To assess the course of neurodegeneration based on retinal layer thickness and integrity analysis in diabetic patients without retinopathy and to evaluate its association with inner retinal reflectivity. This retrospective case-control study included 80 eyes of 80 patients with DM without retinopathy and 40 eyes of 40 healthy subjects with a follow-up of ≥1 year. SD-OCT was used for assessment of retinal reflectivity and macular layer thicknesses. Optical intensity ratios (OIRs) were defined as the mean OCT reflectivity of ganglion cell and inner nuclear layer to the mean reflectivity of RPE. After Bonferroni correction, thinning in pericentral, superior and nasal sectors in total retina, superior ganglion cell, pericentral and nasal inner plexiform, and superior inner retinal layers, as well as thickening in inferior and pericentral outer plexiform layer remained significant in the study group (p < 0.0125). Ganglion cell layer OIR significantly correlated with the changes in superior retina (r = 0.278, p = 0.013), central inner retina (r = 0.247, p = 0.027), and pericentral retinal thickness (r = 0.240, p = 0.032), and no eyes had disruption of retinal layers in the study group initially or finally. Ganglion cell layer reflectivity significantly correlated with the amount of pericentral retinal thinning during the time course in the diabetic group, which was more prominent in the inner retinal layers.