Testing intravitireal toxicity of bevacizumab (Avastin)

Purpose: To evaluate the retinal toxicity of varying doses of bevacizumab when injected intravitreally in rabbits. Bevacizumab has been approved by the US Food and Drug Administration for the treatment of metastatic colorectal cancer. Materials and Methods: Twelve New Zealand albino rabbits were used for this study and divided into four groups. Four concentrations of bevacizumab were prepared: 500 mu g/0.1 mL, 1.0 mg/0.1 mL, 2.5 mg/0.1 mL, and 5.0 mg/0.2 mL. Each concentration was injected intravitreally in one eye of each of three rabbits; 0.1 mL volume of sterile balanced saline solution was injected into the contralateral eyes. Slit-lamp and funduscopic examinations were performed and the animals were observed for 2 weeks for signs of infection, inflammation, or toxicity. A baseline electroretinogram (ERG) was performed before the drug treatment and at day 14 before the animals were killed. The enucleated eyes were prepared for histologic evaluation of retinal toxicity. Results: Histologic and ERG results in all groups showed no retinal toxicity. However, some inflammatory cells were found in the vitreous at the 5-mg dose. Conclusions: Intravitreal bevacizumab did not appear toxic to the retina in albino rabbits at a concentration of 2.5 mg. Intravitreally injected bevacizumab should be evaluated for efficacy in choroidal neovascularization and macular edema.