OSLI Retina

May/June 2013

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Practical Retina Incorporating current trials and technology into clinical practice Current concepts in managing wet AMD suboptimally responsive to anti-VEGF therapy by James C. Major Jr., MD, PhD Seenu M. Hariprasad Practical Retina Editor For our second Practical Retina column, Dr. James C. Major from Houston, Texas, was asked to comment on the current management of wet AMD patients who are suboptimal responders to anti-VEGF therapy. We are all aware that there is great discussion and wide variability regarding how we define suboptimal responders. Regardless of the definition, we can agree that there are numerous patients in our practices who do not respond as well as expected — either based on visual acuity, imaging, or dosing frequency. At ASRS last fall, Dr. Major presented research on this topic, and he will summarize his findings in this column. I am certain that his insights and review of new clinical trial data will be educational for the entire retina community. Seenu M. Hariprasad, MD Drugs that target vascular endothelial growth factor — bevacizumab, ranibizumab, and most recently aflibercept — have revolutionized the management of neovascular age-related macular degeneration, causing a positive response in many patients. Nevertheless, many patients with wet AMD experience persistent vascular leakage despite treatment with a monthly injection of an anti-VEGF. This poses an everyday challenge to their care providers. James C. Major Jr. The 2012 Preferences and Trends Survey administered by the American Society of Retina Specialists revealed that 66.5% of retina specialists use bevacizumab monotherapy to treat typical wet AMD with subfoveal choroidal neovascularization (CNV) of up to 1 disc diameter in size. Of the survey respondents, 44% indicated that they would recommend a switch to aflibercept after previous non-response to bevacizumab monotherapy. Switching was needed in the case of persistent cysts, subretinal fluid, or pigment epithelial detachment (PED), with subretinal fluid being the strongest determiner to switch. In the Comparison of AMD Treatments Trials (CATT), vascular leakage persisted at 1 year in more than half of study participants: 53% in the ranibizumab group and 71% in the bevacizumab group. Thus, many patients with wet AMD respond suboptimally to continued anti-VEGF therapy. Some patients may incompletely anatomically respond with improvement in measured OCT leakage, while other patients show essentially no improvement. Tachyphylaxis, differences in anti-VEGF drug levels between patients, and the rate of medication clearance can theoretically help to explain these suboptimal results. More importantly, what can be done to manage disease in these patients? Because we assume that better anatomical results (eg, no diffuse or intraretinal cysts, subretinal fluid, or pigment epithelial detachment) translate to better visual results, it becomes important to dry the macula. In the PIER study, eyes with no qualitative optical coherence tomography activity showed an improved visual outcome compared with those exhibiting OCT activity.1 There are essentially three approaches for accomplishing this goal. The first approach would be to increase the frequency of the anti-VEGF injection regimen. Clinically, this amounts to injecting with a biweekly bevacizumab injection or alternating monthly ranibizumab with monthly bevacizumab for net biweekly anti-VEGF injection. The improvement in drug binding has been theoretically summarized and anecdotal evidence exists, but clinical prospective data are lacking.2 Moreover, the treatment doi: 10.3928/23258160-20130503-01 May/June 2013 • Vol. 44, No. 3 225

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