Multimodal Imaging of the Initial Stages of Diabetic Retinopathy: Different Disease Pathways in Different Patients

The objective of this study was to evaluate the prevalence of different disease pathways (ischemia, neurodegeneration, and edema) in the initial stages of diabetic retinopathy. In this retrospective cross-sectional study, eyes were grouped by diabetic retinopathy severity using the 7-field Early Treatment Diabetic Retinopathy Study (ETDRS) protocol (levels 10-20, 35, and 43-47). Neurodegeneration was identified by thinning of the retinal nerve fiber layer and/or ganglion cell layer. Edema was identified by thickening of the inner nuclear layer, outer plexiform layer, or full retina. Ischemia was identified by metrics of retinal vessel density. Imaging was performed in 142 eyes from 142 patients (28% women) aged 52-88 years. Vessel density (ischemia) was significantly different between the ETDRS groups (P < 0.020). On multivariate regression analysis, it remained significantly different between stages of the disease and showed associations with age (P < 0.001), sex (P = 0.028), and metabolic control (P = 0.034). No significant differences between ETDRS groups were found in retinal thinning (neurodegeneration) or retinal thickness (edema). Eyes with the same ETDRS retinopathy grading from different patients with diabetes showed that the prevalence of different disease pathways varies between patients, even within the same severity group. Ischemia (capillary dropout) is the only disease pathway that shows correlation with retinopathy severity and metabolic control.