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Background: To evaluate the feature of different retinal layer segmentation in neuromyelitis optica spectrum disorders (NMOSD) with spectral-domain optical coherence tomography (SD-OCT) and to compare it with that in multiple sclerosis (MS), healthy controls (HC), and idiopathic optic neuritis (ION). Methods: We retrieved four electronic databases, including Pubmed, Embase, Cochrane Library, and Web of Science from inception to September 1st, 2021. A meta-analysis was performed to compare different retinal layer segmentation thicknesses between patients with or without a history of optic neuritis (ON) in NMOSD and the control group, including patients with MS, HC, and ION. Results: Forty-two studies were included and the interval between the last ON onset and examination was greater than 3 months. Compared with that in HC eyes, the loss of retinal nerve fiber layer (RNFL) and macular ganglion cell and inner plexiform layer (GC-IPL) was serious in NMOSD eye especially after ON. Moreover, compared with that in ION eyes or MS-related-ON eyes, the injury to the peripapillary retinal nerve fiber layer (pRNFL) was severe in NMOSD-related-ON eyes. In addition, the correlation coefficient between pRNFL and prognostic visual acuity was 0.43. However, the one-arm study revealed the inner nuclear layer (INL) was thickened in NMOSD-related-ON eyes compared with HC eyes. Conclusions: Inclusion of the RNFL and macular GC-IPL is recommended for monitoring disease progression and attention should be paid to changes in the INL.