Transcript Effect of corticosteroids on visual recovery

Case
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HPI: 37 y/o ♂ presents with 6-day history of blurry vision OS.
– (+) redness, tearing, pruritis; Ø floaters/photopsias/diplopia
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ROS: Unremarkable, except upper face pressure
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POHX: ø corrective wear/trauma/surgeries/laser
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PMHX: Hyperlipidemia, obesity, sleep apnea s/p bilateral inf.
turbinate reduction, sinusitis, eustachian tube dysfunction
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FHX: DM; cancer; Paget’s dz
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SHX: Occ. ETOH; ø tobacco/IVDA
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ALL: Codeine
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Meds: ø
Case
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20/30
-1.00+0.25x160  20/20
20/70
-0.50+0.25x056  NI
VA sc
Motility: Full OU
21
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IOPT
21
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External/SLE: Unremarkable, except mild papillary
reaction OU
Differential Diagnosis
Anterior ischemic optic neuropathy
 Optic neuritis (idiopathic, demyelinating, infectious)
 Infectious optic neuropathy (sinusitis, syphilis, lyme
disease)
 Inflammatory optic neuropathy (sarcoidosis, SLE & other
vasculitides)
 Infiltrative optic neuropathy (leukemia, lymphoma)
 Posterior scleritis
 Compressive optic neuropathy
 Optic disc drusen
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More Information…
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History & ocular exam
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Humphrey visual field
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Imaging
More History & Exam…
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Ocular exam:
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Scheduled for HVF; MRI +
contrast/FLAIR sequence
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History:
14/14
– Color vision
1/14
 75% red de-saturation
OS
Full
– CVF
Constricted
Pupils: 1.8 log APD OS
– Next day: VA sc OS 20/400
– Pain with upgaze
– Further probing…past episodes
of diplopia & muscle weakness
More Information…
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History & ocular exam
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Humphrey visual field
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Imaging
More Information…
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History & ocular exam
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Humphrey visual field
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Imaging
Imaging
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MRI
– Head  discontinued/limited study
 1.2cm hyperintense FLAIR signal in the corpus
callosum
 Non-specific finding: inflammatory, infectious,
demyelinating plaque, or neoplastic lesion
More Information…
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History & ocular exam
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Humphrey visual field
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Imaging
Definitions
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Papillitis
– More common in children
 Post - or para infectious; post immunizations
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Retrobulbar neuritis
– More common in adults
 Multiple sclerosis (MS)
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Neuroretinitis
– Least common
 Viral infections; catscratch fever, syphilis,
lyme dz
Epidemiology
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Annual incidence: 5/100,000
– Prevalence: 115/100,000
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Age: 20-50 yrs
– ♀ mean age: 30.2 (9-55yrs)
– ♂ mean age: 31.1 (16-60yrs)
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More common in ♀
– ♀:♂  1.8:1
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Caucasians of northern European descent
– Rare in Asians & Africans
Demyelinating
Diseases
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Isolated optic neuritis
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Multiple sclerosis (MS)
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Devic dz (neuromyelitis optica)
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Schilder dz
Multiple Sclerosis
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70% of MS pts  evidence of optic neuritis (ON)
– 1st manifestation in 20%
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1st episode of ON & nrl brain MRI  16% develop MS within 5
yrs
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1st episode of ON & ø signs of MS  50% with demyelinating
lesions on brain MRI
–  risk of developing clinical definite MS (CDMS) within 5-10 yrs
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CDMS: 2 attacks > 24hrs, separated > 1 month, separate parts
of the CNS + abnormal neurologic exam
Pathophysiology
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Autoreactive abs & T-Cells cross blood-brain barrier & damage
myelin  demyelination
– Genetic & environmental factors predispose to an
autoimmune response
 Genetic: HLA-Dw2; HLA-DR2
 Environmental: Infection, stress, systemic antigens &
metabolites
Pathophysiology
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Early:
– Myelin sheath loss
– Preservation of axons
–  macrophages,
lymphocytes & plasma
cells
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Late:
– Loss of axons
– Astrocytic proliferation
 glial scar (plaque)
Anatomy of Optic
Neuritis
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Optic nerve head: 45%
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Retrobulbar: 61%
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Intracanalicular: 34%
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Intracranially (prechiasmatic): 5%
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Chiasmatic: 2%
Clinical Symptoms
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70% unilateral
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Retrobulbar pain (53-88%)
– Dull ache/sinus pain +/- globe tenderness
– Esp. with EOM
– Precedes visual symptoms
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Subacute visual loss
– Haze, cloud or dimness
– Progresses over 2-7 days
 < 20/60: 52%
 20/70-20/100: 48%
 < 20/200: 38%
Clinical Symptoms
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Obscuration of vision in
bright light
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Dyschromatopsia
– ALWAYS present
–  vividness of
saturated colors
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Photopsias/phosphenes
– Induced with horizontal
EOM/loud noise
Uthoff’s Phenomenon
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50% of cases of ON
– Active or recovered
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Transient obscuration of vision with  body temp
– Exercise
– Hot bath/shower
– Hot weather
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Bad prognostic sign:
–  presence of multifocal white matter lesions on brain MRI
–  conversion to CDMS within 3.5 yrs
–  recurrent ON
Clinical Signs
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Optic nerve dysfunction:
– Dyschromatopsia
 Esp. for red
– Visual acuity
– APD
– Contrast sensitivity
– Optic disc
 64.7% nrl appearance
 +/- temporal disc pallor in
fellow eye
– Stereo–acuity
– Visual field defects:
 Central 30° >
altitudinal/arcuate > focal
central/cecocentral
scotomas
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Other Findings:
– Peripheral retinal venous
sheathing
– Uveitis
 Mild defects in fellow eye
Optic Neuritis Treatment
Trial
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15 centers in the U.S. (1988-92)
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457 pts: acute unilateral ON & ø MS
– 18-46 yrs of age; 77% ♀; 85% caucasian
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3 treatment groups:
– (1) IV methylprednisolone 250mg Q6hrs x 3 days  11 days
PO prednisone (1mg/kg)
– (2) PO prednisone (1mg/kg) x 14 days
– (3) Placebo
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Baseline gadolinium-enhanced MRI of brain/orbits
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1° visual outcome measures: visual acuity, color vision,
contrast sensitivity & visual field; 2° outcome measure:
development of CDMS
ONTT
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Effect of corticosteroids on speed & degree of visual
recovery
– PO steroids VS placebo: ø statistically significant difference in
speed of visual recovery/degree of visual recovery at 6 months
– IV steroids VS placebo: Faster visual recovery within first 2 wks;
after 6 months ø difference in visual acuity between 3 treatment
groups
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Effect of corticosteroids on visual recovery
– All pts showed improvement in vision within 1 month
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Identification of factor(s) which may affect visual recovery
– Degree of initial loss of vision best predictor of 6 month visual
acuity outcome
ONTT
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Identification of side-effects of short-term use of
corticosteroids
– All pts reported sleep disturbances, mood changes, stomach upset,
skin flushing & weight gain
 IV steroid group: 1 case each of psychotic depression & acute
pancreatitis
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Visual Field Profile of pts with ON
– Variable patterns
 Chiasmal/retrochiasmal defects  76% with abnormal baseline MRI
– 68.8% of fellow eyes with mild, but abnormal VF
ONTT
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Gadolinium - enhanced, T2-weighted brain/orbit MRI  likelihood of
developing CDMS
– 5-yr data, MS risk:
 Ø lesions = 16%
 1-2 lesions = 37%
 > 3 lesions = 51%
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Effects of corticosteroids on development of MS
– IV steroids:  risk of CDMS in pts with an abnormal MRI (> 2 white
matter lesions) during first 2 yrs
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Effect of corticosteroids on recurrent ON
– PO steroids  rate of recurrent ON
 30% of pts: > 1 new episode of ON in either eye by 2nd yr; IV
steroid group: 13%; placebo group: 16%
  recurrence in pts subsequently diagnosed with MS
CHAMPS/ETOMS
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CHAMPS: Controlled High-risk Subjects Avonex Multiple Sclerosis
Prevention Study; ETOMS: Early Treatment of Multiple Sclerosis
– Pts with 1st episode of clinical demyelinating syndrome + lesions on brain
MRI associated with  risk for CDMS
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CHAMPS: placebo VS IFN ß-1a (Avonex) 30mcg IM weekly x 18
months
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ETOMS: placebo VS IFN ß-1a (Rebif) 22mcg SC weekly x 24 months
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CHAMPS & ETOMS:  conversion (44% & 24%, respectively) to CDMS
within 18 to 24 months in IFN ß-treated groups.
–  # of new/enlarging MRI lesions
–  time to occurrence of second relapse
Recommendations
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Typical acute monosymptomatic demyelinating ON
– Gadolinium - enhanced MRI of brain/orbits to determine risk for
CDMS
 > 2 white matter lesions (> 3mm in diameter, >1 lesion
periventricular/ovoid:)  risk for CDMS
– IV methylprednisolone 1gm/day x 3 days  oral prednisone
(1mg/kg/day) x 11 days  4-day taper (20mg, then 10mg, then
0mg, then 10mg)
– Avonex 30mcg IM weekly or Rebif 22mcg SC weekly
 < 2 white matter lesions or pt with prior ON/known MS: use of IV
methylprednisolone considered on an individual basis
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Oral prednisone ALONE should be avoided
THE IMPACT OF THE ONTT ON PRACTICES OF
OPHTHALMOLOGISTS & NEUROLOGISTS
Reported Δ
(%)
Less Use
(%)
More Use
(%)
Prednisone
Alone
Ophthal
90
100
0
Neuro (n=114)
95
100
0
Ophthal
67
8
92
Neuro (n=109)
82
4
96
Ophthal
(n=118)
32
40
60
Neuro (n=107)
24
54
46
(n=112)
IV solumedrol
+ PO
prednisone
(n=97)
ø treatment
•Trobe et al. The impact of the ONTT on the practices of ophthalmologists & neurologists. Ophthal. 1999; 106:2047-53
Prognosis
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Maximal visual recovery usually reached by 6 months
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ONTT: + treatment
– 1-yr VA:
 > 20/40: 90%
– 5-yr VA:
 > 20/25: 87%; 20/25-20/40: 7%; 20/50-20/190: 3%; < 20/200:
3%
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Abnormalities may be seen/perceived in other visual parameters
despite return to normal acuity
– ONTT
 63% of pts reported vision not recovered by 6 months
– 80% -> 1-4 abnormal visual parameters
– 20% -> all 4 visual parameters normal
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A mild APD may remain
Back to our patient…
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Assessment: Acute optic neuritis
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Plan:
– 1gm IV solumedrol x 3 days  60mg PO prednisione daily x 11 days  PO
taper
– F/U 1 month  Neuro-ophthalmology: VA OS 20/3020/20; color vision 10/14;
VF
– Referred to Neurology (2 months later)
VA OS 20/20
(+) paresthesias right torso; binocular diplopia; bilateral INO
LFT’s, ANA, ANCA, ESR, RF, Anti-DNA, Anti-SSA/SSB  negative
MRI (cervical & thoracic spine): Herniated disc; several T2 hyperintense signals
throughout cervical spine consistent with MS
 Diagnosis: Relapsing/remitting MS
 Started on Rebif 44mcg SC 3x/wk
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HVF
Take Home Points…
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Classic triad: (1) loss of vision (2) eye pain (3) dyschromatopsia
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Atypical ON ( visual loss progressing > 1 wk, vitritis, > 45 yrs of
age, ø pain): work-up for another etiology
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Typical cases & ø history of ON/MS: IV + PO steroids +/- IFN ß1a
– Anti-ulcer medication
– Steroid-dependent optic neuropathies (neoplastic, paraneoplastic
& inflammatory) worsen when off steroids; ø typical of ON
Bibliography
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BCSC. Neuro-ophthalmology. AAO. 2004-05
BCSC. Pathology. AAO. 2004-05
Yanoff. Ophthalmology, 2nd Ed. Mosby. 1263-66
Kanski. Clinical Ophthalmology, 5th Ed. Butterworth Heinemann. 601-03. 2003
E-medicine: Optic Neuritis
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practices of ophthalmologists and neurologists. Ophthalmology. 1999;106:2047–53.
Jacobs LD, Beck RW, Simon JH, et al. Intramuscular interferon β-1a therapy initiated during a first
demyelinating event in multiple sclerosis. N Engl J Med. 2000;343:898–904.
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CHAMPS Study Group. Interferon β-1a for optic neuritis patients at high risk for multiple sclerosis.
Am J Ophthalmol. 2001;132:463–71
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Comi G, Filippi M, Barkhof F, et al. Effect of early interferon treatment on conversion to definite
multiple sclerosis: a randomized study. Lancet. 2001;357: 1576–82.