High- and low-risk profiles for the development of multiple sclerosis within 10 years after optic neuritis: experience of the optic neuritis treatment trial

Arch Ophthalmol. 2003 Jul;121(7):944-9. doi: 10.1001/archopht.121.7.944.


Objective: To identify factors associated with a high and low risk of developing multiple sclerosis after an initial episode of optic neuritis.

Methods: Three hundred eighty-eight patients who experienced acute optic neuritis between July 1, 1988, and June 30, 1991, were followed up prospectively for the development of multiple sclerosis. Consenting patients were reassessed after 10 to 13 years.

Results: The 10-year risk of multiple sclerosis was 38% (95% confidence interval, 33%-43%). Patients (160) who had 1 or more typical lesions on the baseline magnetic resonance imaging (MRI) scan of the brain had a 56% risk; those with no lesions (191) had a 22% risk (P<.001, log rank test). Among the patients who had no lesions on MRI, male gender and optic disc swelling were associated with a lower risk of multiple sclerosis, as was the presence of the following atypical features for optic neuritis: no light perception vision; absence of pain; and ophthalmoscopic findings of severe optic disc edema, peripapillary hemorrhages, or retinal exudates.

Conclusions: The 10-year risk of multiple sclerosis following an initial episode of acute optic neuritis is significantly higher if there is a single brain MRI lesion; higher numbers of lesions do not appreciably increase that risk. However, even when brain lesions are seen on MRI, more than 40% of the patients will not develop clinical multiple sclerosis after 10 years. In the absence of MRI lesions, certain demographic and clinical features seem to predict a very low likelihood of developing multiple sclerosis. This natural history information is a critical input for estimating a patient's 10-year multiple sclerosis risk and for weighing the benefit of initiating prophylactic treatment at the time of optic neuritis or other initial demyelinating events in the central nervous system.

Publication types

  • Clinical Trial
  • Multicenter Study
  • Randomized Controlled Trial
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Acute Disease
  • Adolescent
  • Adult
  • Anti-Inflammatory Agents / therapeutic use
  • Brain / pathology
  • Cohort Studies
  • Female
  • Humans
  • Magnetic Resonance Imaging
  • Male
  • Methylprednisolone Hemisuccinate
  • Middle Aged
  • Multiple Sclerosis / diagnosis
  • Multiple Sclerosis / drug therapy
  • Multiple Sclerosis / epidemiology*
  • Optic Neuritis / diagnosis
  • Optic Neuritis / drug therapy
  • Optic Neuritis / epidemiology*
  • Prednisone
  • Prospective Studies
  • Risk Factors
  • Sex Factors
  • United States / epidemiology


  • Anti-Inflammatory Agents
  • Methylprednisolone Hemisuccinate
  • Prednisone