Bevacizumab in High-Risk Corneal Transplantation: A Pilot Multicenter Prospective Randomized Control Trial

Thomas H. Dohlman, Matthew McSoley, Francisco Amparo, Tatiana Carreno-Galeano, Mengyu Wang, Mohammad Dastjerdi, Rohan Bir Singh, Giulia Coco, Antonio Di Zazzo, Hasanain Shikari, Ujwala Saboo, Kimberly Sippel, Jessica Ciralsky, Sonia H. Yoo, Matheus Sticca, Tais H. Wakamatsu, Somasheila Murthy, Pedram Hamrah, Ula Jurkunas, Joseph B. CiolinoJose A.P. Gomes, Victor L. Perez, Jia Yin, Reza Dana

Research output: Contribution to journalArticlepeer-review

5 Scopus citations


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 5 clinical centers in the United States, India, and Brazil. Participants: Patients aged > 18 years undergoing high-risk penetrating keratoplasty, defined as corneal neovascularization (NV) in 1 or more quadrants ≥2 mm from the limbus or extension of corneal NV to the graft-host junction in a previously failed graft. Methods: Patients were randomized to receive subconjunctival bevacizumab (2.5 mg/0.1 ml) or placebo at the time of surgery, followed by topical bevacizumab (10 mg/ml) or topical placebo, administered 4 times per day for 4 weeks. Main Outcome Measure: The 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% confidence interval, 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 1 year in the bevacizumab treatment group compared with the control group. This study may have been underpowered 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.

Original languageEnglish (US)
Pages (from-to)865-879
Number of pages15
Issue number8
StatePublished - Aug 2022
Externally publishedYes


  • Angiogenesis
  • Corneal transplantation
  • Neovascularization
  • Penetrating keratoplasty
  • Vascular endothelial growth factor

ASJC Scopus subject areas

  • Ophthalmology


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