Background

Iritis, or anterior uveitis, is the most common form of ocular inflammation

encountered. It is a common cause of a painful red eye. Inflammation of
the iris may appropriately be termed iritis, whereas inflammation of the
iris and the ciliary body is called iridocyclitis. Iritis may be subdivided
into 2 broad categories: granulomatous and nongranulomatous.

This article addresses nongranulomatous iritis, although iritis due to a

granulomatous disease process may have a nongranulomatous
appearance. For information about granulomatous disease, see Uveitis,
Anterior, Granulomatous. The most common form of nongranulomatous
anterior uveitis is acute anterior uveitis (AAU), which is associated with
the HLA-B27 allele in half to two thirds of patients.

Pathophysiology
The exact pathophysiology is not known. Inflammation of the iris and
the ciliary body causes a breakdown of the blood-ocular barrier. This
condition allows both protein and WBCs to extravasate into the
aqueous, resulting in the typical iritis signs of cell and flare. Frequently,
the cause is idiopathic, but certain ocular and systemic diseases may
be the underlying cause of the iritis.[1]

In the case of HLA-B27, associated AAU speculation about molecular

mimicry has yet to be substantiated in humans. The microbiome (gut
and other resident microorganisms) in disease, and the observation that
rats transgenic for HLA-B27 do not form ankylosis or other evidence of
disease until the gut is colonized suggest a possible connection to
disease. Indeed, subclinical colitis has been demonstrated in patients
with uveitis.

Epidemiology
Frequency
United States
Iritis is the most frequent form of uveitis that is encountered by
ophthalmologists. In one community-based study, anterior uveitis
accounted for more than 90% of all cases of uveitis. The annual
incidence rate is approximately 8 cases per 100,000 population.[2]

International
No particular geographic distribution for iritis has been noted.

Mortality/Morbidity
← Morbidity arises from iritis and any associated
disease process, if present.
← Episodes of AAU are often associated with pain,
photophobia, decreased vision, and the need for follow-up visits,
which impact quality of life.
← Patients may develop posterior synechiae, and, if
severe, a secluded pupil and subsequent angle-closure glaucoma
may result.
← Associated ocular complications (eg, cataract,
glaucoma, macular edema, hypotony) may result in severe vision
loss.
Race
No significant racial differences exist. HLA-B27–associated anterior
uveitis is more common in Caucasians.

Sex
No significant sexual differences exist. Although, the male-to-female
ratio of ankylosing spondylitis, which is a common cause of iritis, is 3:1.
[3]

Age
Iritis may develop in patients of any age but most commonly in the
fourth and fifth decade of life.

History
Inquire about the patient's complete medical history, to include all
medical conditions, surgeries, medications, and ocular history (eg,
history of iritis, trauma, surgery). Perform a detailed review of systems.
This is critical, as the history and the review of systems in many cases
will suggest a diagnosis.

Critical review questions include, but are not limited to, asking about
recent ocular trauma, back stiffness, arthritis, rashes, shortness of
breath, urethral discharge or dysuria, swollen lymph nodes, diarrhea,
blood in stools, recent insect bites, sexually transmitted diseases
(STDs), and tuberculosis (TB) exposure.

Inquire about the onset of the symptoms. Most cases of acute anterior
uveitis begin with the sudden onset of redness, pain, and photophobia.

Family history is important as well. Inquire if there is a family history of

uveitis or other symptoms in family members that might suggest
associated diseases, such as a spondyloarthropathy or other human
leukocyte antigen (HLA)-B27 processes.[4]

Inquire in particular about the following symptoms:

← Dull, aching eye pain occurs and may worsen when one touches
 the eye through the eyelid. Pain may be referred to the temple or
periorbital region.
0 Pain is usually abrupt in onset.
1 Photosensitivity to light, especially sunlight, worsens the
patient's discomfort.
←
← Redness with no mucopurulent discharge is seen. Patients rarely
have a watery discharge or tearing. Some forms of iritis, such as
Fuchs iridocyclitis, may have no symptoms other than loss of
vision or glare from associated cataract.
← Decreased vision may be noted.
← Most cases of AAU are unilateral, although the same eye is not
always involved in different episodes. Tubulointersitial nephritis
(TINU) is a rare syndrome that is often associated with a bilateral
anterior uveitis of sudden onset.
Physical
← Vision: Visual acuity is usually normal or only slightly
decreased, although in severe episodes the acuity can be very
low.
← Intraocular pressure (IOP) is often lower in the eye
with iritis when compared to the fellow eye. This is secondary to a
decrease in aqueous production by the inflamed ciliary body.
However, in some cases, the IOP may be elevated as a result of
altered aqueous outflow; this may be more common in viral
anterior uveitis.
← Conjunctiva: Typically, the eye has a perilimbal
injection termed ciliary flush. Less commonly, generalized
redness of the bulbar conjunctiva may be present. This is not
found in Fuchs heterochromic iridocyclitis or the anterior uveitis
associated with juvenile idiopathic arthritis.
← Cornea
• Keratic precipitates (KPs) may be present. These clusters of
WBCs collect on the endothelium. In nongranulomatous
iritis, they tend to be small and are usually located over the
inferior half of the cornea. Keratic precipitates in acute
anterior uveitis associated with ankylosing spondylitis are

shown below.
• Fine keratic precipitates in a patient with ankylosing spondylitis–associated
acute anterior uveitis.
• Stellate-shaped KPs, uniformly spread over the endothelium, are
typical of Fuchs heterochromic iridocyclitis, as shown in the
image below, and also may be seen in herpetic viral

anterior uveitis.
• Small stellate keratic precipitates with fine filaments in a patient with Fuchs
heterochromic iridocyclitis.
• Calcific band keratopathy can occur in chronic uveitides as in the
uveitis associated with juvenile idiopathic arthritis. Corneal
stromal edema may be present secondary to viral
endotheliitis or endothelial dysfunction due to uveitic
glaucoma or extensive anterior chamber inflammation.
Cytomegalovirus infection in nonimmunosuppressed
patients can cause corneal edema that may even recur in
corneal grafts.[5]
←
← Anterior chamber: Flare, cells, and/or hypopyon may
be present.
• Anterior chamber flare, resulting from extra protein in the
aqueous, is usually present and can be graded using the
SUN Working Group Grading Scheme for Anterior
Chamber Flare:[6]
• 0 = None
• 1+ = Faint
• 2+ = Moderate (iris and lens detail clear)
• 3+ = Marked (iris and lens detail hazy)
• 4+ = Intense (fibrin or plastic aqueous)
• Cells, the hallmark of iritis, are present in the aqueous. They
should be graded by severity under high-magnification slit
lamp examination in a 1 X 3-mm field of light, as described
by the SUN Working Group Grading Scheme for Anterior
Chamber Cells.
• 0<1
• 0.5 = 1-5 cells
• 1+ = 6-15 cells
• 2+ = 16-25 cells
• 3+ = 26-50 cells
• 4+ = More than 50 cells
• Hypopyon, if present, is highly suggestive of diseases associated
with HLA-B27; with Behçet disease; or, less commonly, with
an infection-associated iritis. Hypopyon is shown in the

image below.
• Acute anterior uveitis with plasmoid aqueous and hypopyon in a patient with
ulcerative colitis.
←
← Iris
• Posterior synechiae may be present. Inflammatory nodules are
usually not present in nongranulomatousiritis, although
Koeppe nodules can be present in Fuchs
heterochromiciridocyclitis. Sector atrophy of the iris, if
present, suggests herpes zoster as the etiology of the
inflammation and patchy or generalized iris atrophy
suggests herpes simplex uveitis. Iris changes may be seen
in CMV anterior uveitis as well. Iris atrophy is shown in the

image below.
• Iris atrophy in a patient with herpes simplex virus–associated anterior uveitis.
• Heterochromia and loss of iris stromal detail are suggestive of
Fuchs heterochromic iridocyclitis. An example is shown in
 the image below.
• Fuchs heterochromic iridocyclitis with cataract and iris heterochromia.
←
← Lens and anterior vitreous: Lenticular precipitates
may be present on the anterior lens capsule. Posterior
subcapsular cataracts may be present if the patient has had
repeated episodes of iritis.
• Cells are commonly seen in the anterior vitreous. They represent
either an iridocyclitis or a spillover of cells from the anterior
chamber into the retrolental space. This may happen even
in Fuchs iridocyclitis.
• Occasionally, patients with HLA-B27 disease have an intense
vitritis, papillitis, and cystoid macular edema.
←
Causes
It is important to ascertain whether the uveitis is unilateral or bilateral,
symptomatic (pain and photophobia), and acute (lasting less than 3
months) or chronic.

Unilateral, sudden onset, acute

← Acute anterior uveitis
• Idiopathic
• Diseases associated with HLA-B27 (usually is a unilateral acute
anterior uveitis with a high tendency to recur sometimes in
the contralateral eye)
• Ankylosing spondylitis
• Reactive arthritis
• Inflammatory bowel disease
• Psoriasis
• Behçet's disease
• Sarcoidosis
• Trauma
• Infections
• Herpes zoster, herpes simplex, cytomegalovirus
• Syphilis
• Postoperative or metastatic endophthalmitis
←
Unilateral, chronic
← Infections
• Herpes zoster, herpes simplex, cytomegalovirus
• Syphilis
• Fuchs heterochromic iridocyclitis (which may be due to rubella, at
least in some cases)
←
← Sarcoidosis
← Chronic postoperative endophthalmitis
Bilateral
← Sarcoidosis
← Lyme disease
← Fuchs heterochromic iridocyclitis, rarely
← Juvenile idiopathic arthritis
Tubulointerstitial nephritis and uveitis syndrome (TINU)

Differential Diagnoses
← Anterior chamber reaction secondary to posterior uveitis or retinal
detachment
← Foreign Body, Intraocular
← Juvenile Xanthogranuloma
← Leukemias
← Ocular Rosacea
← Pigment dispersion syndrome
← Posner-Schlossman Syndrome
Uveitis-glaucoma-hyphema syndrome

Laboratory Studies
← A comprehensive review of the patient's past medical
history and a review of systems should guide the laboratory
evaluation, and the workup should be tailored accordingly.
0 If a patient presents with a first episode of nongranulomatous
iritis and if the medical history and the review of systems
are unremarkable, laboratory studies may not be not
indicated. Some uveitis specialists recommend specific
antitreponemal serologies on all patients with uveitis.
1 Iritis that is recurrent, unusual in severity, unresponsive to
medical therapy, unusually persistent, or bilateral should be
thoroughly evaluated.
←
← The following list of laboratory studies may be
requested. At minimum, chest radiography (see Imaging Studies)
and a rapid plasma reagin (RPR) test with a specific treponemal
serology, such as the fluorescent treponemal antibody absorption
 (FTA-ABS) test, should be ordered.
0 The RPR test and the FTA-ABS test, or serologic tests for
syphilis, should be ordered for each patient who undergoes
a laboratory evaluation for uveitis.
1 The erythrocyte sedimentation rate (ESR), serum lysozyme
level, and angiotensin-converting enzyme (ACE) test may
help in evaluating the patient for sarcoidosis. However,
these are not very sensitive or specific.
2 HLA-B27 typing.
3 Antinuclear antibody (ANA) and, possibly, rheumatoid factor
(RF) may be indicated if juvenile idiopathic arthritis is
suspected.
4 Lyme serologic testing should be ordered if Lyme disease is
suspected (although if no history otherwise consistent with
Lyme disease or exposure, the predictive positivity of a
positive test is very low).
5 Serum creatinine, urinalysis including urinary beta-2
microglobulin levels should be obtained if TINU is
suspected.
6 A paracentesis for polymerase chain reaction (PCR) or culture
may be considered if there is a question of viral anterior
uveitis or other infectious uveitis.
←
Imaging Studies
← Chest radiography helps to rule out sarcoidosis and
tuberculosis. However, it is not very sensitive or specific.
← High-resolution chest CT is more sensitive for
sarcoidosis than plain radiography and should be ordered if the
radiographs are negative and if sarcoidosis is highly suspected as
the etiology of the ocular inflammation.
← Sacroiliac, lumbar, or thoracolumbar spine
radiographs may be ordered if ankylosing spondylitis is
suspected.
Procedures
If a patient presents with a secluded pupil from extensive
posterior synechiae, iris bombe with angle-closure glaucoma may be
present. In this case, an iridotomy may be necessary.

Medical Care
← Cycloplegia: A long-acting cycloplegic agent, such as
cyclopentolate, homatropine, scopolamine, or even atropine,
should be used to help relieve both pain and photophobia and to
prevent the formation of posterior synechiae in acute
symptomatic anterior uveitis. However, prolonged use of strong
 cycloplegic drops is often not necessary; in fact, letting the pupil
move a little may prevent posterior synechiae from forming in the
dilated position.
← Corticosteroids: Topical corticosteroids are the
mainstays of therapy and should be used aggressively during the
initial phases of therapy.
0 For the most common acute anterior uveitis (eg, associated
with HLA-B27), topical corticosteroids such as prednisolone
acetate 1% are usually started at every hour initially, rarely
more frequently for very severe episodes.
1 Difluprednate (Durezol) can be used at a less frequent dose
schedule than prednisolone acetate 1% and may be useful
when increased effect or improved compliance is needed.
2 A subconjunctival injection of depot-steroids (eg, Celestone)
may be used if the patient poorly complies with topical
therapy or if the iritis is not responding to topical
corticosteroids alone. A sub-tenon injection with a longer-
acting corticosteroid, such as triamcinolone acetate, is
reserved for more prolonged episodes, especially if there is
cystoid macular edema that is not resolving with topical
therapy).
3 In severe cases of acute anterior uveitis, the addition of oral
corticosteroids to the treatment regimen may be necessary.
4 Therapy for increased intraocular pressure as indicated
5 In viral anterior uveitis, antiviral therapy (including valganciclovir
for CMV) may be useful, but this is not well established.
6 Fuchs heterochromic anterior uveitis does not usually require
corticosteroid treatment.
In chronic cases, such as in the anterior uveitis associated with juvenile
rheumatoid arthritis, systemic immunomodulatory corticosteroid-sparing
agents may be required.

Medication Summary
In acute anterior uveitis, topical corticosteroids and a cycloplegic agent
should be started immediately, unless an infectious etiology is
suspected. If the eye is not adequately responding to topical therapy
within a week to 10 days, or if the disease is very severe, the addition of
either oral corticosteroids or a periocular injection of corticosteroids to
the treatment regimen may be necessary as long as no systemic
contraindications or evidence of infection is present. The injection of
steroids may be contraindicated in a known steroid responder or in a
patient with an already elevated IOP.

Tapering of steroid therapy is guided by the clinical response on follow-

up examination. Topical nonsteroidal anti-inflammatory drugs (NSAIDs)
tend to be of little or no benefit in the treatment of iritis.
Immunomodulatory and immunosuppressive medications may be useful
in patients who are unresponsive to corticosteroids, in patients with
chronic uveitis, or in patients who develop adverse effects of
corticosteroid therapy.

A number of agents have been used, including methotrexate,

azathioprine, cyclosporin A, mycophenolate mofetil, cyclophosphamide,
and chlorambucil. Myelosuppression and secondary infection are
among the most common adverse effects of these agents.

Tumor necrosis factor alpha (TNF-alpha) inhibitors may be useful in

patients with the seronegative spondyloarthropathies, including AS.
TNF-alpha inhibitors that are available include infliximab, etanercept,
and adalimumab. Reports suggest that infliximab is effective in reducing
the number of flares of anterior uveitis in patients with AS. Adalimumab
may also be effective, but there is evidence that etanercept is not.[7]

An internist or a rheumatologist should be involved in the management

of patients treated with immunomodulatory agents.

Corticosteroids
Class Summary
These are the mainstays of therapy for iritis and help to stabilize the
blood-aqueous barrier.

View full drug information

Prednisolone acetate 1% (Pred Forte, Econopred)
Decreases inflammation by suppressing migration of
polymorphonuclear leukocytes and by reversing increased capillary
permeability.

View full drug information

Prednisone (Deltasone)
Can be used if topical therapy inadequate to treat iritis. Decreases
inflammation by suppressing migration of polymorphonuclear
leukocytes and by reversing increased capillary permeability.

Cycloplegics
Class Summary
These agents help prevent or break posterior synechiae and reduce
ciliary body–induced pain.

View full drug information

Cyclopentolate HCl 1% (Cyclogyl)
Prevents spasm of ciliary muscle and iris sphincter. Induces mydriasis
in 30-60 min and cycloplegia in 25-75 min.