establishing a lacrimal pathway in DCR operation can be achieved by

several techniques. The use of large anterior nasal mucosa and lacrimal
sac flaps, with no posterior flaps anastomosis may be used to simplify the
operation. The large anterior flaps are easier to suture, but they need to
be elevated and anchored anteriorly, to the subcutaneous tissues in
order to prevent blockage of the lacrimal pathway by the large flaps.
Postoperative soft tissue infection may predispose to failure of DCR

surgery. Antibiotic therapy for established postoperative infection is less
effective than preventative therapy in improving the success rate of
surgery. It is recommended that all patients undergoing open lacrimal
surgery should receive prophylactic antibiotics (e.g. Cephalexin or
erythromycin).
• external or endonasal laser-assisted approach?
Endonasal laser DCR is a rapidly developing surgical procedure for the

treatment of nasolacrimal duct obstruction. C-DCR with Jones tube may
also be performed by an endoscopic technique The use of modern
endolacrimal endoscopic instruments has improved the results after
endonasal lacrimal surgery. Endonasal DCR has many potential
advantages over conventional external DCR:
1. Less disruption of the inner canthus region.

2. Enhanced haemostasis.
3. Avoidance of scar.
External-DCR, when compared with endonasal laser-DCR, seems to

provide superior results, in primary acquired nasolacrimal duct
obstruction. The success rate of endonasal laser-DCR is thought to be
14
less than the external conventional approach mainly due to the closure of
the ostium. In one study, the success rate at 1 year after surgery was
91% for external-DCR and 63% for endonasal laser-DCR after primary
surgery. Intraoperative use of Mitomycin C has been tried to increase
the success rate but, in some studies it failed to do so. Endonasal laser-
DCR seems to need some adjunctive treatment (e.g. lacrimal intubation)
to improve maintenance of the nasal mucosal opening.
Endonasal laser treatment has also been thought to be unsuitable for

canalicular obstruction disease. A recent study, however, showed that
an erbium YAG laser, attached to a flexible endoscope may be used for
treating obstructive lesion at the level of the upper and lower canaliculi,
when inserted into the canaliculi. Silicon intubation is required in these
cases.
• probing of the nasolacrimal system
When DCR surgery is contraindicated or considered inappropriate for

elderly patients, probing of the nasolacrimal duct, may be used instead.
Probing is effective, easy and does not appear to affect future surgical
treatment if required. This procedure is reported to be successful in about
82% of eyes. Silicon intubation of the nasolacrimal duct may also be
used. The treatment leads to complete or partial resolution in a high
percentage of patients. Recurrence may also occur in some patients.
Failure of the procedure does not seem to affect later DCR surgery.
• balloon dacryocystoplasty
Dacryocystoplasty is a new method for treatment of nasolacrimal duct

obstruction. The procedure can be carried out under topical anaesthesia
to the conjunctiva, infiltration anaesthesia to the infra-trochlear area and
to the nose. A 0.018 inch guide wire is then passed through the lacrimal
canaliculus to the nose, and a French balloon angioplasty catheter is
then passed through the nasolacrimal duct in a retrograde manner till it
reaches the nasolacrimal sac. The balloon is then inflated and left in situ
for 3-4 minutes after which it is deflated and removed.
The advantages of this procedure is that it is easy to perform under local

anaesthesia as a day case, can be repeated and does not change the
anatomy of the lacrimal passages. A conventional DCR operation can be
carried out later if this procedure fails. In children with congenital
nasolacrimal duct obstruction balloon catheter dilatation of the lacrimal
drainage system offers an alternative to silicon tube intubation. This
technique is generally effective in the treatment of congenital
nasolacrimal duct obstruction as a primary procedure and also after
failure of probing or silicon intubation. Balloon Dacryocystoplasty may
also be suitable for the treatment of partial obstruction below the level of
the lacrimal sac, but it is not effective for treatment of complete
obstruction of the lacrimal drainage system.
15
congenital nasolacrimal duct obstruction

Epiphora is a common symptom in young children, it is often due to
delayed canalisation of the nasolacrimal duct. Congenital nasolacrimal
duct obstruction affects about 20% of all infants. The majority of cases
resolve spontaneously, and 60% of eyes resolve spontaneously, without
treatment, before the age of 18 months. There is also a 50% chance of
spontaneous resolution during the period between 12 and 18 months of
age.
The traditional teaching is that, probing of the duct should be tried within
the first year of life if this procedure was to succeed. Both early (at 6
months) and late (at 12 months) probing have been shown to have a
similar high success rate (99%). Success rate seems to be slightly higher
in the younger age group. Increasing frequency of epiphora seems to be
associated with lower success rate.
Probing beyond the first year of age is also reported to be highly

successful, and the cure rate does not seem to vary significantly at
intervals of increasing age. Delaying nasolacrimal duct probing beyond
the first year does not appear to lead to more lacrimal dysfunction in later
years. Epiphora in later childhood may be due to other atopic conditions
rather than due to persistent stenosis of the nasolacrimal duct.
When probing fails to open the nasolacrimal duct obstruction, closed

silicon tube intubation (e.g. Crawford system) may be used. This
procedure may be difficult to carry out due to the compact anatomy of the
nose in children, and the need to retrieve the metal tube from the nose.
The Ritleng lacrimal intubation system is a new easy technique that
provides bicanalicular intubation of the nasolacrimal duct without the
need to retrieve any metal probes from the inferior meatus. The
technique involves the introduction of a Prolene guide thread, into a
tubular Ritleng probe, into the inferior meatus. A silicon tube, firmly
attached to the Prolene thread, is then drawn into the nasolacrimal duct
as the Prolene thread is pulled out of the nose.
Another new type of silastic tube that can be used for mono-canalicular
intubation in congenital nasolacrimal duct obstruction is the Monoka
tubes. The tube is inserted into the nasolacrimal duct through the upper
punctum, it is then anchored to the upper punctum by a special wide
flange. The overall success rate reported in some reports is 79% (which
is lower than the reported success rate with the bicanalicular technique).
One of the main complications of this tube is that it can easily pulled out
by the child. The upper punctum flange may also rub against the cornea
causing corneal abrasion. This tube has also been used in the treatment
of traumatic lacerations of the lower canaliculus.
16
canalicular trauma
Lacrimal canalicular damage may occur due to trauma, animal bites or
following excision of lid tumours. Various methods have been used to
repair the canalicular damage. These methods include direct
reconstruction and anastomosis of the canaliculi, pig tail probe and also
mono-canalicular intubation. Data from the literature do not conclusively
favour any of this methods over the others. It is very important that,
during repair of a mono-canalicular laceration, that great care should be
taken that the other canaliculus is not damaged. Simple repair of lid
injuries without any canalicular repair is probably better than any repair
which might prejudice the patency of the other canaliculus.
17
Diseases of the Orbit

idiopathic orbital myositis
Orbital myositis is a localised non-specific orbital inflammatory condition
that can affect any of the extraocular muscles. It is often an isolated
disorder but it has also been reported in association with upper
respiratory tract infections, myocarditis, Lyme disease and Herpes Zoster
infection. Bilateral orbital myositis has also been described in patients
with high grade non-Hodgkin lymphomas. It is believed that these
features constitute a paraneoplastic syndrome to the lymphoma.
Patients with unexplained enlargement of the extraocular muscles should

have a full medical examination with or without muscle biopsy to exclude
any underlying malignancy. The mechanism of orbital inflammation is not
known. Human orbital fibroblasts produce chemokines, interleukin 8 and
monocytes chemotactic protein.
Patients often present with orbital pain (which increases on eye

movements), redness, diplopia and headache. This condition should be
differentiated from dysthyroid eye disease, orbital pseudotumour, orbital
cellulitis, other conditions associated with ocular muscle enlargement and
other causes of globe retraction (Duane’s, generalised fibrosis syndrome,
blow out fracture). CAT, MRI and ultrasound scan show swelling of the
muscle insertion and reduced reflectivity of the muscle belly. The
condition often responds dramatically to systemic steroids in the acute
stages.
Dexamethasone is found to be a potent inhibitor to interleukin 8 and

monocytes chemotactic protein, in contrast to cyclosporin which seems to
enhance interleukin 8 production and suppress monocytes chemotactic
protein. This observation may explain the lack of response to cyclosporin
in orbital inflammatory disease that respond to steroids. In the more
chronic stages, a second line anti-inflammatory drugs may be needed
(e.g. methotrexate and orbital irradiation). Treatment for squint should be
delayed for at least three months to allow spontaneous recovery or full
recovery after steroid treatment or the full development of any restrictive
motility disorder.
preseptal and orbital cellulitis

Orbital cellulitis can affect any age. The disease is, however more
common in the paediatrics age group. The disease may be classified
according to severity to several stages:
1. Lid oedema due to preseptal infection.

2. Post-septal orbital cellulitis with proptosis, restricted eye movements.
3. Sub-periosteal abscess.
18
4. Orbital abscess.
5. Complication due to posterior extension (e.g. cavernous sinus
thrombosis endophthalmitis, and meningitis).
Patients in stage 1 can be treated conservatively or with oral antibiotics

on an out-patient basis. Stages 2 or above should be admitted to hospital
for daily examination and intravenous antibiotics.
The ophthalmic and orbital venous plexus is in direct contact with other
facial and intracranial plexuses with a valve-less system making direct
spread from the ear, sinuses or facial injuries, and also spread from the
orbit backward, easy.
It has always been thought that orbital cellulitis, in children should be

treated aggressively as it is often caused by Haemophilus sp. infection
and can be sight threatening. In a retrospective study of 70 cases with
preseptal and orbital cellulitis, the incidence of Haemophilus associated
bacteraemia, in children, was very low. Streptococcal infection was the
main infecting organism. The incidence of severe preseptal cellulitis
caused by group A streptococcal infection is increasing, especially after
post-traumatic preseptal cellulitis. Streptococcal toxic shock syndrome
secondary to group A beta haemolytic streptococcal preseptal cellulitis
has been described. In sexually active patients with peri-orbital infection,
Neisseria gonorrhoeae should also be considered as a possible causal
organism, especially if there is a previous history of sexually transmitted
diseases. The infection in these cases represents auto-inoculation from
an asymptomatic episode of genital gonorrhoea. Nasal cocaine abuse
may be associated with cartilaginous and bony orbital destruction due to
ischaemia which may be complicated with pre-septal orbital cellulitis.
Some clinician recommend blood culture as routine. The yield of this test
seems to be very low. Blood culture, CSF analysis, and urine tests
seems to be very important mainly in children younger than three years
of age. Culturing specimens from the throat is also fruitless as most
children will have positive results of organism considered normal to the
throat flora.
Plain X ray as routine are also thought to be of no value as most children

will have some degree of opacification in the maxillary or the ethmoid
sinuses. CAT scan is recommended, however, in cases where surgery is
considered, or when there is no progress with medical treatment to rule
out orbital or sub-periosteal abscess.
19
thyroid eye disease

pathogenesis
Grave’s ophthalmopathy tends to follow hyperactive thyroid conditions,

but it can also precedes the thyroid dysfunction. Most ophthalmologists
believe that dysthyroid eye disease is most probably due to an auto-
immune disease. The primary target cell is believed to be the orbital
fibroblasts. Proliferation of fibroblasts and glycosaminoglycan has been
shown in this disease. Glycosaminoglycan is a hydrophilic molecule that
absorbs extra-cellular fluid and causes increase in the orbital volume. A
recent study, on biopsies taken from extraocular muscles, demonstrated
that T-cells are much more involved in the early stages of the disease
and that early activation of fibroblasts occurs. Early intervention by
aggressive immunosuppression therapy may, thus, prevent later fibrosis
of extraocular muscles.
Viral causes have also been suggested. In a study of 93 patients, a

strong correlation was found between Graves disease and Human T-Cell
lymphotropic virus type 1 (HTLV-type 1) uveitis. Human T-Cell
lymphotropic virus type 1 is a retrovirus that is highly endemic in the
Caribbean islands, parts of central Africa and south west Japan. It is not
known if these 2 auto-immune diseases (uveitis and Graves disease)
occur independently as a part of infection by this virus, or if there might
be a link between the two disease.
The cause of the variation between the course of ocular manifestations

and systemic manifestation in Grave’s disease is not known. The ocular
manifestations in Grave’s disease may depend on the presence or
absence eof certain HLA antigens HLA-DR 14 and DQ 1 Antigens have
been found in higher levels in patients with severe ophthalmopathy. They
may be genetic markers of ocular predisposition to severe
ophthalmopathy.
dysthyroid eye disease and glaucoma
There has been some evidence that primary open angle glaucoma is
associated with hypothyroidism. 23.4% of primary open angle glaucoma
patients are believed to also have hypothyroidism, and about 10.9% of
glaucoma patient have undiagnosed hypothyroidism. Poor glaucoma
control may be reversed after the diagnosis and the treatment of
associated hypothyroidism. Patients with hypothyroidism seem to have
poor aqueous humour outflow facilities when measured using tonometry
and tonography techniques, this poor outflow facilities improve after the
treatment of hypothyroidism. A recent study showed that the prevalence
of normal-tension glaucoma as well as open-angle glaucoma and ocular
hypertension was significantly higher among patients with Graves
disease than in the general population. A study in the UK, on the other
hand, examined 100 consecutive patients with primary open angle
20
glaucoma and found that there is no association of hypothyroidism with

glaucoma.
Another study, in Holland, found that the prevalence of primary open

angle glaucoma was similar in the general population as in patients with
Grave’s ophthalmopathy. It seems that only a prolonged duration of
active thyroid associated orbitopathy in association with ocular
hypertension is correlated with progression to glaucomatous damage.
Patients with chronic thyroid associated orbitopathy need special
attention and close follow-up to prevent optic nerve damage caused by
raised IOP. In dysthyroid patients with elevated IOP and visual field
defects, orbital decompression and ocular muscle surgery may lower the
IOP.
management
Most patients with dysthyroid eye disease needs only conservative

treatment. More invasive treatment is indicated in progressive disease.
Disease activity, In dysthyroid eye disease, can be assessed by:
1. The STIR sequence on the MRI.

2. Ocular movements restriction (as measured by the Hess chart or by
the field of binocular single vision).
3. The extraocular muscle size on CAT scan.
4. Changes in the uniocular field of fixation also appear to reflect changes
in the disease activities and can be used to select and monitor patients
for immunosuppression treatment. Uniocular field of fixation can be
measured by fixing on a size 3, 4E target on the Goldmann machine.
Systemic steroids and orbital radiotherapy have been used in the

treatment of active dysthyroid eye disease. Approximately 65% of
patients with Graves disease respond successfully to steroids treatment
or to retrobulbar radiotherapy treatment. The determinant of the response
are generally unknown. Combined orbital radiotherapy and medical
immunosuppression, by low dose steroids and azathioprine, seems to be
more effective than either method on its own. The combined treatment
may also lead to a fewer side affects of steroid and a reduction in the
need for surgical intervention. Antioxidant agents (e.g. allopurinol and
nicotinamide) are also thought to be associated with encouraging results
in the treatment of mild and moderately severe Graves' ophthalmopathy.
The two drugs have previously been shown to prevent in vitro fibroblast
proliferation.
The effect of systemic treatment for the hyperthyroidism on the eye

disease is not known. Radio-active iodine treatment for Grave’s disease
may be followed by the appearance or worsening of ophthalmopathy
more often than after medical treatment (methimazole). The worsening
21
effect is often transient and may be prevented by systemic steroid

treatment.
• orbital surgical decompression
Orbital decompression is indicated in dysthyroid eye diseases in the

presence of exposure keratitis, optic neuropathy, and also in the
presence of disfiguring proptosis. Various approaches have been used
previously (lateral, trans-ethmoidal, three wall, four wall, or coronal
decompression). The most commonly used technique is the trans-
ethmoidal approach. The operation may be complicated with several
and potentially serious complications.
Postoperative diplopia is seen after all types of decompression with any

approach (about 19% in all cases). Many factors contribute to its
incidence. The most important factor is probably the state of the
extraocular muscles preoperatively. Complete loss of vision may occur
after optic nerve decompression surgery. Visual recovery may still occur
even after a protracted blindness. The mechanism of visual loss after
surgery may be due to traction or ischaemic injury to the nerve or due to
vasospasm of the central retinal artery or due to orbital oedema.
Trans-conjunctival orbital decompression, through a lateral wall

approach ab interno, has recently been described for one, two, or three
wall orbital decompression in patients with Graves' ophthalmopathy. The
technique has the advantages of low incidence of induced diplopia and
peri-orbital hypaesthesia, hidden and small incision, minimal surgical
trauma to the temporalis muscle, and fast patient recovery. The main
disadvantage is the limited exposure of the posterior medial and lateral
wall.
Trans-nasal endoscopic approach can offer both medial and inferior wall
decompression without the disfiguring external facial scars. The
endoscopic approach achieves good enough decompression with regard
to saving visual acuity and optic nerve protection, but not for proptosis
relieve. Motility disorders may occur as with the other methods of
decompression. The procedure can be performed under local
anaesthesia. Infection within the frontal sinus can cause secondary
orbital cellulitis or abscess after endoscopic orbital decompression
when the frontal sinus ostium is obstructed by orbital fat or scar tissue.
Early signs and symptoms of a frontal sinus infection can be easily
misdiagnosed as progression of the patient's thyroid eye disease.
Awareness of this possible complication followed by appropriate early
intervention will prevent a potentially blinding condition.
Orbital fat decompression may also be used as a surgical alternative to

bony decompression in patients with an enlarged orbital fat compartment
and in whom extraocular muscle enlargement is not the main cause of
optic neuropathy,
22
• extraocular muscle surgery
Patients with tight inferior rectus muscle, may present with the symptoms
of flashing lights in up gaze, which may be due to “the phosphene
phenomena” as a result of compression of the inferior rectus muscle or
due to the traction of its insertion.
In dysthyroid eye disease, euthyroid state should be maintained, and a

stable orthoptic measures should be established for six months before
any squint surgery is considered. Tight muscles may be recessed by an
adjustable suture technique aiming to under-correct the vertical
deviation at the time of surgery. Late over-correction after inferior rectus
recessions is a known complication in thyroid and non-thyroid eye
disease patients which may be due to scar contracture near the
Lockwood ligament that may pull the inferior rectus muscle anteriorly,
thus slackening the anterior aspect of the muscle. Patients should be
intentionally under-corrected by about 4-6 prism D. Under-correction after
Inferior rectus recession surgery may also occur in some patients.
• lid surgery
Upper lid retraction is one of the main disfiguring problems in patients

with dysthyroid eye disease. In Graves disease, the peak of the upper
eyelid contour is often displaced laterally and persistent lateral under-
correction is a main problem after upper lids retraction surgery in
patients with dysthyroid eye disease. Lower eye lid retraction is also a
problem in patients with dysthyroid eye disease. Dysthyroid eye disease
patients with lid retraction often develop over-action of the Glabellar
muscles resulting in the typical thyroid face with frown lines. Botulinum
toxins A denervation is effective in relieving these muscle over-activity.
The need for Glabellar muscles denervation is often reduced when the lid
retraction is treated.
Surgical treatment is often carried out by a donor scleral graft. Virus

transmission is however a definite risk in these cases. Partial tenotomy
and anti-metabolite is another alternative treatment. Donor scleral grafts
seem to lead to longer lasting results.
23
Uveitis
general considerations
Uveitis is estimated to account for 10% of severe visual loss in the

Western world. Uveitis patients often do not suffer from ocular disease
alone; approximately 25% to 50% have an underlying systemic disease.
HLA-B27 associated uveitis, CMV retinopathy and toxoplasmosis uveitis
are among the most common causes.
About 4% of uveitis patients develop bilateral legal blindness. The major

reasons for loss of vision in patient with posterior uveitis are macular
oedema due to breakdown of the blood-retina barrier, direct inflammatory
damage to the retina, or retinal vessels closure with consequent
ischaemic changes.
aetiology
In about 33% of patients with intraocular inflammation no specific cause

can be found. Investigations of serum antibodies titres give little
information about the cause of uveitis. Paracentesis and aqueous
analysis is recommended in the investigation of uveitis conditions with
unknown cause. Cytological and immunological studies may be
performed with the ocular fluids. Analysis of ocular fluids by the
polymerase chain reaction tests seems to be a promising diagnostic
technique. Aqueous and serum levels of interferon and interleukin-2
are elevated in patients with uveitis. Elevated serum interferon may
predispose the patient to more serious loss of vision.
Ultrasound biomicroscopy of the anterior segment is a useful tool in

monitoring cases of anterior uveitis. In difficult cases, in which diagnosis
can not be made by less invasive methods. Intraocular biopsy of
choroido-retinal tissues may help in making the diagnosis. The technique
of intraocular biopsy would also help in differentiating intraocular
inflammatory lesions from neoplastic lesion presenting as intraocular
inflammation. The risk of such a procedure should be weighed against its
possible benefits.
Uveitis typically present for the first time in the 3rd or 4th decades. Uveitis
presenting for the first time in the elderly in not rare. Idiopathic causes
accounts for most cases. It may also be associated with systemic
diseases (diabetes, sarcoidosis, hypothyroidism) and herpes zoster
infection.
Masquerade syndrome refers to uveitis secondary to systemic disease.

The commonest causes are intraocular lymphoma (Hodgkin and non-
Hodgkin types) and melanoma. Diagnosis of CNS lymphoma is often
difficult as all the signs and symptoms associated with disease is non-
specific. Vitritis seems to be the only universal sign in CNS lymphoma.
Lymphoma associated uveitis may be steroid responsive. Vitreous biopsy
is recommended only in patients with abnormal looking vitreous cells,
poor response to steroids or classical chorioretinal lesions in the
presence of vitritis when progressive anterior segment inflammation
disease threatens vision.
Uveitis in children is uncommon. Juvenile rheumatoid arthritis-

associated uveitis is the main cause of children uveitis (41.5%), followed
by idiopathic uveitis (21.5%), and pars planitis (15.3%). Patients with
Juvenile rheumatoid arthritis-associated uveitis have the highest rate of
complications which include cataract (71%), glaucoma (30%), band
keratopathy (66%), and hypotony (19%).
treatment
The appropriate treatment and choice of immunosuppressive therapy

for uveitis depends on cause as well as the extent and severity of the
inflammatory process. Treatment should be commenced when sight
threatening inflammation is present. Before considering and commencing
immunosuppressive therapy for uveitis, infectious causes must be
excluded. Poor visual prognosis in patients with posterior uveitis may be
predicted by fluorescein angiography (macular ischaemia). Systemic
immunosuppression in these patients should be used with caution.
Several other immunosuppressive agents have been used to treat

uveitis. These agents include: steroids cyclosporin A, azathioprine which
may be used either as an alternative to Cyclosporin A in combination with
steroids or in addition to Cyclosporin A and steroid therapy. Treatment
with systemic immunosuppression (with or without steroids) for chronic
ocular inflammations does not appear to be associated with a higher risk
of developing systemic side effects than treatment with systemic steroids
only.
Immunosuppression can be achieved by steroids as primary therapy in

acute / active stages of disease. Steroids may be administered by
several routes. Topical steroids is often the main line of treatment of
simple anterior uveitis. Care should be taken in prolonged topical steroids
treatment as corneal stromal calcification may develop after topical
steroid-phosphate medication, in spite of normal serum levels of calcium
and phosphorus.
Uniocular, mild intraocular inflammation is often treated with orbital floor

steroids to avoid systemically induced side effects. 48% of patients have
a positive response to the orbital floor injections with a mean duration of
action of nine weeks. After a peribulbar injection of 5 mg of

dexamethasone, an average intravitreal dexamethasone concentration is
reached with a 75 times greater anti-inflammatory potency than
physiological levels. Dexamethasone concentration in serum is also
increased several folds. Peribulbar injection should not be considered as
a local treatment as it results in serum levels comparable to those
achieved by a high oral dose.
Long term control is then maintained with low dose Cyclosporin A as

primary therapy, with or without low doses of steroids. Additional
immuno-suppressants may be required when inflammation is present
despite the low dose therapy with Cyclosporin A and steroids. Patients
should be reassessed two weeks after induction of immunosuppression
and thereafter at four week intervals until stability is achieved.
50% of patients, with posterior pole chronic uveitis, unresponsive to

steroids alone are controlled on Cyclosporin A or a combination of
Cyclosporin A and steroids. Cyclosporin A, in contrast to steroids,
specifically inhibits the helper T-cells function mainly through the
reversible inhibition of the interleukin-2 production. Low doses of
Cyclosporin A (2.5-5.0 mg/kg daily) when used alone or in combination
with other immune-suppressive agents seem to be effective in achieving
inflammatory control with a favourable visual outcome and reduced renal
complications.
The Cyclosporin A associated nephrotoxicity may also be further reduced

if the drug treatment is initiated with a very low dose and incremental
increase in the dose as required. Cyclosporin monitoring according to T6
(6 hours after the morning dose) levels is associated with optimal
immunosuppression and stable renal function. The Cyclosporin dose
may be adjusted to achieve a Cyclosporin T6 level of 150 to 250 ng /ml.
A sustained release device for intra-vitreous cyclosporin treatment is

proved to be effective in the treatment of posterior uveitis in animal
models. Therapeutic levels of the drug remain in the vitreous for up to 6
months while blood levels remain very low. This method of treatment may
be used in resistant cases in humans. Topical Cyclosporin A may be
used in external eye inflammatory diseases. It seems to induce a marked
reduction in the number of immunocompetent cells in the conjunctival
epithelium and substantia propria
FK 506 is a new immune-suppressive agent isolated from Streptomyces

tsukubaensis. It ha been shown that this agent has a similar immune-
suppressive action similar to that of Cyclosporin. A multi-centre study has
shown that treatment with FK 506 produced therapeutic effects in a dose
dependent manner. The recommended dose of FK 506 for cases with
refractory uveitis is 0.1-0.15 mg/Kg body weight /day. It is also
recommended to maintain the trough of blood level between 15-25 ng /
ml. Treatment may be associated with some side effects e.g. renal
impairment, neurological and gastrointestinal symptoms and also

hyperglycaemia.
Monoclonal antibody (mab-Campath-1H) therapy is a new treatment

that has recently been used successfully in the treatment of resistant
cases of chronic inflammation. Campath-1 therapy may provide a long-
lasting remission in patients with resistant intraocular inflammatory
diseases. The mechanism of action of this new method is not clearly
understood.
Some types of uveitis may be resistant to all methods of

immunosuppression. Intravenous immunoglobulin can benefit some of
these refractory cases. The use of Intravenous immunoglobulin for uveitis
should be limited because of its cost, toxicity, the requirement for
repeated administration.
Cystoid macular oedema is a common complication after uveitis. Optical

coherence tomography appears to be, at least, as goof as fluorescein
angiography in detecting cystoid macular oedema. The oedema may be
treated with steroids, Diamox, vitrectomy, and grid laser
photocoagulation. Acetazolamide appear to improve visual acuity in
patients with chronic iridocyclitis with CMO, especially in patients younger
than 55 years of age. The dose of acetazolamide should be adjusted
according to the visual acuity and the amount of the cystoid macular
oedema.
Pars plana vitrectomy with or without lensectomy may improve vision in

patients with chronic uveitis. Pars plana vitrectomy also results in marked
reduction in activity of the inflammation and also in the frequency or
recurrences. Grid laser photocoagulation may be beneficial if performed
at an early stage. A temporary increase in the oedema and in the patients
central scotoma may occur in the early posterior operative period.
Specific types of uveitis
Toxoplasmosis
Ocular involvement in toxoplasmosis is often congenital. Recurrent
toxoplasmosis has traditionally been considered to be due to a
reactivation of congenital infection. Postnatal acquired infection may also
occur.
Congenital toxoplasmosis may have long term ocular, endocrinological

and neurological complications (e.g. pan-hypopituitarism, gonads failure
with dwarfism, precocious puberty, thyroid deficiency, diabetes mellitus
and obstructive hydrocephalus with dilated third ventricle and optic
atrophy). Many children with congenital toxoplasmosis have severe
retinal changes at birth. Chorioretinal and macular scars are the most
common eye finding. The central, bilateral lesions, especially the macular
ones, are more common in the congenital form, while the acquired form
tends to be unilateral, discrete and solitary. Severe intraocular
inflammation may also be associated with a higher incidence of retinal
detachment and retinal breaks.
Acquired ocular toxoplasmosis should be considered in all patients with

acquired disease, of any age group, that present with unilateral focal
retinochoroiditis, even without associated old retinal scars in the posterior
segment. Ocular involvement may complicate both the acute and the
chronic phase of the disease. Treatment of these patients with anti-
toxoplasmosis medications may help in preventing late choroido-retinal
scars.
Acquired toxoplasmosis infection is often asymptomatic. The disease

may also present with fever, malaise and lymphadenopathy. Acquired
infection is often associated with Ig M, A, and high levels of Ig G. In
patients with unilateral focal retinochoroiditis anti-toxoplasmosis Ig G and
Ig M antibodies should be determined to help with the diagnosis. In acute
acquired toxoplasmosis, the antibody titres are usually very high and
therefore serology could be very useful in making the diagnosis.
The absence of circulating antibodies does not exclude ocular

involvement. Clinical diagnosis can be confirmed by analysing the
intraocular antibody response by the immunofluorescent technique. The
intraocular response in these patients may be different from the serum
response. Verification of toxoplasmosis infection can also be carried out
by using the polymerase chain reaction test on small ocular samples
from the aqueous or the vitreous.
Immunocompromised patients may develop lethal disseminated

toxoplasmosis and / or toxoplasmic encephalitis. Ocular disease is not
common in such cases. Ocular involvement may, however, be atypical
with such features as bilateral multifocal lesions
Necrotising retinochoroiditis is the hallmark of ocular involvement. Retinal

vasculitis with inflammatory signs in the anterior or the posterior segment
may also be the only ocular manifestation in the early stages of the
acquired disease. The pathogenesis of the disease is not completely
understood. tissue destruction may be due to parasite -induced damage,
damage from parasite-secreted toxins, immune mediated mechanism, or
due to an anti-retinal autoimmune mechanism. The last mechanism of
anti-retinal autoimmune mechanism has been suggested after some
reports showed that there is an increased activity of anti-retina antibodies
in the sera of toxoplasmosis patients.
Initial ocular involvement may be caused by the presence of the

proliferating parasite in the eye. Administration of systemic steroids in the
acute phase may be associated with more tissue damage. Anti-
Toxoplasma drugs are often needed. The usual indications for
treatment of ocular toxoplasmosis include:
1. Lesions in the papillo-macular area which threaten visual acuity.

2. Large retinal lesions (>2 disc diameters) with marked vitritis.
3. All lesions in immunocompromised patients.
4. It is also recommended that any active lesion in children should be
treated, regardless of its location, as peripheral lesions in children
could cause retinal detachment or macular dragging.
Despite prompt response to anti-parasitic drug therapy, prolonged

treatment is usually required and patients may have retinitis reactivation
after discontinuing treatment. Sulphadiazine, Pyrimethamine,
Clindamycin, and Trimethoprim have traditionally been used in the
treatment of toxoplasmosis. Azithromycin may also be used for patients
who can not tolerated other methods of treatment. The drug, however
does not appear to prevent recurrent disease. Atovaquone is a new drug
that selectively inhibits mitochondrial electron transport chain in protozoa
organisms. The drug has been used successfully in the treatment of
pneumocystitis carinii Infections in AIDS patients. The drug also seems to
be well tolerated as an alternative treatment for toxoplasmosis, when
given 750 mg four times a day for 3 months. Mild side effects may occur
in some patients.
The resistance to treatment in T. gondii is primarily due to macrophages

activated by T-cell lymphokines, oxygen radicals and also cytotoxic T-
cells. Nitric oxide also appears to play an important role in the protection
against T. gondii. The inhibition of nitric oxide production in mice results
in a marked increase in the symptoms of ocular inflammation. The
expression of nitric oxide synthetase gene is inhibited by steroid. The use
of anti-inflammatory drugs that have no negative effect on nitric oxide
production should, therefore, be considered
Presumed ocular histoplasmosis Syndrome (POH

Syndrome)
Ocular infection with the fungus Histoplasma capsulatum may present
with the classical features of presumed ocular histoplasmosis syndrome
in healthy patients, or with an acute onset of granulomatous uveitis or
panophthalmitis in immunocompromised patients. Presumed ocular
histoplasmosis syndrome is characterised by the following:
• Multiple choroidal spots (Histo spots).

• Peripapillary atrophic changes.
• Disciform macular scar.
• No vitritis.
• HLA-B7 sero-positivity.
• Residence in an endemic area (Midwest of the USA).
presumed ocular histoplasmosis -like retinopathy have also been

reported in several conditions e.g. Fuchs’ heterochromic cyclitis, punctate
inner choroiditis and myopia. The characteristic features of the syndrome
may be due to several different aetiological factors.
81% of patients retain a visual acuity of 20/20 in one eye for a period of 5
years, while 20% of patients retain this visual acuity in both eyes. The risk
of choroidal neovascular membrane development and visual
deterioration appears to be higher in patients with ocular histoplasmosis
and Histo spots in the macular area. Estimates of an annual increase of
the choroidal neovascular membrane in the second eye in patients with
ocular histoplasmosis ranges from 2% to 12%.
Medical treatment with anti-fungal drugs does not seem to have any role
in the treatment of the disease. systemic steroids may be given for the
acute stages of the disease when there is macular lesion.
Choroidal neovascular membrane associated with ocular histoplasmosis

can be treated with laser photocoagulation or by surgical excision. The
visual results of eyes with presumed ocular histoplasmosis syndrome
and extra- or juxta-foveal choroidal neovascular membrane that have
been treated with laser photocoagulation show continued long term
benefit from the treatment. Recurrences of the choroidal neovascular
membrane occur in 23% of the treated eyes during a mean follow up
period of 9.6 years, continued follow up is indicated.
Surgical excision of subfoveal choroidal neovascular membrane may be

an effective therapeutic modality. Factors possibly associated with a
favourable visual prognosis include younger patient age and the absence
of previous laser photocoagulation.
Juvenile rheumatoid arthritis-associated uveitis

Juvenile rheumatoid arthritis-associated uveitis is a serious disease that
is often associated with a guarded visual prognosis. The mean age of
onset of uveitis is 13 years, with females having on average 4 years
earlier onset of disease compared to males. 93% of patients have
chronic, 5% have recurrent, and 2% have an acute monophasic disease
course.
Male sex, shorter duration of uveitis, older age at disease onset and a
shorter delay in presentation to a sub-specialist are good prognostic
factors regarding the visual outcome. Cataract, glaucoma, and corneal
changes are known complications. Disc neovascularisation may also
occur in some children. The disc new vessels may respond to oral
steroids. Secondary glaucoma occurs in about 14% to 27% of patients.
Although some cases of uveitic glaucoma can be controlled with medical
therapy, the long-standing effects are disappointing. The Molteno implant
appears to be useful and well tolerated in controlling IOP in patients with
glaucoma secondary to juvenile rheumatoid arthritis.
Systemic steroids may be needed in severe inflammation. Medium and

long term treatment with systemic steroids is often associated with
significant side effects. Cyclosporin A is effective in the treatment of
refractory non-infectious uveitis in children. It is also safe for the short
and medium term use. Continuos monitoring of kidney function, and
blood pressure is important.
Pars planitis, and Intermediate Uveitis

The aetiology of intermediate uveitis is unknown in the majority of cases.
The disease is probably caused by an immune mediated disease. HLA-
DR2 is found in 50%-70% of white pars planitis patients compared to
20%-25% of control. 72% of patient are positive for HLA-DR I5. The
disease is thought to belong to a group of HLA-DR l5-related disorders,
which includes multiple sclerosis, optic neuritis, and narcolepsy. Raised
serum levels of interleukin-8 are also found in patients with active
intermediate uveitis of unknown cause. Raised level also seem to
predispose patients to future systemic diseases.
Long term complications of pars planitis include cystoid macular oedema,

epiretinal membrane formation, vitreous haemorrhage, cataract,
glaucoma and peripheral neovascularisation at the vitreous base and
also possibly multiple sclerosis.
Multiple Sclerosis has been reported to precede or follow pars planitis.

The presence of peri-phlebitis increases the risk of developing optic
neuritis or multiple sclerosis. Patients who are HLA-DR 15 positive and
have intermediate uveitis may have systemic findings of other HLA DR
15 related disorders.
Cataract occurs in 36%-42% of patients with pars planitis due to both the
chronic inflammation and the steroid treatment. Limited visual results is
often due to CMO, epiretinal membrane or optic atrophy. Patients with
significant cataract appear to be at a higher risk of developing retinal
detachment. Firm vitreo-macular adhesions traction as well as the
presence of inflammatory cells in the vitreous is believed to be the main
cause of CMO.
A step-ladder approach, in treating pars planitis cases, by topical and

regional steroids, NSAIDs, oral steroids, retinal cryotherapy and
immunosuppressive therapy, has been recommended. Posterior sub-
Tenon injection of Triamcinolone is effective in decreasing cystoid
macular oedema and also improving visual acuity especially in young
patients. This technique ensure a more direct contact between the
medication and the globe and may lead to higher intraocular
concentration. It may also reduce the need for systemic steroids and its
complications. Sub-Tenon injection of steroids may be associated with
increased IOP which might last for up to 3 to 14 weeks. Deep sub-Tenon
injection of steroids does not appear to be associated with increased
IOP.
Cryotherapy of the peripheral exudate can also be effective in steroids

resistant patients. Peripheral cryotherapy appears to be effective in the
treatment of peripheral neo-vascularisation, but may be associated with
the development of rhegmatogenous retinal detachment. Peripheral
scatter laser photocoagulation (with or without pars plana vitrectomy) is
also as effective as cryotherapy in causing regression of the peripheral

neovascularisation, regression of the inflammatory process and the
cystoid macula oedema, with less incidence of retinal detachment.
Behcet’s disease
Behcet’s disease, is the leading cause of endogenous uveitis in Japan.
The disease is responsible for 10-15% of the acquired blindness in
Japan. The most common ocular feature of Behcet’s disease is recurrent
attacks of anterior uveitis. Posterior ocular segment involvement may
also occur and may cause blindness. Sudden onset of bilateral vision
loss may be associated with bilateral retinal vascular disease and
macular ischaemia. The conjunctiva is not often clinically involved in
patients with Behcet’s disease. However immuno-histochemical studies
have shown some conjunctival abnormalities in active and inactive
cases.
There are several sets of clinical criteria that has been established for the
diagnosis of the Behcet disease. Most of these sets are based on finding
some major and minor features of the disease. The disease can also be
classified into complete or incomplete forms depending on the number of
major or minor features present.
major features minor features

• recurrent oral ulcers of the mouth • arthritis
• intestinal ulcers
• vascular occlusion, obliteration or
aneurysms
• neuro-psychiatric symptoms.
The first two years after diagnosis is the most critical period for eye
involvement. It is difficult to predict, in which patient the eyes will be
involved and what the outcome will be. Young age is the most significant
factor for eye involvement. Vascular thrombosis, central nervous system
involvement and male gender are other risk factors.
The disease is known to be associated with HLA B51 in Japanese and in

the Irish people. Auto-immunity to retinal specific antigens may play a
role in the ocular inflammation. In the active stages of the disease, the
ratio of D arabinatol (which is a major metabolite of candida species) /
creatinine show higher values than in the controls. It is suggested that D
arabinatol (or other metabolite of the candida species) may be related in
part to the active phase of Behcet’s disease.
Behcet disease is often treated with immunosuppressive drugs (e.g.

steroids, azathioprine, or cyclosporin), or with cytotoxic drugs (e.g.
chlorambucil, colchicine, or cyclophosphamide). Side effects from
systemic use of the Cyclosporin may limit it’s use. Intravitreal devices that
provide sustained delivery of Cyclosporin are promising new treatment
for chronic cases of uveitis in humans. Therapeutic levels of the drug
remain in the vitreous for up to 6 months while blood levels remain very
low. Treatment with Interferon alpha-2 with or without a small dose of
steroids may also be used with good results, and may also prevent retinal
and optic nerve damage.
Birdshot Chorioretinopathy
Birdshot chorioretinopathy is characterised by bilateral, multiple white
creamy patches at the level of pigment epithelium and choroid, vitritis,
vasculopathy with leakage, cystoid macular oedema and optic disc
oedema. The disease is more common in white, female patients in their
40s to 50s. It is presumed to be an auto-immune disease (HLA-A29 is
positive in 94% of patients). Ocular Lyme disease may also play a role
in the pathogenesis of Birdshot chorioretinopathy. Abnormalities in the
small choroidal vessels within the birdshot lesions have been
demonstrated by Indocyanine green angiography. Th disease may be
treated with systemic steroids or cyclosporin.
Treatment with systemic and periocular steroids has inconsistent results

and may be associated with side effects. Vision can be preserved by the
use of low dose (2.5-5 mg/Kg daily) of Cyclosporin A. This low dose of
Cyclosporin A does not seem to be associated with significant
nephrotoxicity or increased blood pressure. The dose of systemic
cyclosporin may be considerably reduced if ketoconazole is added to the
treatment, ketoconazole delays the metabolism of cyclosporin. This
combination of treatment seems to be safe and effective.
Vogt-Koyanagi-Harada (VKH) syndrome

VKH Syndrome is a bilateral chronic panuveitis associated with systemic
manifestation. The disease may present with ocular or extraocular
manifestations, the following table demonstrate some of the common
ocular and extraocular features:
Ocular manifestations Extraocular manifestations

• Granulomatous uveitis. • Headache, and orbital pain.
• Non-rhegmatogenous retinal • Stiff neck.
detachment. • Vertigo.
• Optic nerve head swelling. • Hearing difficulties and tinnitus.
• Choroidal neovascular membrane. • Sensitivity to touch to both hair and skin.
• De-pigmentation of the posterior • Vitiligo, alopecia and poliosis.
pole.
The aetiology of VKH is unknown but it is thought to be an auto-immune

disease. It has been suggested that the cell mediated immune process
involving melanocytes plays an important role in the pathogenesis of the
disease. In clinical practice, detecting melanin laden macrophages in
CSF provides useful information on the activity of the patient's systemic
immunological reactions. HLA-DR 4 is significantly related to VKH
Syndrome in Caucasian European patients.
In VKH syndrome 66% of patients retain visual acuity of 20/30 or better,

the 3 main vision threatening complications are:
Cataract.
Glaucoma.
Choroidal neovascular membrane.
Risk factor for the development of cataract include long standing

recurrence anterior uveitis and systemic steroids treatment for 6 months
or more. If intraocular inflammation is controlled, cataract extraction
operation can be safely and effectively performed with significant
increase in the visual acuity.
Glaucoma occur in about 38% of patients with Vogt-Koyanagi-Harada

syndrome, it may be an open angle or angle closure glaucoma due to
pupillary block. Angle closure glaucoma may be the first manifestation of
the disease. Shallowing of the anterior chamber may be caused by
swelling of the ciliary body and cilio-choroidal detachment secondary to
the uveitis. Many patients require surgical treatment e.g. laser or surgical
peripheral iridectomy, broad iridectomy or filtration operations with or
without anti-metabolites.
Eyes with choroidal neovascular membrane have a tendency for

recurrent or chronic anterior or posterior inflammation. The choroidal
neovascular membrane are often located in the peripapillary subfoveal or
extra-foveal regions. Systemic pulse or posterior sub-Tenon steroids or
occasionally laser photocoagulation may be required for the choroidal
neovascular membrane.
Eye movement may be abnormal in patients with Vogt-Koyanagi-Harada,

53% of patients show horizontal jerky nystagmus that is completely
inhibited with visual fixation and some patients have defective smooth
pursuit movements with reduced gain on the side of nystagmus. Impaired
eye movement in these patients may be due to asymmetry of vestibular
function secondary to the labyrinthine inflammation.
The main line of treatment is systemic steroids. The dose needed to

control the disease may be very high. Cyclosporin has also been
successfully used.
Uveitis Associated with HLA-B27

HLA B27 is positive only in 10% of normal controls. About 50% of
patients with acute anterior uveitis are associated with HLA B27. Acute
anterior uveitis is the most common form of uveitis in HLA B27 positive
patients. Most patients have associated systemic illnesses e.g. sero-
negative spondylitis, inflammatory bowel disease and Reiter’s syndrome.
The systemic diseases are frequently undiagnosed before the onset of
the uveitis.
Acute non-granulomatous anterior uveitis is the most common form of

uveitis. HLA B27 associated uveitis may be associated with severe sight
threatening posterior segment manifestations, as well as anterior
segment manifestations in some patients.
The most common findings in the posterior segment include severe and
diffuse vitritis, papillitis, retinal vasculitis and pars plana exudates.
Cystoid macular oedema and epiretinal membrane are common causes
of visual impairment in posterior segment disease. These patients may
need to be treated by aggressive systemic immune-suppressive therapy.
A subgroup of patients may have a severe and bilateral disease which
may be associated with severe complications.
Sarcoidosis
Sarcoidosis is a multi-systemic disease of unknown aetiology. The
cause of the disease is not completely known. Infections and
environmental factors may play a role in the pathogenesis of the disease.
Other aetiological factors e.g. Epstein Barr virus, atypical mycobacterium
and fungi have been suggested. The immuno-pathogenesis of the
disease is thought to be mediated via antigenic activation of alveolar
macrophages and T lymphocytes.
Ophthalmic involvement in the disease is reported to be between 25%

to 50%. The onset of ocular involvement in sarcoidosis is often bilateral, it
may precede or follow the systemic disease. Ocular sarcoidosis may also
be isolated. The ocular prognosis of sarcoid uveitis does not appear to be
related to the extent of the disease. The presence of extraocular
manifestations of the disease does affect the visual outcome. The
presence of uveitis seems to increase the risk of having CNS
involvement.
Most patients have anterior or intermediate uveitis alone. 91% have

chronic disease, 7% have recurrent flares and only a minority of patients
have a monophasic acute course of the disease. Choroiditis is
frequently found in patients with posterior segment inflammation
associated with the disease. The most frequent pattern is well
circumscribed pre-equatorial choroidal de-pigmentation that becomes
associated with retinal pigment epithelial hyper- or hypo-pigmentation
with time. Extensive confluent choroiditis with retinal pigment epithelial
changes resembling serpiginous choroiditis may also occur. Patients with
sarcoidosis may also present with multiple placoid choroidal lesions
resembling acute posterior multifocal pigment epitheliopathy.
Retinal vasculitis may also occur. It may be ischaemic or non-

ischaemic. The ischaemic type is often due to localised thrombosis. The
disease should be considered in the differential diagnosis of ischaemic
retinal vasculitis. Uhthoff phenomena is typically associated with
demyelinating optic neuritis. The phenomena has also been described
with sarcoidosis.
Orbital sarcoidosis is rare and almost always unilateral when it is not

involving the lacrimal gland. Orbital sarcoidosis may be associated with
painful or painless extra-ocular muscles involvement with diplopia.
Sarcoidosis of the anterior visual pathway may also present with Uhthoff
phenomena.
diagnosis
There is no pathognomonic feature of ocular sarcoidosis. The definitive

diagnosis of the disease can only be made by a positive biopsy showing
a non-caseating granulomatous, non-infectious inflammatory process.
Chest x-ray often show hilar lymph nodes enlargement, with nodular
shadowing or fibrosis of the lung. Serum angiotensin converting
enzyme levels also reflect the activity of the disease (it is elevated in 30-
80% of clinically active disease). Normal levels, however, do not exclude
the disease especially in isolated organ involvement as in ocular disease.
false positive results may also occur in some other conditions e.g.
tuberculosis, histoplasmosis, and Hodgkin disease). Gallium scans have
been shown to be useful in the diagnosis of this condition, the scan
typically show increased uptake in the lungs, mediastinum, parotid and
salivary glands. The combination of raised serum angiotensin converting
enzyme and whole body gallium scan is considered sensitive and
specific enough for the diagnosis of the disease even if the chest X-ray is
normal. In suspicious cases, trans-bronchial lung biopsy can establish
the diagnosis of sarcoidosis by showing a non-caseating epithelioid
granuloma. Pulmonary function tests may also show restrictive
features. The Kveim test is now rarely used because of the risk of HIV
transmission.
treatment
The main treatment in sarcoidosis is by systemic, topical, or orbital floor

injection steroids. Treatment is often indicated for several months as
premature cessation of the treatment may result in flare up of the
disease. Methotrexate also seems to be effective as a steroid sparing
drug.
Human T-cell lymphotropic virus type 1-associated

uveitis
Human T-Cell lymphotropic virus type 1 is a retrovirus that is highly
endemic in the Caribbean islands, parts of central Africa and south west
Japan. The virus is a well known cause of:
1. Adult T-Cell leukaemia and lymphoma.

2. Certain types of (idiopathic) uveitis.
3. Non-neoplastic inflammatory disorder (e.g. myelopathy and tropical
spastic paraparesis).
The uveitis associated with this virus often affects one or both eyes in
middle-aged adults, it may be an isolated ocular condition or may be
associated with other conditions (e.g. myelopathy).
Uveitis seen in seropositive patients have significantly higher incidence of

floaters, vitreous opacities, retinal vasculitis and intermediate uveitis than
in sero-negative patients. It is often mild to moderate and resolves in a
few weeks with steroid treatment. About 14.5% of patients develop
vascular lesions in the retina (grey white granular deposits scattered on
the retinal veins or arteries in the posterior pole). These lesions often
resolve either spontaneously or with steroid treatment. Human T-Cell
lymphotropic virus infection can also present by ocular inflammation
similar to acute retinal necrosis.
Onchocerciasis
Onchocerciasis is a major global public health problem. It is estimated
that about 18,000,000 individuals affected with the disease with a further
68,000,000 at risk of the infection. Blindness prevalence exceeding 10%
have been reported in heavily affected populations. It is thought that the
presence of micro-filaria is important for the induction of the disease but
the progression of the disease may be related to the micro-filaria or to
other immunological factors. The main drugs used in the treatment of the
disease are:
• DEC
• Suramin sodium
• Ivermectin
• Amocarzine
DEC has been the most frequently used drug in onchocerciasis. It is a

micro-filaricidal that regularly produces a marked eosinophilic reaction.
The side effects of the drug are dermatitis, headache and vertigo. It has
also been suggested that DEC might also result in impairment of vision,
in particular through the precipitation of optic neuropathy. Suramin
sodium treatment may be associated with photophopsia, uveitis, optic
atrophy, vortex keratopathy, and also hyperopic refractive shift. These
ophthalmic side effects seem to be common but they are not considered
a dose limiting toxic reactions. Administration of suramin requires hospital
admission and monitoring since it is given intravenously. The drug may
also cause reversible nephrotoxicity and idiosyncratic reactions in some
people. Ivermectin improves the anterior segment lesions and also
reduces the incidence of optic atrophy. The drug can be given in four 6
monthly doses followed by annual doses. The response of posterior
segment lesions are variable and there is a highly significant rate of
deterioration and emergence of new lesions. Ivermectin does not appear
to precipitate or exacerbate optic neuritis unlike the drug DEC.
Amocarzine is a new macro- and micro-filaricidal drug.
Trauma Of The Eye And The Orbit
Traumatic hyphaema
Trauma is the commonest cause of hyphaema in children. Child abuse,
and tumours e.g. retinoblastoma and xanthogranuloma are other cause
of hyphaema in children. In adults the disease can also be caused by iris
neovascularisation and by abnormal vascular tuft on the pupils. Raised
IOP and corneal staining are major complication of hyphaema. The IOP
may initially be raised in large hyphaema. Some eyes may also show
varying degrees of hypotony after the initial IOP rise. Corneal staining
occurs in about 5.6% of all cases of hyphaema. The incidence of the
disease is increased in more than 50% hyphaema and also in hyphaema
of longer than 6 days of duration.
Secondary hyphaema is a major complication in traumatic hyphaema. It

occurs in about 22% of cases. Secondary haemorrhage seems to be
significantly more frequent in:
• African patients
• Eyes with initial visual acuity of 20/200 or less.
• Initial hyphaema more than one third of anterior chamber.
• Delayed attention for more than one day after injury.
• Elevated intraocular pressure at the time of first examination.
• Sickle cell trait disease .
• Patients receiving anticoagulants.
Secondary haemorrhage seems to be very rare in white children (who

do not take aspirin). The release of melanin into the anterior chamber
during ocular trauma may be partly responsible for the susceptibility of
darker-pigmented individuals to more serious complications following a
traumatic hyphaema, which may be due to occlusion of the trabecular
meshwork with melanin-laden macrophages.
Most ophthalmologists admit patient with traumatic hyphaema for

observation. Close Outpatient follow-up of traumatic hyphaema appears
to be safe and effective. Hospitalisation for hyphaema does not appear
to decrease the rate of re-bleeding. Decreased vision with traumatic
hyphaema generally results from other causes not affected by Inpatient
management. Outpatient treatment needs daily examination and
measuring of IOP. Outpatient observation is not recommended in
uncooperative patients. Hospitalisation is recommended in cases with
sickle cell disease, secondary bleeding, more than 50% hyphaema, and
when there is a suspicion of penetrating injury.
The use of systemic anti-fibrinolytic drugs in the treatment of traumatic

hyphaema is controversial. Aminocaproic acid, is an anti-fibrinolytic agent
which reduces the incidence of re-bleeding when given orally or topically.
The drug is believed to stop clot lysis. It is not recommended in cases
with more than 75% of hyphaema.
Surgical evacuation of the hyphaema and blood clot is indicated in

resistant cases, cases with more than 75% of hyphaema, cases with
increased IOP resistant to medical treatment. Evacuation may be carried
out by a paracentesis or by a two ports vitrectomy approach. Surgical
evacuation is better delayed for 4 days after the onset of the disease.
Bungee jumping
Bungee jumping may be associated with several complications.
Scattered superficial retinal and pre-retinal haemorrhages and cotton
wool spots in the macular areas of each eye have been reported in
patient who noticed blurred vision after jumping head first. Sub-
conjunctival haemorrhage may also develop. The retinopathy may be
typical of Purtscher’s traumatic retinopathy which is thought to be due to
an abrupt rise of intravascular pressure in the upper part of the body.
Ocular morbidity in bungee jumping may also be due to the cord itself.
Corneal lacerations, hyphaema, angle recession, irido-dialysis, lens
subluxation and retinal detachment have been reported
Air bag injuries

The frequency of air bag eye injuries is increasing, even after a low
impact collision, e.g. during parking. Corneal endothelial cell loss,
complete angle recession, multiple iris sphincter ruptures, loss of
accommodation, corneo-scleral laceration, and cataract have all been
reported in patients following an air bag eye injury. Posterior segment
injuries may also occur. Commotio retinae, choroidal rupture, intraretinal,
subretinal and vitreous haemorrhage, retinal tears, and retinal dialysis
with retinal detachment have all been reported before. Patients
sustaining air bag injuries should undergo complete ocular examination.
Most of ocular injuries are due to the mechanical force. Corneal injury
may also result from the release of the powder used in cars air bag.
Corneo-scleral laceration due to passenger-side airbag inflation has also
been described.
Traumatic optic neuropathy

In traumatic optic neuropathy, mega-dose of steroids and optic nerve
canal decompression have been advocated for the treatment. Visual
results seem to be better in patients younger than 4o years of age than in
older patients. Interval between the injury and surgery, preoperative
visual acuity, and the optic canal fracture does not seem to affect the
outcome. A recent comparative non-randomised study found no clear
benefit for either corticosteroid therapy or optic canal decompression
surgery. It was concluded, in this study, that it would be reasonable to
decide to treat or not treat on an individual patient basis.
Recurrent corneal abrasions

Recurrent corneal erosions may be due to corneal trauma or basement
membrane dystrophy. Patients with epithelial basement membrane
dystrophy are more likely to present with chronic recurrent symptoms
than trauma related cases. Epithelial basement membrane dystrophy is
also a risk factor for failure of treatment. Chronic recurrent corneal
ulceration may also be associated with smoking amphetamine (known as
ice) abuse in healthy people. Corneal vascularization and oedema may
also be associated with the ulceration. Complications of recurrent corneal
epithelial erosion are infrequent, they include anterior uveitis, stromal
scarring, and stromal infiltrates.
• surgical treatment
The commonest method of treatment of traumatic corneal abrasion is by

topical antibiotics, cycloplegic, and padding of the eye. Many patients
report loss of vision, blurring of vision or intermittent fuzziness of vision in
the uncovered eye while wearing an eye patch. This seems to be more
common if the dominant eye is covered. These visual symptoms may be
due to binocular rivalry suppression by the patched eye. Patients should
be informed about this possibility as these visual symptoms may occur
while driving.
Although many patients with recurrent corneal abrasions respond well to

conservative treatment, resistant cases may require further intervention.
Many methods have been tried for the treatment of resistant recurrence
cornea abrasions including anterior keratectomy, micro-diathermy,
needle anterior stromal puncture, excimer laser photo-keratectomy and
YAG laser anterior stromal puncture.
Anterior stromal puncture may be used in recurrent corneal abrasions,

and also in bullous keratopathy. Anterior stromal puncture can be carried
out on the slit lamp in the following way:
• A 20 gauge ½ inch needle is used to create two to three punctures per

a square millimetre in the corneal epithelium.
• The penetration depth of the needle is often about ¼ of the corneal
stromal thickness.
• The needle is held at 60 degree angle to the corneal surface.
• About 200 punctures are carried out depending on the surface area of
the epithelial bullae.
• Systemic analgesics and topical antibiotics are used after the
treatment .
A new technique, YAG laser , or excimer laser photo-induced corneal

adhesions, has been described. A number of 0.4 to 0.5 m J. pulses of
laser is applied to the Bowman’s layer through an intact epithelium.
Electron microscopy studies show minute foci of disruption in the
Bowman’s layer with new collagen formation and fine fibrils connecting
the basal epithelial cells to the new collagen. The minimal discomfort
associated with the YAG laser photo-induced adhesions treatment may
be advantageous compared with the severe pain reported by patients
during the re-epithelialisation period after excimer laser treatment.
Photo-therapeutic keratectomy, in selected patients may also be used.

The creation of a smooth new bed for migrating epithelium may result in
new hemidesinosomal adhesion complexes. A combination of PRK and
Photo-therapeutic keratectomy is effective in the alleviation of symptoms
and prevention of recurrences of corneal erosion. Extensive excimer
laser ablation is required to prevent recurrence and to alleviate symptoms
completely.
Amniotic membrane transplantation may be considered an alternative

method for treating persistent epithelial defects and sterile ulceration that
are refractory to conventional treatment and before considering treatment
by conjunctival flaps or tarsorrhaphy.
Blow out fracture

Orbital floor fracture is typically associated with:
• restricted eye movements, mainly upwards and laterally.

• subcutaneous emphysema.
• decreased sensation in the distribution of the infra-orbital nerve.
• enophthalmos.
When hypertropia and vertical diplopia are noted after orbital trauma a
posterior orbital floor fracture should be suspected. Characteristic
features on CAT scan may include depressed fracture of the orbital floor,
extending posteriorly to the maxillary sinus. The inferior rectus muscle
may also appear to loop down in the depressed fracture and then upward
to insert in the globe at a very steep angle. Infra-duction may be
diminished due to changes in the effective origin and insertion of the
inferior rectus muscle.
Trapdoor-type fractures, usually involving the orbital floor, are common in

the paediatric age group. These features may be small with minimal
soft-tissue incarceration, making the findings on computed tomography
scans quite subtle at times. Marked motility restriction and
nausea/vomiting should alert the physician to the possibility of a trapdoor-
type fracture and the need for prompt surgical intervention. Missed orbital
wall fracture may cause a post-enucleation syndrome. All patients
presenting with this syndrome with a suggestive trauma history should
have a CAT scan for the orbit to exclude this treatable condition.
Orbital volume measurements by CAT Scan is important in predicting

whether surgical treatment would be needed. Orbital volume
measurements may show discrepancy, between the two eyes, in patients
who have orbital floor fracture. Large discrepancy between the two orbits
indicates that surgical treatment may be needed.
Orbital floor exploration and repair should be undertaken if the motility

disorder persists for 10 to 15 days. Orbital floor fracture with entrapment
of the inferior rectus muscle may be associated with oculo-cardiac
reflex. Patients may present with bradycardia, nausea, and syncope
associated with upward gaze. The finding of oculo-cardiac reflex in
patient with orbital floor fracture should be considered as an indication for
urgent surgical repair.
Orbital floor implants may be used in the treatment of orbital floor

fracture. Complications of orbital floor implants include: implant extrusion,
motility restriction, haemorrhage about the implant causing proptosis and
diplopia, Infection, and Mydriasis (mainly due to manipulations of the
inferior oblique muscle, and the ciliary ganglion). Medopar is a high
density porous polyethylene material that has been used successfully in
the treatment of orbital and facial fractures repair. The materiel has the
following advantage: low cost, well tolerated, non antigenic, good

resistance to infections, it can also promotes tissue in-growth, and has
the ability to pass sutures through it.
Post-traumatic endophthalmitis
Post-traumatic endophthalmitis, generally, has poor results partly
because it includes poly-microbial infections among other causes.
Endophthalmitis caused by coagulase negative seems to be associated
with the best visual outcome. Intraocular foreign bodies, rural areas
settings and delayed primary repair, and disruption of the crystalline lens
are associated with increased risk of endophthalmitis. Streptococcal
organisms are the most common infecting organism in children (unlike
adults where the commonest organism is Staphylococcus epidermidis
and Bacillus). Bacillus cereus is often associated with very poor visual
and anatomical outcome because the organism produces a number of
exotoxins that often result in cell death and tissue necrosis.
A favourable outcome may be achieved by prompt pars plana vitrectomy

and intravitreal antibiotics. Intravitreal broad spectrum antibiotics remain
the treatment of choice for this condition. Oral Ciprofloxacin also achieves
intravitreal levels exceeding minimal inhibitory concentration for common
ocular pathogens suggesting that this drug could be a good prophylactic
measure in post-traumatic endophthalmitis. Ciprofloxacin has a good
activity against staphylococcus, bacillus and most gram negative
organisms including Pseudomonas species.

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Welcome to…

How to use the book?

New chapter 4 GP’s

External eye Corneal surgery Cataract surgery

Glaucoma Medical retina Vitreoretinal surgery

Paediatric Neuroophthalmology Tumours

Ocular adnexa Uveitis Trauma

Double click here for last

• In the table of contents, click on any arrow-head pointing to the

• You can also change the magnification of the screen by the

Nowadays, when medical knowledge is changing with such an alarming

I intend to update my book every three months by producing a new

I believe the book can make a useful addition to any ophthalmologist

I have included a New Chapter, in this edition, about the common

Magdy Nofal is an ophthalmic surgeon in Torbay general hospital, Torquay,

Magdy Nofal can be contacted by any of these methods:

Tel. number "work"

You can also visit his web site at

Common Ophthalmic Presentations NEW

This chapter is aimed at GPs, Optometrists and non-

Acute red eye.

Disease Main manifestations What to do? Comments

• If conjunctivitis does not resolve in a few days, with topical antibiotics

Differential diagnosis of conjunctivitis

Disease Main manifestations What to do? Comments

• If severe purulent fulminating conjunctivitis occur very rapidly, think of

• Purulent conjunctivitis in a new born (ophthalmia neonatorum) should

Causes and differential diagnosis of Ophthalmia neonatorum

Causes Features What to do?

A short summery of uveitis

The common causes of anterior uveitis include:

• Idiopathic, (the most common type).

Disease Main manifestations

Disease Main manifestations

• Investigations of patients with anterior uveitis are often tailored

Disease Main manifestations

Common causes of infectious uveitis

Disease Main manifestations

Common causes of non-infectious uveitis

Disease Main manifestations

spot, good prognosis for vision.

intermediate uveitis “pars planitis”

main features Other features treatment others

Corneal fluorescein staining

Differential diagnosis of keratitis and corneal ulcers

Disease Main manifestations What to do? Comments

keratitis be very painful, associated with blepharitis. treatment,

Sudden onset of painful loss of vision.

With a red eye Without a red eye

Disease Main manifestations What to do? Comments

• Anterior ischaemic optic neuropathy may be non-arteritic, vision loss is

Sudden onset of painless loss of vision

Disease Main manifestations What to do? Comments

of similar problem in the

Types and causes of retinal detachment

Rhegmatogenous Exudative Traction

Differential diagnosis of the common intraocular tumours more

Gradual loss of vision

Disease Main manifestations What to do?

The main types of stromal corneal dystrophies are: