Natural history of corneal nerve morphology in mild neuropathy associated with type 1 diabetes: development of a potential measure of diabetic peripheral neuropathy.

PURPOSE To investigate longitudinal changes of subbasal nerve plexus (SNP) morphology and its relationship with conventional measures of neuropathy in individuals with diabetes. METHODS A cohort of 147 individuals with type 1 diabetes and 60 age-balanced controls underwent detailed assessment of clinical and metabolic factors, neurologic deficits, quantitative sensory testing, nerve conduction studies, and corneal confocal microscopy at baseline and four subsequent annual visits. The SNP parameters included corneal nerve fiber density (CNFD), branch density (CNBD), and fiber length (CNFL), and were quantified using a fully automated algorithm. Linear mixed models were fitted to examine the changes in corneal nerve parameters over time. RESULTS At baseline, 27% of the participants had mild diabetic neuropathy. All SNP parameters were significantly lower in the neuropathy group compared with controls (P < 0.05). Overall, 89% of participants examined at baseline also completed the final visit. There was no clinically significant change to health and metabolic parameters and neuropathy measures from baseline to the final visit. Linear mixed model revealed a significant linear decline of CNFD (annual change rate, -0.9 nerve/mm(2), P = 0.01) in the neuropathy group compared with controls, which was associated with age (β = -0.06, P = 0.04) and duration of diabetes (β = -0.08, P = 0.03). In the neuropathy group, absolute changes of CNBD and CNFL showed moderate correlations with peroneal conduction velocity and cold sensation threshold, respectively (r, 0.38 and 0.40, P < 0.05). CONCLUSIONS This study demonstrates dynamic small fiber damage at the SNP, thus providing justification for our ongoing efforts to establish corneal nerve morphology as an appropriate adjunct to conventional measures of diabetic peripheral neuropathy.