Abstract
Purpose :
MKIs have been shown to inhibit vascular leakage clinically in the treatment of wet AMD, DME and RVO. The approved anti-VEGFs are effective; however, their short duration creates burden on the practice and patient. Our goal is to develop a long-acting intravitreal biodegradable implant effective in managing the disease for ~12+ months. We investigated the tolerability and efficacy of, an MKI biodegradable ocular implant, to inhibit retinal vascular leakage in the DL-AAA Dutch-Belted rabbit model.
Methods :
Multiple biodegradable implant formulations were developed and tested in-vitro for drug release kinetics. Then formulations were selected based on in-vitro release kinetics to be tested in the rabbit model of a vascular leakage. DL-AAA rabbits were induced 8 weeks prior to study start. Seven DL-AAA female rabbits received 1 implant OD and 1 placebo implant OS, and 3 received 2 implants OU. Eyes were monitored using fluorescein angiography (FA), aide Angle (55°) IR imaging, and slit lamp ophthalmic exams including McDonald-Shadduck scoring at Days 1, 8 and monthly thereafter. To assess tolerability, 3 naïve female Dutch Belted rabbits received 1 implant OD and sham injection OS, and 3 rabbits received 2 implants OD and 2 placebo implants OS. Plasma was collected to monitor systemic drug exposure.
Results :
Administration of 1 and 2 MKI biodegradable implants showed significant inhibition of retinal vascular leakage compared to placebo on FAs beginning at Day 8 and continuing for 22 months. Both 1 and 2 implants provided maximal inhibition of vascular leakage. Observations consistent with intravitreal injections were observed and resolved by Day 29. Systemic exposure was minimal, with values near or below the lower limit of quantitation.
Conclusions :
An MKI biodegradable ocular implant, was well tolerated in naïve DB rabbit eyes and significantly inhibited retinal vascular leakage in the DL-AAA rabbit model for 22 months. If confirmed clinically, this novel MKI biodegradable implant could offer a long duration therapeutic alternative in the treatment of wet AMD, DME, and RVO.
This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.