1. Updates on Optic Neuritis Briar Sexton Neuro-ophthalmology Clinical Day Friday, November 18, 2005

2. Introduction Optic neuritis Atypical optic neuritis Treatment of optic neuritis Optic neuritis and MS

3. 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

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

5. Fundus Signs of Optic Neuritis

6. 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

7. 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

8. Fundus Photos: Atypical ON

9. Corticosteroid Dependent Optic Neuritis Another atypical optic neuritis –Response to steroids –Vision falls with taper –Requires investigation

10. 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

11. Visual Fields Central scotomas Paracentral scotomas Altitudinal defects

12. Neuroimaging MRI –FLAIR sequencing –Gadolinium enhancement Optic nerve sheath enhancement with gad Periventricular white matter lesions on FLAIR

13. MRI: Nerve Sheath Enhancement

14. MRI: White Matter Lesions

15. 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

16. 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

17. 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

18. The ONTT and Oral Prednisone Routing vs. Dose? –Probably dose: Greater CD4 than CD8 effect

19. 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

20. Prognosis Severity of initial visual loss is related to final visual outcome Most recover well –74% ≥ 20/20 –92% ≥ 20/40

21. Visual Sequelae Optic nerve head pallor will develop VF deficits may persist Uhtoff’s phenomenon Pulfrich phenomenon

22. 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

23. 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

24. 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

25. 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

26. 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

27. 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

28. Managing Optic Neuritis and MS Positive MRI –Consider immunomodulatory therapy ie interferon or glatiramer acetate Patients should be seen by neurology

29. 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

30. Conclusions Patients must be investigated for demyelination Remember the atypical optic neuritis