Tear Biomarkers and Corneal Sensitivity as an Indicator of Neuropathy in Type 2 Diabetes

BACKGROUND: Diabetic peripheral neuropathy (DPN) is a debilitating, progressive complication of type 2 diabetes. The high cost of management leads to amputations in approximately 6% of individuals with DPN in poor-resource settings due to medical noncompliance or lack of finances. Having an effective means of early detection of DPN is crucial for early intervention, which would have a major impact in alleviating its social, economic, and medical burden. OBJECTIVES: To explore the potential of 31 tear biomarkers involved in both corneal growth and development and inflammatory pathways in screening for diabetic peripheral neuropathy (DPN). Additionally, the utility of aesthesiometry for measuring corneal damage in DPN was assessed. METHODS: This screening test pilot study recruited 90 participants from a tertiary hospital in Lima, Peru. Participants were categorized into three groups based on diabetes and neuropathy status. Tears were collected on Schirmer strips, and proteins were measured by both ELISA and multiplex-bead assay. Corneal sensitivity was measured by aesthesiometry, and DPN was measured through vibration perception threshold testing. RESULTS: A total of 89 participants were included in the analysis. The mean age was 55.7+1.46, and 58.4% were female. After adjusting for potential confounders, MMP-9 and TGF-alpha levels showed a strong upward trend in participants with DPN when compared to those with diabetes alone, though not significant. Decreased corneal sensitivity, as measured by aesthesiometry, was negatively correlated with MMP-9 levels (p<0.01) in individuals with DPN. Aesthesiometry was significantly decreased in individuals with DPN when compared to participants with diabetes alone (p<0.01) and normal controls (p<0.01). CONCLUSIONS: Although tears are a simple and inexpensive resource with promise to help detect DPN, it is an insufficient standalone tool for detecting DPN based on the present study. Aesthesiometry is a simple, inexpensive, and accurate method to assess corneal damage associated with DPN, and its integration into screening practices has potential to improve detection of DPN in poor-resource settings.