Local Bevacizumab Treatment May Safeguard High-Risk Corneal Transplants

Rejecting corneal graft in man's eye
Rejecting corneal graft. Close-up of a man’s eye showing tissue rejection of a corneal graft. The grafted tissue appears cloudy. Note the zigzag of stitches holding it in place. The cornea is a thin transparent membrane over the front of the eye. It acts like a lens, focusing light, and protects the structures below. Corneal grafts are carried out when the cornea is damaged or diseased but the rest of the eye is healthy. The donor tissue most often comes from another person, but the rejection rate is low because the cornea lacks blood vessels (and hence lacks white blood cells). This graft is eight months old and has begun to reject despite the use of oral and local steroid drugs.
An investigation into subconjunctival and topical bevacizumab treatments for positive, but not significant, effect on endothelial rejection.

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.

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