Longitudinal Relationship Between Retinal Diabetic Neurodegeneration and Progression of Diabetic Retinopathy in Patients With Type 2 Diabetes

Purpose: To investigate the longitudinal relationship between diabetic retinal neurodegeneration and the progression of diabetic retinopathy (DR) by measuring macular ganglion cell–inner plexiform layer (mGCIPL) thickness in patients with type 2 diabetes (T2DM). Design: Retrospective cohort study. Methods: T2DM patients with no DR or mild nonproliferative DR (NPDR) followed up for ≥4 years were included in this study. DR was graded according to retinal photography, and mean parafoveal mGCIPL thickness was measured using optical coherence tomography with at least a 6-month interval from baseline. Hazard ratios (HR) for predicting 2-step progression and development of proliferative DR (PDR) were calculated using Cox proportional hazard modeling using baseline clinical factors. Results: Of 87 eyes of T2DM patients, 39 (44.8%) exhibited 2-step DR progression and 6 (6.9%) experienced progression to PDR. Patients with DR progression exhibited longer T2DM duration, thinner mGCIPL, greater mGCIPL thinning rate, severe cardiac autonomic neuropathy (CAN), lower peripheral nerve-conduction velocity, and higher glycated hemoglobin A1c level. Multivariate regression modeling revealed that baseline mGCIPL thickness (HR = 0.94), mGCIPL thinning rate (HR = 1.924), CAN score (HR = 1.248), and conduction velocity of peripheral nerves (HR = 0.894) were significant predictive factors for DR progression (area under the curve = 0.92). Conclusion: Progressive loss of mGCIPL is an independent risk factor for progression in early-stage DR. Further assessment of autonomic and peripheral nerve functions can increase sensitivity in predicting aggravation of DR in patients with T2DM.