Structural changes in the retina and cornea during diabetic neuropathy

Abstract

Purpose: To examine the relationship between neuroretinal thickness and corneal nerve fiber length (CNFL) relative to diabetic neuropathy (DN) status in patients with diabetes mellitus (DM)

Methods: In this cross-sectional study, we examined 25 diabetic patients without DN, 10 patients with mild DN, 8 patients with severe DN, and 9 controls without diabetes. DN status was assigned based on a combination of clinical symptoms, signs, and neurophysiologic testing. Patients underwent optical coherence tomography (OCT) imaging of the retina, in vivo confocal microscopy (IVCM) of the corneal sub-basal nerve plexus, and nerve conduction velocity (NCV) testing. DOCTRAP software was used to segment inner retinal layer boundaries. Post-hoc analysis of the OCT and IVCM images was performed to quantify the average thickness of each retinal layer and the average CNFL. ANOVA was used to assess for differences in retinal thickness, CNFL, and NCV among the subjects. Pearson correlations were used to evaluate the relationship between NCV and the retinal and corneal parameters.

Results: All 25 diabetic patients without DN had type 1 DM, and the remaining patients with DN had type 2 DM. There were no significant differences in average retinal nerve fiber layer, ganglion cell/inner plexiform layer, inner nuclear layer, outer plexiform layer, outer nuclear layer/inner segment, outer segment, retinal pigment epithelial, or total retinal thicknesses among the 4 groups. Patients with type 2 DM and severe DN had reduced corneal nerves (CNFL ± SD = 12.5 ± 6.1 mm/mm²) compared to controls (20.7 ± 2.2 mm/mm²) (p=0.009). Persons with type 1 DM without DN also had reduced CNFL (15.1 ± 4.7 mm/mm²) relative to controls (p=0.033). Peroneal NCV was reduced only in severe DN (mean velocity ± SD = 32.4 ± 4.1 m/s) relative to controls (45.8 ± 6.9 m/s) (p<0.001). While none of the retinal thickness measurements correlated with peroneal NCV, CNFL was significantly correlated with this metric (r=0.57, p=0.003).

Conclusions: In this cross-sectional pilot study, nerve density in the corneal sub-basal nerve plexus was reduced in type 2 DM patients with severe DN and in type 1 DM patients without DN compared to controls. This suggests that IVCM of the corneal sub-basal nerve plexus may be a more sensitive indicator of peripheral nerve degeneration in type 1 vs. type 2 DM.

Keywords: 479 cornea: clinical science • 498 diabetes • 550 imaging/image analysis: clinical