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EW RETINA 62 June 2015 by Matt Young and Gloria D. Gamat EyeWorld Contributing Writers Vitreous Institute and Superspecialty Eye Hospital, Vijayawada, India, at the 2015 AIOC. Compared to the every 4 weeks injection with Lucentis, Eylea's recommended dosage is an injection into the eye every 8 weeks (after 3 initial monthly injections), thus potentially reducing the economic burden to patients. The less fre- quent injections and no monitoring requirements between them provide patients and their caregivers with fewer follow-up clinic visits. Currently, Eylea seems to be the longest-acting anti-VEGF available, according to Dr. Venkata. Further, patients not responding to other anti-VEGFs seem to respond better to Eylea, he noted. "The Eylea injection every 2 months seems to be better compared to monthly Lucentis," Dr. Venkata said. "Results are comparable to Lucentis, but the responses are much greater than in Avastin or Lucentis." EW Editors' note: Drs. Gurram, Kumar, and Venkata have no financial interests related to their comments. Contact information Gurram: drmmgi@yahoo.co.in Kumar: drgramu@gmail.com Venkata: drgvnarendra@gmail.com that, then switch to another drug or do combination therapy," he said. "Because Macugen is a selective anti-VEGF inhibitor, Lucentis and Avastin become the better option with patients. Further, do combina- tion therapy: anti-VEGF with steroid or anti-VEGF with PDT or anti-VEGF with thermal lasers, especially if you suspect polyps." However, the strategy for late responders is not as straightforward. "Extend the therapy. Do not stop the therapy if the patient is not responding because some are late responders," Dr. Kumar said. "If the lesion is small, they will respond early. If there is a large lesion, large edema, it would require extended treatment." Eylea for resistant AMD? The newest addition to anti-VEGF therapies, aflibercept (Eylea, Regen- eron Pharmaceuticals, Tarrytown, N.Y.), has been approved by the FDA for wet AMD since November 2011. Some research conducted on Eylea has concluded that it is an effective alternative to Lucentis and Avastin for the treatment of wet AMD, with the additional benefit of less frequently required injections. "Eylea traps the VEGF-A mol- ecules with much higher affinity than other anti-VEGF agents," said Narendra G. Venkata, MD, vitreo- retinal surgeon, Aravinda Retina lesser the response. Also, with lower initial reading ability, the chance of responding appears to be reduced. Most importantly, the treatment protocol used may affect the re- sponse rate." Treatment strategy There are cases of late responders and non-responders in the manage- ment of wet AMD using anti-VEGFs, thus pushing clinicians to switch gears in their treatment strategy. "Whether late responders or non-responders, my approach is the same: I will switch to another anti- VEGF," Murali Mohan Gurram, MD, DNB, FRCS, FICO, MCh, MBA, consultant retinal surgeon, Sree Netralaya Eye Hospital, Hyderabad, India, said in a presentation at the 2015 AIOC. In clinical practice, in cases when the first approved anti-VEGF agent pegaptanib (Macugen, Pfizer, New York) didn't work, the approach was quite straightforward: switch to an alternative anti-VEGF that has a higher response rate. Since its Food and Drug Administration (FDA) approval in June 2006, ranibizumab (Lucentis, Genentech, San Francisco) has been one alternative anti-VEGF. Thus, in cases of treatment failures and treatment disappointments in wet AMD management, clinicians have turned to Lucentis and its off-label form, bevacizumab (Avastin, Genentech), as potentially potent alternatives. Presenting several challenging cases of wet AMD, Dr. Kumar shared his experiences on when to apply the treat-and-observe, treat-and- extend and combination therapy protocols. "If a patient is not responding to anti-VEGF treatment despite your AMD diagnosis and continuous treatment, recheck your diagnosis," Dr. Kumar explained. "[Do that and] check for co-existing conditions, change to combination therapy or extended therapy." Like Dr. Mohan, Dr. Kumar agreed that non-responders should be switched to another anti-VEGF agent. "In non-responders, suspect co-existing conditions and check for What to do if anti-VEGFs fail? A lthough there is no universally agreed upon definition for treatment failure, treatment failure exists in the management of wet AMD. "Some patients, despite your best efforts, fail treatment, and they represent the most challenging cases," Ram Kumar, MD, chair- man, managing director and chief vitreo-retina consultant, Nethra Eye Institute, Hyderabad, India, said during a presentation at the 2015 All India Ophthalmological Conference (AIOC) in New Delhi. Defining treatment failures in wet AMD In the case of wet AMD, according to Dr. Kumar, there are varied defini- tions of treatment failure. "Broadly, you can say that there is treatment failure when multiple anti-VEGF treatments have been applied, and fluid or leakage is still persisting as seen on OCT or in angiography," Dr. Kumar explained. "Or when you have given your treat- ment but the patient is still losing vision." After all, the ultimate goal in the management wet AMD is im- provement of vision. However, there are cases that clinicians refer to as "treatment disappointments." If continuous monthly injec- tions are required to keep the mac- ula dry and you stop treatment and the patient worsens, this would be a disappointment, Dr. Kumar said. Continuing injections at this point may not produce the desired result. When the treatment produces a decrease in edema but no improve- ment in final visual acuity, this also would not be favorable. There are several factors in- volved in treatment failures in AMD: the stage of wet AMD, the patient's initial reading ability, and treatment protocol. "If it is a large wet AMD, the response will be bad," Dr. Kumar said. "The bigger the lesion, the Handling treatment failures for wet AMD