Effect of Subconjunctival and Intraocular Bevacizumab Injections on Corneal Neovascularization in a Mouse Model

PURPOSE: This study sought to evaluate the efficacy of bevacizumab (Avastin), an anti-VEGF agent, in the reduction of corneal neovascularization in a rodent model, and compare between the effect of intraocular and subconjunctival injection. METHODS: Corneal neovascularization was induced by application of a mixture of 75% silver nitrate and 25% potassium nitrate to the corneal center of the right eye of 125 mice. Immediately thereafter, 75 eyes were treated with subconjunctival, anterior chamber, or intravitreal injection of bevacizumab. The remaining mice served as a control. The groups were compared at different postoperative time points for percentage area of neovascularization evaluated by digital photos, the presence of corneal stromal vascular endothelial cells studied by immunohistochemical staining, and VEGF levels measured by real-time PCR. RESULTS: In the untreated eyes, percentage area of neovascularization increased from 11.3 +/- 7% on day 2 to 20 +/- 8.9% on day 4, 47 +/- 25.4% on day 8, and 51 +/- 24.7% on day 10. The percentage area of neovascularization following subconjunctival injection was 7 +/- 2.9% on day 2, 15.7 +/- 6% on day 4, 32.2 +/- 15.2% on day 8, and 39.7 +/- 14.5% on day 10. The percentage area of neovascularization following anterior chamber injection was 14.4 +/- 3% on day 2, 16.5 +/- 6.3% on day 4, 26.3 +/- 6.5% on day 8, and 19.8 +/- 1.2% on day 10. The percentage area of neovascularization following intravitreal injection was 11 +/- 2.5% on day 2, 14.7 +/- 5% on day 4, 23.5 +/- 6.5% on day 8, and 24.2 +/- 14.9% on day 10. CONCLUSIONS: Bevacizumab injections partially inhibit the growth of corneal neovascularization induced by acute chemical injury in a mouse model. The intraocular routes of injection were found to be the most effective, and the subconjunctival route of injection yielded the earliest peak response.