Updates on Optic Neuritis

Briar Sexton Neuro-ophthalmology Clinical Day Friday, November 18, 2005

Introduction

Optic neuritis Atypical optic neuritis Treatment of optic neuritis Optic neuritis and MS

Optic Neuritis: Epidemiology

Incidence: 1-5 per 100 000 per year Highest incidence in
Caucasians Countries with high latitudes: genetics? Springtime Ages 20-49 Women

Optic Neuritis

Sub-acute, monocular visual loss Painful extraocular movements RAPD Dyschromatopsia Decreased contrast sensitivity VF deficits

Fundus Signs of Optic Neuritis

Investigations
Based on ONTT results for typical optic neuritis

Demyelination is the most common cause No need for laboratory investigation

i.e. ESR, ANA

Need to do MRI of the brain

Assess MS risk

Atypical Optic Neuritis

Atypical symptoms
Unusual tempo of onset Absence of pain Co-morbidity

Atypical signs
Progressive decline in vision > 2/52 Severe/hemorrhagic disc edema Uveitis: vitritis, retinitis, choroiditis Persistent ON sheath enhancement on MRI

Fundus Photos: Atypical ON

Corticosteroid Dependent Optic Neuritis

Another atypical optic neuritis
Response to steroids Vision falls with taper Requires investigation

Atypical Optic Neuritis: Work-up

Laboratory investigations
CBC, ESR, ANA, MHA-ATP, ACE Lyme, Baronella, TB skin test

CXR Consider LP Make sure MRI images optic nerve/orbits

Visual Fields
Central scotomas Paracentral scotomas Altitudinal defects

Neuroimaging
MRI
FLAIR sequencing Gadolinium enhancement

Optic nerve sheath enhancement with gad Periventricular white matter lesions on
FLAIR

MRI: Nerve Sheath Enhancement

MRI: White Matter Lesions

The Optic Neuritis Treatment Trial (ONTT)

Objective: to evaluate the role of
corticosteroids in the treatment of unilateral optic neuritis

Inclusion criteria: unilateral optic neuritis

The ONTT: Methods

Randomization to one of 3 groups
1. IV steroids: 250 mg methylprednisolone qid x 3 days, oral prednisone (1mg/kg) x 11 days 2. Oral steroids: prednisone 1mg/kg/day x 14 days 3. Oral placebo: 14 days

ONTT: Results
IV steroids
More rapid recovery but same endpoint Protective v. placebo at 2 years, not 3

Oral prednisone
Higher rate of new ON attacks at 1 year Highest rate of relapse at 5 years

The ONTT and Oral Prednisone

Routing vs. Dose?
Probably dose: Greater CD4 than CD8 effect

Prognosis
Natural history: worsening over days to
weeks followed by spontaneous recovery
79% of patients begin to recover by 3/52 93% of patients show improvement by 5/52

Ongoing clinical improvement to 1 year VEP latency improves to 2 years

Prognosis
Severity of initial
visual loss is related to final visual outcome

Most recover well

74% 20/20 92% 20/40

Visual Sequelae
Optic nerve head pallor will develop VF deficits may persist Uhtoffs phenomenon Pulfrich phenomenon

Optic Neuritis Recurrence

From the ONTT

35% of patients experienced recurrence in the

previously affected eye or an attack in the fellow eye at 10 years

Recurrence rate was double in those with CDMS

Recurrence rate highest in the oral steroid group

Sub-clinical Optic Neuritis

Not all optic neuritis attacks are clinically
evident Sisto et al 2005
VEP abnormalities in 54.4% of CD-MS patients asymptomatic for visual impairment

Vidovic et al 2005
70% of visually asymptomatic MS patients had GVF defects consistent with optic neuritis

Optic Neuritis and MS

Clinical diagnosis
2 demyelinating attacks separated in time and space Sequential optic neuritis in one eye than the other meets the criteria Discrete attacks in the same eye meets the criteria

Radiologic: Mac Donald Criteria

Optic Neuritis and MS

Lessell et al. 1988: 58% of optic neuritis at
15 years in initially isolated cases

38-50% of all CDMS develops optic

neuritis at some point

Radiologic Predictors of MS 10 year ONTT data

White matter lesions on MRI
Risk is 22% if no baseline brain lesions Risk is 56% if 1 baseline lesion Risk increases with increasing lesions

Clinical Predictors of MS ONTT 10 year data

Low risk if no MRI lesions and
Male gender Optic disc swelling

No CDMS in subset with above and one of

No pain Severe disc edema Peripapillary hemorrhages Retinal exudates

Managing Optic Neuritis and MS

Positive MRI
Consider immunomodulatory therapy ie interferon or glatiramer acetate

Patients should be seen by neurology

CHAMPS Study
Effect of Interferon B 1a treatment in
patients with optic neuritis and MRI changes compatible with MS
Significantly less CDMS Less progression of MRI lesions

Conclusions
Patients must be investigated for
demyelination

Remember the atypical optic neuritis