The Diagnostic Performance and Clinical Relevance of Corneal Confocal Microscopy (CCM) in Patients with Diabetic Peripheral Neuropathy (S44.001)

OBJECTIVE: Assess the diagnostic performance and clinical relevance of CCM in diabetic neuropathy (DPN). BACKGROUND: Small unmyelinated axons are injured early in DPN. CCM noninvasively visualizes small corneal axons and is a promising diagnostic tool. DESIGN/METHODS: 68 diabetic patients were recruited from those undergoing annual retinopathy screening. 44 had DPN. CCM measured nerve fiber length (NFL) density (NFD), branch density (NFBD) and tortuosity (TC). Results were compared to 100 controls. Each patient underwent intraepidermal nerve fiber density (IENFD), nerve conduction studies (NCS), Utah Early Neuropathy Score (UENS), Neuropathy Total Symptom Score-6 (NTSS-6), 6 minute walk test (6MWT), Norfolk Quality of Life - Diabetic Neuropathy (NQOL-DN) and a visual analog pain scale (VAS). RESULTS: There were significant differences between diabetic and controls in NFL (24.3 +/- 8.2 vs. 28.1 +/- 7.1 mm/mm2, p<0.008), NFD (47.5 +/- 15 vs. 69.1 +/- 18 fibers/mm2, p<0.001), and TC (0.121 +/- 0.40 vs. 0.165 +/- 0.38 , p<0.001). Diabetics with DPN had significantly lower NFL (22.7 +/- 8.3 vs. 26.9 +/- 7.5 mm/mm2, p<0.04), NFD (44.6 +/- 14 vs. 52.6 +/- 15 fibers/mm2, p<0.03), and NFBD (118 +/- 61 vs. 151 +/- 56 branches/mm2, p<0.03) than those without DPN. CCM ROC analysis evaluated diagnostic performance. Area under the curve (AUC) was: NFL 0.665, NBD 0.677, NFD 0.675, sural amplitude 0.765, peroneal motor conduction velocity 0.717 and IENFD 0.735. IENFD correlated with NTSS-6 (cc -0.363, p<0.002), NQOL-DN (cc -0.269, p< 0.027), VAS (-0.278, p<0.02) and UENS (cc -0.488 p<0.001). NFL, NFD and NFBD each correlated with 6MWT distance (cc 0.373, p<0.002, 0.308 p<0.14 and 0.350 p<0.004). CONCLUSIONS: Among CCM measures, NFL and NFD best distinguish diabetic patients from controls, and those with DPN. CCM’s diagnostic performance is slightly lower than IENFD. IENFD correlates with symptoms, signs and QOL, whereas CCM correlates with overall functional status. Disclosure: Dr. Smith has received personal compensation for activities with CSL Behring, Grifols, and Allergan. Dr. Smith has received research support from NIH, the ADA, and Impeto. Dr. Smith has received personal compensation in an editorial capacity for NeuroLear Dr. Kowalsky has nothing to disclose. Dr. Hauer has nothing to disclose. Dr. Aperghis has nothing to disclose. Dr. Singleton has nothing to disclose.