Purpose: To re-evaluate the population-based incidence of optic neuritis in the era of aquaporin-4-immunoglobulin G (AQP4-IgG) and myelin oligodendrocyte glycoprotein (MOG)-IgG, which are biomarkers of optic neuritis that is distinct from multiple sclerosis (MS). Over the past 15 years, 2 new biomarkers have been discovered that allow for further characterization of the cause of atypical optic neuritis: AQP4-IgG and MOG-IgG. Design: Retrospective, population-based cohort. Setting: population-based. Participants: all residents of Olmsted County, Minnesota, with optic neuritis diagnosed between January 1, 2000, and December 31, 2018. Methods: The Rochester Epidemiology Project database was used to identify patients. Sera were tested for AQP4-IgG and MOG-IgG by using a live-cell-based flow cytometry assay. Main outcome measurements were the incidence and cause of optic neuritis. Results: Optic neuritis was diagnosed in 110 patients, providing an annual incidence of 3.9 per 100,000. The final diagnosis was MS in 57%, idiopathic in 29%, MOG-IgG-associated disorder in 5%, AQP4-IgG-seropositive neuromyelitis optic spectrum disorder (NMOSD) in 3%, infectious type in 2%, sarcoidosis in 2%, seronegative NMOSD in 1%, and medication-related in 1%. All 3 patients positive for AQP4-IgG had more than 1 optic neuritis attack, 2 with residual no light perception vision in at least 1 eye. Among MOG-IgG-positive patients, 4 of 6 patients had recurrent optic neuritis, and all 6 had a final visual acuity of 20/30 or better. Conclusions: At a population level, AQP4-IgG and MOG-IgG account for 9% of optic neuritis and are associated with recurrent attacks, but MOG-IgG optic neuritis has a better visual outcome than AQP4-IgG optic neuritis.
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