Suppression of Neovascularization by Topical and Subconjunctival Bevacizumab After High-Risk Corneal Transplantation

Purpose: To assess the effectiveness of topical and subconjunctival bevacizumab in suppressing vascularization in graft and host bed after high -risk corneal transplantation. Design: Secondary analysis of prospective, randomized, double-blind, placebo -controlled multicentric clinical trial. Participants: The study includes patients aged > 18 years who underwent high -risk penetrating keratoplasty, which was defined as corneal vascularization in > 1 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 Measures: 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 groups. The mean age of patients who received bevacizumab was 61.2 +/- 15.9 years, and the mean age of 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 with the control group (61.5%; P < 0.0001). In the bevacizumabtreated group, invasion area was reduced by 75.8% as compared with 46.5% in the control group. The vessel area was similar at 52 weeks postprocedure 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, the vessel area was significantly higher in repeat (9.76% +/- 0.32%) compared with 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 with 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. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article. Ophthalmology Science 2024;4:100492 (c) 2024 by the American Academy of Ophthalmology. This is an open access article under the CC BY -NC -ND license (http://creativecommons.org/ licenses/by-nc-nd/4.0/).