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Final Optic Neuritis Treatment Trial Follow-up

The Optic Neuritis Study Group

Arch Neurol. 2008;65(6):727-732.

Objective  To assess the risk of developing multiple sclerosis (MS) after optic neuritis and the factors predictive of high and low risk.

Design  Subjects in the Optic Neuritis Treatment Trial, who were enrolled between July 1, 1988, and June 30, 1991, were followed up prospectively for 15 years, with the final examination in 2006.

Setting  Neurologic and ophthalmologic examinations at 13 clinical sites.

Participants  Three hundred eighty-nine subjects with acute optic neuritis.

Main Outcome Measures  Development of MS and neurologic disability assessment.

Results  The cumulative probability of developing MS by 15 years after onset of optic neuritis was 50% (95% confidence interval, 44%-56%) and strongly related to presence of lesions on a baseline non–contrast-enhanced magnetic resonance imaging (MRI) of the brain. Twenty-five percent of patients with no lesions on baseline brain MRI developed MS during follow-up compared with 72% of patients with 1 or more lesions. After 10 years, the risk of developing MS was very low for patients without baseline lesions but remained substantial for those with lesions. Among patients without lesions on MRI, baseline factors associated with a substantially lower risk for MS included male sex, optic disc swelling, and certain atypical features of optic neuritis.

Conclusions  The presence of brain MRI abnormalities at the time of an optic neuritis attack is a strong predictor of the 15-year risk of MS. In the absence of MRI-detected lesions, male sex, optic disc swelling, and atypical clinical features of optic neuritis are associated with a low likelihood of developing MS. This natural history information is important when considering prophylactic treatment for MS at the time of a first acute onset of optic neuritis.

Author Affiliations: The investigators of the Optic Neuritis Study Group who were active in the 15–year phase of the study are listed below.
Optic Neuritis Study Group Investigators*
(Clinical Centers): Michael Brodsky, MD, and Sarkis Nazarian, MD, University of Arkansas, Little Rock (Dr Brodsky is now with Mayo Clinic and Mayo Foundation, Rochester, Minnesota); Silvia Orengo-Nania, MD, and George J. Hutton, MD, Baylor College of Medicine, Houston, Texas; Edward G. Buckley, MD, and E. Wayne Massey, MD, Duke University, Durham, North Carolina; M. Tariq Bhatti, MD, and Melvin Greer, MD, University of Florida, Gainesville (Dr Bhatti is now with Duke University); James Goodwin, MD, University of Illinois, Chicago; Michael Wall, MD, University of Iowa, Iowa City; Peter J. Savino, MD, and Thomas Leist, MD, Neuro-Ophthalmologic Associates, Philadelphia, Pennsylavania; Neil R. Miller, MD, and David Irani, MD, Johns Hopkins University, Baltimore, Maryland; Jonathan D. Trobe, MD, and Wayne Cornblath, MD, University of Michigan, Ann Arbor; David I. Kaufman, DO, and Eric Eggenberger, DO, Michigan State University, East Lansing; Mark J. Kupersmith, MD, Roosevelt Hospital, New York, New York; William T. Shults, MD, and Leslie McAllister, MD, Devers Eye Institute, Portland, Oregon; and Steve Hamilton, MD, Neuro-ophthalmic Consultants Northwest, Seattle, Washington.
(Coordinating Centers): Roy W. Beck, MD, PhD, Mariya Dontchev, MPH, Robin L. Gal, MSPH, and Craig Kollman, PhD, Jaeb Center for Health Research, Inc, Tampa, Florida; John L. Keltner, MD (visual field reading center director) University of California, Davis; and Craig H. Smith, MD (executive committee member and former clinical center principal investigator) (Dr Smith is now with Genentech, Inc, San Francisco, California).
*Drs Goodwin, Leist, and McAllister are not ONTT authors.

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