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A comparator cohort of PwMS without a recent episode of AON were similarly tracked (n\u00a0=\u00a073). Mixed\u2010effects linear regression models were used.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Accelerated atrophy of the occipital gray matter (GM), calcarine GM, and thalamus was seen in the AON cohort, as compared with the non\u2010AON cohort (\u22120.76% vs \u22120.22% per year [<jats:italic>p<\/jats:italic>\u00a0=\u20090.01] for occipital GM, \u22121.83% vs \u22120.32% per year [<jats:italic>p<\/jats:italic>\u00a0=\u20090.008] for calcarine GM, \u22121.17% vs \u22120.67% per year [<jats:italic>p<\/jats:italic>\u00a0=\u20090.02] for thalamus), whereas rates of whole\u2010brain, cortical GM, non\u2010occipital cortical GM atrophy, and T2 lesion accumulation did not differ significantly between the cohorts. In the AON cohort, greater AON\u2010induced reduction in ganglion cell+inner plexiform layer thickness over the first year was associated with faster rates of whole\u2010brain (r\u00a0=\u00a00.32, <jats:italic>p<\/jats:italic>\u00a0=\u20090.04), white matter (r\u00a0=\u00a00.32, <jats:italic>p<\/jats:italic>\u00a0=\u20090.04), and thalamic (r\u00a0=\u00a00.36, <jats:italic>p<\/jats:italic>\u00a0=\u20090.02) atrophy over the study period. Significant relationships were identified between faster atrophy of the subcortical GM and thalamus, with worse visual function outcomes after AON.<\/jats:p><\/jats:sec><jats:sec><jats:title>Interpretation<\/jats:title><jats:p>These results provide <jats:italic>in\u2010vivo<\/jats:italic> evidence for anterograde trans\u2010synaptic degeneration following AON in PwMS, and suggest that trans\u2010synaptic degeneration may be related to clinically\u2010relevant visual outcomes. ANN NEUROL 2023;93:76\u201387<\/jats:p><\/jats:sec>","DOI":"10.1002\/ana.26529","type":"journal-article","created":{"date-parts":[[2022,10,11]],"date-time":"2022-10-11T10:58:32Z","timestamp":1665485912000},"page":"76-87","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Trans\u2010Synaptic Degeneration Following Acute Optic Neuritis in Multiple Sclerosis"],"prefix":"10.1002","volume":"93","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7880-8948","authenticated-orcid":false,"given":"Olwen C.","family":"Murphy","sequence":"first","affiliation":[{"name":"Division of Neuroimmunology and Neurological Infections, Department of Neurology Johns Hopkins University  Baltimore MD USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8812-1637","authenticated-orcid":false,"given":"Elias S.","family":"Sotirchos","sequence":"additional","affiliation":[{"name":"Division of 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