Retinal and Corneal Neurodegeneration and Their Association with Systemic Signs of Peripheral Neuropathy in Type 2 Diabetes

Abstract

To determine the extent of retinal and corneal neurodegeneration and investigate the association with intraepidermal neuronal loss and diabetic peripheral neuropathy (DPN) in type 2 diabetes. Prospective, cross-sectional study. Single-center study of 94 patients with type 2 diabetes patients (157 eyes), divided into groups: the groups without diabetic retinopathy (DR) (n= 68); the nonproliferative DR (NPDR) group (n= 48); and the proliferative DR (PDR) group (n= 41). Patients were imaged with optical coherence tomography and confocal microscopy for macular and peripapillary neuroretinal layer thicknesses and corneal nerve length/density, respectively. Distal leg skin punch biopsies and 2 neurological scores were used to depict intraepidermal nerve fiber density (IENFD) and clinical DPN. Among neuroretinal layers, solely the peripapillary retinal nerve fiber layer was decreased in PDR (96μm; 95% confidence interval [CI], 92-100μm) versus no DR (103μm; 95% CI, 100-106μm) eyes and only after exclusion of outliers (P= .01). Corneal nerve fiber length and density were statistically significantly reduced in the NPDR group (23.0mm/mm2; 95% CI, 20.0-26.00mm/mm2 and 14.3mm; 95% CI, 14.5-16.63mm, respectively) and the PDR group (18.6mm/mm2; 95% CI, 14.9-22.30mm/mm2 and 11.7mm; 95% CI, 10.2-13-3mm, respectively) versus the no DR group (25.5mm/mm2; 95% CI, 23.3-27.70mm/mm2 and 15.6mm; 95% CI, 14.5-16.6mm, respectively), and in the PDR versus the NPDR group. IENFD was statistically significantly reduced in the NPDR (2.0/mm; 95% CI, 1.4-2.7/mm) and PDR stage (1.4/mm; 95% CI, 0.9-2.1/mm) versus in eyes without DR (3.6/mm; 95% CI, 2.9-4.6/mm). A low correlation between intraepidermal and corneal fiber loss was found with both neurological scores (P < .05). Retinal neurodegenerative changes may develop independently of the microvascular alterations defining DR. Corneal and intraepidermal neuronal loss is more pronounced in advanced stages of DR, indicating a positive severity correlation between DR and DPN.