Patients with typical acute monosymptomatic demyelinating optic neuritis should receive gadolinium-enhanced magnetic resonance imaging (MRI) of the brain and orbits to determine if they are at high risk for the subsequent development of clinically definite multiple sclerosis (CDMS). The presence of >or=2 white matter lesions (>or=3 mm in diameter, at least 1 lesion periventricular or ovoid) indicates high risk for CDMS; the following treatment should be considered for such patients: 1. Intravenous methylprednisolone sodium succinate (1 gram IV/day for 3 days) followed by oral prednisone (1 mg/kg/day for 11 days) with 4-day taper (20 mg on day 1, 10 mg on days 2 and 4); 2. Interferon beta 1-a (Avonex 30microg intramuscularly [IM] weekly, or Rebif 22 microg subcutaneously [SQ] weekly). These two drugs have been shown to reduce the short-term risk of CDMS in high risk monosymptomatic patients. In monosymptomatic patients with <2 white matter lesions, and in patients for whom CDMS has been established, IV methylprednisolone treatment followed by oral prednisone should be considered on an individual basis. Treatment in these patients may hasten visual recovery, but does not affect long-term visual outcome. Oral prednisone alone, without prior treatment with IV methylprednisolone, may increase the risk for recurrent optic neuritis and should be avoided.