Suppression of neovascularization by topical and subconjunctival bevacizumab following high-risk corneal transplantation

PURPOSE To assess the effectiveness of topical and subconjunctival bevacizumab in suppressing vascularization in graft and host bed following high-risk corneal transplantation. DESIGN Secondary analysis of prospective, randomized, double-blind, placebo-controlled multi-centric clinical trial. PARTICIPANTS The study includes patients over 18 years old who underwent high-risk penetrating keratoplasty, which was defined as corneal vascularization in 1 or more quadrants of the corneal graft and host bed excluding the limbus. Methods Patients were randomized to treatment and control groups. The patients in the treatment group received subconjunctival injection of bevacizumab (2.5 mg/0.1 ml) on the day of the procedure followed by topical bevacizumab (10 mg/ml) 4 times per day for 4 weeks. The patients in control group received injection of vehicle (0.9% sodium chloride) on the day of procedure followed by topical vehicle (carboxymethylcellulose sodium 1%) 4 times a day for 4 weeks. Main outcome measure Vessel and invasion area of vessels in the corneal graft and host beds. Results This study included 56 eyes of 56 patients who underwent high-risk corneal transplantation, with equal numbers in the bevacizumab and vehicle (control) treatment group. The mean age of patients who received bevacizumab was 61.2 ± 15.9 years and those treated with vehicle was 60.0 ± 16.1 years. The vessel area at baseline was comparable in the bevacizumab (16.72 ± 3.19%) and control groups (15.48 ± 3.12%, p=0.72). Similarly, the invasion areas were also similar in the treatment (35.60± 2.47%) and control (34.23 ± 2.64%, p=0.9) groups at baseline. The reduction in vessel area was significantly higher in the bevacizumab treated group (83.7%) over a period of 52 weeks compared to the control group (61.5%, p<0.0001). In the bevacizumab treated group, invasion area was reduced by 75.8% as compared to 46.5% in the control group. The vessel area was similar at 52 weeks post-procedure in cases of first (3.54 ± 1.21%) and repeat (3.80 ± 0.40%) corneal transplantation in patients who received bevacizumab treatment. In the vehicle treated patients, vessel area was significantly higher in repeat (9.76 ± 0.32%) compared to first (8.06 ± 1.02%, p<0.0001) penetrating keratoplasty. In the bevacizumab treatment group invasion areas at week 52 were comparable in first (11.70 ± 3.38%) and repeat (11.64 ± 1.74%) procedures, whereas invasion area was significantly higher in repeat (27.87 ± 2.57%) as compared to first (24.11 ± 2.17%) penetrating keratoplasty in vehicle treated patients. Conclusions In patients undergoing vascularized high-risk corneal transplantation, bevacizumab is efficacious in reducing vascularization of corneal graft and host bed, thereby reducing the risk of corneal graft rejection in vascularized host beds.