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

PURPOSE

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.

DESIGN

Prospective, cross-sectional study.

METHODS

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.

RESULTS

Among neuroretinal layers, solely the peripapillary retinal nerve fiber layer was decreased in PDR (96 μm; 95% confidence interval [CI], 92-100 μm) versus no DR (103 μm; 95% CI, 100-106 μm) eyes and only after exclusion of outliers (P = .01). Corneal nerve fiber length and density were statistically significantly reduced in the NPDR group (23.0 mm/mm; 95% CI, 20.0-26.00 mm/mm and 14.3 mm; 95% CI, 14.5-16.63 mm, respectively) and the PDR group (18.6 mm/mm; 95% CI, 14.9-22.30 mm/mm and 11.7 mm; 95% CI, 10.2-13-3 mm, respectively) versus the no DR group (25.5 mm/mm; 95% CI, 23.3-27.70 mm/mm and 15.6 mm; 95% CI, 14.5-16.6 mm, 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).

CONCLUSIONS

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.