Effects of Topical and Subconjunctival Bevacizumab in High-Risk Corneal Graft Survival

Abstract

Purpose: : To investigate whether corneal graft survival could be improved by topical or subconjunctival bevacizumab (Avastin) in a murine model of vascularized high-risk corneal transplantation.

Methods: : Prior to corneal transplantation, intrastromal sutures were placed for 2 weeks in the corneas of BALB/c mice, causing an intense degree of angiogenesis. Allogeneic corneal transplantation was performed using C57BL/6 donor mice. Topical bevacizumab (2.5%) was delivered 3 times a day for 3 weeks in one treatment group, while 0.02 ml (0.5mg) of bevacizumab was injected subconjunctivaly at days 0, 4, 8, and 15 post-transplantation in the other treatment group. Control groups received either topical or subconjunctival phosphate buffered saline. Grafts were examined twice a week for 8 weeks by slit-lamp microscopy and photographed once a week by slit-lamp digital camera, and scored for opacity as well as neovascularization.

Results: : All corneal transplants in the control groups were rejected by 3 weeks after transplantation. All corneal grafts in the topical treatment group were also rejected, although not until 4 weeks post-transplantation. Interestingly, in the subconjunctival treatment group, 33% of corneal grafts survived out to 8 weeks post-transplantation (P = 0.008).

Conclusions: : Subconjunctival bevacizumab could potentially offer an alternative or adjunctive measure to conventional therapies in preventing graft rejection in vascularized high-risk corneal transplantation.

Keywords: neovascularization • transplantation • vascular endothelial growth factor