Abstract

Introduction: Density of sub-epithelial corneal nerves have been promoted as a surrogate marker for early diagnosis of DPN. As an alternative, we developed an objective functional test of corneal sensitivity (Invest Ophthalmol Vis Sci. 2016, 57: 2412-9). In this study we provide verification of this methodology in human subjects with DPN. Methods: Following verification of DPN, response to a drop of isotonic vs. 5% NaCl (hypertonic) solution was recorded (primary endpoint). Ratio of time that the eyelids were closed from 10s to 60s following application of each solution were quantified using an image analysis program. Results: We examined 24 subjects with type 2 diabetes and 12 age-matched controls. The presence of DPN in diabetes vs. control subjects was verified by completing the Michigan Neuropathy Screening Instrument questionnaire and lower extremity examination including amplitude and conduction velocity of the sural nerve. The presence of eye discomfort was examined for each subject by completing the DEQ5 and Ocular Surface Disease Index (OSDI) questionnaires. DPN was confirmed in all subjects with diabetes as well as presence of mild to moderate ocular surface disease. Two control subjects had mild ocular surface disease but no peripheral neuropathy. Cochet-Bonnet filament esthesiometer examination revealed significant corneal sensitivity impairment in subjects with diabetes vs. control subjects (5.64 ± 0.08 vs. 5.97 ± 0.03 cm, respectively). Corneas of subjects with diabetes were also significantly less sensitive vs. controls to application of hypertonic solution (0.18 ± 0.01 vs. 0.29 ± 0.04, respectively). Data is presented as mean ± S.E.M. There was no difference in sensitivity to the isotonic solution. Conclusion: Corneal nerves that penetrate the epithelium and sprout near the surface of the eye and are the first to exhibit the "dying-back" phenomenon associated with DPN. Clinical evaluation of the sensitivity of these nerves could be a valuable method for early detection of DPN. Disclosure M.A.Yorek: Consultant; Novo Nordisk. M.Correia: Research Support; Eli Lilly and Company, Novartis, Novo Nordisk. R.Kardon: None. P.Poolman: Stock/Shareholder; FaceX LLC. Funding U.S. Department of Veterans Affairs (RX000889)

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