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These multiple associations based on a variety of clinical, radiological, and biological criteria that have changed over time have led to overlapping phenotypes: a single ON case can be classified in several ways simultaneously or over time. As early, intensive treatment is often required, its diagnosis should be rapid and precise. In this review, we present the current state of knowledge about diagnostic criteria for ON aetiologies in adults and children, we discuss overlapping phenotypes, and we propose a homogeneous classification scheme. Even if distinctions between typical and atypical ON are relevant, their phenotypes are largely overlapping, and clinical criteria are neither sensitive enough, nor specific enough, to assure a diagnosis. For initial cases of ON, clinicians should perform contrast enhanced MRI of the brain and orbits, cerebral spinal fluid analysis, and biological analyses to exclude secondary infectious or inflammatory ON. Systematic screening for MOG-IgG and AQP4-IgG IgG is recommended in children but is still a matter of debate in adults. Early recognition of neuromyelitis optica spectrum disorder, MOG-IgG-associated disorder, and chronic relapsing idiopathic optic neuritis is required, as these diagnoses require therapies for relapse prevention that are different from those used to treat multiple sclerosis.<\/jats:p>","DOI":"10.1177\/11206721211028050","type":"journal-article","created":{"date-parts":[[2021,7,3]],"date-time":"2021-07-03T03:29:22Z","timestamp":1625282962000},"page":"754-766","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":12,"title":["Optic neuritis classification in 2021"],"prefix":"10.1177","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1306-1908","authenticated-orcid":false,"given":"Jean-Baptiste","family":"Ducloyer","sequence":"first","affiliation":[{"name":"Department of Ophthalmology, University Hospital of Nantes, Nantes, 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