Safety of intravitreal quinupristin / dalfopristin in an animal model

Abstract

Purpose: To evaluate the retinal toxicity of varying doses of quinupristin-dalfopristin when injected intravitreally in rabbits.

Methods: Design: Randomized controlled trial. Twenty-two rabbits were used for this study and divided into four groups. Four concentrations of quinupristin-dalfopristin were prepared: group 1: 0.01mg/0.1ml; group 2: 0.1mg/0.1ml, group 3: 1mg/0.1ml and group 4: 10mg/0.1ml. Each concentration was injected intravitreally in one eye of each of six rabbits of each group; 0.1 mL volume of sterile balanced saline solution was injected into the contralateral eyes. Basal and weekly ERG (measuring mesopic implicit times and amplitudes), fundus photographs and macular OCT were performed and the animals were observed for 4 weeks for signs of inflammation or toxicity. At the end of follow-up the animals were killed. The enucleated eyes were prepared for histologic evaluation of retinal toxicity.

Results: There was a statistically significant difference between all groups (Friedman test, p < 0.01). In groups 1 and 2 there were no statistically significant differences between basal and follow-up measures of each group and between them (Wilcoxon rank-sum test, p =1.0). In contrast, comparisons of amplitude and implicit times of groups 3 and 4 showed high statistically significant differences between basal and follow-up measures, as well as between follow-up measures of injected and control eyes (p < 0.01). Groups 1 and 2 showed no ERG changes compared to groups 3 and 4 (Wilcoxon rank-sum test, p < 0.01). Only groups 3 and 4 revealed severe vitreous inflammation and hemorrhage. There were no significant histopathological changes in groups 1 and 2.

Conclusions: Intravitreal quinupristin/dalfopristin doses of 0.01mg/0.1ml and 0.1mg/0.1ml showed no signs of retinal toxicity.

Keywords: 688 retina • 503 drug toxicity/drug effects