Macula microvascular impairment is an indicator of retinal pathology in neuromyelitis optica spectrum disorders (NMOSD). We used the spectral-domain optical coherence tomographic angiography (SD-OCTA) to measure the multiple retinal microvascular plexus to evaluate the changes that occur before optic neuritis. Methods: 28 seropositive aquaporin-4 antibody (AQP-4 Ab) NMOSD patients (19 eyes with optic neuritis and 9 eyes without optic neuritis) and 30 sex-and age-matched controls were included. SD-OCT was used to image and measure the capillary plexus of the retina (radial peripapillary capillaries, RPC; superficial retinal capillary plexus, SRCP; deep retinal capillary plexus, DRCP). Results: Eyes without optic neuritis and with optic neuritis were significantly decreased in the RPC, SRCP and DRCP when compared with healthy controls (P < 0.05) respectively. NMOSD eyes with multiple optic neuritis showed significantly reduced densities in the RPC (P = 0.001) and SRCP (P = 0.011) when compared with NMOSD eyes without optic neuritis. NMOSD eyes with multiple optic neuritis (45.76 ± 4.14%) showed reduced DRCP density when compared with eyes with single optic neuritis (46.88 ± 3.80%), a significant difference was not seen (P = 0.545). Visual acuity showed significant correlations with RPC density (Rho =-0.676, P < 0.001), pRNFL thickness (Rho =-0.448, P = 0.017), SRCP density (Rho =-0.561, P = 0.002) and DRCP density (Rho =-0.471, P = 0.011) in NMOSD respectively. Conclusions: Reduced DRCP density was seen regardless of optic neuritis; our study suggests that DRCP changes although microvascular changes occur in NMOSD, these changes may be significant in the DRCP.