Transcript Epiretinal Membranes in Macular Dysfunction

Unexplained Visual Loss
Laura S. Gilmore, MD
Grand Rounds
September 9, 2005
Texas Tech University HSC
Lubbock, TX
Discussant: Kenn Freedman, MD
History
• Chief Complaint: Vision loss, OD>OS
• HPI: 22yo WF with progressively deteriorating
vision over 2-3 months, worse OD, with no
associated neurologic symptoms.
• PMH: Dx’d with Crohn’s Disease 4 years ago, on
remicaide and prednisone. Currently suspect for MS.
• Ocular History: 20/20, no glasses. One episode 1
year ago of OD blurring, with associated slurring of
speech, difficulty walking, and involuntary eye
movements. Spontaneously resolved.
• FH: migraines, blindness secondary to glaucoma
• SH: +tobacco
• Meds: Remicaide, prednisone
Physical Exam
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VS: BP 100/70, pulse 64, RRR
VA: OD 20/400, BC 20/160; OS 20/40, BC NI
Color: 5/9 OD, 8/9 OS
Amsler: Central blur OD, nl OS
VF: constricted OD, hemifield defect OS
Pupils: Round, reactive, No APD
Motility: Full OU
IOP: 16 OU
Ant segment: Clear, D/Q, no synechiae
DFE: normal OU, no disc pallor/elevation/heme
Visual Field
Workup
• MRI brain/orbits with/without contrast
• DM, thyroid w/u per PCP, reportedly
negative
• ESR, CRP, CBC, FTAbs, ACE, B12, folate,
BUN/CR, ANA
Results
• Strongly ANA positive-nucleolar
– High prevalence in Progressive Systemic Sclerosis, a
diffuse progressive form of scleroderma, and in some
rheumatic diseases
– Lower prevalence in SLE
• MRI negative except small, 5mm pituitary
microadenoma on left side. No plaques or other
tumors. No optic nerve involvement.
• Prior MRI at similar episode 1 year ago reportedly
with small brainstem lesion, not apparent on this
study. Films not available. Several MRIs in 3 prior
MS w/u’s-normal
Differential Diagnosis
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Optic neuropathy
Retrobulbar neuritis
Brain/visual pathway lesion
MS
PSS
SLE
Rheumatic disease
Granulomatous processes (syphilis, sarcoid)
Medication side effect
Next Steps
• Increase PO prednisone, referral to
Rheumatology RE ANA, Neurology 2nd
opinion, D/W GI RE medications for
Crohn’s
• Why?
– Remicaide has been reportedly associated with
vision loss, visual field defects, onset and/or
exacerbation of demyelinating disease
Remicaide
• Anti-TNF antibody first introduced in Autumn
1999
• Used in tx of RA, Crohn’s, spondyloarthropathy,
juvenile idiopathic arthritis, Behcet’s, Wegener’s,
HLA-B27 + uveitis, chronic severe refractory
uveitis, psoriasis
• Reported side effects: infections, development of
ANA and anti-dsDNA antibodies, lupus-like
syndrome, lymphoma, exacerbation of or
development of demyelinating disease, CHF,
injection-site reactions
• Side effects seem to be cumulative, often
occurring after third dose; usually dosed q 4 or 8
weeks
Case Reports
• 3 cases of toxic anterior optic neuropathy after
remicaide, with cecocentral VF defects that did
not improve with steroid tx and with ONH pallor
first evident at 2 months (10)
• Rare cases of clinical sx and/or MRI changes
suggestive of MS or optic neuritis (10)
• Increases MRI activity in MS pts (11)
• Report of onset of a demyelinating process after
the institution of remicaide tx for Crohn's disease.
(8,9)
• Report of a 35-year-old woman with colitis who
developed MS symptoms after treatment with
remicaide (2)
Course
• VA OD subjectively slightly improved at 6 week
f/u, 6 weeks post cessation of remicaide, but obj
essentially stable (BCVA 20/200); OS stable
• No change in VA after 6 weeks
• HVF slightly improved 3 months after first exam,
but still with dense cecocentral scotoma OD
• 3 months post first exam, first sign of early
temporal pallor OU. Possible early optic atrophy?
• Neuro has dx’d as MS, d/c’d remicaide and
continued prednisone
• Pt lost to f/u with us after 3 month appt
Photos, 3 months out
Visual Field, 3 months out
Summary
• Anti-TNF alpha antibody preparations are
becoming TOC for several diseases
• Emerging side effects of these medications include
visual changes, as well as MS-like processes
• Long-term care studies still evolving
• Therefore must keep meds in mind; is it truly MS?
Or MS induced by tx? Or prior, undiagnosed MS
exacerbated by tx? Or unknown mechanism and
effects that just looks like MS?
Bibliography
1: Daniel CL, Moreland LW. Infliximab: additional safety data from an open label study.J Rheumatol. 2002
Apr;29(4):647-9.
2: Enayati PJ, Papadakis KA. Association of anti-tumor necrosis factor therapy with the development of
multiple sclerosis.
J Clin Gastroenterol. 2005 Apr;39(4):303-6.
3: Foroozan R, Buono LM, Sergott RC, Savino PJ. Retrobulbar optic neuritis associated with infliximab.
Arch Ophthalmol. 2002 Jul; 120(7):985-7. Erratum in: Arch Ophthalmol 2002 Sep;120(9):1188.
4: Hochberg MC, Legwohl MG, Plevy SE, Hobbs KF, Yocum DE. The benefit/risk profile of TNF-blocking
agents: findings of a consensus panel. Sem Arthritis Rheum. 2005 Jun;34(6):819-36.
5: Mejico, LJ. Infliximab-associated retrobulbar optic neuritis. Arch Ophthalmol. 2004 May; 122(5):793-4.
6: Scheinfeld N. A comprehensive review and evaluation of the side effects of the tumor necrosis factor
alpha blockers etanercept, infliximab and adalimumab. J Dermatolog Treat. 2004 Sep;15(5):280-94.
7: Strong BY, Erny BC, Herzenberg H, Razzeca KJ. Retrobulbar optic neuritis associated with infliximab in
a patient with Crohn’s disease. Ann Intern Med. 2004 Apr 20;140(8):W34.
8: Thomas CW Jr, Weinshenker BG, Sandborn WJ. Demyelination during anti-tumor necrosis factor alpha
therapy with infliximab for Crohn's disease. Inflamm Bowel Dis. 2004 Jan;10(1):28-31.
9: Tran TH, Milea D, Cassoux N, Bodaghi B, Bourgeois P, LeHoang P. Optic neuritis associated with
infliximab. J Fr Ophthalmol. 2005 Feb;28(2):201-4.
10:Tusscher MP, Jacobs PJ, Busch MJ, de Graaf L, Diemont WL. Bilateral anterior toxic optic neuropathy
and the use of infliximab. BMJ. 2003 Mar 15;326(7389):579.
11:van Oosten BW, Barkhof F, Truyen L, Boringa JB, Bertelsmann FW, von Blomberg BM, Woody JN,
Hartung HP, Polman CH. Increased MRI activity and immune activation in two multiple sclerosis
patients treated with the monoclonal anti-tumor necrosis factor antibody cA2. Neuro. 1996
Dec;47(6):1531-4.