AIM: To evaluate the thickness of the retinal layers in the macula using spectral-domain optical coherence tomography (SD-OCT) in patients with neuromyelitis optica (NMO). METHODS: Spectralis SD-OCT, utilizing automated macular layer segmentation, was performed in 26 NMO patients and 26 healthy controls. Visual function including visual field tests and pattern visual evoked potential were recorded in study subjects. RESULTS: Forty-one eyes from 26 NMO patients and 52 eyes from 26 age- and sex-matched healthy controls were included. Besides total macular volume, peri-paipillary retinal nerve fiber layer (RNFL) thickness, the thickness of macular RNFL, ganglion cell layer (GCL) and inner plexiform layer (IPL) were also significantly reduced in NMO patients compared to those inhealthy controls (P<0.000). No differences were found in the thickness of macular inner nuclear layer (INL), outer plexiform layer (OPL), and outer nuclear layer (ONL) between the two groups. Reversely, the outer retinal layer (ORL) was shown to be thicker in NMO than controls (P<0.05). Compared with the peri-papillary RNFL thickness, the GCL thickness was demonstrated to correlate with visual function better. CONCLUSION: The study provides in vivo evidence of retinal neural loss in NMO patients and demonstrates a better structure-function correlation between retinal ganglion cell and visual function than peri-papillary RNFL does. In addition, no evidence of primary neural damage is found. Besides, the photoreceptor cells and retinal pigments epithelial (RPE) cells presumably proliferated in compensation in NMO after retinal neural loss.