Background To investigate the optical coherence tomography angiography (OCTA) characteristics of diabetic macular edema (DME) at different stages. Methods This study was a cross-sectional study. Patients diagnosed with DME were recruited. DME was classified into early, advanced, and severe DME. The vessel density (VD) in the superficial vascular plexus (SVP), deep vascular plexus (DVP) and foveal avascular zone (FAZ) parameters, including FAZ area, FAZ perimeter, acircularity index and foveal VD in a 300-μm-wide region around the FAZ (FD-300), were calculated by the AngioVue software. A multivariate generalized estimating equation was used to evaluate the associations between visual acuity and OCTA metrics. Results Ninety-two eyes from 74 patients with DME were included in this study. Compared to early (P = 0.006) and advanced DME (P = 0.003), the acircularity index was higher in severe DME. Both whole and parafoveal VD in the DVP decreased in eyes with severe DME compared to early DME (P = 0.018, P = 0.005, respectively) and advanced DME (P = 0.035, P = 0.012, respectively). In the multivariate generalized estimating equation, DME severity, FAZ area and foveal thickness were positively associated with worse visual acuity (P = 0.001, P = 0.007 and P = 0.001, respectively). Conclusion Compared to early and advanced DME, severe DME showed increased irregularity in the FAZ and more extensive vessel damage in the DVP. Greater severity level of DME, larger FAZ area, and increased foveal thickness could be risk factors for poor visual acuity. Trial registration The protocol was published in the Chinese Clinical Trial Registry (ChiCTR2000033082).

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