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To investigate the diagnostic performance of structural and vascular changes to detect MSNON from controls, we performed a cross\u2010sectional study of 76 eyes from 51 MS participants and 117 eyes from 71 healthy controls. Retinal macular ganglion cell complex (GCC), retinal nerve fiber layer (RNFL) thicknesses, and capillary densities from the superficial (SCP) and deep capillary plexuses (DCP) were obtained from the Cirrus AngioPlex. The best structural parameter for detecting MS was compensated RNFL from the optic nerve head (AUC = 0.85), followed by GCC from the macula (AUC = 0.79), while the best vascular parameter was the SCP (AUC = 0.66). Combining structural and vascular parameters improved the diagnostic performance for MS detection (AUC = 0.90; <jats:italic>p<\/jats:italic>&lt;0.001). 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