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.
- INCLUSION CRITERIA: COHORT 1: Unilateral optic neuritis. - Typical demyelinating optic neuritis based on the best clinical judgment of the investigators. - Symptom onset within 46 weeks of enrollment OR patients with history of optic neuritis who were followed from symptom onset under a Neuroimmunology Branch natural history or screening protocol. - For women of childbearing potential, willing to use acceptable forms of contraception (i.e. hormonal contraception (birth control pills, injected hormones, vaginal ring), intrauterine device, barrier methods (condom or diaphragm) with spermicide or they have undergone surgical sterilization (hysterectomy, tubal ligation, or vasectomy in a partner) for the study duration. - Able to provide informed consent. - Willing and able to participate in all aspects of the trial. COHORT 2: Healthy volunteers. - No medical history that would interfere with study result interpretation, in the best clinical judgment of the investigators. - Age greater than or equal to 18 years and less than or equal to 50 years. - Able to provide informed consent. - Willing and able to participate in all aspects of the trial. EXCLUSION CRITERIA: - History of signs or symptoms suspicious for MS, in the best clinical judgment of the investigators. - Pateints-Disease-modifying therapy for MS prior to the onset of the current episode of optic neuritis (excludes oral or intravenous glucocorticoids: Healthy Volunteers - Previous or current use of disease-modifying therapy for MS (excluding oral or intravenous glucocorticoids. - Previous history of clinical optic neuritis or a systemic disease associated with optic neuritis (e.g. sarcoidosis, lymphoma). - Current or prior optic neuropathy (e.g. trauma, ischemia, glaucoma, optic nerve drusen). - Previous history of a retinal disease (e.g. diabetic retinopathy, retinal drusen) other than uveitis. - Previous history of an ophthalmic disease that in the best judgment of the investigator could affect ophthalmic imaging results. - Previous history of a systemic disease that may mimic MS (e.g. neurosyphilis, neurosarcoidosis, CNS ymphoma, Si(SqrRoot)(Delta)gren s syndrome). - Previous history of a systemic disease that in the best judgment of the investigator could confound study outcome. - Current use of a TNF-alpha inhibitor (e.g. etanercept). - Habitual use of illicit drugs that in the best judgment of the investigators could confound study outcome. - Pregnant or breast-feeding. - Unwilling to co-enroll on a Neuroimmunology Branch natural history or screening protocol currently 89-N-0045. - Contraindication to MRI scanning.