Corneal and Intraepidermal Nerve Fiber Pathology Best Detect Development and Progression of Diabetic Peripheral Neuropathy

Background/Objectives: To assess which measure of neuropathy best detects the progression of diabetic peripheral neuropathy (DPN) in type 1 diabetes (T1DM). Methods: Patients with T1DM (n = 56) underwent assessment of the neuropathy symptom profile (NSP), neuropathy disability score (NDS), warm perception threshold (WPT), nerve conduction studies [peroneal motor nerve conduction velocity (PMNCV) and amplitude (PMNA); sural sensory NCV (SSNCV) and amplitude (SSNA)], intraepidermal nerve fiber density (IENFD; only eight follow-up biopsy paired results were available), and corneal confocal microscopy (CCM) [corneal nerve fiber density (CNFD); branch density (CNBD); and length (CNFL)] at baseline and after a mean of 5.77 ± 1.71 years. Results: Despite a significant improvement in HbA1c (p = 0.0005) and LDL (p = 0.018) there was a reduction in CNFD (p = 0.036), CNBD (p = 0.0006), CNFL (p = 0.007), IENFD (p = 0.047) and SSNCV (p = 0.001), but no change in NSP, NDS, WPT, PMNCV, PMNA, and SSNA. Conclusions: Corneal nerve fiber degeneration is more consistently detected over time in patients with T1DM than changes in symptoms, signs, thermal thresholds, or nerve conduction studies, supporting its utility as a sensitive marker to evaluate DPN progression and therapeutic efficacy in clinical trials of DPN.