Abstract
Purpose :
Translational ophthalmic research and novel drug discovery are dependent on valid animal models and accurate, objective means to assess disease status. Rabbit models, commonly used in studies of drug development, have also been useful for advancing the understanding of Dry Eye Disease (DED). Advanced keratographic units (AKU) have shown prior validity and reproducibility in human patients, but reproducibility has not been validated in animal models. Here we validate the reliability of an AKU (Oculus Keratograph 5M, Wetzlar, Germany) commonly used in clinical practice to measure DED parameters in rabbits.
Methods :
12 New Zealand White (NZW) were measured using an AKU. Minor modifications to the device (tilt of 20 degrees; headrest for animals) were required to allow for successful measurements in rabbits. Standard AKU measures of DED including first and average non-invasive keratographic break-up time (NIKBUT); nasal, temporal, and central tear meniscus height (TMH); and limbal and bulbar conjunctival redness grading (RG) were taken. Also, measurements of palpebral fissure height (PFH), temporal angle size (TAS), and corneal irregularity (CI) were made. All measurements were taken 3 separate times at baseline. The coefficient of variation was calculated for each measurement using Excel and compared to prior data for changes in these variables seen with DED induction.
Results :
The CV was under 15% for most measures, including TMH nasal (10.2), TMH central (9.0), TMH temporal (8.9), PFH (3.9), TAS (3.8), NIKBUT length (1.8), NIKBUT average (12.9), and RG bulbar (10.2). NIKBUT first (38.9), RG limbal (22.9), and CI (19.7) had higher CV values at baseline (Table 1). With the exception of NIKBUT length, the CV for all variables was much less than previously reported change in these values observed with the induction of acute DED.
Conclusions :
The AKU used in this study, and commonly used in clinical practice, can be successfully modified to objectively measure DED in rabbits. Measurements of DED taken with this device can be done with good reproducibility with most measures having CV less than 15%. With the exception of NIKBUT length, the CV for all measures studied was much less then previously reported changes in these variables after induction of DED. These methods can enhance translational research and aid in the development of ophthalmic therapeutics for DED.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.