Purpose: To provide clinical evidence of the associations between retinal neuronal degeneration and microvasculopathy in diabetic retinopathy (DR).Methods: This case-control study included 76 patients (76 eyes) with type 2 diabetes mellitus (DM), and refraction error between -3.0 and +3.0 D. The eyes were assigned into DM (without DR), non-proliferative DR (NPDR), and proliferative DR (PDR) groups. Age-, sex-, and refractive error-matched normal subjects were enrolled as controls. The mean retinal thickness (mRT), the relative mean thickness of the retinal nerve fiber layer (rmtRNFL, mtRNFL/mRT), ganglion cell layer (rmtGCL), ganglion cell complex (rmtGCC) layer, foveal avascular zone area (FAZa), FAZ perimeter (FAZp), FAZ circularity index (FAZ-CI), and vessel density (VD) in superficial capillary plexus (SCP) and deep capillary plexus (DCP) were assessed by swept-source optical coherence tomography (OCT) and OCT angiography (OCTA). Group comparison and Spearman's partial correlation coefficient analysis were applied to evaluate the correlation between these morphological parameters.Results: rmtRNFL, FAZa, and FAZp in SCP and DCP increased with the DR severity (p(rmtRNFL) < 0.001; p(FAZa, SCP) = 0.001; p(FAZa), (DCP) = 0.005; p(FAZp), (SCP) < 0.001; p(FAZp), (DCP) < 0.001). The rmtGCL, FAZ-CI in SCP and DCP, and VD in DCP decreased with the DR severity (p(rmtGCL) = 0.002, p(FAZ-CI), (SCP) = 0.002; p(FAZ-CI, DCP) < 0.001, p(VD), (DCP) < 0.001). After controlling age, sex, duration of diabetes, and hypertension, the rmtRNFL, FAZa in SCP and DCP, and FAZp in SCP and DCP were correlated with the severity of DR (p < 0.05), while VD in SCP and DCP, FAZ-CI, and rmtGCL were negatively correlated with the severity of DR (p < 0.05). The rmtGCL was negatively correlated with the FAZa in SCP (r = -0.34, p = 0.002) and DCP (r = -0.23, p = 0.033), and FAZp in SCP (r = -0.37, p = 0.001) and DCP (r = -0.32, p = 0.003), but positively correlated with VD in SCP (r = 0.26, p = 0.016), VD in DCP (r = 0.28, p = 0.012), and FAZ-CI in DCP (r = 0.31, p = 0.006).Conclusions: rmtRNFL, FAZ-CI in SCP and DCP, and FAZp in SCP are strong predictors of the severity of DR. The ganglion cell body loss is highly correlated with increased FAZp and FAZa, decreased FAZ-CI, and reduced VD with the severity of DR.