Diagnosis of Neuropathy and Risk Factors for Corneal Nerve Loss in Type 1 and Type 2 Diabetes: A Corneal Confocal Microscopy Study

Abstract

Objective: To assess the diagnostic utility of corneal confocal microscopy (CCM) for diabetic peripheral neuropathy (DPN) and the risk factors for corneal nerve loss.

Research design and methods: A total of 490 participants, including 72 healthy control subjects, 149 with type 1 diabetes, and 269 with type 2 diabetes, underwent detailed assessment of peripheral neuropathy and CCM in relation to risk factors.

Results: Corneal nerve fiber density (CNFD) (P < 0.0001 and P < 0.0001), corneal nerve fiber branch density (CNBD) (P < 0.0001 and P < 0.0001), and corneal nerve fiber length (CNFL) (P < 0.0001 and P = 0.02) were significantly lower in patients with type 1 and type 2 diabetes compared with control subjects. CNFD (P < 0.0001), CNBD (P < 0.0001), and CNFL (P < 0.0001) were lower in type 1 diabetes compared with type 2 diabetes. Receiver operating characteristic curve analysis for the diagnosis of DPN demonstrated a good area under the curve for CNFD of 0.81, CNBD of 0.74, and CNFL of 0.73. Multivariable regression analysis showed a significant association among reduced CNFL with age (β = -0.27, P = 0.007), HbA_1c (β = -1.1; P = 0.01), and weight (β = -0.14; P = 0.03) in patients with type 2 diabetes and with duration of diabetes (β = -0.13; P = 0.02), LDL cholesterol (β = 1.8, P = 0.04), and triglycerides (β = -2.87; P = 0.009) in patients with type 1 diabetes.

Conclusions: CCM identifies more severe corneal nerve loss in patients with type 1 diabetes compared with type 2 diabetes and shows good diagnostic accuracy for DPN. Furthermore, the risk factors for a reduction in corneal nerve fiber length differ between type 1 and type 2 diabetes.