Eyeworld

OCT 2016

EyeWorld is the official news magazine of the American Society of Cataract & Refractive Surgery.

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EW SECONDARY FEATURE 106 October 2016 by Stefanie Petrou-Binder, MD, EyeWorld Contributing Writer interval is at least 12 weeks. From there, patients are followed PRN and treatment is restarted if recurrent disease activity is observed. Once a patient recurs, Dr. Clark would recommend employing a treat and extend approach to find a safe, fixed, extended treatment interval. He explained that he approach- es the treatment of the patient's sec- ond eye in a different, more cautious manner. "If the second eye requires treatment, I will go very slowly with the way I extend treatment inter- vals, once dry. I typically don't ex- tend past 8 to 10 weeks, and I never pull them off of therapy unless they tell me they don't want treatment anymore. The consequences are too high for a monocular patient," he said. Once the retina is dry, Dr. Clark applies different injection intervals for patients with wet AMD, retinal vein occlusion (RVO), and diabetic macular edema (DME). "In AMD patients, I typically increase the interval between injections by small, 1-week intervals because recurrences can be very severe. Recurrences in AMD can manifest as submacular hemorrhages or retinal pigment epithelial tears. The risk of losing more vision makes the potential consequences of a recurrence much more severe in AMD than they are in RVO and DME. For that reason, I am somewhat aggressive in treating AMD," Dr. Clark said. Reducing the burden of frequent anti-VEGF injections on patients and caretakers is a feasible goal in wet AMD management, according to Dr. Clark. "I am an enthusiastic advo- cate of utilizing treat and extend for anti-VEGF therapy in retinal diseases. I think if it is done correctly, we can achieve outcomes similar to monthly therapy and reduce the treatment burden. The key is to not allow pa- tients to have significant recurrences of disease activity," Dr. Clark said. "You have to be careful and tailor your treat and extend algorithm to the individual diagnosis." perform a monthly OCT exam to observe changes in the macula and determine if the anatomy is improv- ing and the lesion is drying. Once the lesion has dried completely, I try to wean them off the medica- tion. The best way to do this, in my experience, is to begin to treat and extend intervals, first extending to 6 weeks, then 8 weeks between in- jections. After a few more injections at 8-week intervals, I stop injections and continue to observe the patient closely. If there is recurrence, I re- start injections immediately. This is a strategy that really works," he said. Close observation is the key to keeping the lid on exacerbations in wet macular degeneration, Dr. Ferreira said, and despite the noted success of both bevacizumab and ranibizumab, each patient reacts dif- ferently to treatment. He explained, "When I begin treatment on a wet AMD patient, if I do not obtain enough improvement in central ret- inal thickness on OCT after the first injection, I will inject once more with the same agent. If OCT and vision have not improved within another month and the angiogram is still leaky, I will switch the medi- cation. At this point, I will opt for an agent with a different mech- anism of action, like aflibercept [Eylea, Regeneron Pharmaceuti- cals, Tarrytown, New York/Bayer, Leverkusen, Germany]." Dr. Ferreira sees aflibercept as an excellent choice when bevacizum- ab doesn't work for the wet AMD patient. In his experience, retinas unresponsive to bevacizumab dried quickly with aflibercept, in some cases within 4 weeks of the first injection. He applies an injection every 4 weeks until the macula is dry, which usually occurs by the second or third monthly injection, and if the macula remains dry and vision improves, he extends afliber- cept injections at 6-week and then 8-week intervals. "Again, the key is to keep close observation. Even after complete resolution of the lesion, we cannot have a long stretch of time without following up with patients. After knowing which drug the patient responds to and which interval led to recurrence, I can individualize the intervals and choice of drug. I make sure to follow patients within that time frame, figuring out the best interval to treat the patient based on what I learned from treat and extend," he said. Unfortunately, visual improve- ment and OCT findings do not always correlate, resulting in further treatment challenges despite one's best efforts. "Sometimes there is a gap between visual recovery and OCT improvement," Dr. Ferreira noted, "where you have improve- ment in one without observing simultaneous improvement in the other. Also, evidence of leakage is not necessarily a sign of vision loss. You have to look for areas of hemorrhage, which is more strong- ly associated with visual loss, as blood is toxic to the RPE and to the photoreceptors. I check for leakage monthly on OCT and do an angio- gram every 3 months or so to make sure there are no extrafoveal lesions or leakage," Dr. Ferreira said. Intervals Intervals between injections are dictated by the treatment response and whether one or both eyes are affected, said Lloyd Clark, MD, Palmetto Retina Center, West Co- lombia, South Carolina. In patients with one affected eye, Dr. Clark will usually treat with anti-VEGF for 12 weeks. If the disease is inactive at 12 weeks, he will begin a PRN approach to reduce the number of injections, follow the patient closely for about 4 weeks, and administer anti-VEGF only if needed. "I will increase the interval between injections each time I see the patient and only introduce treatment back if they have disease activity. I will typically give an exudative AMD patient one chance to go off treatment. If there is disease recurrence, I will reinsti- tute treatment for an extended peri- od of time, if not for life," he said. For patients who have normal visual function in the fellow eye, Dr. Clark will consider discontinuing therapy if the disease-free treatment Anti-VEGF therapy is all about fine-tuning F ixed interval injections of anti-vascular endothelial growth factor (VEGF) agents have lost their shine for the long-term management of exudative age-related macular degeneration (AMD), as mounting evidence has demonstrated a lack of precision using this approach. Over- and undertreating wet AMD patients by applying treatments at fixed intervals risks recurrence and disease progression on the one hand, and uncomfortable, expensive, and un- necessary treatments on the other. Specialists agree that a carefully adjusted treatment regimen involv- ing regular patient visits and close observation is the ideal treatment approach to tackle exudative AMD and retinal vascular disease. Howev- er, the physician may tweak a given regimen according to individual patient needs to achieve best results. Three retina specialists discussed their drugs of choice and shared practical advice on the best ways to apply treatments in cases of wet AMD and retinal vascular disease. First drug, second drug For many patients, choosing the best anti-VEGF agent for exudative AMD management may simply be a ques- tion of money, according to Claudio Ferreira, MD, Eye Centers of Florida, Fort Meyers, Florida. "Although off-label for wet AMD, bevacizum- ab [Avastin, Genentech, South San Francisco] is the drug of choice for 50 to 60% of eye doctors in the U.S. because of its cost effectiveness, compared to the much pricier agent ranibizumab [Lucentis, Genentech], which is FDA-approved for wet AMD," Dr. Ferreira said. "Clinical trials such as the CATT study have shown Avastin to be fairly equal to Lucentis for the treatment of wet AMD." "I normally treat my patients with Avastin," Dr. Ferreira contin- ued. "I treat them on a month- ly basis applying one injection per month over 3 to 4 months. I From too wet or too dry to just right

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