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To compare the retinal nerve fiber layer (RNFL) in eyes of patients with relapsing remitting multiple sclerosis (RRMS), neuromyelitis optica (NMO) and chronic relapsing inflammatory optic neuritis (CRION).Evaluation of 62 patients with RRMS, NMO, and CRION in a cross-sectional study with spectral domain optical coherence tomography.A total of 124 eyes were evaluated (96 RRMS, 18 NMO, and 10 CRION). Frequency of optic neuritis for each disease was: 34% for RRMS, 84% for NMO, and 100% for CRION. Visual acuity and RNFL thickness were significantly worse in NMO and CRION eyes than in RRMS, but there were no differences between NMO and CRION eyes. A RNFL of 41 μm was 100% specific for optic neuritis associated with NMO and CRION when compared to RRMS.This study established RNFL values to differentiate optic neuritis of RRMS from NMO and CRION. Although similarities observed between NMO and CRION eyes might suggest that they are within the same disease spectrum, it is still recommended that these 2 conditions be differentiated on clinical grounds. Optical coherence tomography serves as an additional diagnostic tool and can be used to monitor disease progression.