REFERENCES

1. Mizuo G, Nakamura B. On new discovery in dark adaptation inOguchi’s disease. Acta Societatis Ophthalmologicae Japonicae 1914;18: 73–127.

2. Oguchi. C. Ueber eine Abart von Hemeralopie. Acta SocietatisOphthalmologicae Japonicae 1907; 11: 123–34.

3. Hirose T. Electroretinogram in night blindness. Acta SocietatisOphthalmologicae Japonicae 1952; 56: 732–41.

4. Francois J, Verriest G, DeRouck A. La maladie d’Oguchi. Oph-thalmologica 1956; 131: 11–40.

5. Nagata M. Studies on the photopic ERG of the human retina. JapJ Ophthalmology 1962; 7: 96–124.

Etanercept associated opticneuropathy

ABSTRACT

We report the case of a 14-year-old boy who developed opticneuropathy subsequent to the use of etanercept.There have been 15reported cases of anti-TNF-a-associated optic neuropathy to dateand their characteristics are reviewed in this report, as well aspossible pathophysiologic mechanisms behind such phenomenon.Such cases demonstrate the importance of prompt ophthalmologicevaluation of visual changes in patients being treated with anti-TNF-aantagonists.

Key words: adalimumab, etanercept, infliximab, optic neuritis,optic neuropathy.

INTRODUCTION

Tumour necrosis factor-alpha (TNF-a) inhibitors are increasinglyutilized in treatment of autoimmune diseases, but may exacerbate orcause demyelinating diseases.1 These medications may also beeffective in treating refractory orbital inflammatory disease (OID).2

We report a rare case of atypical optic neuritis occurring afteretanercept therapy in a child with idiopathic OID and examineprior reports that associate optic neuropathy with anti-TNF-aagents.3–11

CASE REPORT

A 14-year-old Hispanic boy presented with 1 week of painless visionloss in the left eye 2 months after a dose of etanercept. Best correctedvisual acuity was 6/4.5 right eye and 6/60 left eye and visual fieldsshowed a left central scotoma. No Ishihara colour plates wereidentified with the left eye and he had an objective left relativeafferent pupillary defect (RAPD) and subjective decrease in bright-ness of 50%. Fundoscopic exam of the optic disc was normal andfluorescein angiography showed no abnormalities. There were noperiorbital inflammatory signs. Orbital MRI revealed gadoliniumenhancement of the left optic nerve consistent with optic neuritis.High dose intravenous solumedrol (1 g/day for 3 days) was used withprompt clinical improvement however, visual function recovery was

incomplete. At 3-month follow up, the patient had a best correctedvisual acuity in the left eye of 6/24 and correct identification of 7/15Ishihara colour plates.

Thirty-two months prior to onset of optic neuropathy, thepatient presented with pain, diffuse orbital inflammation and opticdisc oedema and was diagnosed with idiopathic OID. Symptomspromptly resolved with oral prednisone (80 mg per day). However,inflammation returned following a short steroid course of 12 daysand the care of the patient was referred for additional evaluationand management. Reinstitution of oral steroid resulted in resolutionof OID, but he was refractory to a slow taper of oral steroids.Addition of methotrexate as a steroid sparing agent did not resolvethe steroid dependency and etanercept therapy was added.

Etanercept (25 mg SQ twice weekly), methotrexate (12.5–17.5 mg/week), and prednisone (2–6 mg/day) were used for16 months during which time the OID was completely controlled.Four months prior to onset of optic neuropathy, the visual acuitieswere documented at 6/4.5 right eye and 6/6 left eye, the opticdisc appeared normal, and the orbital exam was entirely withinnormal range. Etanercept was discontinued by the patientbecause of financial burden 2 months prior to onset of opticneuropathy.

DISCUSSION

A major question about this case is whether the occurrence ofatypical optic neuritis was related to the use of etanercept. Althoughit could be argued that this was associated with underlying OIDrather than etanercept therapy, prior episodes of OID were clini-cally distinct and there was no evidence for OID at the onset ofoptic neuritis.

Review of the literature reveals 15 reported cases (19 eyes) ofanti-TNF-a-associated optic neuropathy (Table 1).3–11 Four casesoccurred in adolescents, all with use of etanercept, although thismay be secondary to prescribing patterns. Visual acuity on presen-tation ranged from 6/9 to finger counting and, in contrast to typicaloptic neuritis, pain was mentioned as a clinical symptom in only sixcases. Four patients had bilateral involvement, two with simulta-neous disease and two with sequential optic neuritis separated by1–2 months. Optic nerve enhancement on gadolinium-enhancedMRI was documented in six patients, although MRI results wereunavailable for four cases. The majority of patients (8/15) had no orpartial recovery of visual acuity, in distinction from patients withtypical optic neuritis in which the majority of patients experiencesignificant visual recovery.

The time between the last dose of anti-TNF-a therapy and theonset of optic neuropathy varied from 3 days to two and a halfmonths. It has been postulated that demyelinating events occur as acumulative effect of multiple doses of anti-TNF-a therapy, which isconsistent with reported cases where most patients received morethan one dose before developing optic neuropathy.3 However,because of the wide range in the interval before onset of disease andthe half lives of the medications (102 � 30 h for etanercept, 8–9.5days for infliximab, and 10–20 days for adalimumab), the effects ofanti-TNF-a therapy may be related to changes in the balance ofimmunologic homeostasis rather than the concentration of drug inthe body. These changes may have sustained effects on the immu-nologic milieu of the central nervous system. Other potentialmechanisms for the association of anti-TNF-a therapy with demy-elinating disease include upregulation of TNF-a production in thecentral nervous system.12

680 Letters to the Editor

© 2007 The AuthorsJournal compilation © 2007 Royal Australian and New Zealand College of Ophthalmologists

Tabl

e1.

Cha

ract

eris

tics

ofal

lrep

orte

dca

ses

ofop

tic

neur

opat

hyas

soci

ated

wit

han

ti-T

NF-

aag

ents

Cas

eA

geSe

xSy

stem

icco

ndit

ion

Med

icat

ion

No.

ofdo

ses

orti

me

ontx

prio

rto

onse

t

Inte

rval

betw

een

last

dose

&on

set

Eye

Sym

ptom

sM

RI

findi

ngs

Dia

gnos

isR

ecov

ery

(VA

)R

efer

ence

visi

onlo

ss(V

A)

Pain

155

FR

AIn

flixi

mab

9do

ses

3da

ysO

SYe

s(6

/15)

Yes

On

enha

ncem

ent

Ret

robu

lbar

opti

cne

urit

isFu

ll(6

/9)

4

254

MR

AIn

flixi

mab

3do

ses

3do

ses

34da

ys34

days

OD

OS

Yes

(6/9

)Ye

s(6

/9)

unk

unk

Nor

mal

Nor

mal

Ant

erio

rop

tic

neur

opat

hyA

nter

ior

opti

cne

urop

athy

Non

eN

one

3 3

362

FR

AIn

flixi

mab

3do

ses

4do

ses

40da

ys12

days

OS

OD

Yes

(6/2

4)Ye

s(6

/24)

unk

unk

Nor

mal

Nor

mal

Ant

erio

rop

tic

neur

opat

hyA

nter

ior

opti

cne

urop

athy

Non

eN

one

3 3

454

MR

AIn

flixi

mab

3do

ses

3do

ses

2w

eeks

2.5

mon

ths

OD

OS

Yes

(6/3

0)Ye

s(6

/30)

unk

unk

Nor

mal

Nor

mal

Ant

erio

rop

tic

neur

opat

hyA

nter

ior

opti

cne

urop

athy

unk

unk

3 3

550

FC

rohn

sIn

flixi

mab

unk

3w

eeks

OS

Yes

Yes

On

enha

ncem

ent

Ret

robu

lbar

opti

cne

urit

isFu

ll(n

orm

al)

5

645

FC

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flixi

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1w

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(6/2

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bulb

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Full

(6/6

)6

745

FPs

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mab

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onth

s1

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kO

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s(6

/20)

Yes

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Ret

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7

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3m

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neur

itis

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(6/2

4)9

1017

FJR

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Part

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9

1121

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18m

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unk

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10 10

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10

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1455

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11

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Letters to the Editor 681

© 2007 The AuthorsJournal compilation © 2007 Royal Australian and New Zealand College of Ophthalmologists

CONCLUSION

As anti-TNF-a therapy is increasingly used, it becomes importantto characterize associated complications. The cases of optic neur-opathy underscore the importance of increasing awareness in phy-sicians and patients of possible ocular sequelae and support promptophthalmologic referral with early treatment when such complica-tions develop.

ACKNOWLEDGEMENT

This report was supported in part by Research to Prevent Blindness(RPB) & Inc., New York (Dr Gordon).

Vicky Chang MD1, Deborah McCurdy MD2 andLynn K Gordon MD3,4

1Department of Medicine, 2Division of Allergy, Immunology andRheumatology, 3Department of Ophthalmology, David Geffen School

of Medicine at UCLA, and 4Ophthalmology Section, Greater LosAngeles VA Healthcare System, Los Angeles, California, USA

Received 16 January 2007; accepted 24 April 2007.

REFERENCES

1. Magnano MD, Robinson WH, Genovese MC. Demyelinationand inhibition of tumor necrosis factor (TNF). Clin Exp Rheumatol2004; 22 (5 Suppl. 35): S134–40.

2. Garrity JA, Coleman AW, Matteson EL, Eggenberger ER,Waitzman DM. Treatment of recalcitrant idiopathic orbitalinflammation (chronic orbital myositis) with infliximab. AmJ Ophthalmol 2004; 138: 925–30.

3. Tusscher MPM, Jacobs PJC, Busch MJ, Graaf L, Diemont WL.Bilateral anterior toxic optic neuropathy and the use ofinfliximab. BMJ 2003; 326: 579.

4. Foroozan R, Buono LM, Sergott RC, Savino PJ. Retrobulbaroptic neuritis associated with infliximab. Arch Ophthalmol 2002;120: 985–7.

5. Mejico LJ. Infliximab-associated retrobulbar optic neuritis. ArchOphthalmol 2004; 122: 793–4.

6. Strong BYC, Erny BC, Herzenberg H, Razzeca KJ. Retrobulbaroptic neuritis associated with infliximab in a patient with Crohndisease. Ann Intern Med 2004; 140: W34.

7. Tran TH, Milea D, Cassoux N, Bodaghi B, Bourgeois P,LeHoang P. Optic neuritis associated with infliximab. J Fr Oph-talmol 2005; 28: 201–4.

8. Noguera-Pons B, Borras-Blasco J, Romero-Crespo I, Anton-Torres R, Navarro-Ruiz A, Gonzalez-Ferrandez JA. Optic neuri-tis with concurrent etanercept and isoniazid therapy. AnnPharmacother 2005; 39: 2131–4.

9. Tauber T, Daniel D, Barash J, Turetz J, Morad Y. Optic neuritisassociated with etanercept therapy in two patients withextended oligoarticular juvenile idiopathic arthritis. Rheumatology2005; 44: 405.

10. Tauber T, Turetz J, Barash J, Avni I, Morad Y. Optic neuritisassociated with etanercept therapy for juvenile arthritis.J AAPOS 2006; 10: 26–9.

11. Chung JH, Van Stavern GP, Frohman LP, Turbin RE.Adalimumab-associated optic neuritis. J Neurol Sci 2006; 244:133–6.

12. Robinson WH, Genovese MC, Moreland LW. Demyelinatingand neurologic events reported in association with tumornecrosis factor alpha antagonism: by what mechanisms couldtumor necrosis factor alpha antagonists improve rheumatoidarthritis but exacerbate mulptiple sclerosis? Arthritis Rheum 2001;44: 1977–83.

Optic perineuritis as a rare initialpresentation of sarcoidosis

ABSTRACT

Sarcoidosis is a multisystem granulomatous disorder of unknownaetiology and establishing the correct diagnosis can be challenging.Although dysfunction of the anterior visual pathways is uncommon, itis the most common neuro-ophthalmological manifestation of thiscondition and given the potential for irreversible, severe visual loss,prompt diagnosis and treatment are essential.We describe a patientwith optic perineuritis as a rare initial presentation of sarcoidosis anddiscuss the underlying pathophysiology and management.

Key words: neurosarcoidosis, optic nerve, optic neuropathy, sar-coidosis, uveitis.

INTRODUCTION

Sarcoidosis is a multisystem granulomatous disorder of unknownaetiology with a peak incidence in the third and fourth decades oflife. The prevalence varies between different racial groups from 10per 100 000 among white Caucasians to 50 per 100 000 amongAfrican Americans.1 The lungs are affected primarily (90%) butocular (25–50%) and neurological (5–18%) involvement are bothwell described and may be the presenting clinical features of thisdisease.2,3 Although dysfunction of the anterior visual pathways isuncommon (1–5%), it is the most common neuro-ophthalmologicalmanifestation of sarcoidosis.3 We describe a patient with opticperineuritis as a rare initial presentation of sarcoidosis and discussthe underlying pathophysiology and management.

CASE REPORT

A 57-year-old man was referred to us by his optician with possiblebilateral optic disc swelling. The patient was visually asymptomaticand he only described a 3-month history of general malaise. Therewere no specific systemic symptoms and there was no relevant pastmedical or ophthalmic history. His unaided visual acuity was 6/5both eyes, there was no afferent pupillary defect and colour visionwas normal. There was no conjunctival injection but there wasevidence of mild anterior uveitis in both eyes. The right optic discwas markedly swollen with peripapillary haemorrhages and therewas early swelling of the nasal aspect of the left optic disc (Fig. 1).The patient’s neurological and general medical examinations wereunremarkable. His Goldmann visual fields were normal except forslightly enlarged blind spots and fluorescein angiography did notreveal any vasculitis. Routine bloods, inflammatory markers, serumangiotensin converting enzyme level, syphilis and HIV serology

682 Letters to the Editor

© 2007 The AuthorsJournal compilation © 2007 Royal Australian and New Zealand College of Ophthalmologists