The Different Effects of Early and Late Bevacizumab (Avastin) Injection on Inhibiting Corneal Neovascularization and Conjunctivalization in Rabbit Limbal Insufficiency

PURPOSE. To compare the effects of early, mid, and late subconjunctival injection of bevacizumab on corneal neovascularization (NV) and conjunctivalization in a rabbit limbal insufficiency model. METHODS. Limbal insufficiency was created surgically, and subconjunctival injections of 2.5 mg bevacizumab twice weekly for 1 month were started immediately (early group), 1 week (mid group), and 1 month after injury (late group). The corneal epithelial alterations, stromal opacity, centricity, extent, and PICS (percentage of involved corneal surface) of the corneal NV were evaluated. The expression of cytokeratins K3, K4, K12, K13, and MUC5 by the corneal surface cells was examined by immunohistochemistry. RESULTS. Bevacizumab significantly inhibited corneal NV in the early and mid, but not the late, treatment groups at 4 weeks after treatment (PICS: P < 0.01 in the early group, P < 0.01 in the mid group, and P > 0.05 in the late group). Early and mid treatment produced significant inhibition of corneal alteration (P < 0.01 in the early group and P = 0.03 in the mid group) and stromal opacity (P < 0.01 in the early group and P = 0.02 in the mid group) at 4 months after treatment but not in the late group. The immunohistochemistry of cytokeratin on the corneal surface cells at 1 month after treatment was K3(+), K4(-), K12(+), K13(-), and MUC5(-) in the early group; K3(+), K4(+), K12(+), K13(+), and MUC5(-) in the mid group; and K3(+), K4(+), K12(-), K13(+), and MUC5(+) in the late treatment group. CONCLUSIONS. Early and mid bevacizumab injection inhibited corneal NV, epithelial alteration, and stromal opacity in limbal insufficiency, but late treatment did not. Early treatment with bevacizumab seems to be clinically beneficial in the management of limbal injury such as chemical burn. (Invest Ophthalmol Vis Sci. 2010;51:6277-6285) DOI:10.1167/iovs.09-4571