Decreased Blink Response to Hyperosmolar Eye Drops Detects Reduced Corneal Sensitivity for Diagnosing Human Diabetes Peripheral Neuropathy: A Pilot Study

PURPOSE: To verify an objective functional test of corneal sensitivity for detection of diabetes peripheral neuropathy (DPN) in human subjects with type 2 diabetes. METHODS: Ratio of time that the eyelids were closed over 50 seconds (10-60 seconds postinstillation) after application of isotonic versus 5% NaCl (hypertonic) solution were quantified using a video-based image analysis program. RESULTS: We examined 14 subjects with DPN and 8 controls. DPN was verified using multiple screening methods. Eye discomfort was examined by completing Dry Eye (DEQ5) and Ocular Surface Disease Index questionnaires. Cochet-Bonnet filament esthesiometer examination revealed significant corneal mechanical sensitivity impairment in subjects with DPN versus control. Corneas of patients with DPN showed significantly less chemical sensitivity versus controls to application of hypertonic solution (controls: 0.232 ± 0.039 vs. DPN: 0.159 ± 0.054; P = 0.0019; Cohen d = 1.46). Sensitivity to the isotonic NaCl solution was not significantly different between groups (P = 0.28). Receiver operator characteristic curves showed an area under the curve of 0.90 (95% CI: 0.75-1.00) for 5% NaCl chemical sensitivity and 0.75 (95% CI: 0.60-0.91) for Cochet-Bonnet mechanical sensitivity for differentiating normal subjects from patients with DPN. CONCLUSIONS: This pilot study demonstrates that clinical video-based objective evaluation of the chemical sensitivity of the corneal nerves may provide a valuable method for noninvasive detection of DPN. This test offers advantages of objectivity and biological specificity for epithelial-penetrating C-fiber nerve endings. Validation in larger, more diverse cohorts and development of automated smartphone-based implementations are needed before clinical translation.