Validation of an Advanced Keratography Unit to Measure Dry Eye Disease in an Animal Model - Implications for Clinical Use

Abstract

Purpose : Dry Eye Disease (DED) is a common condition whose pathophysiology and treatment are still actively being researched. Absence of a universally accepted animal model for DED research poses a barrier to further development of our understanding. All animal models have limitations in how they translate to the human condition in both disease physiology and assessment. Here we show the ability of an advanced keratography unit (AKU) already used in clinical practice to effectively measure DED status in rabbits.

Methods : Numerous measures of DED using an advanced keratography unit (AKU) were made before and after DED was induced in 15 New Zealand White (NZW) and 4 Dutch Belted (DB) rabbits with concanavalin A. Standard DED measures included first and average non-invasive keratographic break-up time (NIKBUT), tear meniscus height (TMH), meibomography, and Tearfilm dynamic (TFD). Other measures included palpebral fissure height (PFH), temporal angle size (TAS), and corneal irregularity (CI). A normative dataset for parameters in each species was created.

Results : First and average NIKBUT, PFH, and TAS (9.14±5.48, 17.14±2.94, 10.7±1.0, 122 ± 10 respectively) significantly decreased following DED induction (4.54±2.63, 12.93±3.33, 7.1±3.0, 81±32 respectively; all p<0.001). TMH (0.21±0.03) and CI (0.021± 0.008 ) both increased (0.27±0.09, 0.040±0.017 respectively; both p<0.003) after DED induction. The data were similar if looking at DB and NZW groups separately. Meibomography and TFD were not useful discriminating DED.

Conclusions : We present normative data values for a panel of DED and other metrics collected with an AKU. Statistically significant changes in the expected direction were observed for NIKBUT, PFH, TAS and CI following induction of DED. The significant change in TMH was in the wrong direction suggesting other compensatory responses are occurring. The results indicate this AKU (Oculus Keratograph 5M) can measure DED status in this rabbit model. AKU technology has potential to improve diagnostic capability in DED research using rabbit models. This non-invasive, objective quantification of DED can improve translational research allowing for improved fidelity between methods of DED assessment in rabbit and human DED. Such benefits may be especially useful in studies new pharmacologic treatments for DED.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.