Neuro-Ophthalmology, 2014; 38(5): 260263

! Informa Healthcare USA, Inc.

ISSN: 0165-8107 print / 1744-506X online
DOI: 10.3109/01658107.2014.923914

C ASE REPORT

Orbital Apex Syndrome Secondary to Herpes Zoster

Ophthalmicus
Seyda Ugurlu1 Sevinc Atik2, and Seher Saritepe Imre2

1
Department of Ophthalmology, Izmir Katip Celebi University, Izmir, Turkey, 2Department of Ophthalmology,
Izmir Katip Celebi University, Ataturk Teaching and Research Hospital, Izmir, Turkey

ABSTRACT
A 49-year-old woman who complained of lacrimation, foreign body sensation, and eyelid oedema presented to
our outpatient clinic. External examination identified erythematous rash with vesicles on the left eyelid, dorsum
of the nose, and forehead of the patient. She was diagnosed to have herpes zoster ophthalmicus (HZO), and was
started on oral brivudine and topical acyclovir. On the third day of the treatment, visual acuity of left eye was
reduced; left blepharoptosis and total ophthalmoplegia had developed. Orbital magnetic resonance imaging
(MRI) showed enlargement of the extraocular muscles, and perineural enhancement of the optic nerve on that
side. Oral brivudine was replaced with intravenous acyclovir, and oral corticosteroid was initiated. Complete
resolution of proptosis and restriction of eye movements were achieved, and significant improvement of visual
acuity was observed within a week.
Orbital apex syndrome, a severe and rare complication of herpes zoster infection, can develop despite antiviral
treatment. Rapid institution of appropriate therapy may provide complete recovery.
Keywords: Brivudine, herpes zoster ophthalmicus, ophthalmoplegia, orbital apex syndrome

INTRODUCTION medical history revealed prior presentation to a

different ophthalmology clinic 5 days ago; she had
Orbital apex syndrome (OAS) is a clinical condition used topical antibiotic and corticosteroid drops with
characterised with optic nerve dysfunction in associ- minimal improvement.
ation with oculomotor nerve, trochlear nerve, abdu- External examination identified an erythematous
cens nerve, and ophthalmic branch of the trigeminal rash with vesicles on the left eyelid, dorsum of the
nerve palsies. This syndrome can be caused by nose, and forehead of the patient. Snellen visual
inflammatory, infectious, neoplastic, iatrogenic, trau- acuity was 20/50 and 20/20 in her left and right eyes,
matic, and vascular conditions.1 respectively. Eye movements were free in all direc-
In this case report, we present a patient with OAS tions. Biomicroscopic examination of the left eye
caused by herpes zoster ophthalmicus (HZO). The revealed chemosis, and multiple dendritic lesions
clinical features, radiologic imaging findings, and scattered over the cornea. Intraocular pressures were
treatment modalities are discussed. 16 mm Hg in both eyes. Fundus examination was
within normal limits bilaterally. The patient was
started on oral brivudine (125 mg/day) and topical
CASE REPORT acyclovir five times daily in the left eye. She came in
for follow-up 3 days after starting the treatment. The
A 49-year-old woman presented to our outpatient examination revealed increased number of skin
clinic with the complaints of lacrimation, foreign body lesions and reduction of the visual acuity of left eye
sensation, and eyelid oedema of the left eye. Her past to 20/200. She was noted to have left upper eyelid

Received 10 March 2014; revised 3 May 2014; accepted 3 May 2014; published online 26 June 2014
Correspondence: Seyda Ugurlu, Department of Ophthalmology, Katip Celebi University, Ataturk Teaching and Research Hospital, Izmir,
Turkey. E-mail: [email protected]

260
 Orbital Apex Syndrome 261

blepharoptosis and non-pulsatile proptosis of the left follow-up visit, 5 months after the initial presentation,
eye. There was paralysis of elevation, depression, the best-corrected visual acuity was 20/30 in the left
adduction, and abduction of the left eye (Figure 1). eye.
Her left pupil was dilated and unreactive to light.
There were corneal keratic precipitates and 4 plus DISCUSSION
cells in the anterior chamber, with severe fibrinous
reaction in the left eye. Orbital Magnetic resonance HZO is a clinical situation resulting from involvement
imaging (MRI) was obtained, and it showed enlarge- of the ophthalmic division of the fifth cranial nerve by
ment of the extraocular muscles of the left eye along herpes zoster virus. Ophthalmoplegia has been
with perineural enhancement of the left optic nerve reported to occur in 1129% of cases with HZO.2
(Figure 2a and b). Oculomotor nerve palsy is the most frequently
The patient was hospitalised; oral brivudin was involved nerve, followed by the abducens nerve
stopped. Intravenous acyclovir (30 mg/kg three times palsy.3 Orbital apex syndrome (OAS), where all
per day) and oral prednisolone (1 mg/kg/day) along extraocular muscles, ophthalmic branch of the fifth
with topical corticosteroids were started. Acute clin- cranial nerve, and pupil are involved, is, however, a
ical signs showed regression within a week; blephar- very rare manifestation of HZO.1,4 A PubMed search
optosis had resolved, and the patients vision with the key words HZO and OAS revealed six
improved to 20/100 in the left eye. Oral prednisolone cases in the English literature.
was tapered gradually. Intravenous acyclovir treat- Herpes zoster infection is believed to cause OAS
ment (15 days) was followed by oral acyclovir either by direct viral invasion, vascular compromise,
treatment (5  800 mg), and was continued for or tissue oedema.5,6 In the current case, orbital apex
3 months on tapering doses. involvement was evident within 3 days of vesicular
During her follow-up, gradual improvement of eruption; MRI had revealed thickened extraocular
proptosis and complete recovery of extraocular motil- muscles and perineural enhancement of optic nerve.
ity of the left eye was observed (Figure 3). On her last The mechanism with which the ophthalmoplegia

FIGURE 1 The appearance of the patient on the 3rd day of vesicular eruption. Note the development of proptosis, blepharoptosis, and
restriction of ocular movements in all directions.

FIGURE 2 Orbital MRI images, axial (a) and coronal (b), revealed enlargement of extraocular muscles, enhancement of optic nerve
and signals within orbital fat, suggesting the presence of an inflammatory process.

! 2014 Informa Healthcare USA, Inc.

262 S. Ugurlu et al.

FIGURE 3 Complete resolution of proptosis, blepharoptosis, and ocular motility restriction at the 5th-month follow-up visit.

developed is unclear, yet both tissue oedema and brivudine had not been previously reported in patients
direct viral invasion might have played a role. with OAS secondary to HZO. Valacyclovir and
Varicella-zoster infection is typically more severe in vidarabine had been used with success.4 It is not
immunocompromised patients, elderly persons, neo- possible to identify the reason of clinical worsening;
nates, and pregnant women. Many of the previously however, intravenous administration of an antiviral
published orbital apex syndrome cases have been agent with better pharmacokinetics may be more
reported in association with either immune deficiency appropriate in the case of OAS development.
and/or triggering events. Arda et al. reported a 75- The current patient showed significant improve-
year-old male presenting with OAS who had history ment during the follow-up period; her vision
of trauma and concomitant viral infection.5 Kattah improved to 7/10 with full recovery of extraocular
and Kennerdell reported an OAS case in a patient motility. Similar improvement was observed in pre-
with Hodgkin lymphoma.7 Another case was pub- viously reported cases, even in cases with immune
lished by Saxena et al. of a 29-year-old patient who suppression. Of the two cases described by Kattah
had human immunodeficiency virus (HIV) infection.8 and Kennerdell, however, only one had recovery of
Dhingra et al. reported a 63-year-old man with motility and regression of proptosis. The other 54-
multiple myeloma and OAS resulting from HZO.9 year-old patient with left orbital apex syndrome
The current patient is a 49-year-old woman with no developed total blindness. She had been given oral
other medical problems. She was relatively younger prednisone (80 mg/day); concomitant use of antiviral
than most of the cases previously published in the agents was not reported.7
literature, and had no chronic illness, immune defi- OAS is a rare complication of herpes zoster
ciency, trauma, or triggering events. infection. Systemic corticosteroid use together with
Various antiviral agents such as acyclovir, valacy- antiviral agents seems to provide adequate control of
clovir, famciclovir, and brivudine are available for the disease, and results in significant recovery of
herpes zoster infections. Acyclovir, the most com- visual dysfunction and ocular motility. Close follow-
monly used agent, is limited with the need for up of the patients with HZO is essential to detect signs
frequent daily administration. Brivudine is a nucleo- and symptoms suggesting orbital apex syndrome,
side analogue with high and selective antiviral activ- even in immune competent patients.
ity against varicella-zoster and herpes simplex virus
type 1. It has been approved for the treatment of
herpes zoster in several countries. It had been used in Declaration of interest: The authors report no
a case of acute retinal necrosis with success.10 On the conflicts of interest. The authors alone are responsible
other hand, the authors of a recent review comparing for the content and writing of the paper.
acyclovir, valacyclovir, famciclovir, and brivudine
concluded that superior pharmacokinetics and more Note: Figures 1 and 3 of this article is available in
convenient dosing regimens of valaciclovir and fam- colour online at http://informahealthcare.com/oph.
ciclovir made them the preferred treatment option.11
In the current case, oral brivudine therapy was
started as the initial systemic antiviral therapy, as REFERENCES
suggested by our dermatology department. Despite
[1] Yeh S, Foroozan R. Orbital apex syndrome. Curr Opin
brivudine therapy, the clinical presentation progressed
Ophthalmol 2004;15:490498.
to orbital apex syndrome. Changing the therapeutic [2] Covucci A. Paresis of cranial nerves 3, 4 and 6 associated
regimen to intravenous acyclovir and oral prednisol- with herpes zoster ophthalmicus: a case report. Clin Eye Vis
one resulted in significant improvement. Use of oral Care 1999;11:159163.

Neuro-Ophthalmology
 Orbital Apex Syndrome 263

[3] Marsh RJ, Dulley B, Kelly V. External ocular motor palsies in [8] Saxena R, Phuljhele S, Aalok L, Sinha A, Menon V,
ophthalmic zoster: a review. Br J Ophthalmol 1977;61: Sharma P, Mohan A. A rare case of orbital apex syndrome
677682. with herpes zoster ophthalmicus in a human immunode-
[4] Kurimoto T, Tonari M, Ishizaki N, Monta M, Hirata S, ficiency virus-positive patient. Indian J Ophthalmol 2010;
Oku H, Sugasawa J, Ikeda T. Orbital apex syndrome asso- 58:527530.
ciated with herpes zoster ophthalmicus. Clin Ophthalmol [9] Dhingra S, Williams G, Pearson A. Severe, permanent
2011;5:16031608. orbital disease in herpes zoster ophthalmicus. Orbit 2008;
[5] Arda H, Mirza E, Gumus K, Oner A, Karakucuk S, 27:325327.
Sirakaya E. Orbital apex syndrome in herpes zoster [10] Vij O, Bornfeld N, Roggendorf M, Fiedler M, Schilling H.
ophthalmicus. Case Rep Ophthalmol Med 2012;2012:854503. [Brivudine as an alternative systemic therapy to aciclovir
[6] Krasnianski M, Sievert M, Bau V, Zierz S. External and ganciclovir in acute retinal necrosis syndrome due to
ophthalmoplegia due to ocular myositis in a patient with varicella-zoster virus]. Klin Monbl Augenheilkd 2003;220:
ophthalmic herpes zoster. Neuromuscul Disord 2004;14: 710715.
438441. [11] McDonald EM, de Kock J, Ram FS. Antivirals for manage-
[7] Kattah JC, Kennerdell JS. Orbital apex syndrome second- ment of herpes zoster including ophthalmicus: a system-
ary to herpes zoster ophthalmicus. Am J Ophthalmol 1978; atic review of high-quality randomized controlled trials.
85:378382. Antivir Ther 2012;17:255264.

! 2014 Informa Healthcare USA, Inc.