Background: Neuromyelitis optica (NMO) is a CNS demyelinating disease characterized by relatively selective injury to the optic nerves and spinal cord. As the prognosis and treatment differ between NMO and multiple sclerosis (MS), distinguishing these two diseases in patients presenting optic neuritis (ON) is important. Previous reports have described vascular changes such as attenuation of peripapillary vascular tree and focal arteriolar narrowing in ophthalmoscopic findings of NMO ON. However, clear and quantitative difference of vascular changes between ON in NMO and MS have not described. Methods: Visual function testing and fundus photography were performed in age-matched 22 MS (31 ON eyes) and 51 NMO (88 ON eyes) patients with a history of ON. For evaluating retinal vascular change, the diameters of retinal artery and vein on optic disc margin were measured by the KOWA-VK-2 software on the image of fundus photography. Results: Retinal artery and vein thinning was seen in NMO ON eyes (77.92 microm,SD 12.6), relative to MS ON eyes (88.38 microm, SD 11.6) (p<0.001). The difference was more marked in the retinal vein of NMO ON eyes (77.97 microm,SD 10.7) compared with MS ON eyes (121.58 microm, SD 18.4) (p<0.0001). This difference was found after the adjustment of visual acuity (p<0.05) or visual contrast sensitivity (p<0.05). Intriguingly, more severe visual impairment was correlated with thinner diameter of retinal artery and vein in NMO ON eyes. However, in MS ON eyes, visual impairment was not correlated with the degree of vascular thinning Conclusions: NMO ON is characterized by marked vascular thinning which was correlated with visual impairment. This finding suggests that NMO ON is associated with more severe retinal vascular injury than MS ON, in which reflects the different pathogenesis between NMO and MS. Measurement of retinal vascular diameter may be useful as a surrogate marker of NMO.