Eyeworld

JULY 2021 | EYEWORLD | 113 C References 1. Kim SW, et al. The effect of topical bevacizumab on corneal neovascularization. Ophthalmol- ogy. 2008;115:e33–38. 2. Bahar I, et al. Subconjunctival bevacizumab injection for corne- al neovascularization. Cornea. 2008;27:142–147. 3. Yeung S, et al. Combined use of subconjunctival and intra- corneal bevacizumab injection for corneal neovascularization. Cornea. 2011;30:1110–1114. 4. Yin J, Jacobs DS. Long-term outcome of using Prosthetic Replacement of Ocular Surface Ecosystem (PROSE) as a drug delivery system for bevacizum- ab in the treatment of corneal neovascularization. Ocul Surf. 2019;17:134–141. While there have been some small studies and case reports previously on this topic, Dr. Dohlman said there have been no prospective, randomized, placebo-controlled studies in the literature evaluating bevacizumab in corneal transplantation. "The study we are working on is a prospective, randomized, double-masked, placebo-controlled study that, to our knowl- edge, is the largest clinical study on this topic to date," he said. In the study, Dr. Dohlman and his col- leagues compared bevacizumab to placebo in high-risk corneal transplantation, with the bevacizumab group receiving a subconjunctival injection of 2.5 mg/0.1 ml (2.5%) at the time of surgery and topical 1% bevacizumab four times per day for 4 weeks. The control group received a subconjunctival injection of 0.9% saline at the time of surgery and carboxymethylcellulose four times per day for 4 weeks. Patients were followed for 52 weeks for any adverse effects and to track efficacy, which included rate of en- dothelial immune rejection and rate of overall graft failure. There were 43 patients in each group. Dr. Dohlman noted that bevacizumab has been used for corneal neovascularization at dif- ferent concentrations both topically and subcon- junctivally. "Subconjunctival injection allows for higher and more lasting drug availability, while the advantage of topical application is that it is easy to administer, although the penetration of bevacizumab into the corneal stroma is lower Dr. Slomovic mentioned an additional study in Cornea from 2011 3 that introduced an intra- stromal approach as well as subconjunctival injection. "We found that was very effective," he said, noting that there were no complications in either study. The second study included 12 patients with the same total dosage. "With our first study, we didn't think there was enough of the bevacizumab by giving subconjunctival at the limbus to reach the distal part of the vessel," Dr. Slomovic said. "So we combined that with an intrastromal injection, and we got a bit more regression." He added that he thinks using an injection approach may be better than topical because of the longer duration of contact. Dr. Slomovic said that using bevacizumab for these patients may be most efficacious when the neovascularization is localized to a small number of clock hours, like in those with herpes zoster, herpes simplex, or infectious keratitis. He said it's not as helpful in diffuse vascularization, like limbal stem cell disease or a vascularized corneal transplant. Subconjunctival and topical bevacizumab in corneal transplantation Thomas Dohlman, MD, highlighted his work using bevacizumab for corneal transplantation. Dr. Dohlman is working as part of a team at Massachusetts Eye and Ear along with Reza Dana, MD, and others to analyze the data of a multicenter trial evaluating the safety and effi- cacy of bevacizumab in high-risk corneal trans- plantation. The preliminary data was presented late last year. "Corneal transplantation is the most com- monly performed form of solid organ transplan- tation, and we know that one of the greatest predictors of corneal transplant rejection and failure is host bed neovascularization," Dr. Dohlman said. "These vascularized, 'high-risk' grafts have uniformly worse outcomes when compared to 'low-risk' transplants performed in avascular host beds." Dr. Dohlman noted that he has investigated the role of VEGF inhibition in animal models of corneal transplantation, which fueled his interest in the current research. continued on page 114 Patient with corneal neovascularization Source: Thomas Dohlman, MD

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