ObjectiveTo investigate disease-specific foveal shape changes in patients with neuromyelitis optica spectrum disorders (NMOSDs) using foveal morphometry.MethodsThis cross-sectional study included macular spectral domain optical coherence tomography scans of 52 eyes from 28 patients with aquaporin-4 immunoglobulin G (AQP4-IgG)-seropositive NMOSD, 116 eyes from 60 patients with MS, and 123 eyes from 62 healthy controls (HCs), retrospectively, and an independent confirmatory cohort comprised 33/33 patients with NMOSD/MS. The fovea was characterized using 3D foveal morphometry. We included peripapillary retinal nerve fiber layer (pRNFL) thickness and combined macular ganglion cell and inner plexiform layer (GCIPL) volume to account for optic neuritis (ON)-related neuroaxonal damage.ResultsGroup comparison showed significant differences compared with HC in the majority of foveal shape parameters in NMOSD, but not MS. Pit flat disk area, average pit flat disk diameter, inner rim volume, and major slope disk length, as selected parameters, showed differences between NMOSD and MS (p value = 0.017, 0.002, 0.005, and 0.033, respectively). This effect was independent of ON. Area under the curve was between 0.7 and 0.8 (receiver operating characteristic curve) for discriminating between NMOSD and MS. Pit flat disk area and average pit flat disk diameter changes independent of ON were confirmed in an independent cohort.ConclusionsFoveal morphometry reveals a wider and flatter fovea in NMOSD in comparison to MS and HC. Comparison to MS and accounting for ON suggest this effect to be at least in part independent of ON. This supports a primary retinopathy in AQP4-IgG–seropositive NMOSD.