A local anti-vascular endothelial growth factor (VEGF) regimen had a positive, but not clinically significant, effect on patients who have undergone vascularized high-risk corneal transplantation, according to research published in Ophthalmology. The researchers report no statistically significant differences in the 52-week rate of endothelial rejection of patients with corneal transplants who were administered either local bevacizumab or a placebo.  However, researchers say that patients who received the bevacizumab did demonstrate some benefits upon analysis.

The researchers conducted a pilot prospective, multi-center, randomized, double-blind, placebo-controlled clinical trial to determine the efficacy of local (subconjunctival and topical) bevacizumab treatment in adult patients undergoing vascularized high-risk corneal transplantation.

High-risk penetrating keratoplasty was defined as corneal neovascularization (NV) in 1 or more quadrants that were at least 2 mm from the limbus, or in patients with a previously failed graft, extension of the corneal NV to the graft-host junction.

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Patients were administered either subconjunctival bevacizumab (2.5mg/0.1ml) or placebo during surgery and received topical bevacizumab (10mg/ml) or topical placebo, respectively, administered 4 times/day for 4 weeks. The primary endpoint was 52-week endothelial immune rejection rate.

A total of 92 patients, with a mean age of 62±16 years, were randomized to receive bevacizumab (n=48) or placebo (n=44). The 52-week endothelial rejection rate was 10% in the bevacizumab group and 19% in the placebo group (P =.20). 

The researchers also conducted a post-hoc extended follow up in patients (n=59; 69%) at the lead study site. At a median follow-up duration of 207 and 176 weeks in the bevacizumab and placebo groups, the endothelial rejection rate was 3% and 38%, respectively (P =.003). A Cox regression analysis revealed that treatment with bevacizumab had a hazard ratio of 0.15 (95% confidence interval, 0.03-0.65; P =.01).

“In [this pilot study], local treatment with bevacizumab did not lead to a statistically significant improvement in the 52-week rate of endothelial rejection in high-risk corneal transplants, but the study may have been underpowered. [P]ost-hoc analyses suggest a positive effect of bevacizumab on graft survival,” according to the study authors.


Dohlman TH, McSoley M, Amparo F, et al. Bevacizumab in high-risk corneal transplantation: a pilot multi-center prospective randomized control trial. Ophthalmology. Published online March 28, 2022. doi:10.1016/j.ophtha.2022.03.024