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Ocular Immunology and Inflammation

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Herpes Zoster Ophthalmicus with Orbital Apex

Syndrome—Difference in Outcomes and Literature

Jie Jie Lim , Yu Ming Ong, M. Zain Wan Zalina & May May Choo

To cite this article: Jie Jie Lim , Yu Ming Ong, M. Zain Wan Zalina & May May Choo (2017):
Herpes Zoster Ophthalmicus with Orbital Apex Syndrome—Difference in Outcomes and Literature
Review, Ocular Immunology and Inflammation, DOI: 10.1080/09273948.2017.1327604

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Published online: 16 Jun 2017.

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Download by: [Cornell University Library] Date: 16 June 2017, At: 12:29
Ocular Immunology & Inflammation, 2017; 00(00): 1–7
©2017 Taylor & Francis Group, LLC
ISSN: 0927-3948 print / 1744-5078 online


Herpes Zoster Ophthalmicus with Orbital Apex

Syndrome—Difference in Outcomes and Literature
Jie Jie Lim, MD , Yu Ming Ong, MBBS, MOphthal3, M. Zain Wan Zalina, MBBch BAO, MS (Ophthal)
, and
May May Choo, MBBS, M.Med, M.Oph, FRCS2

Department of Ophthalmology, Hospital Selayang, Selangor, Malaysia, 2Department of Ophthalmology,
University of Malaya, Kuala Lumpur, Malaysia, and 3Department of Ophthalmology, Hospital Sultanah
Bahiyah, Alor Setar, Kedah, Malaysia

Keywords: Herpes zoster ophthalmicus, Orbital apex syndrome, Varicella zoster infection

Herpes zoster ophthalmicus (HZO) is caused by reactiva- vision. She had reduced oral intake as well. The patient did
tion of latent varicella zoster virus infection in the trigem- not seek treatment at that time.
inal ganglion, involving the ophthalmic division of the At presentation, there were dried and scarred skin
trigeminal nerve (V1). Ocular involvement occurs in lesions over her left forehead and periorbital region in
20–70% of patients with HZO1 and may include blephar- the distribution of the ophthalmic division of the trigem-
itis, keratoconjunctivitis, iritis, scleritis, and acute retinal inal nerve. Visual acuity in the left eye was perception to
necrosis. Neurological complications are less frequent light. The left eye was proposed with complete ophthal-
compared to ocular complications and may include moplegia and the presence of relative afferent pupillary
ophthalmoplegia, optic neuritis, ptosis, and rarely orbital defect. There was complete left upper lid ptosis.
apex syndrome (OAS). OAS involves dysfunction of V1, Intraocular pressures were 12 (OD) and 07 (OS) mmHg.
the oculomotor nerve (III), the trochlear nerve (IV), and Left eye conjunctiva was injected. The cornea was hazy
the abducens nerve (VI), as well as dysfunction of the with the presence of epithelial defect and reduced corneal
optic nerve (II). Herpes zoster ophthalmicus is a rare sensation. The posterior segment view was obscured.
cause of OAS. Here, we report two cases of HZO with B-scan ultrasonography showed no obvious posterior seg-
orbital apex syndrome. We conducted a thorough litera- ment involvement. Examination of the right eye showed
ture review to assess the prevalence of our reported cases. that it was normal. Computed tomographic (CT) scan of
the brain and orbit turned out normal (see Figures 1 and 2).
A diagnosis of left herpes zoster ophthalmicus with
METHOD orbital apex syndrome and neurotrophic cornea ulcer
was made. She was treated with oral acyclovir (800mg 5
Case Series times a day), oral prednisolone 40mg od and topically, she
was treated with artificial tears eyedrops, dexamethasone
0.1% eyedrops, oxytetramycin ointment, and homatro-
RESULT pine eyedrops. Patient was maintained on oral acyclovir
800mg 5 times a day and oral prednisolone tapered over a
Case 1 total duration of 2 months.
She was discharged after two weeks, with residual
A 77-year-old woman with underlying hypertension pre- minor epithelial defects. Her left eye vision remained
sented with complete left upper eyelid ptosis. Three weeks at perception of light at the time of discharge.
prior to presentation, she had vesicular skin lesions over The patient was closely monitored as an outpatient
the left periorbital region and forehead. She also experi- with biweekly follow-ups. During this period, she
enced left eye pain, redness, and progressive blurring of developed secondary bacterial keratitis and was read-

Received 27 December 2016; revised 27 April 2017; accepted 3 May 2017; published online 16 June 2017
Correspondence: Jie Jie Lim, Department of Ophthalmology, Hospital Selayang, Lebuh Raya Selayang-Kepong, 68100 Batu Caves, Selangor,
Malaysia. E-mail:


TABLE 1. Reported cases of herpes zoster ophthalmicus with orbital apex syndrome.

Time of Time of administration of

Case Initial onset of antiviral after the onset of Administration of systemic Final Systemic
Reports Age Gender VA OAS HZO steroid VA Full recovery of EOM Causes of poor vision association
J. Lim et al.

Dhingra 63 Male 20/200 5th day 5th day Oral prednisolone for 2 HM Minimal improvement of OD pale Multiple
et al (iv acyclovir and months 4th and 6th cranial nerve myeloma
2008 (5) converted to oral
Ugarte 80 female HM 2.5 week 1st day Oral prednisolone for 2 6/9 6th month - -
et al (oral acyclovir) months
2010. (6)
Saxena 29 female 20/640 2 weeks 2nd week Oral prednisolone, taper over 20/ 4th week - HIV
et al (oral acyclovir with 10 days. 25
2010 (7) HAART)
Kurimoto 81 female 6/12 17 days 10th day Iv prednisolone 6/6 20th week, except for
T at al (iv vidarabine) abduction
2011. (8)
Arda et al 75 male CF 2 days 1st day Oral prednisolone. CF 5th month, partial Mature cataract,
2012 (9) (oral valacyclovir then improvement of the epithelial defect,
changed to iv acyclovir EOM. fibrinoid reaction in
after diagnosis of OAS AC
being established)
Alexia 61 male CF 5 days 5th day Oral prednisolone 6/12 10th week. -
Merino (iv acyclovir) For 10 weeks
et al
Mar 2014
CY Lee at 78 male 3/60 5 days 5th day Oral prednisolone 6/30 12 weeks, with residual - -
al (iv acyclovir) 12 weeks limitation of abduction
Jan 2015 and paralysis of the left
(11) upper eyelid.
Kalamkar 65 male PL 10 days 10th day IV methylprednisolone for 3 PL 3 months, except limited OD pale -
C et al. (oral acyclovir) days, then oral abduction
Jun 2016 prednisolone tapered over 2
(12) mths
Verhaeghe 80 male CF 7 days 1st day IV methylprednisolone for 15 6/15 5 months OD pale
et al (initially oral acyclovir, days – started after 7 days
Jun 2016 then admit for iv of iv acyclovir, then oral for
(13) acyclovir) 2 months.
Our 77 female PL 3 weeks 3 weeks (oral acyclovir) Oral prednisolone PL 6 weeks Extensive cornea Hypertension
patient For 2 weeks scarring and
of case 1. vascularization
secondary to bacterial
Our 65 male 3/60 4 weeks 1st day Not initiated. 6/24 6 weeks Nuclear sclerosis Diabetes
patient (oral acyclovir) mellitus
of Case 2

Ocular Immunology & Inflammation

Herpes Zoster Ophthalmicus with Orbital Apex Syndrome 3

FIGURE 1. Case 1. First presentation of the patient showed limitation of the extra ocular muscle movement of the left eye.

FIGURE 2. Case 1. Cornea was hazy with the presence of epithelial defect.

mitted to the ward for treatment (see Figures 3 and 4). At 2 months, her extraocular muscle movements
Her bacterial keratitis resolved after intensive treat- were full. However, there was still partial ptosis. Her
ment with topical antibiotics (gentamicin eyedrops vision remained poor due to extensive vascularization
and ceftazidime eyedrops). and scarring of the cornea.

© 2017 Taylor & Francis Group, LLC

4 J. Lim et al.

FIGURE 3. Case 1. There was improvement seen in the extra ocular muscle movement on second admission (three weeks after initial

FIGURE 4. Case 1. Although there was improvement on extra ocular muscle movement, there was secondary bacterial infection
associated with hypopyon.

Case 2 upper lid ptosis, poor vision, and left-sided headache.

One week prior to this, there were vesicular lesions
A 65-year-old Chinese man with underlying diabetes which were distributed over the left forehead and left
mellitus complained of redness and pain in the left eye periorbital region. He had been treated with oral acy-
for a duration of four weeks. He also had complete left clovir by his primary care doctor. At the time of

Ocular Immunology & Inflammation

Herpes Zoster Ophthalmicus with Orbital Apex Syndrome 5

FIGURE 5. Case 2. Left ptosis with multiple scars on the fore- FIGURE 7. Case 2. Left eye ptosis resolved with bilateral ortho-
head, upper eyelid, side of nose, and tip of nose. Injected con- phoria. (at resolution)
junctiva and corneal haziness. (on initial presentation)

There were multiple small healed depressed scars,

and some had overlying scabs in the left periorbital
region, forehead, cheek, and nose. Complete ptosis
was present in the left eye. The left pupil was dilated
(7mm) and non-reactive to light. There was reverse
Marcus Gunn. The right pupil was 5 mm in size and
reactive. The eye was exo-deviated by 15° (Hirschberg
corneal light reflex). There was total ophthalmoplegia.
Intraocular pressures were 18 (OD) and 20 (OS)
mmHg. The left conjunctiva was injected, and left
corneal sensation was absent. Small punctate erosions
were present on the left cornea, and a small corneal
ulcer with thinning was seen infero-nasal to the pupil
measuring 1.7 mm × 1.7 mm. The cornea was hazy.
Fundus view was also not clear (see Figures 5 and 6).
The right eye anterior and posterior segments were
normal with no diabetic retinopathy seen.
A provisional diagnosis of left herpes zoster
ophthalmicus with orbital apex syndrome was made,
and the patient was commenced on treatment with
topical acyclovir 5 times a daily and hourly ocular
lubricants. A further continuation of oral acyclovir
was prescribed for 10 days.
The patient’s vision improved to 6/24 at 3 weeks
review, and there was partial recovery of the left ocu-
FIGURE 6. Case 2. Left pupil dilated, eye injected, and central
cornea were hazy. (on initial presentation) lomotor nerve. The anterior chamber was quiet with
no cells detected. Acyclovir ointment was tapered, and
topical lubricants were reduced to four hourly inter-
presentation to the ophthalmology clinic, his left vision vals as corneal was clear with mild haziness inferona-
was 2/60 with no improvement using the pin-hole. sally. All the epithelial defects had healed. At 6 weeks,
Right eye vision was 6/24 and 6/12 with a pin-hole. there was mild ptosis, but full eye movements were

© 2017 Taylor & Francis Group, LLC

6 J. Lim et al.

detected. Vision had remained the same, and this was immunocompetent patients with herpes zoster who
attributed to worsening of nuclear sclerosis. However, fulfill any of the following criteria: (1) 50 years of
cataract extraction will be deferred for another 6 age; (2) have moderate or severe pain; (3) have mod-
months in view of the recent inflammatory condition erate or severe rash; or (4) have non-truncal
in the eye (see Figure 7). involvement.14
The current practice is to treat individuals with a
new episode of herpes zoster with 7 to 14 days of
DISCUSSION antiviral treatment. However, based on Miserocchi
et al‘s report, it was found that there is a decreased
Herpes zoster ophthalmicus (HZO) is defined as frequency of recurrent episodes from 3.4 to 2.1 epi-
herpes zoster involvement in the ophthalmic division sodes per year in patients treated with prophylactic
of the trigeminal nerve. It accounts for 10–20% of oral acyclovir or valacyclovir for at least 1 year. The
herpes zoster cases. It could involve a spectrum of optimal time for initiation of systemic antiviral treat-
presentation, such as blepharitis, keratoconjunctivitis, ment is within 72 hours after the onset of rash.
iritis, scleritis, and acute retinal necrosis. Diagnosis of While the optimal therapy for OAS secondary to
herpes zoster ophthalmicus is relatively straightfor- HZO remains unclear, the current mainstay of treat-
ward and is usually based on typical clinical presenta- ment is combined administration of systemic acyclovir
tion of rashes and pain. Often no tests are required. and steroids.5,15 In the reported cases, most of the
Orbital apex syndrome (OAS) is a rare and serious cases showed good improvement in response to the
complication of herpes zoster ophthalmicus. OAS is a treatment with systemic acyclovir and steroids. One of
spectrum of disease which involves damage to the the reported cases was treated with vidarabine due to
oculomotor nerve, trochlear nerve, abducens nerve, compromised renal function. She also achieved good
and ophthalmic division of the trigeminal nerve, in vision at the end of the treatment. Three of these
association with optic nerve dysfunction. It was first patients did not achieve good vision despite treatment
reported by Ramsell in 1967.2 Both our patients pre- with systemic antivirals and steroids. The poor vision
sented with this rare but severe complication of HZO for the three reported cases was all attributed to optic
—orbital apex syndrome. In our cases, imaging had atrophy.
excluded other common causes of OAS such as hemor- In the cases of our two patients, the first patient
rhage, neoplasm, and cavernous sinus thrombosis.3 presented to us with a severe form of orbital apex
Others blood investigations turned out normal. Based syndrome only at the third week after the onset of
on clinical presentation, we diagnosed them with rashes. Oral acyclovir and systemic steroid treatment
herpes zoster ophthalmicus with orbital apex syn- were started at the third week of onset. The effective-
drome after the imaging. ness of acyclovir therapy in our patient has been
Cases of herpes zoster ophthalmicus complicated reduced due to the delay in initiation of treatment,6
with orbital apex syndrome are extremely rare. From while the second case represents a milder case that
the literature reviews, we found some reported cases was probably attributed to early administration of
with neuropathy. Womack et al (1983) reported three oral acyclovir by the general practitioner. However,
of 86 patients with HZO seen at Mayo clinic had the optimal time for initiation of treatment is within
ocular motor palsies (3.4%)1 . Marsh (1977) reported 72 hours from the onset of the rash.5,15
that 9.8% of patients with HZO in the Moorfield Eye The true mechanisms by which optic neuropathy
Hospital study had extraocular muscle palsy, with and extraocular muscle paralysis occur in patients
cranial nerve III dysfunction in four of the patients.4 with OAS due to HZO are not completely understood.
Incidence of cranial nerve II dysfunction was only in Postulated mechanisms include extensive inflamma-
0.4% of the patients in the Moorfield Eye Hospital tion around the posterior ciliary nerves and vessels
study.4 with ocular ischemia, orbital soft tissue edema with
HZO associated with orbital apex syndrome has direct compression of cranial nerves III, IV, and VI,
only been reported in isolated cases. Over the past 10 and direct spread of VZV from cranial nerve V to
years, there were nine isolated cases of HZO with OAS cranial nerves III, IV, and VI. Different mechanisms
reported in the literature (see Table 1).5–13 may lead to different clinical manifestations and
The age range of the patients was 29–81 years old, prognoses.4,11
with most of the patients being elderly. There were The proportion of patients who achieve resolution
two cases reported with background of immunosup- of ptosis, ophthalmoplegia, and reduced visual acuity
pressive state—one of the patients was a HIV patient, remains unknown.16 Complete or near-complete reso-
while the other patient had multiple myeloma. In both lution of ophthalmoplegia due to HZO has been
our cases, the patients were elderly and the second reported to occur in 76.5% of cases and may take
patient had underlying diabetes. between 2 weeks and 1.5 years (mean 4.4 months).5
Based on Dworkin et al (2007), systemic antiviral In our first patient, resolution of ophthalmoplegia
therapy is recommended as first-line treatment for all took 6 weeks, with residual of partial ptosis. Her

Ocular Immunology & Inflammation

Herpes Zoster Ophthalmicus with Orbital Apex Syndrome 7

visual acuity did not improve due to extensive scar- 2. Ramsell TG. Complications of herpes zoster ophthalmicus.
ring and vascularization of the cornea from secondary Am J Ophthalmol. 1967;63:1796–1798.
3. Yeh S, Foroozan R. Orbital apex syndrome. Curr Opin
bacterial keratitis. Our second patient regained com- Ophthalmol. 2004;15:490–498. Lippincott Williams & Wilkins.
plete recovery of ophthalmoplegia at 6 weeks. His 4. Marsh R, Dulley B, Kelly V. External ocular motor palsies in
visual acuity returned to 6/24 after treatment. ophthalmic zoster: A review. Br J Ophthalmol. 1977;61:677–682.
5. Dhingra S, Williams G, Pearson A. Severe, permanent orbi-
tal disease in herpes zoster ophthalmicus. Orbit.
CONCLUSION 6. Ugarte M., Dey D, Jones CA. Ophthalmoplegia secondary
to herpes zoster ophthalmicus. BMJ Case Reports. 2010. doi:
Orbital apex syndrome is a rare but severe complica- 10.1136/bcr.12.2009.2532.
tion of HZO. The mainstay of treatment is a combined 7. Saxena R, Phuljhele S, Aalok L, et al. A rare case of orbital
administration of systemic acyclovir and corticoster- apex syndrome with herpes zoster ophthalmicus in a
human immunodeficiency virus positive patient. Indian J
oids together with topical acyclovir and topical ster- Ophthalmol. 2010;58:527–530.
oids for the anterior segments involvement. Early 8. Kurimoto T, Tonari M, Ishizaki N, et al. Orbital apex syn-
administration of systemic acyclovir and systemic ster- drome associated with herpes zoster ophthalmicus. Clin
oid aid in improving the outcome. Serious and poten- Ophthalmol. 2011;5:1603–1608.
tially blinding complications of herpes zoster 9. Arda H, Mirza E, Gumus K, et al. Orbital apex syndrome in
Herpes Zoster ophthalmicus. Case Reports in
ophthalmicus should be suspected, especially in Ophthalmological Medicine Volume Article ID 854503,
patients with risk factors such as diabetes mellitus, 2012,4 page.
advanced age and immunodeficiency states. Medical 10. Merino-Iglesias A, Montero JA, Calabuig-Goena M, et al.
officers or general practitioners should refer patients Orbital apex syndrome secondary to herpes zoster virus
with herpes zoster ophthalmicus to ophthalmologists infection. BMJ Case Rep. 2014 Mar 10;2014. doi: 10.1136/
as early as possible to commence treatment with anti- 11. Lee C-Y. Orbital apex syndrome: An unusual complication
virals to improve the prognosis. of herpes zoster ophthalmicus. BMC Infectious Diseases.
12. Kalamkar C, Radke N, Mukherjee A, et al. A rare case of
DECLARATION OF INTEREST orbital apex syndrome in herpes zoster ophthalmicus. J Clin
Diagn Res. 2016 Jun;10(6):ND04–5.
13. Verhaeghe F, Villain M, Labauge P, et al. Orbital apex
The authors report no conflicts of interest. The authors syndrome secondary to herpes zoster ophthalmicus. J
alone are responsible for the content and writing of the Neuroophthalmol. 2016 Jun;36(2):147–151.
article. 14. Dworkin, et al. Recommendations for the management of
herpes zoster. Robert H. Dworkin. 2007;44(Suppl1): S26CID.
15. Shin HM, Lew H, Yun YS. A case of complete ophthalmo-
plegia in herpes zoster ophthalmicus. Korean J Ophthalmol.
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