Monitoring the Evolution of Dry Eye Disease in Rabbits with Advanced Ocular Keratography: Implications for Translational Studies

Purpose: Experimental studies of Dry Eye Disease (DED) using animal models are hampered by the lack of reliable, easy-to-use assays that can adequately diagnose disease or monitor effects of novel treatments. The Oculus Keratograph 5 M, an advanced keratography unit (AKU), has shown promise, enjoying recent clinical use. We assessed whether this AKU could be used in DED studies in the rabbit, perhaps the ideal experimental animal for this disease. Methods: All measures were made in strictly controlled temperature and humidity spaces. A panel of AKU parameters was measured in 15 New Zealand White rabbits at baseline, after Concanavalin A induced DED, and following recovery. Eyelid aperture and corneal irregularity were also measured. A subset of these parameters was measured in patients and compared with those from rabbits. Results: AKU parameters in both humans and rabbits showed similar patterns and coefficients of variation (CV). Measurements of tear and eyelid architecture were more reproducible than tear film function in both species. The CV for most parameters were less than the observed changes in the respective parameters after DED induction. In rabbits, all parameters improved returning close to baseline following DED recovery. In the rabbit, additional measures (eyelid aperture and corneal irregularity) not traditionally associated with DED, also demonstrated changes that evolved over the development and recovery of DED. Conclusions: AKU technology can effectively detect changes in multiple parameters during the evolution and resolution of DED in rabbits. DED parameters showed similar patterns for most variables in both humans and rabbits demonstrating great potential of this device in translational research. The AKU can also follow additional parameters evaluating the responses of the lacrimal functional unit. Our findings document the applicability of this technology for translational studies of DED and underscores its potential to further refine understanding of the disease pathophysiology.