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

InvestigationsBased 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 groups1. 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

• Uhtoff’s phenomenon

• Pulfrich phenomenon

Optic Neuritis RecurrenceFrom 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 MS10 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 MSONTT 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