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July 2010, Issue 43


Combination Treatment with Epimacular Brachytherapy and Anti-VEGF Therapy for Age-Related Macular Degeneration


Pravin Dugel, MD
Managing Partner
Retinal Consultants of Arizona
Phoenix, Arizona

doctorBy the year 2020, age-related macular degeneration (AMD) is expected to affect 3 million people in the United States (U.S.) alone; another 7 million in the U.S. may be at “substantial risk” of developing neovascular AMD.1 As the global population ages to well over 100 million by 2050, the burden on healthcare systems worldwide related to treating this chronic disease will be overwhelming. AMD has been reported to have an impact on quality of life deemed as significant as moderate cardiac angina or symptomatic HIV.2

Currently, the most widely used treatments for neovascular AMD are the anti-vascular endothelial growth factor (anti-VEGF) agents ranibizumab and bevacizumab. They have gained rapid acceptance in the retina community because of their favorable efficacy and acceptable safety profiles.3 Unfortunately, the vision benefits achieved with these two drugs are lost when their monthly injection treatment regimen is not followed.4

In an effort to reduce the treatment burden on patients, physicians, and health care systems, several combination treatment options are being evaluated. An innovative technology commonly referred to as epimacular brachytherapy is currently under investigation in a phase III randomized, controlled, multicenter, international clinical study (CABERNET). The CABERNET study is fully enrolled (n=450) and the one-year results are expected in late 2010. Epimacular brachytherapy is also under investigation in a pilot study evaluating the safety and efficacy of the therapy in patients who require frequent, chronic treatment with anti-VEGF agents. The MERITAGE study [“A Study of the NeoVista Ophthalmic System for the Treatment of Subfoveal CNV Associated With Wet AMD in Patients That Require Persistent Anti-VEGF Therapy (MERITAGE)] (Clinicaltrials.gov identifier: NCT00809419) enrolled only patients with active, exudative AMD that persisted despite continuous, frequent anti-VEGF treatment (n=50), in an attempt to reduce the overall treatment burden in this patient population. Preliminary observations (n=16) suggest that a single procedure of epimacular brachytherapy reduced patients’ need for ongoing anti-VEGF therapy. Importantly, 63% of patients showed some improvement in visual acuity, with 50% gaining at least five letters or more at six months. A 50% reduction in the re-injection rate was noted as compared to the injection rates six months prior to receiving epimacular brachytherapy. The 1-year follow up results from these patients should be available in late 2010.5,6

A considerable concern to various government healthcare systems worldwide is the cost of AMD treatment, especially given the increasingly older population. Costs of treating neovascular AMD with ranibizumab hover around $55,000 for two years of anti-VEGF injections per patient.7 Recent studies have indicated epimacular brachytherapy in combination with anti-VEGF drugs is more cost effective than anti-VEGF alone.8-10 If the results from CABERNET and MERITAGE continue to support the earlier outcomes, combination treatment of epimacular brachytherapy with anti-VEGF medication may have the potential for a positive global impact on treatment burden and healthcare costs associated with the management of neovascular AMD.


  1. Eye Diseases Prevalence Research Group. Prevalence of age-related macular degeneration in the United States. Arch Ophthalmol. 2004;122:564-472.
  2. Brown GC, Brown MM, Sharma S, et al. The burden of age-related macular degeneration: A value-based medicine analysis. Trans Am Ophthalmol Soc. 2005:103:173-186.
  3. Rosenfeld PJ, Brown DM, Heier JS, et al. Ranibizumab for neovascular age-related macular degeneration. N Engl J Med. 2006;355:1419-1431.
  4. Awh C. HORIZON extension trial of ranibizumab (Lucentis) for neovascular age-related macular degeneration (AMD): first-year safety and efficacy results. Paper presented at: 26th Annual Meeting of the American Society of Retina Specialists; Maui, Hawaii: Oct. 12, 2008.
  5. Dugel P. Radiation for AMD: Internal Approach. Paper presented at: Retinal Physician Symposium 2009; March 2009; Paradise Island, Bahamas.
  6. Dugel P. Macular EpiRetinal Brachytherapy in Treated Age Related Macular Degeneration Patients: MERITAGE 1, Preliminary VA Outcomes. Paper presented at: AAO Retina Subspecialty Day; October 2009: San Francisco, CA.
  7. Rich W. "Reimbursement scenario evolves with new practice patterns." In Efficiency Study: Measuring the AMD Treatment Burden and Practice Impact, Retinal Physician, Eds. June 2009.
  8. Brown GC, Brown MM, Brown HC, Irwin B, Roth Z. The comparative effectiveness and cost-effectiveness of intraocular 90Sr brachytherapy/intravitreal VEGF inhibitor for neovascular macular degeneration. www.evidence-based-ophthalmology.com. 2009;107-122.
  9. Brown GC, Brown MM, Brown HC, Kindermann S, Sharma S. A value-based medicine comparison of interventions for subfoveal neovascular macular degeneration. Ophthalmology. 2007;114(6):1170-1178.
  10. Brown MM, Brown GC, Brown HC, Peet J. A value-based medicine analysis of ranibizumab for the treatment of subfoveal neovascular macular degeneration. Ophthalmology. 2008;115(6):1039-1045.


Ingrid U. Scott, MD, MPH,  Editor

Professor of Ophthalmology and
Public Health Sciences,
Penn State College of Medicine


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