Risk of Multiple Sclerosis After Optic Neuritis

Optic neuritis is the most common acute disease of the optic nerve in young adults.¹ The prototypical presentation is a unilateral decrease in central vision that occurs over 1 or more days, associated with retrobulbar aching that is aggravated by eye movement. Decreased color vision and an afferent pupillary defect are characteristic. Spontaneous recovery occurs over a few weeks in most patients. No treatment has been shown to affect final visual outcome; oral corticosteroids are contraindicated because of an increased likelihood of recurrent disease.²

Although usually self-limited, the significance of optic neuritis is as a possible harbinger of multiple sclerosis. Approximately 17% of patients with multiple sclerosis will have had optic neuritis as a sentinel event,³ and a large proportion of patients with optic neuritis will eventually develop multiple sclerosis.⁴ With the availability of immunomodulatory treatments⁵ (such as interferon β-1a, interferon β-1b, and glatiramer acetate), which decrease the number of recurrences in multiple sclerosis, it is important to determine factors that influence the likelihood of developing multiple sclerosis in a patient with optic neuritis.

The Optic Neuritis Treatment Trial's 10-year results, published this month in the Archives of Ophthalmology,⁶ is the most rigorous long-term study of a carefully followed-up cohort of patients with optic neuritis. This report reflects the 10- to 13-year follow-up of a group of patients initially enrolled in a randomized controlled trial.² Patients with optic neuritis were enrolled and randomly assigned to receive intravenous methylprednisolone (250 mg intravaneously 4 times daily), oral prednisone (1 mg/kg every day), or placebo. There was no difference between the groups in the long-term visual outcome nor in the rates of developing clinically diagnosed multiple sclerosis.

However, several features other than treatment assignment in the Optic Neuritis Treatment Trial affected the likelihood of developing clinical multiple sclerosis, which occurred in 38% of patients. The most important was the presence of 1 or more white-matter lesions on magnetic resonance imaging (MRI) scan of the brain, which more than doubled the risk. Among the 169 patients with typical brain lesions on baseline MRI scan, 56% developed multiple sclerosis compared with 22% of the 191 patients with no baseline brain lesions. Among patients with normal baseline MRI scans, the risk of developing multiple sclerosis was significantly lower in men than women (hazard ratio, 0.35; 95% confidence interval, 0.12-0.98). The study also identified a subgroup in whom multiple sclerosis never developed. These patients all had a normal baseline MRI scan result and either complete loss of vision, absence of pain, or the presence of specific atypical retinal findings.

These findings have important implications for the physician caring for a patient with suspected optic neuritis. First, an MRI scan result is necessary to help assign the patient to a low-risk or high-risk group, if immunomodulatory treatment is contemplated. Protocols directed at the optic nerve or special sequences are usually unnecessary unless the diagnosis is in doubt. Second, a dilated ophthalmoscopic examination should be performed by a physician with expertise in optic nerve pathology and retinal diseases. Some patients with otherwise typical optic neuritis may have other diseases, and perhaps such patients are represented in the low-risk group in the Optic Neuritis Treatment Trial. Correct diagnosis is aided by neuro-ophthalmologic or ophthalmologic input.

The decision to institute immunomodulatory treatment in a patient with isolated optic neuritis will depend on an assessment of the patient's risk assignment and an evaluation of the evidence supporting early treatment. Several studies have demonstrated that subclinical damage occurs in multiple sclerosis,⁷ even while patients are asymptomatic. Instituting treatment early in the course of disease, even before a second clinical event, would theoretically result in better patient outcomes. However, evidence for this from randomized controlled trials is not available. Until results of such studies are published, choosing to initiate immunomodulatory treatment in patients with optic neuritis should primarily depend on their risk of multiple sclerosis.

Corresponding Author and Reprints: Leonard A. Levin, MD, PhD, University of Wisconsin Medical School, 600 Highland Ave, Room K6-456 CSC, Madison, WI 53792 (e-mail: lalevin@facstaff.wisc.edu).