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34 EW FEATURE February 2011 Retinal pharmacotherapy for the anterior segment surgeon January 2013 Anti-VEGF agents changing diabetic retinopathy treatment paradigm by Erin L. Boyle EyeWorld Senior Staff Writer Carl Baker, M.D. Tamer H. Mahmoud, M.D. Drugs are increasingly becoming first-line treatment option T he traditional first-line treatment paradigm for proliferative retinopathy and clinically significant diabetic macular edema has been laser treatment followed by surgery in advanced cases, but that is shifting with the approval of an anti-VEGF agent. "Only in recent years with the advent of anti-vascular endothelial growth factor (VEGF) therapy has there been a paradigm shift in the treatment of diabetic macular edema (DME)," said Sharon D. Solomon, M.D., Katharine M. Graham Professorship, associate professor of ophthalmology, Wilmer Eye Institute, and Johns Hopkins University, School of Medicine, Baltimore. "Several randomized, multicenter clinical trials have demonstrated that intravitreal anti-VEGF therapy alone or in combination with focal or grid laser is more efficacious with respect to increasing visual acuity from baseline and reducing central retinal thickness compared to laser AT A GLANCE • The first-line treatment for proliferative retinopathy and DME is changing to intravitreal anti-VEGF therapy. • In August 2012, Lucentis was approved for use in the treatment of DME. • Surgical innovations are assisting treatment of proliferative retinopathy. • The future of treatment could include slow-releasing delivery methods. Dante J. Pieramici, M.D. therapy alone in patients with DME," she said. Thomas W. Stone, M.D., partner, vice-president, Retina Associates of Kentucky, Lexington, Ky., said the treatment paradigm for diabetic retinopathy is in a "state of transition." "For many years we've had excellent data on the use of macular photocoagulation in this disease, but over the past few years, the use of injectable medication has been shown to be as good, if not better, than laser," he said. "In many cases, the first-line treatment is to initiate anti-IOL in proper position postopVEGF medication and determine how the patient responds before deciding on laser or other treatments." Innovations in treatment Diabetic retinopathy is usually treated when it is in the proliferative stage, unless patients have retinal swelling, or DME, which is often more commonly treated first. In August 2012, the U.S. FDA approved the anti-VEGF agent Lucentis (ranibizumab, Genentech, San Francisco) for the treatment of DME. It was previously approved for the treatment of wet age-related macular degeneration and macular edema following retinal vein occlusion. Another anti-VEGF agent, Avastin (bevacizumab, Genentech), has not been approved for the treatment of proliferative diabetic retinopathy or DME, but can be used off-label. Most recently, EYLEA (aflibercept, Regeneron Pharmaceuticals, Tarrytown, N.Y.), also known as VEGF Trap-Eye, was approved by the FDA for wet AMD and macular edema following central retinal vein occlusion, but could be used Sharon D. Solomon, M.D. off-label for DME and proliferative retinopathy as well. "There is a growing consensus that anti-VEGF treatment plays an important role in the management of diabetic macular edema, and there is quite a lot of interest in the role that anti-VEGF injections may play in proliferative diabetic retinopathy as well," said Carl Baker, M.D., Paducah Retinal Center, Paducah, Ky., and vice-chair, Diabetic Retinopathy Clinical Research Network. "Overall, the management of diabetic retinopathy is improving. Better screening is yielding earlier detection and better visual outcomes. Better medical management of systemic hypertension and hyperglycemia is delaying the progression of ophthalmic disease." Surgical techniques have also evolved for proliferative retinopathy cases warranting surgery, said Tamer H. Mahmoud, M.D., associate professor, vitreoretinal surgery, Duke University Eye Center, Durham, N.C. Advancements have been allowing for smaller gauge surgery of 23-, 25-, and 27-gauge vitrectomy. "It is possible nowadays to do complex cases with smaller gauges, and the new vitrectomy probes have ports, or the opening of the vitrectomy probe, very close to the end, making it much easier and safer to get closer to the areas of traction and be able to dissect those from the surface of the retina," he said. In complex surgical cases that need bimanual technique, multiple possibilities are also available, Dr. Mahmoud said. "Options include using a lighted pick, together with forceps or scissors or a soft tip to detach the adherent hyaloid, or insert a chandelier to be able to have access with forceps and scissors. In very complex cases, Thomas W. Stone, M.D. use the tissue manipulator and membrane peeler cutter scissors with light supplied by the three-way tissue manipulator as well as diathermy at the tip," he said. Role of laser Thermal laser photocoagulation was the treatment of choice in DME cases since the 1990s, when the landmark Early Treatment Diabetic Retinopathy Study (ETDRS) found that focal photocoagulation reduced risk of moderate visual loss in DME patients, Dr. Solomon said. Then, the more recent Diabetic Retinopathy Clinical Research Network (DRCR.NET) Protocol I showed that intravitreal ranibizumab with laser was more effective than laser only in DME with foveal center involvement at one year. Recent three-year results confirm the effectiveness of injections, Dr. Solomon said. Additional studies with similar findings include the READ-2 Study, the RESOLVE Study, the RESTORE Study, and the RISE and RIDE Studies. However, those studies have largely examined central-involved DME, so in threatening but non-central macular edema cases, treatment with laser is still often the best solution, said Dante J. Pieramici, M.D., California Retina Consultants, Santa Barbara, Calif. "If the edema does not involve the center of the retina, and is threatening the center of the retina, then either we can do traditional laser therapy or we might consider just watching that patient and when it does involve the center of the retina, then consider using antiVEGF therapy," Dr. Pieramici said. Dr. Baker said there are limited data treating patients with excellent vision with anti-VEGF treatment alone in studies on the subject.