Aflibercept action in a rabbit model of chronic retinal neovascularization: Reversible inhibition of pathologic leakage with dose-dependent duration

PURPOSE. We establish and characterize the chronic retinal neovascularization (RNV) induced by intravitreal (IVT) injection of DL-α-aminoadipic acid (AAA) in a rabbit model and investigate the extent and duration of inhibitory actions induced by IVT aflibercept on the RNV. METHODS. Rabbits received a single IVT injection of AAA, with weekly follow-up fundus photography, fluorescein angiography (FA), and optical coherence tomography (OCT). After 10 weeks, they received a single IVT aflibercept or control injection. RNV leakage was quantified from FA by image analysis with Photoshop. Some eyes were collected for histologic analysis. RESULTS. IVT AAA produced neuronal degeneration over a large fraction of the retina. RNV formed in the damaged area and by 10 weeks exhibited stable morphology and leakage, which persisted for at least 65 weeks. Control IVT injections did not affect RNV leakage, but IVT aflibercept completely blocked RNV leakage. The inhibition was reversible (i.e., the leakage returned as the drug cleared), and the duration of antileak effects with 500 µg aflibercept was approximately 8 weeks. Partial regression of the pathologic vasculature also occurred with aflibercept, with reestablishment as the drug cleared. CONCLUSIONS. This model mimics a chronic human disease in its stability and persistence, and the antileak action of aflibercept is fully reversible with a dose-dependent duration. Therefore, this large eye model is uniquely suitable for investigations into the efficacy and duration of action of novel formulations and pharmacotherapies for retinal vascular diseases, and for studying the underlying pathobiology of retinal angiogenesis.