Association of corneal nerve parameters with nerve abnormalities and neuropathic pain in prediabetes and type 2 diabetes: the Maastricht Study

AIMS/HYPOTHESIS: Corneal confocal microscopy is a valuable technique for assessing neuropathy; however, whether it can distinguish painful from painless neuropathy remains uncertain and existing evidence is based on the results of smaller studies. This study assessed the association of corneal nerve parameters with abnormalities identified by electromyography (EMG) and neuropathic pain in a large population with and without (pre)diabetes. METHODS: In this study we included cross-sectional data for 3425 participants from the Maastricht Study. Wide-field corneal confocal microscopy (WF-CCM) was performed using fully automated analysis of three corneal nerve parameters: corneal nerve branch density (CNBD), corneal nerve fibre density (CNFD) and corneal nerve fibre length (CNFL). An axonal degeneration composite score comprising compound muscle action potential amplitudes (peroneal and tibial) and the sensory nerve action potential amplitude of the sural nerve was created by categorising EMG amplitudes as normal or indicating minor (≤10th percentile), moderate (≤5th percentile) or severe (≤2.5th percentile) abnormalities. Neuropathic pain was determined as a modified Douleur Neuropathique en 4 Questions (DN4) interview score ≥3. RESULTS: The mean age of the participants was 59.2 years; 51.6% were female, 15% had prediabetes (defined as impaired fasting glucose, impaired glucose tolerance or both) and 19% had type 2 diabetes. The median diabetes duration was 3.0 years. Regression analyses revealed statistically significant associations between the axonal degeneration EMG score and WF-CCM parameters (CNFL: β=-0.51 [95% CI -0.78, -0.24]; CNFD: β=-1.56 [95% CI -3.04, -0.08]; CNBD: β=-3.08 [95% CI -5.51, -0.64]; all p<0.05) but no statistically significant associations between neuropathic pain and WF-CCM parameters (CNFL: β=-0.06; CNFD: β=-1.15; CNBD: β=-0.22; all p>0.1). CONCLUSIONS/INTERPRETATION: The study found associations between the axonal degeneration EMG score and WF-CCM, but no associations were observed between neuropathic pain and WF-CCM parameters, suggesting that WF-CCM has limited value in assessing neuropathic pain.