TY - JOUR
T1 - Bevacizumab in High-Risk Corneal Transplantation
T2 - A Pilot Multicenter Prospective Randomized Control Trial
AU - Dohlman, Thomas H.
AU - McSoley, Matthew
AU - Amparo, Francisco
AU - Carreno-Galeano, Tatiana
AU - Wang, Mengyu
AU - Dastjerdi, Mohammad
AU - Singh, Rohan Bir
AU - Coco, Giulia
AU - Di Zazzo, Antonio
AU - Shikari, Hasanain
AU - Saboo, Ujwala
AU - Sippel, Kimberly
AU - Ciralsky, Jessica
AU - Yoo, Sonia H.
AU - Sticca, Matheus
AU - Wakamatsu, Tais H.
AU - Murthy, Somasheila
AU - Hamrah, Pedram
AU - Jurkunas, Ula
AU - Ciolino, Joseph B.
AU - Gomes, Jose A.P.
AU - Perez, Victor L.
AU - Yin, Jia
AU - Dana, Reza
N1 - Publisher Copyright: © 2022 American Academy of Ophthalmology
PY - 2022/8
Y1 - 2022/8
N2 - 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.
AB - 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.
KW - Angiogenesis
KW - Corneal transplantation
KW - Neovascularization
KW - Penetrating keratoplasty
KW - Vascular endothelial growth factor
UR - https://www.scopus.com/pages/publications/85130474733
UR - https://www.scopus.com/pages/publications/85130474733#tab=citedBy
U2 - 10.1016/j.ophtha.2022.03.024
DO - 10.1016/j.ophtha.2022.03.024
M3 - Article
C2 - 35358592
SN - 0161-6420
VL - 129
SP - 865
EP - 879
JO - Ophthalmology
JF - Ophthalmology
IS - 8
ER -