PURPOSE: To compare the optical coherence tomography (OCT)/OCT angiography (OCTA) measures in patients with neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody disease (MOGAD). METHODS: Twenty-one MOG, 21 NMOSD, and 22 controls were enrolled in our study. The retinal structure [retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GCIPL)] was imaged and assessed with the OCT; OCTA was used to image the macula microvasculature [superficial vascular plexus (SVP), intermediate capillary plexus (ICP), and deep capillary plexus (DCP)]. Clinical information such as disease duration, visual acuity, and frequency of optic neuritis and disability was recorded for all patients. RESULTS: Compared with NMOSD patients, MOGAD patients showed significantly reduced SVP density ( = 0.023). No significant difference ( > 0.05) was seen in the microvasculature and structure when NMOSD-ON was compared with MOG-ON. In NMOSD patients, EDSS, disease duration, reduced visual acuity, and frequency of ON significantly correlated ( < 0.05) with SVP and ICP densities; in MOGAD patients, SVP correlated with EDSS, duration, reduced visual acuity, and frequency of ON ( < 0.05), while DCP density correlated with disease duration, visual acuity, and frequency of ON. CONCLUSIONS: Distinct structural and microvascular changes were identified in MOGAD patients compared with NMOSD patients suggesting that the pathological mechanisms are different in NMOSD and MOGAD. Retinal imaging the SS-OCT/OCTA might have the potential to be used as a clinical tool to evaluate the clinical features associated with NMOSD and MOGAD.