HERPES ZOSTER OPHTHALMICUS WITH ORBITAL APEX SYNDROME … · Herpes zoster ophthalmicus (HZO) is...

20
For Peer Review Only HERPES ZOSTER OPHTHALMICUS WITH ORBITAL APEX SYNDROME – DIFFERENCE IN OUTCOMES AND LITERATURE REVIEW. Journal: Ocular Immunology and Inflammation Manuscript ID NOII-2016-0409.R3 Manuscript Type: Letter to the Editor Date Submitted by the Author: 27-Apr-2017 Complete List of Authors: Lim, Jie Jie; Hospital Selayang, Ophthalmology ; University of Malaya, Ophthalmology Ong, Yu Ming; Hospital Sultanah Bahiyah, Ophthalmology M. Zain, Wan Zalina; Hospital Sultanah Bahiyah, Ophthalmology Choo, May May; University of Malaya, Ophthalmology Keywords: Herpes zoster ophthamicus, acyclovir, antivirals, orbital apex syndrome, steroids URL: http://mc.manuscriptcentral.com/noii E-mail: [email protected] Ocular Immunology and Inflammation

Transcript of HERPES ZOSTER OPHTHALMICUS WITH ORBITAL APEX SYNDROME … · Herpes zoster ophthalmicus (HZO) is...

For Peer Review Only

HERPES ZOSTER OPHTHALMICUS WITH ORBITAL APEX

SYNDROME – DIFFERENCE IN OUTCOMES AND LITERATURE

REVIEW.

Journal: Ocular Immunology and Inflammation

Manuscript ID NOII-2016-0409.R3

Manuscript Type: Letter to the Editor

Date Submitted by the Author: 27-Apr-2017

Complete List of Authors: Lim, Jie Jie; Hospital Selayang, Ophthalmology ; University of Malaya,

Ophthalmology Ong, Yu Ming; Hospital Sultanah Bahiyah, Ophthalmology M. Zain, Wan Zalina; Hospital Sultanah Bahiyah, Ophthalmology Choo, May May; University of Malaya, Ophthalmology

Keywords: Herpes zoster ophthamicus, acyclovir, antivirals, orbital apex syndrome, steroids

URL: http://mc.manuscriptcentral.com/noii E-mail: [email protected]

Ocular Immunology and Inflammation

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HERPES ZOSTER OPHTHALMICUS WITH ORBITAL APEX SYNDROME – DIFFERENCE IN OUTCOMES AND

LITERATURE REVIEW.

JJ Lim1,3

, YM Ong2, W.Zalina M. Zain

2 , May May Choo

3

1Department of Ophthalmology, Hospital Selayang, Selangor.

2Department of Ophthalmology, Hospital Sultanah Bahiyah, Alor Setar, Kedah.

3 Department of Ophthalmology, University of Malaya, Kuala Lumpur

Introduction :

Herpes zoster ophthalmicus (HZO) is caused by reactivation of latent varicella zoster virus infection in

the trigeminal ganglion, involving the ophthalmic division of the trigeminal nerve (V1). Ocular

involvement occurs in 20–70% of patients with HZO1, and may include blepharitis, keratoconjunctivitis,

iritis, scleritis and acute retinal necrosis. Neurological complications are less frequent compared to

ocular complications, and may include ophthalmoplegia, optic neuritis, ptosis, and rarely orbital apex

syndrome (OAS). OAS involves dysfunction of V1, the oculomotor nerve (III), the trochlear nerve (IV) and

the abducens nerve (VI), as well as dysfunction of the optic nerve (II). Herpes zoster ophthalmicus is a

rare cause of OAS. Here, we report two cases of HZO with orbital apex syndrome. We conducted a

thorough literature review to assess the prevalence of our reported cases.

Method:

Case Series

Result:

Case 1

A 77 year-old woman with underlying hypertension, presented with complete left upper eyelid ptosis.

Three weeks prior to presentation, she had vesicular skin lesions over the left periorbital region and

forehead. She also experienced left eye pain, redness and progressive blurring of vision. She had

reduced oral intake as well. The patient did not seek treatment at that time.

At presentation, there were dried and scarred skin lesions over her left forehead and periorbital region

in the distribution of the ophthalmic division of the trigeminal nerve. Visual acuity in the left eye was

perception to light. The left eye was proptosed with complete ophthalmoplegia and presence of relative

afferent pupillary defect. There was complete left upper lid ptosis. Intraocular pressures were 12 (OD)

and 07 (OS) mmHg. Left eye conjunctiva was injected. The cornea was hazy with the presence of

epithelial defect and reduced corneal sensation. The posterior segment view was obscured. B-scan

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ultrasonography showed no obvious posterior segment involvement. Examination of the right eye

showed that it was normal. Computed tomographic (CT) scan of the brain and orbit turned out normal.

A diagnosis of left herpes zoster ophthalmicus with orbital apex syndrome and neurotrophic cornea

ulcer was made. She was treated with oral acyclovir (800mg 5 times a day), oral prednisolone 40mg od

and topically, she was treated with artificial tears eyedrops, dexamethasone 0.1% eyedrops,

oxytetramycin ointment and homatropine eyedrops. Patient was maintained on oral acyclovir 800mg 5

times a day and oral prednisolone tapered over a total duration of 2 months.

She was discharged after two weeks, with residual minor epithelial defects. Her left eye vision remained

at perception of light at the time of discharge.

The patient was closely monitored as an outpatient with biweekly follow-ups. During this period she

developed secondary bacterial keratitis and was readmitted to the ward for treatment. Her bacterial

keratitis resolved after intensive treatment with topical antibiotics (gentamicin eyedrops and

ceftazidime eyedrops).

At 2 months, her extraocular muscle movements were full. However, there was still partial ptosis. Her

vision remained poor due to extensive vascularisation and scarring of the cornea.

Case 2

A 65 year-old Chinese man with underlying diabetes mellitus, complained of redness and pain in the left

eye for a duration of four weeks. He also had complete left upper lid ptosis, poor vision and left sided

headache. One week prior to this there were vesicular lesions which were distributed over the left

forehead and left periorbital region. He had been treated with oral acyclovir by his primary care doctor.

At the time of presentation to the ophthalmology clinic, his left vision was 2/60 with no improvement

using the pin-hole. Right eye vision was 6/24, and 6/12 with a pin-hole.

There were multiple small healed depressed scars and some had overlying scabs in the left peri-orbital

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 15o (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 x 1.7 mm.

The cornea was hazy. Fundus view was also not clear. The right eye anterior and posterior segment 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.

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The patient’s vision improved to 6/24 at 3 weeks review and there was partial recovery of the left

oculomotor nerve. The anterior chamber was quiet with no cells detected. Acyclovir ointment was

tapered and topical lubricants were reduced to 4 hourly intervals as corneal was clear with mild haziness

inferonasally. All the epithelial defects had healed. At 6 weeks, there was mild ptosis but full eye

movements were detected. Vision had remained the same and this was attributed to worsening of

nuclear sclerosis. However, cataract extraction will be deferred for another 6 months in view of the

recent inflammatory condition in the eye.

Discussion:

Herpes zoster ophthalmicus (HZO) is defined as herpes zoster involvement in the ophthalmic division of

the trigeminal nerve. It accounts for 10-20% of herpes zoster cases. It could involve a spectrum of

presentation, such as blepharitis, keratoconjunctivitis, iritis, scleritis and acute retinal necrosis. Diagnosis

of herpes zoster ophthalmicus is relatively straightforward and is usually based on typical clinical

presentation of rashes and pain. Often no tests are required.

Orbital apex syndrome (OAS) is a rare and serious complication of herpes zoster ophthalmicus. OAS is a

spectrum of disease which involves damage to the oculomotor nerve, trochlear nerve, abducens nerve

and ophthalmic division of the trigeminal nerve, in association with optic nerve dysfunction. It was first

reported by Ramsell in 19672.

. Both our patients presented with this rare but severe complication of

HZO – orbital apex syndrome.In our cases, imaging had excluded other common causes of OAS such as

hemorrhage, neoplasm and cavernous sinus thrombosis.3 Others blood investigations turned out

normal. Based on clinical presentation, we diagnosed them with herpes zoster ophthalmicus with orbital

apex syndrome after the imaging.

Cases of herpes zoster ophthalmicus complicated with orbital apex syndrome are extremely rare. From

the literature reviews, we found some reported cases with neuropathy. Womack et al (1983) reported 3

of 86 patients with HZO seen at Mayo clinic had ocular motor palsies (3.4%)1

. Marsh (1977) reported

9.8% of patients with HZO in the Moorfield Eye Hospital study had extraocular muscle palsy, with cranial

nerve III dysfunction in 4 of the patients 4.

Incidence of cranial nerve II dysfunction was only in 0.4% of

the patients in the Moorfield Eye Hospital study.4

HZO associated with orbital apex syndrome has only been reported in isolated cases. Over the past 10

years, there were 9 isolated cases of HZO with OAS reported in the literature (5-13)

.

The age range of the patients was 29-81 years old, with most of the patients being elderly. There were

two cases reported with background of immunosuppressive state – one of the patients was a HIV

patient while the other patient had multiple myeloma. In both our cases, the patients were elderly and

the second patient had underlying diabetes.

Based on Dworkin et al (2007), systemic antiviral therapy is recommended as first-line treatment for all

immunocompetent patients with herpes zoster who fulfill any of the following criteria: (1) 50 years of

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age; (2) have moderate or severe pain; (3) have moderate or severe rash; or (4) have non-truncal

involvement. 14

The current practice is to treat individuals with a new episode of herpes zoster with 7 to 14 days of

antiviral treatment. However, based on Miserocchi et al ‘s report, it was found that there is a decreased

frequency of recurrent episodes from 3.4 to 2.1 episodes per year in patients treated with prophylactic

oral acyclovir or valacyclovir for at least 1 year. The optimal time for initiation of systemic antiviral

treatment is within 72 hours after the onset of rash.

While the optimal therapy for OAS secondary to HZO remains unclear, the current mainstay of

treatment is combined administration of systemic acyclovir and steroids5,15

. In the reported cases, most

of the cases showed good improvement in response to the treatment with systemic acyclovir and

steroids. One of the reported cases was treated with vidarabine due to compromised renal function. She

also achieved good vision at the end of the treatment. Three of these patients did not achieve good

vision despite treatment with systemic antivirals and steroids. The poor vision for the three reported

cases were all attributed to optic atrophy.

In the cases of our two patients, the first patient presented to us with a severe form of orbital apex

syndrome only at the third week after the onset of rashes. Oral acyclovir and systemic steroid treatment

was started at the third week of onset. The effectiveness of acyclovir therapy in our patient have been

reduced due to the delay in initiation of treatment6, while the second case represents a milder case that

was probably attributed to early administration of oral acyclovir by the general practitioner. However,

the optimal time for initiation of treatment is within 72 hours from the onset of the rash5,15

.

The true mechanisms by which optic neuropathy and extraocular muscle paralysis occur in patients with

OAS due to HZO are not completely understood. Postulated mechanisms include extensive inflammation

around the posterior ciliary nerves and vessels with ocular ischemia, orbital soft tissue edema with

direct compression of cranial nerves III, IV and VI, and direct spread of VZV from cranial nerve V to

cranial nerves III, IV and VI. Different mechanisms may lead to different clinical manifestations and

prognoses.4,11

The proportion of patients who achieve resolution of ptosis, ophthalmoplegia and reduced visual acuity

remains unknown. 16

Complete or near-complete resolution of ophthalmoplegia due to HZO has been

reported to occur in 76.5% of cases, and may take between 2 weeks and 1.5 years (mean 4.4 months)5.

In our first patient, resolution of ophthalmoplegia took 6 weeks, with residual of partial ptosis. Her visual

acuity did not improve due to extensive scarring and vascularisation of the cornea from secondary

bacterial keratitis. Our second patient regained complete recovery of ophthalmoplegia at 6 weeks. His

visual acuity returned to 6/24 after treatment.

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Case

Reports

Age Gende

r

Initial

VA

Time of

onset of

OAS

Time of

administration of

antiviral after the

onset of HZO

Administration

of systemic

steroid

Final

VA

Full recovery

of EOM

Causes of

poor vision

Systemic

association

Dhingra et al

2008 (5)

63 male 20/200 5th

day 5th

day

(iv acyclovir and

converted to oral

acyclovir)

Oral

prednisolone

for 2 months

HM Minimal

improvemen

t of 4th and

6th

cranial

nerve

OD pale Multiple

myeloma

Ugarte et al

2010. (6)

80 female HM 2.5 week 1st

day

(oral acyclovir)

Oral

prednisolone

for 2 months

6/9 6th

month - -

Saxena et al

2010 (7)

29 female 20/640 2 weeks 2nd

week

(oral acyclovir

with HAART)

Oral

prednisolone,

taper over 10

days.

20/25 4th

week - HIV

Kurimoto T

at al

2011. (8)

81 female 6/12 17 days 10th day

(iv vidarabine)

Iv prednisolone 6/6 20th week,

except for

abduction

Arda et al

2012 (9)

75 male CF 2 days 1st

day

(oral valacyclovir

then changed to

iv acyclovir after

diagnosis of OAS

being

established)

Oral

prednisolone.

CF 5th

month,

partial

improvemen

t of the EOM.

Mature

cataract,

epithelial

defect,

fibrinoid

reaction in AC

Alexia

Merino

61 male CF 5 days 5th

day Oral 6/12 10th

week. -

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Iglesias et al

Mar 2014

(10)

(iv acyclovir) prednisolone

For 10 weeks

CY Lee at al

Jan 2015

(11)

78 male 3/60 5 days 5th

day

(iv acyclovir)

Oral

prednisolone

12 weeks

6/30 12 weeks,

with residual

limitation of

abduction

and paralysis

of the left

upper eyelid.

- -

Kalamkar C

et al.

Jun 2016

(12)

65 male PL 10 days 10th

day

(oral acyclovir)

IV

methylprednisol

one for 3 days,

then oral

prednisolone

tapered over 2

mths

PL 3 months,

except

limited

abduction

OD pale -

Verhaeghe

et al

Jun 2016

(13)

80 male CF 7 days 1st day

(initially oral

acyclovir, then

admit for iv

acyclovir)

IV

methylprednisol

one for 15 days

– started after 7

days of iv

acyclovir, then

oral for 2

months.

6/15 5 months OD pale

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Our patient

of case 1.

77 female PL 3 weeks 3 weeks

(oral acyclovir)

Oral

prednisolone

For 2 months.

PL 6 weeks Extensive

cornea

scarring and

vascularisation

secondary to

bacterial

keratitis

Hypertension

Our patient

of Case 2

65 male 3/60

4 weeks 1st

day

(oral acyclovir)

Not initiated. 6/24

6 weeks Nuclear

sclerosis

Diabetes

mellitus

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Conclusion:

Orbital apex syndrome is a rare but severe complication of HZO. The mainstay of treatment is a

combined administration of systemic acyclovir and corticosteroids together with topical acyclovir and

topical steroids for the anterior segments involvement. Early administration of systemic acyclovir and

systemic steroid aid in improving the outcome. Serious and potentially blinding complications of herpes

zoster ophthalmicus should be suspected, especially in patients with risk factors such as diabetes

mellitus, advanced age and immunodeficiency states. Medical officers or general practitioners should

refer patients with herpes zoster ophthalmicus to ophthalmologists as early as possible to commence

treatment with antivirals to improve the prognosis.

DECLARATION OF INTEREST

The authors report no conflicts of interest. The authors alone are responsible for the content and writing

of the paper.

Reference :

1. Womack LW, Liesegang TJ. Complications of herpes zoster ophthalmicus. Arch Ophthalmol.

1983;101:42.

2. Ramsell TG. Complications of herpes zoster ophthalmicus. Am J Ophthalmol. 1967;63:1796–8.

3. Steven Yeh and Rod Foroozan. Orbital Apex Syndrome. Curr Opin Ophthalmol 15:490–498. 2004

Lippincott Williams & Wilkins.

4. Marsh R, Dulley B, Kelly V. External ocular motor palsies in ophthalmic zoster: a review. Br J

Ophthalmol. 1977;61:677–82.

5. Dhingra S, Williams G, Pearson A. Severe, permanent orbital disease in herpes zoster

ophthalmicus. Orbit. 2008;27:325–7.

6. Marta Ugarte. Ophthalmoplegia secondary to herpes zoster ophthalmicus. BMJ Case Reports

2010.

7. Rohit Saxena, Swati Phuljhele, Lalit Aalok, Ankur Sinha, Vimla Menon, Pradeep Sharma, Anant

Mohan. A rare case of orbital apex syndrome with herpes zoster ophthalmicus in a human

immunodeficiency virus positive patient. Indian J Ophthalmol: 2010;58:527-530

8. Kurimoto T, Tonari M, Ishizaki N, Monta M, Hirata S, Oku H, Sugasawa J, Ikeda T. Orbital apex

syndrome associated with herpes zoster ophthalmicus. Clin Ophthalmol. 2011;5:1603-8.

Page 8 of 19

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Ocular Immunology and Inflammation

123456789101112131415161718192021222324252627282930313233343536373839404142434445464748495051525354555657585960

For Peer Review Only

9. Hatice Arda, ErtugrulMirza, Koray Gumus, Ayse Oner, Sarper Karakucuk, and Ender Sırakaya.

Orbital Apex Syndrome in Herpes Zoster Ophthalmicus. Case Reports in Ophthalmological

Medicine Volume 2012, Article ID 854503, 4 page

10. Merino-Iglesias A, Montero JA, Calabuig-Goena M, Giraldo-Agudelo LF. Orbital apex syndrome

secondary to herpes zoster virus infection. BMJ Case Rep. 2014 Mar 10;2014.

11. Chun-Yuan Lee. Orbital apex syndrome: an unusual complication of herpes zoster ophthalmicus.

BMC Infectious Diseases 2015, 15:33.

12. Kalamkar C, Radke N, Mukherjee A, Radke S. A Rare Case of Orbital Apex Syndrome in Herpes

Zoster Ophthalmicus. J Clin Diagn Res. 2016 Jun;10(6):ND04-5.

13. Verhaeghe F, Villain M, Labauge P, Daien V. Orbital Apex Syndrome Secondary to Herpes Zoster

Ophthalmicus. J Neuroophthalmol. 2016 Jun;36(2):147-51.

14. Dworkin et al.R ecommendations for the Management of Herpes Zoster. Robert H. Dworkin. S26

CID 2007:44 (Suppl 1)

15. Shin HM, Lew H, Yun YS. A case of complete ophthalmoplegia in herpes zoster ophthalmicus.

Korean J Ophthalmol. 2005;19:302–4.

16. Sanjay S et al. Complete Unilateral Ophthalmoplegia in Herpes Zoster Ophthalmicus. J Neuro-

Ophthalmology 2009 Dec;29(4):325-37.

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Case Reports Age Gender Initial

VA

Time of

onset of

OAS

Time of

administration of

antiviral after the

onset of HZO

Administration of

systemic steroid

Final

VA

Full recovery

of EOM

Causes of poor

vision

Systemic

association

Dhingra et al

2008 (5)

63 male 20/200 5th

day 5th

day

(iv acyclovir and

converted to oral

acyclovir)

Oral prednisolone

for 2 months

HM Minimal

improvement

of 4th and 6th

cranial nerve

OD pale Multiple

myeloma

Ugarte et al

2010. (6)

80 female HM 2.5 week 1st

day

(oral acyclovir)

Oral prednisolone

for 2 months

6/9 6th

month - -

Saxena et al

2010 (7)

29 female 20/640 2 weeks 2nd

week

(oral acyclovir with

HAART)

Oral

prednisolone,

taper over 10

days.

20/25 4th

week - HIV

Kurimoto T at

al

2011. (8)

81 female 6/12 17 days 10th day

(iv vidarabine)

Iv prednisolone 6/6 20th week,

except for

abduction

Arda et al

2012 (9)

75 male CF 2 days 1st

day

(oral valacyclovir

then changed to iv

acyclovir after

diagnosis of OAS

being established)

Oral

prednisolone.

CF 5th

month,

partial

improvement

of the EOM.

Mature

cataract,

epithelial

defect, fibrinoid

reaction in AC

Alexia Merino

Iglesias et al

Mar 2014 (10)

61 male CF 5 days 5th

day

(iv acyclovir)

Oral prednisolone

For 10 weeks

6/12 10th

week. -

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CY Lee at al

Jan 2015 (11)

78 male 3/60 5 days 5th

day

(iv acyclovir)

Oral prednisolone

12 weeks

6/30 12 weeks,

with residual

limitation of

abduction and

paralysis of

the left upper

eyelid.

- -

Kalamkar C et

al.

Jun 2016 (12)

65 male PL 10 days 10th

day

(oral acyclovir)

IV

methylprednisolo

ne for 3 days,

then oral

prednisolone

tapered over 2

mths

PL 3 months,

except limited

abduction

OD pale -

Verhaeghe et

al

Jun 2016 (13)

80 male CF 7 days 1st day

(initially oral

acyclovir, then

admit for iv

acyclovir)

IV

methylprednisolo

ne for 15 days –

started after 7

days of iv

acyclovir, then

oral for 2 months.

6/15 5 months OD pale

Our patient of

case 1.

77 female PL 3 weeks 3 weeks

(oral acyclovir)

Oral prednisolone

For 2 weeks

PL 6 weeks Extensive

cornea scarring

and

vascularisation

secondary to

bacterial

keratitis

Hypertension

Our patient of

Case 2

65 male 3/60

4 weeks 1st

day

(oral acyclovir)

Not initiated. 6/24

6 weeks Nuclear

sclerosis

Diabetes

mellitus

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

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

114x83mm (72 x 72 DPI)

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

150x106mm (72 x 72 DPI)

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

127x90mm (72 x 72 DPI)

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Figure 5. Case 2. Left ptosis with multiple scars on the forehead, upper eyelid, side of nose and tip of nose. Injected conjunctiva and corneal haziness. (on initial presentation).

114x128mm (300 x 300 DPI)

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Figure 6. Case 2. Left pupil dilated, eye injected and central cornea was hazy (on initial presentation).

113x127mm (300 x 300 DPI)

Page 18 of 19

URL: http://mc.manuscriptcentral.com/noii E-mail: [email protected]

Ocular Immunology and Inflammation

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For Peer Review Only

Figure 7. Case 2. Left eye ptosis resolved with bilateral orthophoria. (at resolution).

114x129mm (300 x 300 DPI)

Page 19 of 19

URL: http://mc.manuscriptcentral.com/noii E-mail: [email protected]

Ocular Immunology and Inflammation

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