Use of VEGF inhibitors studied in different retinal diseases

Anti-VEGF therapy has met with widespread acceptance in the ophthalmic community, and a recent poll of retinal specialists suggest it is being used off-label, as well as formally studied in clinical trials, for conditions other than age-related macular degeneration, including proliferative diabetic retinopathy (PDR) and diabetic macular edema (DME). Anti-VEGF therapy, however, has yet to be studied in a randomized controlled clinical trial of diabetic retinopathy, according to Francesco Boscia, MD, professor, Department of Ophthalmology and Otolaryngology, Bari, Italy.

In lieu of completed trials on diabetic retinopathy on which to report, Dr. Boscia summarized a series of studies on anti-VEGF therapy for other retinal diseases. Pegaptanib (Macugen, Pfizer/OSI), bevacizumab (Avastin, Genentech), and ranibizumab (Lucentis, Genentech) all have been evaluated. Overall, the use of VEGF inhibitors is promising, although the adverse events should not be ignored, he said. Large clinical trials will be needed to demonstrate whether these agents are effective for long-term therapy.

More studies have been performed on bevacizumab, either alone or in combination therapy, than the other two drugs. Summarizing results, Dr. Boscia reported that bevacizumab showed better results than sham or laser treatment up to about 12 weeks, after which it had no advantage. Combined laser photocoagulation and bevacizumab did not appear to have any beneficial effect. In other studies, triamcinolone produced better results than anti-VEGF therapy, whereas combined triamcinolone and bevacizumab seemed to be effective.

In trials for PDR, one small study showed regression with pegaptanib. Several studies have shown benefit from treatment with bevacizumab and laser photocoagulation, although the effects were sometimes short-lived. There also is a risk of tractional retinal detachment, Dr. Boscia said.

Researchers also are exploring anti-VEGF agents as adjunctive therapy for pars plana vitrectomies, with mixed results. Although bevacizumab was well tolerated and reduced active neovascularization, its effect on postoperative bleeding was questionable.