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11.What were the objectives of the ONTT?

The ONTT was a multicentered, randomized, prospective clinical trial to determine whether corticosteroid treatment of optic neuritis was beneficial. A secondary objective was to determine the risk of developing MS in patients with optic neuritis. The patients who participated in the ONTT were randomized to three treatment arms. One group of patients received oral placebo; one group received oral prednisone, 1 mg/kg for 14 days; and one group received IV solumedrol, 250 mg every 6 hours for 3 days, followed by oral prednisone, 1 mg/kg for 11 days.

12.What were the conclusions of the ONTT regarding treatment of optic neuritis?

No treatment group had statistically significant better visual acuity at 6 months. However, patients treated with IV solumedrol began to recover vision more quickly. The surprising result was that patients treated with oral prednisone, 1 mg/kg for 14 days, had an increased incidence of recurrence of optic neuritis in the affected or contralateral eye. The researchers concluded that oral prednisone in a dose of 1 mg/kg is contraindicated in the treatment of optic neuritis.

13.What was the strongest predictor for the development of MS?

An abnormal magnetic resonance imaging (MRI) scan (Fig. 31-1) was found to be the strongest predictor for development of clinically definite MS at 2 years. Placebo-treated patients whose MRI scan at study entry showed two or more periventricular white matter lesions >3 mm had a 36% chance of developing MS within 2 years. Patients with one lesion had a 17% chance, and patients with no signal abnormalities had only a 3% chance.

14.What were the other predictors for developing MS?

Previous optic neuritis in the fellow eye, previous nonspecific neurologic symptoms, race (white), and family history of MS were associated with an increased risk of developing MS.

15.What were the conclusions of

the ONTT about the effect of treatment on the risk of developing MS?

The results of the ONTT showed that IV solumedrol significantly decreased the risk of developing MS at 2 years. Most of the beneficial effect was seen in patients with abnormal MRI scans, because patients with normal MRI scans had a low incidence of MS, regardless of treatment. Among patients with two or more signal abnormalities on MRI, MS developed in 36% treated with placebo, 32% treated with prednisone, and 16% treated with IV

solumedrol. Thus the risk of developing MS at 2 years was cut in half by treatment with

IV solumedrol. After 2 years, the beneficial effect seemed to wear off, and at 3 years the three groups had a similar incidence of MS.

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3.Beck RW, Trobe JD: What we have learned from the Optic Neuritis Treatment Trial. Ophthalmology 102:1504–1508, 1995.

4.Burde RM, Savino PJ, Trobe JD: Clinical Decisions in Neuro-Ophthalmology, 2nd ed. St. Louis, Mosby, 1992.

5.Jacobs LD, Beck RW, Simon JH, et al: Intramuscular interferon beta-1a therapy initiated during a first demyelinating event in multiple sclerosis. N Engl J Med 343:898–904, 2000.

6.Optic Neuritis Study Group: High and low risk profiles for the development of multiple sclerosis within 10 years after optic neuritis. Arch Ophthalmol 121:944–949, 2003.

7.Optic Neuritis Study Group: Visual function more than 10 years after optic neuritis: experience of the optic neuritis treatment trial. Am J Ophthalmol 137:77–83, 2004.