Abstract
Purpose :
Age-related macular degeneration and diabetic retinopathy are leading causes of visual impairment. Current treatments involve intravitreal injections of anti-VEGF agents; however, many patients still experience vision loss, highlighting an unmet need for effective treatment. We evaluated the safety and bioactivity of an intravitreal implant of carboxyamidotriazole (CAI), an anti-angiogenic drug adapted for ocular angiogenesis complexed with Poly (lactic-co-glycolic acid), CAI-PLGA, in a rabbit model of increased permeability and angiogenesis. CAI-PLGA in vitro releases a bioeffective concentration of CAI with linear kinetics for 60 days.
Methods :
New Zealand white rabbits (n=18) were divided into three cohorts: Group 1 (n=3) received a sham intravitreal injection; Group 2 (n=6) received one 700ug injection of aflibercept; and Group 3 (n=9) received a CAI-PLGA intravitreal implant at t=0 days. Vascular permeability and neovascularization were induced with VEGF injections on days 23 and 53. On days 30 and 60, all groups underwent intraocular pressure measurements, vitreous fluorophotometry, and fundus imaging. Animals were sacrificed on day 60 and eyes were enucleated, fixed, sectioned, stained with H&E, and viewed by light microscopy. Retinal layers were measured, and images were assessed for disruptions in architecture and/or neovascularization.
Results :
Vitreous fluorophotometry revealed significantly lower levels of fluorescein in the aflibercept and CAI-PLGA groups compared to sham on days 30 and 60. At day 30, the reduction of peak vitreous fluorescence was similar between aflibercept and CAI-PLGA. At day 60, CAI-PLGA diminished peak fluorescence significantly more than aflibercept. No significant differences in intraocular pressure were observed. Histopathology showed no differences in retinal cell layer thicknesses. There was observable vacuole formation throughout retinal cell layers in the sham group. Increased neovascularization was observed in the sham group compared to the aflibercept and CAI groups. Qualitatively, less vascular engorgement was observed by fundus photography with CAI-PLGA than aflibercept at day 60.
Conclusions :
The CAI-PLGA intravitreal bioerodible implant produced an anti-permeability effect in vivo, with no safety signals, as predicted by in vitro release data, demonstrating potential as a sustained release anti-angiogenic therapy with long-term durability.
This abstract was presented at the 2024 ARVO Annual Meeting, held in Seattle, WA, May 5-9, 2024.