Safety of Bevacizumab on Extraocular Muscle in a Rabbit Model

Abstract

PurposeThe purpose of this study was to investigate the myotoxicity of bevacizumab on extraocular muscles in a rabbit model.MethodsThirty New Zealand white rabbits were used for this study. The animals were evenly divided into two groups. In the first group, 15 rabbits were treated with intramuscular injections of bevacizumab (1.25 mg/0.05 mL) in the right superior rectus muscle and normal saline solution (0.05 mL) in the left superior rectus muscle. In the second group, 15 rabbits were treated with subconjunctival injections of bevacizumab (2.5 mg/0.1 mL) in the right superior subconjunctival area and normal saline solution (0.1 mL) in the left superior subconjunctival area. Five rabbits in each group were sacrificed at one day, two weeks and four weeks after the injections. Extraocular muscle samples were prepared for light microscopic (LM) and electron microscopic (EM) examination. Degrees of acute inflammation were evaluated via CD-11b immunohistochemistry, and global muscle change was investigated using hematoxylin and eosin stains. Intensity of fibrosis was evaluated using Masson trichrome stains, and ultrastructural changes were observed on EM.ResultsWe observed no significant inflammatory cell infiltration, muscle necrosis or fibrotic change in treated and control eyes. EM findings revealed no significant damage to muscle or vascular tissue after bevacizumab injection.ConclusionsWe found no signs of extraocular muscle toxicity after LM and EM intramuscular and subconjunctival bevacizumab injections in a rabbit model.

Safety and tolerability evaluation after repeated intravitreal injections of a humanized anti-VEGF-A monoclonal antibody (PRO-169) versus ranibizumab in New Zealand white rabbits

“…Bevacizumab's effectiveness and safety profile has been confirmed through many preclinical studies, including in vivo studies in numerous species. Many of these have shown that the repeated intravitreal injections of bevacizumab or ranibizumab have no long-term deleterious effects on the electrophysiological and morphologic integrity of the retina [1,[11][12][13][14][15][16][17]. Another preclinical in vivo study reported that after Choroidal Neovascularization (CNV) induction through retinal photocoagulation, PRO-169 administration (1.25 mg per eye) can inhibit the retinal thickness and fluorescein leakage area without toxic effect or adverse events in a rhesus monkey model [4].…”