Abstract
Purpose:
Therapeutics intended for topical administration have the potential to affect corneal thickness by various mechanisms. In non-clinical topical ocular studies, serial in-vivo measurement of CCT can provide a rapid empirical insight into the health of the cornea during study conduct and whether or not any changes in CCT are reversible. The purpose of this study was to evaluate and compare 3 different in-vivo methods of measuring CCT in 2 species commonly used for non-clinical ocular safety evaluations and to provide background data for these methods.
Methods:
Ten dogs (males, initial age 5-7 months) and 12 rabbits (males, age 6-8 months) were evaluated. Animals were sedated in order to reduce eye movements. For handheld ultrasound pachymetry (UP) and specular microscopy (SM), 3 separate measurements were made for each cornea/occasion and averaged for a reported value. CCT was measured and averaged from 2 OCT images/cornea/occasion. Precision was determined for UP and SM using dogs with 2 measurements separated by 6 months and for OCT using rabbits with 4 measurements each separated by 1 week. Measurements were obtained at approximately the same time of day to reduce diurnal variation.
Results:
CCT measurements by UP/SM/OCT in dogs were: 548.5 ± 33 µm/583.5 ± 27 µm/564 ± 49, respectively; rabbits 378 ± 27 µm/394 ± 16 µm/355 ± 23 µm, respectively. Direct comparison showed a difference of 6% between the UP and SM, 3% between UP and OCT and 3% between SM and OCT for dogs; 4% between the UP and SM, 6% between UP and OCT and 10% between SM and OCT for rabbits. Precision as determined by 2 separate measurement occasions in dogs was 0.6% for SM and 0.1% for UP. For OCT precision as determined by 4 separate measurement occasions in rabbits was 4%.
Conclusions:
All 3 methods provided reproducible, precise CCT data in dogs and rabbits allowing for repeat measures during the course of a study when corneal changes are of concern. Reduced precision of the OCT was likely due to a combination of manual measurement and an increased sensitivity to slightly oblique sections. Care should be taken for interpretation if data are acquired using multiple methods considering the inherent differences in baseline CCT obtained by each method.