Longitudinal neural and microvascular changes in type 2 diabetic patients without retinopathy: a 2-year prospective cohort study

To compare the 2-year longitudinal changes in macular ganglion cell-inner plexiform layer thickness (GCIPLT) and superficial capillary plexus (SCP) vessel density between patients with type 2 diabetes mellitus (T2DM) without retinopathy (non-DR) and healthy controls. Prospective observational cohort study. T2DM patients without clinical retinopathy at baseline and after a 2-year follow-up, along with age- and sex-matched healthy controls, were recruited from the community in Guangzhou. Measurements of macular GCIPLT, retinal thickness (RT), and SCP vessel density were conducted at baseline and at the 2-year follow-up. Linear mixed-effects models were used to estimate absolute and relative rates of changes and to compare absolute rates between the two groups. A total of 282 eyes (141 in the control group and 141 in the non-DR group) were included in the analysis. Significant reductions in GCIPT and GCIPLT/RT occurred only in the non-DR group, with GCIPLT decreasing by -0.229 μm/year (95% confidence interval [CI]: -0.313 to -0.144; P < 0.001) and 0.324 % (95%CI: 0.444 to 0.204; P < 0.001), approximately 5-fold faster than the control group. After adjusting for confounding factors, the longitudinal rates of RT, GCIPLT, and GCIPLT/RT were significantly accelerated in the non-DR group compared to the control group by -0.603 μm/year (95% CI: -0.939 to -0.268; P < 0.001), -0.189 μm/year (95% CI: -0.306 to -0.073; P = 0.001), and -0.073 % (95% CI: -0.118 to -0.028; P = 0.001), respectively. While, longitudinal changes in SCP vessel density did not show significant differences between the two groups (P = 0.861). Our findings suggest that neurodegenerative changes may precede microvascular alterations in non-DR patients, indicating that monitoring of GCIPLT is crucial for patients with long-standing diabetes, even in the absence of retinopathy.