Download - Etanercept associated optic neuropathy
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
rohn
sIn
flixi
mab
7do
ses
1w
eek
OS
Yes
(6/2
1)Ye
sN
orm
alR
etro
bulb
arop
tic
neur
itis
Full
(6/6
)6
745
FPs
AIn
flixi
mab
13m
onth
s1
wee
kO
SYe
s(6
/20)
Yes
On
enha
ncem
ent
Ret
robu
lbar
opti
cne
urit
isFu
ll(6
/6)
7
855
MR
AEt
aner
cept
3m
onth
sun
kO
SYe
sun
kD
emye
linat
ing
lesi
ons
Opt
icne
urit
isM
inim
al8
912
FJR
AEt
aner
cept
2.5
mon
ths
unk
OD
Yes
(6/6
0)un
kun
kO
ptic
neur
itis
Part
ial
(6/2
4)9
1017
FJR
AEt
aner
cept
8m
onth
sun
kO
SYe
sun
kun
kO
ptic
neur
itis
Part
ial
9
1121
FJR
AEt
aner
cept
18m
onth
s18
mon
ths
unk
unk
OD
OS
Yes
(6/2
4)Ye
s(6
/24)
unk
unk
unk
unk
Opt
icne
urit
isO
ptic
neur
itis
Non
e(6
/24)
Non
e(6
/24)
10 10
1218
MJS
AEt
aner
cept
11m
onth
sun
kO
DYe
s(F
Cat
20cm
)Ye
sun
kO
ptic
neur
itis
Full
(6/6
0)*
10
1314
MO
IDEt
aner
cept
16m
onth
s2
mon
ths
OS
Yes
(6/6
0)N
oO
nen
hanc
emen
tA
typi
calo
ptic
neur
itis
Part
ial
(6/2
4)
1455
MPs
AA
dalim
umab
8m
onth
s2
wee
ksO
DYe
s(6
/9)
No
On
enha
ncem
ent
Ret
robu
lbar
opti
cne
urit
isFu
ll(6
/6)
11
1540
MR
AA
dalim
umab
12m
onth
sun
kO
DYe
s(6
/120
0)Ye
sO
nen
hanc
emen
tO
ptic
neur
itis
Part
ial
(6/9
)11
*6/
60w
asth
eba
selin
eac
uity
ofth
isey
e;FC
,fing
erco
unti
ng;J
RA
,juv
enile
rheu
mat
oid
arth
riti
s;JS
A,j
uven
ilesp
ondy
loar
thro
path
y;O
D,r
ight
eye;
OID
,orb
ital
infla
mm
ator
ydi
seas
e;O
S,le
ftey
e;Ps
A,p
sori
atic
arth
riti
s;R
A,r
heum
atoi
dar
thri
tis;
TN
F-a,
tum
our
necr
osis
fact
or-a
lpha
;tx,
trea
tmen
t;un
k,un
kow
n;VA
,vis
uala
cuit
y.
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