Optic neuritis: What’s hot and what’s not…

Andrew G. Lee

H. Stanley Thompson Neuro-Ophthalmology Clinic, Departments of Ophthalmology, Neurology, and Neurosurgery, The University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA

Introduction

Optic neuritis (ON) is a common cause of acute visual loss in adults. ON in this manuscript refers to idiopathic or demyelinating optic neuropathy. This paper provides an update on the diagnosis, evaluation and management, treatment and prognosis of ON in adults. Recent clinical trials and new developments in the treatment of multiple sclerosis are emphasized. The ‘typical’ clinical profile for ON is contrasted with the atypical presentations in Table 1.1-11

Table 1. Features of typical versus atypical optic neuritis in adults

This work was supported in part by an unrestricted grant from Research to Prevent Blindness, Inc., N.Y., N.Y., U.S.A.

Address for correspondence: A.G. Lee, MD, Department of Ophthalmology, 200 Hawkins Drive, PFP, Univerisity of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA. E-mail: andrewlee@uiowa.edu

Eye on the Bayou, New Concepts in Glaucoma, Cataract and Neuro-Ophthalmology, pp. 19–23 Transactions of the 54th Annual Symposium of the New Orleans Academy of Ophthalmology, New Orleans, LA, USA, February 18-20, 2005

edited by Jonathan D. Nussdorf

© 2006 Kugler Publications, The Hague, The Netherlands

Visual outcome in ONTT

In the ONTT, although IV steroid sped the rate of recovery, all three treatment arms had good final visual acuity and visual field outcomes. Visual acuity at one year was ≥ 20/40 in 95% of the placebo group, 94% of the IV steroid group, and 91% of the oral prednisone group. In the > 10 year analysis, visual acuity was ≥ 20/20 in 74%; from 20/25 to 20/40 in 18%; from 20/40 to 20/200 in 5%; and < 20/200 in only 3%. Recurrent ON in either eye occurred in 35% and was more frequent in MS (P <.001).15

Treatment of optic neuritis

The ONTT conclusions regarding treatment of ON were as follows: 1. High-dose IV followed by oral corticosteroids sped the rate of visual recovery but did not affect final visual outcome; 2. oral prednisone at conventional doses not only did not improve visual outcome but increased the rate of new attacks of ON and they are probably not indicated; and 3. IV followed by oral corticosteroids reduced the rate of clinically definite MS during the first two years although this effect subsided by three years.16-19

What treatments are available for multiple sclerosis?

Ophthalmologists should be aware that several recent trials have demonstrated the efficacy of new immunomodulatory treatments for MS. For example, the Controlled High-Risk Subject Avonex® Multiple Sclerosis Prevention Study (CHAMPS) was a randomized, double-masked, placebo-controlled, clinical trial (n = 383) of IFN beta 1-a (Avonex®). All patients had an acute first attack of a clinical demyelinating event (e.g., optic neuritis, incomplete transverse myelitis, or brainstem or cerebellar syndrome) and MR demyelinating lesions (i.e., > 2 high signal white matter abnormalities on T2-weighted images). All patients received IV methylprednisolone and then were randomized to either weekly intramuscular (IM) IFN beta-1a (n = 193) or placebo (n = 190).20 There was a 44% reduction in the development of clinically definite MS in the treatment group compared to controls. The IFN treated group also had a relative reduction in the volume of brain lesions (p < 0.001); fewer new or enlarging lesions (p < 0.001); and fewer gadoliniumenhancing lesions (p < 0.001) on cranial MR.20

In another study, the Early Treatment of Multiple Sclerosis (ETOMS) trial, 41 (31%) of 131 patients on interferon beta-1a compared with 62 (47%) of 132 on placebo developed clinically definite MS. The authors concluded that early treatment with interferon beta-1a was effective in reducing conversion to MS and in slowing progressive loss of brain tissue on MR in patients with clinically isolated syndromes (e.g., optic neuritis). In other studies, interferon beta-1a and beta 1-b have shown similar effects for the treatment of MS.20-23

Although the risk for MS is lower for patients with a normal initial MR scan after monosymptomatic ON, these patients still have a 16% chance of developing MS at year five. A repeat cranial MR scan (in six months to one year) might be

considered in these patients to detect new MR lesions over time. In the long-term follow-up of the ONTT cohort there were 108 patients who had not developed clinically definite MS ten to 14 years after enrollment. At least one T2 white matter lesion (> 3 mm) was seen on follow-up MR scan in 27 (44%) of 61 patients with a normal baseline MRI. On the other hand, new MR lesions (> 3 mm) were present in 26 (74%) of 35 patients with an abnormal baseline MR scan. This suggests that there are patients who present with monosymptomatic ON who have no clinical signs or MR evidence of demyelination after more than ten years of follow up. In this same ONTT cohort there were 127 patients with clinically definite MS. Functional Systems Scale and Expanded Disability Status Scale (EDSS) were performed and the disability of most patients was mild (65% had EDSS score < 3.0). The degree of disability was unrelated to baseline MR scan findings. The conclusion was that many patients who develop clinically definite MS following ON have a relatively benign course for at least 10 years.24-25 The decision for and the timing of serial MR scans and consideration for MS treatment should therefore be coordinated with a local neurologist on a case by case basis.

Summary

Ophthalmologists evaluating patients with an acute demyelinating attack of ON should be aware of the results of the ONTT. Although typical ON does not require any laboratory testing or a lumbar puncture, atypical cases may require additional testing. An MR scan of the brain should be considered in all cases of ON and the MR scan provides powerful prognostic information regarding MS that should guide decision making for treatment or referral to a neurologist. Although IV steroids speed the rate of visual recovery in ON they do not affect final visual outcome. Oral steroids in conventional doses should probably not be given for typical ON. New therapies with immunomodulatory therapy (e.g., interferon beta therapy) may reduce the rate of MS even after monosymptomatic demyelinating attacks and the ophthalmologist should coordinate the care of these patients on an individualized basis with a neurologist.26-28

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