Abstract
Purpose :
Nonhuman primates are routinely utilized in ocular preclinical research because of their homology to human ocular anatomy. Intravitreal dosing is one the most investigated dose administration routes, and is performed on more than 150 nonhuman primates annually at Labcorp Drug Development, in Madison, WI. In 2018, our preparation method for intravitreal dosing was changed from swabbing the conjunctiva and eyelids with dilute betadine-soaked cotton-tipped applicators (full preparation), to soaking the globe and conjunctiva with dilute betadine for 2 minutes (limited preparation). Both methods are followed by rinsing with saline. It was hypothesized that a limited preparation may reduce adverse events after dosing compared to a full preparation as betadine has a known potential to cause hypersensitivity reactions.
Methods :
Control animal data from January 2014-June 2021 for all preclinical toxicology studies with intravitreal dosing was retrospectively analyzed. Data recorded included preparation method, control article composition, number of control animals, number of intravitreal injections, post-injection medications and additional procedures performed. Recorded adverse events included squinting, rubbing, face pressing and periorbital swelling.
Results :
Full preparation was used for 96 control animals that were dosed 394 times in total, and limited preparation was used for 107 control animals that were dosed 465 times in total. No differences were noted in control article composition, number of intravitreal injections per study or post-injection medications. However, the number of animals with adverse reactions (Figure 1) and total number of adverse reactions (Figure 2) were reduced using the limited preparation compared to full preparation. Most notably, after changing to a limited preparation method, there was a 68% reduction in the number of animals noted to squint post-dosing, and an 82% reduction in the number of squinting observations.
Conclusions :
The change in preparation from full to limited has decreased the number of adverse events. This reduction in adverse events both improves animal welfare and also allows for a more accurate interpretation of post-injection adverse events in test article-treated animals.
This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.