Adding anti-VEGF to trabeculectomy may yield better wound healing conditions

The antivascular and antifibrotic properties of anti-VEGF agents may be beneficial to long-term safety and outcomes after trabeculectomy.

Malik Y. Kahook

The addition of an intravitreal anti-VEGF agent at the time of trabeculectomy may result in more favorable bleb characteristics compared with mitomycin C alone.

The results of a pilot study by Malik Y. Kahook, MD, indicated that patients treated with MMC and intravitreal Lucentis (ranibizumab, Genentech) at the time of trabeculectomy displayed more diffuse patterns of blebs that were less vascularized than blebs seen in patients treated with MMC alone.

The study included 10 patients, and more follow-up is needed before changing clinical practice, Dr. Kahook said. Since the initial publication of the results, Dr. Kahook has enrolled additional study patients and has initiated an arm of the study consisting of trabeculectomy with ranibizumab alone.

“Combination ranibizumab plus mitomycin resulted in a decrease in the vascularity of blebs and an increase in how diffuse the blebs were with 6 months of follow-up,” Dr. Kahook said. “[This is] just a pilot study, but now we have a total of 26 patients enrolled. We’re going to stop at 40 patients and then look at the different groups over 2 years and see which groups did better.”

Theoretical benefit

MMC has become an integral part of trabeculectomy surgery because studies have shown the agent to be efficacious in achieving target IOP levels after surgical intervention. However, complications associated with the use of MMC have also been recorded, notably cystic bleb formation, late thinning and leaking blebs, endophthalmitis and patient discomfort.

According to Dr. Kahook, the greater efficacy achieved with MMC is a tradeoff in terms of safety. Ideally, he said, alternative agents that are equally effective or adjunctive medications that could lower the required dose of MMC would be used.

Anti-VEGF agents seem appropriate as an alternative or an adjunct medication because of their antivascular and antifibrotic properties. Reducing new vessel formation should theoretically negate the proliferation of inflammatory proteins at the wound site, thereby reducing fibroblast attraction and further scarring.

It may be the antifibrotic qualities of anti-VEGF agents that make them advantageous in this application. Reducing fibrosis should affect wound healing and lead to more favorable wound modulation at the time of surgery.

According to Dr. Kahook, the combination approach is similar to how other complex biological cascades are managed in other areas of medicine. MMC and the anti-VEGF injection would act synergistically to improve wound healing during drainage surgery, while the latter would also reduce complications associated with the former.

“The usual big question is: Are we achieving greater success? The success is usually measured by IOP lowering in glaucoma, and we didn’t see that. We saw that the IOP lowering was essentially the same whether you used anti-VEGF agents or not,” Dr. Kahook said. “In the case of our study, the big question should really be: Is the surgery safer? At this stage, it is too early to answer this question, but it does appear that bleb-related complications might be less when anti-VEGF agents are used in conjunction with MMC.”

Next steps

Dr. Kahook said he has added a third arm to the study in which patients are treated with intravitreal ranibizumab alone at the time of trabeculectomy. That portion of the study is still under way, but “we’re in the process of learning what anti-VEGF agents can do as a standalone wound modulator post-trabeculectomy,” Dr. Kahook said.

“The patients that I’ve seen more recently who received anti-VEGF alone at time of trabeculectomy have healthy-appearing blebs with no avascularity to their blebs and have met their IOP-lowering targets. So we’re getting the benefits of the trabeculectomy without the long-term side effects that usually come at the end of having an avascular bleb,” Dr. Kahook said, adding that longer-term follow-up is needed to tease out differences between the different wound modulators.

“A combination therapy approach to wound modulation — which is a complex, multifaceted pathway — makes sense and mirrors how other chronic diseases are being treated, and could lead to greater success and safety after filtration procedures in the future,” Dr. Kahook said. – by Bryan Bechtel and Erin L. Boyle

Reference:

• Kahook MY. Bleb morphology and vascularity after trabeculectomy with intravitreal ranibizumab: a pilot study. Am J Ophthalmol. 2010;150(3):399-403.

• Malik Y. Kahook, MD, can be reached at Department of Ophthalmology, University of Colorado School of Medicine, Rocky Mountain Lions Eye Institute, 1675 Aurora Court, P.O. Box 6510, Mailstop F-731, Aurora, CO 80045; 720-848-2500; fax: 720-848-5014; e-mail: malik.kahook@ucdenver.edu. Dr. Kahook has received research support from Genentech, Allergan, Alcon, Merck and Actelion. He is a consultant to Alcon, Allergan, Merck and Genentech and a founding member of Shape Ophthalmics LLC.