Optic neuritis can be mimicked by other optic neuropathies and by anterior segment, choroidal or retinal diseases. Retinal diseases may cause central visual loss when they involve the macular or peripapillary area. Central serous retinopathy, hereditary retinal diseases, white dots syndromes and autoimmune retinopathies may present a clinical picture similar to that of optic neuritis. Complete neuro-ophthalmological examination must be performed to differentiate optic nerve damage from other ocular structures involvement. As in optic neuritis, optic disc and macula appearance may be completely normal in several retinal diseases. Fluorescein angiography and electrophysiological testing are relevant for the differential diagnosis in many challenging cases.