Natural History of Optic Neuritis

Objective The goals of this pilot study are: 1. To assess the degree to which subacute changes in clinical, electrophysiological, and imaging measures can robustly predict retinal neuronal loss 12 months after acute optic neuritis. 2. To construct a composite score that integrates these subacute changes, can itself robustly predict retinal neuronal loss 12 months after acute optic neuritis, can be validated in future trials, and is likely to be modulated by drugs that promote tissue repair and neuroprotection in multiple sclerosis (MS). 3. To evaluate the usefulness of specialized magnetic resonance imaging (MRI) measures of the optic nerve in future clinical trials of drugs designed to promote tissue repair and neuroprotection. The primary hypothesis of the study is that peripapillary retinal nerve fiber layer (RNFL) thickness, which is generally agreed to reflect the integrity of optic nerve axons following optic neuritis, and which can be measured using spectral-domain optical coherence tomography (OCT) in the affected eye 12 months following optic neuritis, can be robustly predicted by changes in RNFL thickness between 1 and 3 months following symptom onset. Study Population The following cohorts will be recruited at each of the three study sites: * Up to 30 participants with acute optic neuritis. * Up to 15 healthy volunteers who are group-wise age- and sex-matched to the participants with unilateral optic neuritis. Design This is a one-year, prospective, multi-cohort, multi-site, pilot natural history study. Data obtained at NIH will be compared and aggregated with data obtained at other study sites, specifically the University of Utah-Moran Eye Center (in Salt Lake City) and Hebrew University-Hadassah Medical Center (in Jerusalem, Israel). Data will be gathered at baseline (optional) and at 1, 3, 6, 9, and 12 months in the patient cohort, and at 1, 3, and 12 months in the healthy volunteers. Outcome Measures The primary outcome measure is the RNFL thickness in the affected eye 12 months after optic neuritis. Secondary outcome measures, all measured at 12 months, include: * Measures of optic nerve structure: mean cross-sectional optic-nerve area; mean, parallel, and perpendicular diffusivity; and MTR all within the optic nerve lesion as visualized at baseline. * Measures of brain structure: ventricular volume; T2 lesion volume along the visual pathway both sides considered together. * Measures of retinal structure: ganglion cell layer + inner plexiform layer thickness in the affected eye. * Measures of visual function: low-contrast letter acuity; high-contrast letter acuity; Pelli-Robson contrast sensitivity; object-from-motion detection; visual fields; and critical flicker-fusion frequency all in the affected eye. * Measures of visual physiology: VEP amplitude; VEP latency all in the effected eye.