Case HPI: 37 y/o ♂ presents with 6-day history of blurry vision OS. HPI: 37 y/o ♂ presents with 6-day history of blurry vision OS. –(+) redness, tearing,

CaseCase HPI: 37 y/o HPI: 37 y/o ♂ presents with 6-day history of blurry vision ♂ presents with 6-day history of blurry vision

OS.OS.– (+) redness, tearing, pruritis; Ø floaters/photopsias/diplopia(+) redness, tearing, pruritis; Ø floaters/photopsias/diplopia

ROS: Unremarkable, except upper face pressureROS: Unremarkable, except upper face pressure

POHX: ø corrective wear/trauma/surgeries/laserPOHX: ø corrective wear/trauma/surgeries/laser

PMHX: Hyperlipidemia, obesity, sleep apnea s/p bilateral PMHX: Hyperlipidemia, obesity, sleep apnea s/p bilateral inf. turbinate reduction, sinusitis, eustachian tube inf. turbinate reduction, sinusitis, eustachian tube dysfunctiondysfunction

FHX: DM; cancer; Paget’s dzFHX: DM; cancer; Paget’s dz

SHX: Occ. ETOH; ø tobacco/IVDASHX: Occ. ETOH; ø tobacco/IVDA

ALL: CodeineALL: Codeine

Meds: øMeds: ø

CaseCase 20/30 -1.00+0.25x160 20/30 -1.00+0.25x160 20/20 20/20

VVA scA sc

20/70 -0.50+0.25x056 20/70 -0.50+0.25x056 NI NI

Motility: Full OUMotility: Full OU

2121

IOPIOPTT

2121

External/SLE: Unremarkable, except mild External/SLE: Unremarkable, except mild papillary reaction OUpapillary reaction OU

Differential Differential DiagnosisDiagnosis

Anterior ischemic optic neuropathy Anterior ischemic optic neuropathy Optic neuritis (idiopathic, demyelinating, Optic neuritis (idiopathic, demyelinating,

infectious) infectious) Infectious optic neuropathy (sinusitis, syphilis, Infectious optic neuropathy (sinusitis, syphilis,

lyme disease)lyme disease) Inflammatory optic neuropathy (sarcoidosis, SLE Inflammatory optic neuropathy (sarcoidosis, SLE

& other vasculitides)& other vasculitides) Infiltrative optic neuropathy (leukemia, Infiltrative optic neuropathy (leukemia,

lymphoma)lymphoma) Posterior scleritisPosterior scleritis Compressive optic neuropathyCompressive optic neuropathy Optic disc drusenOptic disc drusen

More InformationMore Information…… History & ocular examHistory & ocular exam

Humphrey visual fieldHumphrey visual field

ImagingImaging

More History & More History & Exam…Exam…

Scheduled for HVF; MRI Scheduled for HVF; MRI ++ contrast/FLAIR sequencecontrast/FLAIR sequence

History:History:– Next day: VNext day: VA sc A sc OS OS 20/40020/400

– Pain with upgazePain with upgaze– Further probing…past Further probing…past

episodes of diplopia & episodes of diplopia & muscle weaknessmuscle weakness

Ocular exam:Ocular exam:

14/1414/14

– Color visionColor vision

1/141/14

75% red de-75% red de-saturation OSsaturation OS

FullFull

– CVFCVF

ConstrictedConstricted

Pupils: 1.8 log APD OSPupils: 1.8 log APD OS

More InformationMore Information…… History & ocular examHistory & ocular exam


ImagingImaging

More Information…More Information… History & ocular examHistory & ocular exam


ImagingImaging

ImagingImaging MRI MRI

– Head Head discontinued/limited study discontinued/limited study 1.2cm hyperintense FLAIR signal in the 1.2cm hyperintense FLAIR signal in the

corpus callosumcorpus callosum Non-specific finding: inflammatory, Non-specific finding: inflammatory,

infectious, demyelinating plaque, or infectious, demyelinating plaque, or neoplastic lesion neoplastic lesion

More Information…More Information… History & ocular examHistory & ocular exam


ImagingImaging

DefinitionsDefinitions PapillitisPapillitis

– More common in More common in childrenchildren Post - or para -Post - or para -

infectious; post -infectious; post -immunizationsimmunizations

Retrobulbar neuritisRetrobulbar neuritis– More common in adultsMore common in adults

Multiple sclerosis (MS)Multiple sclerosis (MS)

NeuroretinitisNeuroretinitis– Least commonLeast common

Viral infections; cat-Viral infections; cat-scratch fever, scratch fever, syphilis, lyme dzsyphilis, lyme dz

EpidemiologyEpidemiology Annual incidence: 5/100,000Annual incidence: 5/100,000

– Prevalence: 115/100,000Prevalence: 115/100,000

Age: 20-50 yrsAge: 20-50 yrs– ♀ ♀ mean age: 30.2 (9-55yrs)mean age: 30.2 (9-55yrs)– ♂♂ mean age: 31.1 (16-60yrs)mean age: 31.1 (16-60yrs)

More common in ♀More common in ♀– ♀♀::♂♂ 1.8:1 1.8:1

Caucasians of northern European descentCaucasians of northern European descent– Rare in Asians & AfricansRare in Asians & Africans

Demyelinating Demyelinating DiseasesDiseases

Isolated optic neuritisIsolated optic neuritis

Multiple sclerosis (MS)Multiple sclerosis (MS)

Devic dz (neuromyelitis optica)Devic dz (neuromyelitis optica)

Schilder dzSchilder dz

Multiple SclerosisMultiple Sclerosis 70% of MS pts 70% of MS pts evidence of optic neuritis (ON) evidence of optic neuritis (ON)

– 11stst manifestation in 20% manifestation in 20%

11stst episode of ON & nrl brain MRI episode of ON & nrl brain MRI 16% develop MS 16% develop MS within 5 yrswithin 5 yrs

11stst episode of ON & ø signs of MS episode of ON & ø signs of MS 50% with 50% with demyelinating lesions on brain MRI demyelinating lesions on brain MRI – risk of developing clinical definite MS (CDMS) within risk of developing clinical definite MS (CDMS) within

5-10 yrs5-10 yrs

CDMS: 2 attacks > 24hrs, separated CDMS: 2 attacks > 24hrs, separated >> 1 month, 1 month, separate parts of the CNS + abnormal neurologic separate parts of the CNS + abnormal neurologic examexam

PathophysiologyPathophysiology Autoreactive abs & T-Cells cross blood-brain barrier & Autoreactive abs & T-Cells cross blood-brain barrier &

damage myelin damage myelin demyelination demyelination– Genetic & environmental factors predispose to an Genetic & environmental factors predispose to an

autoimmune response autoimmune response Genetic: HLA-Dw2; HLA-DR2Genetic: HLA-Dw2; HLA-DR2 Environmental: Infection, stress, systemic antigens & Environmental: Infection, stress, systemic antigens &

metabolitesmetabolites

PathophysiologyPathophysiology Early:Early:

– Myelin sheath lossMyelin sheath loss– Preservation of axonsPreservation of axons macrophages, macrophages,

lymphocytes & lymphocytes & plasma cellsplasma cells

Late:Late:– Loss of axonsLoss of axons– Astrocytic Astrocytic

proliferation proliferation glial glial scar (plaque)scar (plaque)

Anatomy of Optic Anatomy of Optic NeuritisNeuritis

Optic nerve head: 45%Optic nerve head: 45%

Retrobulbar: 61%Retrobulbar: 61%

Intracanalicular: 34%Intracanalicular: 34%

Intracranially (prechiasmatic): 5%Intracranially (prechiasmatic): 5%

Chiasmatic: 2%Chiasmatic: 2%

Clinical SymptomsClinical Symptoms 70% unilateral70% unilateral

Retrobulbar pain (53-88%)Retrobulbar pain (53-88%)– Dull ache/sinus pain +/- globe tendernessDull ache/sinus pain +/- globe tenderness– Esp. with EOMEsp. with EOM– Precedes visual symptomsPrecedes visual symptoms

Subacute visual lossSubacute visual loss– Haze, cloud or dimness Haze, cloud or dimness – Progresses over 2-7 daysProgresses over 2-7 days

<< 20/60: 52% 20/60: 52% 20/70-20/100: 48%20/70-20/100: 48% << 20/200: 38% 20/200: 38%

Clinical SymptomsClinical Symptoms Obscuration of vision in Obscuration of vision in

bright lightbright light

DyschromatopsiaDyschromatopsia– ALWAYS presentALWAYS present vividness of vividness of

saturated colorssaturated colors

Photopsias/phosphenesPhotopsias/phosphenes– Induced with Induced with

horizontal EOM/loud horizontal EOM/loud noisenoise

Uthoff’s Uthoff’s PhenomenonPhenomenon

50% of cases of ON 50% of cases of ON – Active or recoveredActive or recovered

Transient obscuration of vision with Transient obscuration of vision with body tempbody temp– ExerciseExercise– Hot bath/shower Hot bath/shower – Hot weather Hot weather

Bad prognostic sign:Bad prognostic sign:– presence of multifocal white matter lesions on brain presence of multifocal white matter lesions on brain

MRI MRI – conversion to CDMS within 3.5 yrsconversion to CDMS within 3.5 yrs– recurrent ONrecurrent ON

Clinical SignsClinical Signs Optic nerve dysfunction:Optic nerve dysfunction:

– Visual acuityVisual acuity

– Contrast sensitivityContrast sensitivity

– Stereo–acuityStereo–acuity

– Visual field defects: Visual field defects: Central 30° > Central 30° >

altitudinal/arcuate > altitudinal/arcuate > focal central/cecocentral focal central/cecocentral scotomasscotomas

Mild defects in fellow eyeMild defects in fellow eye

– DyschromatopsiaDyschromatopsia Esp. for redEsp. for red

– APDAPD

– Optic discOptic disc 64.7% nrl appearance64.7% nrl appearance +/- temporal disc pallor +/- temporal disc pallor

in fellow eyein fellow eye

Other Findings:Other Findings:– Peripheral retinal venous Peripheral retinal venous

sheathingsheathing

– UveitisUveitis

Optic Neuritis Treatment Optic Neuritis Treatment TrialTrial

15 centers in the U.S. (1988-92)15 centers in the U.S. (1988-92)

457 pts: acute unilateral ON & ø MS457 pts: acute unilateral ON & ø MS– 18-46 yrs of age; 77% ♀; 85% caucasian18-46 yrs of age; 77% ♀; 85% caucasian

3 treatment groups:3 treatment groups:– (1) IV methylprednisolone 250mg Q6hrs x 3 days (1) IV methylprednisolone 250mg Q6hrs x 3 days

11 days PO prednisone (1mg/kg)11 days PO prednisone (1mg/kg)– (2) PO prednisone (1mg/kg) x 14 days(2) PO prednisone (1mg/kg) x 14 days– (3) Placebo(3) Placebo

Baseline gadolinium-enhanced MRI of brain/orbitsBaseline gadolinium-enhanced MRI of brain/orbits

1° visual outcome measures: visual acuity, color 1° visual outcome measures: visual acuity, color vision, contrast sensitivity & visual field; 2° outcome vision, contrast sensitivity & visual field; 2° outcome measure: development of CDMSmeasure: development of CDMS

ONTTONTT Effect of corticosteroids on speed & degree of Effect of corticosteroids on speed & degree of

visual recoveryvisual recovery– PO steroids VS placebo: ø statistically significant PO steroids VS placebo: ø statistically significant

difference in speed of visual recovery/degree of visual difference in speed of visual recovery/degree of visual recovery at 6 monthsrecovery at 6 months

– IV steroids VS placebo: Faster visual recovery within first 2 IV steroids VS placebo: Faster visual recovery within first 2 wks; after 6 months ø difference in visual acuity between 3 wks; after 6 months ø difference in visual acuity between 3 treatment groupstreatment groups

Effect of corticosteroids on visual recovery Effect of corticosteroids on visual recovery – All pts showed improvement in vision within 1 monthAll pts showed improvement in vision within 1 month

Identification of factor(s) which may affect visual Identification of factor(s) which may affect visual recoveryrecovery– Degree of initial loss of vision best predictor of 6 month Degree of initial loss of vision best predictor of 6 month

visual acuity outcomevisual acuity outcome

ONTTONTT Identification of side-effects of short-term use of Identification of side-effects of short-term use of

corticosteroidscorticosteroids– All pts reported sleep disturbances, mood changes, All pts reported sleep disturbances, mood changes,

stomach upset, skin flushing & weight gainstomach upset, skin flushing & weight gain IV steroid group: 1 case each of psychotic depression & IV steroid group: 1 case each of psychotic depression &

acute pancreatitisacute pancreatitis

Visual Field Profile of pts with ONVisual Field Profile of pts with ON– Variable patternsVariable patterns

Chiasmal/retrochiasmal defects Chiasmal/retrochiasmal defects 76% with abnormal 76% with abnormal baseline MRI baseline MRI

– 68.8% of fellow eyes with mild, but abnormal VF68.8% of fellow eyes with mild, but abnormal VF

ONTTONTT 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%

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

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/ETOMSCHAMPS/ETOMS CHAMPS: Controlled High-risk Subjects Avonex Multiple CHAMPS: Controlled High-risk Subjects Avonex Multiple

Sclerosis Prevention Study; ETOMS: Early Treatment of Multiple Sclerosis Prevention Study; ETOMS: Early Treatment of Multiple Sclerosis Sclerosis – Pts with 1Pts with 1stst episode of clinical demyelinating syndrome + lesions on episode of clinical demyelinating syndrome + lesions on

brain MRI associated with brain MRI associated with risk for CDMS risk for CDMS

CHAMPS: placebo VS IFN ß-1a (Avonex) 30mcg IM weekly x 18 CHAMPS: placebo VS IFN ß-1a (Avonex) 30mcg IM weekly x 18 monthsmonths

ETOMS: placebo VS IFN ß-1a (Rebif) 22mcg SC weekly x 24 ETOMS: placebo VS IFN ß-1a (Rebif) 22mcg SC weekly x 24 monthsmonths

CHAMPS & ETOMS: CHAMPS & ETOMS: conversion (44% & 24%, respectively) to conversion (44% & 24%, respectively) to CDMS within 18 to 24 months in IFN ß-treated groups.CDMS within 18 to 24 months in IFN ß-treated groups. # of new/enlarging MRI lesions # of new/enlarging MRI lesions time to occurrence of second relapsetime to occurrence of second relapse

RecommendationsRecommendations Typical acute monosymptomatic demyelinating ONTypical acute monosymptomatic demyelinating ON

– Gadolinium - enhanced MRI of brain/orbits to determine Gadolinium - enhanced MRI of brain/orbits to determine risk for CDMSrisk for CDMS >> 2 white matter lesions (> 3mm in diameter, >1 lesion 2 white matter lesions (> 3mm in diameter, >1 lesion

periventricular/ovoid:) periventricular/ovoid:) risk for CDMSrisk for CDMS– IV methylprednisolone 1gm/day x 3 days IV methylprednisolone 1gm/day x 3 days oral oral

prednisone (1mg/kg/day) x 11 days prednisone (1mg/kg/day) x 11 days 4-day taper 4-day taper (20mg, then 10mg, then 0mg, then 10mg)(20mg, then 10mg, then 0mg, then 10mg)

– Avonex 30mcg IM weekly or Rebif 22mcg SC weeklyAvonex 30mcg IM weekly or Rebif 22mcg SC weekly < 2 white matter lesions or pt with prior ON/known MS: use < 2 white matter lesions or pt with prior ON/known MS: use

of IV methylprednisolone considered on an individual basisof IV methylprednisolone considered on an individual basis

Oral prednisone ALONE should be avoidedOral prednisone ALONE should be avoided

Reported Reported ΔΔ

(%)(%)

Less UseLess Use

(%)(%) More UseMore Use

(%)(%)

PrednisonePrednisone

AloneAlone

Ophthal Ophthal (n=112)(n=112)

9090 100100 00

Neuro Neuro ((n=114)n=114)

9595 100100 00

IV IV solumedrol solumedrol + PO + PO prednisoneprednisone

Ophthal Ophthal (n=97)(n=97)

6767 88 9292


8282 44 9696

øø treatment treatment

Ophthal Ophthal ((n=118)n=118)

3232 4040 6060


2424 5454 4646

THE IMPACT OF THE ONTT ON PRACTICES OF OPHTHALMOLOGISTS & NEUROLOGISTS

•Trobe et al. The impact of the ONTT on the practices of ophthalmologists & neurologists. Ophthal. 1999; 106:2047-53

PrognosisPrognosis Maximal visual recovery usually reached by 6 monthsMaximal visual recovery usually reached by 6 months

ONTT: ONTT: ++ treatment treatment– 1-yr V1-yr VAA::

>> 20/40: 90% 20/40: 90%– 5-yr V5-yr VAA::

>> 20/25: 87%; 20/25-20/40: 7%; 20/50-20/190: 3%; 20/25: 87%; 20/25-20/40: 7%; 20/50-20/190: 3%; << 20/200: 3%20/200: 3%

Abnormalities may be seen/perceived in other visual Abnormalities may be seen/perceived in other visual parameters despite return to normal acuityparameters despite return to normal acuity– ONTTONTT

63% of pts reported vision not recovered by 6 months 63% of pts reported vision not recovered by 6 months – 80% -> 1-4 abnormal visual parameters80% -> 1-4 abnormal visual parameters– 20% -> all 4 visual parameters normal20% -> all 4 visual parameters normal

A mild APD may remainA mild APD may remain

Back to our Back to our patient…patient…

Assessment: Acute optic neuritisAssessment: Acute optic neuritis

Plan:Plan:– 1gm IV solumedrol x 3 days 1gm IV solumedrol x 3 days 60mg PO prednisione daily x 11 days 60mg PO prednisione daily x 11 days

PO taperPO taper

– F/U 1 month F/U 1 month Neuro-ophthalmology: V Neuro-ophthalmology: VAA OS 20/30 OS 20/3020/20; color vision 20/20; color vision 10/14;10/14;

VFVF– Referred to Neurology (2 months later)Referred to Neurology (2 months later)

VVAA OS 20/20 OS 20/20 (+) paresthesias right torso; binocular diplopia; bilateral INO(+) paresthesias right torso; binocular diplopia; bilateral INO LFT’s, ANA, ANCA, ESR, RF, Anti-DNA, Anti-SSA/SSB LFT’s, ANA, ANCA, ESR, RF, Anti-DNA, Anti-SSA/SSB negative negative MRI (cervical & thoracic spine): Herniated disc; several T2 hyperintense MRI (cervical & thoracic spine): Herniated disc; several T2 hyperintense

signals throughout cervical spine consistent with MSsignals throughout cervical spine consistent with MS Diagnosis: Relapsing/remitting MSDiagnosis: Relapsing/remitting MS Started on Rebif 44mcg SC 3x/wkStarted on Rebif 44mcg SC 3x/wk

HVF

Take Home Points…Take Home Points… Classic triad: (1) loss of vision (2) eye pain (3) Classic triad: (1) loss of vision (2) eye pain (3)

dyschromatopsiadyschromatopsia

Atypical ON ( visual loss progressing > 1 wk, vitritis, Atypical ON ( visual loss progressing > 1 wk, vitritis, >> 45 yrs of age, ø pain): work-up for another etiology45 yrs of age, ø pain): work-up for another etiology

Typical cases & ø history of ON/MS: IV + PO steroids Typical cases & ø history of ON/MS: IV + PO steroids +/- IFN ß-1a+/- IFN ß-1a– Anti-ulcer medicationAnti-ulcer medication– Steroid-dependent optic neuropathies (neoplastic, Steroid-dependent optic neuropathies (neoplastic,

paraneoplastic & inflammatory) worsen when off paraneoplastic & inflammatory) worsen when off steroids; ø typical of ONsteroids; ø typical of ON

BibliographyBibliography BCSC. Neuro-ophthalmology. AAO. 2004-05BCSC. Neuro-ophthalmology. AAO. 2004-05 BCSC. Pathology. AAO. 2004-05BCSC. Pathology. AAO. 2004-05 Yanoff. Ophthalmology, 2Yanoff. Ophthalmology, 2ndnd Ed. Mosby. 1263-66 Ed. Mosby. 1263-66 Kanski. Clinical Ophthalmology, 5Kanski. Clinical Ophthalmology, 5thth Ed. Butterworth Heinemann. 601-03. 2003 Ed. Butterworth Heinemann. 601-03. 2003 E-medicine: Optic NeuritisE-medicine: Optic Neuritis Beck RW, Cleary PA, Anderson MA, Beck RW, Cleary PA, Anderson MA, et alet al. A randomized, controlled trial of corticosteroids in the . A randomized, controlled trial of corticosteroids in the

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experience of the Optic Neuritis Treatment Trial. Ophthalmology. 1994; 101:1771–8. experience of the Optic Neuritis Treatment Trial. Ophthalmology. 1994; 101:1771–8. Arnold AC. Visual field defects in the Optic Neuritis Treatment Trial: central vs. peripheral, focal vs. Arnold AC. Visual field defects in the Optic Neuritis Treatment Trial: central vs. peripheral, focal vs.

global. Am J Ophthalmol. 1999;128:632–4 global. Am J Ophthalmol. 1999;128:632–4 Beck RW, Kupersmith MJ, Cleary PA, Beck RW, Kupersmith MJ, Cleary PA, et alet al. Fellow eye abnormalities in acute unilateral optic . Fellow eye abnormalities in acute unilateral optic

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subsequent development of multiple sclerosis. N Engl J Med. 1993;329:1764–9.subsequent development of multiple sclerosis. N Engl J Med. 1993;329:1764–9. Cleary PA, Beck RW, Bourque LB, Cleary PA, Beck RW, Bourque LB, et alet al. Visual symptoms after optic neuritis: results from the Optic . Visual symptoms after optic neuritis: results from the Optic

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Comi G, Filippi M, Barkhof F, Comi G, Filippi M, Barkhof F, et alet al. Effect of early interferon treatment on conversion to definite . Effect of early interferon treatment on conversion to definite multiple sclerosis: a randomized study. Lancet. 2001;357: 1576–82. multiple sclerosis: a randomized study. Lancet. 2001;357: 1576–82.

Documents

Case HPI: 37 y/o ♂ presents with 6-day history of blurry vision OS. HPI: 37 y/o ♂ presents with 6-day history of blurry vision OS. –(+) redness, tearing,