Association between Neurodegeneration and Macular Perfusion in the Progression of Diabetic Retinopathy: A 3-Year Longitudinal Study

Abstract

Objective and purpose: The aim of this study was to explore the relation between retinal neurodegenerative changes and vessel closure (VC) in individuals with nonproliferative diabetic retinopathy (NPDR) in a follow-up period of 3 years.

Design: This is a 3-year prospective longitudinal study with four annual visits.

Participants: This study involved 74 individuals with type 2 diabetes, NPDR, and Early Treatment Diabetic Retinopathy Study grades from 10 to 47, one eye/person. An age-matched healthy control population of 84 eyes was used as control group.

Methods: Participants were annually examined by color fundus photography, spectral domain-optical coherence tomography (SD-OCT) and OCT-angiography (OCTA). VC was assessed by OCTA vessel density maps. SD-OCT segmentations were performed to access central retinal thickness (CRT) and retinal neurodegeneration considered as thinning of the ganglion cell plus inner plexiform layer (GCL + IPL).

Results: Type 2 diabetic individuals presented significantly higher CRT (p = 0.001), GCL + IPL thinning (p = 0.042), and decreased vessel density at the superficial capillary plexus (p < 0.001) and full retina (FR) (p = 0.001). When looking at changes occurring over the 3-year period of follow-up (Table 2), there were statistically significant decreases in GCL + IPL thickness (-0.438 μm/year; p = 0.038), foveal avascular zone circularity (-0.009; p = 0.047), and vessel density in superficial capillary plexus (-0.172 mm-1/year; p < 0.001), deep capillary plexus (DCP) (-0.350 mm-1/year; p < 0.001), and FR (-0.182 mm-1/year; p < 0.001). A statistically significant association was identified between GCL + IPL thinning and decrease in DCP vessel density (β = 0.196 [95% confidence interval: 0.037, 0.355], z = 2.410, p = 0.016), after controlling for age, gender, diabetes duration, hemoglobin A1c level, and CRT.

Conclusions: Retinal neurodegenerative changes show a steady progression during a 3-year period of follow-up in eyes with NPDR and appear to be directly associated with progression in decreased vessel density including vascular closure through preferential involvement of the DCP. Our findings provide evidence that retinal neuropathy is linked with microvascular changes occurring in diabetic patients.

Keywords: Diabetes; Neurodegeneration; Progression; Retinopathy; Vessel closure.

Fig. 1

DCP vessel density and GCL + IPL thickness longitudinal changes. Graphical representation of GCL + IPL thickness and DCP vessel density progression over the 3 years of follow-up. Mean changes in GCL + IPL thickness of −0.438 μm/year (p = 0.038) and in vessel density, particularly in DCP vessel density of −0.350 mm⁻¹/year (p < 0.001), occur over the 3-year time.

Fig. 2

Correlation of GCL + IPL thickness and DCP vessel density changes at each visit. Graphical representation of the longitudinal correlation between GCL + IPL thickness (Y-axis) with DCP vessel density (X-axis) at visit 2 (1-year), visit 3 (2 years), and visit 4 (3 years) of the follow-up. A statistically significant association was identified between GCL + IPL thinning and decrease in DCP vessel density after adjusting for confounding variables as age, gender, diabetes duration, HbA1c level, and CRT thickness (β = 0.196 [95% CI: 0.037, 0.355], z = 2.410, p = 0.016).