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Mark Yorek, Eric Davidson, Matthew Yorek, Lawrence Coppey, Amey Holmes, Pieter Poolman, Randy H Kardon; Corneal Sensitivity to Hyperosmolar Eyedrops: A New Behavioral Assay To Assess Diabetic Peripheral Neuropathy. Invest. Ophthalmol. Vis. Sci. 2016;57(12):6157.
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© ARVO (1962-2015); The Authors (2016-present)
Currently the diagnosis of peripheral neuropathy (PN), which affects about 50% of the diabetic population, is subjective with many patients receiving a diagnosis only after presenting with related symptoms, after significant nerve loss has occurred. Earlier diagnosis and treatment of PN is needed. Recently, in vivo confocal microscopy of sub-epithelial corneal nerve density has been promoted as a surrogate marker for early detection of PN, but imaging of corneal nerves can be challenging as a routine examination and requires sophisticated instrumentation and analysis tools. As an alternative, we have developed a novel and simple screening method that is based on sensitivity of corneal nerves for detecting PN.
Corneas of control and type 2 diabetic rats were given eyedrops of 290 mOsm, 375 mOsm and 900 mOsm solutions and the ocular response video-recorded over a 2.5 min period. In addition, other neuropathic endpoints including cornea sensitivity using Cochet-Bonnet filament test and sub-epithelial cornea nerve density using corneal confocal microscopy were determined.
Diabetic rats had a significantly decreased motor and sensory nerve conduction velocity and were hypoalgesic. Corneal sensitivity as determined using Cochet-Bonnet filament esthesiometer was significantly decreased in diabetic rats compared to control rats. Total nerve fiber length of corneal nerves in the sub-epithelial layer was decreased by about 50% in diabetic rats. Applying the hyperosmotic solutions to the surface of the cornea caused an osmolarity-dependent increase in squinting of the treated eye but not the untreated eye in control rats that was significantly suppressed in diabetic rats. The correlation coefficient for corneal nerves and corneal sensitivity vs. degree of squinting was r = -.64 (p < 0.005) and r = -.63 (p < 0.01). Pretreatment with proparacaine ophthalmic solution totally prevented the behavioral response to the 900 mOsm solution in control rats implicating a neural involvement in the hyperosmotic effect.
These results suggest that evaluation of corneal sensitivity utilizing the neural receptors for osmolality may be an alternative method to monofilament, thermal or vibration threshold tests for the early detection of PN.
This is an abstract that was submitted for the 2016 ARVO Annual Meeting, held in Seattle, Wash., May 1-5, 2016.
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