Bevacizumab in High-Risk Corneal Transplantation: a Pilot Multi-Center Prospective Randomized Control Trial.

Overview

abstract

PURPOSE: To determine the efficacy of local (subconjunctival and topical) bevacizumab (Avastin®) treatment in patients undergoing vascularized high-risk corneal transplantation. DESIGN: Pilot prospective, randomized, double-blind, placebo-controlled clinical trial conducted at five clinical centers in the United States, India and Brazil. PARTICIPANTS: Patients over the age of 18 undergoing high-risk penetrating keratoplasty, defined as corneal neovascularization (NV) in one or more quadrants ≥ 2mm from the limbus or extension of corneal NV to the graft-host junction in a previously failed graft. INTERVENTION: Patients were randomized to receive either subconjunctival bevacizumab (2.5mg/0.1ml) or placebo at the time of surgery, followed by topical bevacizumab (10mg/ml) or topical placebo, administered four times per day for four weeks. MAIN OUTCOME MEASURE: 52-week endothelial immune rejection rate. RESULTS: Ninety-two patients were randomized to receive bevacizumab (n=48) or control (n=44). The 52-week endothelial rejection rate was 10% in the bevacizumab group and 19% in the control group (p=0.20). Post-hoc, extended follow-up at the lead study site showed an endothelial rejection rate of 3% in the bevacizumab group and 38% in the control group (p=0.003). Treatment with bevacizumab was found to have a hazard ratio of 0.15 (95% CI: [0.03-0.65], p=0.01) in a post-hoc Cox regression analysis. CONCLUSIONS: In patients undergoing vascularized high-risk corneal transplantation, there was no statistically significant difference in the rate of endothelial rejection at one year in in the bevacizumab treatment group as compared to the control group. This study may have been under-powered to detect a difference between treatment groups, and taken together, our data suggest that, in the current trial design, bevacizumab has a positive but not (yet) significant effect on endothelial rejection.