Suprachoroidal delivery of bevacizumab in rabbit in vivo eyes: Rapid distribution throughout the posterior segment

Purpose: To test the in-vivo bio-distribution and safety of bevacizumab delivery into the suprachoroidal space (SCS) using a novel injection system in a large eye model. Methods: Bevacizumab (1.25 mg) was injected into the vitreous (IVT, 50 mu L, n = 12) or the SCS, (150 mu L, n = 37) of live rabbits. Immunofluorescence and ELISA were used to assess bevacizumab distribution. Intraocular pressure (IOP) measurements, SD-OCT and fundus imaging, electroretinogram, and histology analysis were performed for safety assessment. Results: Bevacizumab was observed throughout the choroid layers up to the retinal pigment epithelium (RPE), within 1 h following SCS injection. The C-max of bevacizumab in the retina/choroid was 1043 +/- 597 mu g/gr tissue (mean +/- standard error), 40-fold higher than in IVT injected eyes (p = 0.0339). One day following SCS injection, bevacizumab was detected throughout the posterior pole with a two-fold lower concentration. One week post-SCS injection, bevacizumab concentration in the retina/choroid dropped to 2.36 +/- 1.32 mu g/gr tissue (p = 0.034 vs. 1 h), with a half-life of 20 h. No suprachoroidal blebs, retinal detachment, hemorrhages, inflammation or changes in retinal function were observed up to 2 months following SCS injection. Elevated IOP (+16 mmHg) was observed two minutes post-SCS injection and spontaneously returned to baseline levels within 10 minutes. Conclusions: The novel injection system enabled a minimally invasive, safe, and consistent delivery of bevacizumab with rapid distribution throughout the choroid layers up to the RPE in large eyes. Large volumes of anti-angiogenic are delivered in close proximity to the retina due to the high volume distribution.