pseudophakic patients. Overall, 88% of patients maintained vision, 63% gained vision, and 50% gained one or more lines of vision. The most common adverse events were subconjunctival hemorrhage (20%), ocular pain (14%), echymosis (8%), cataract progression (6%), and vitreous hemorrhage (4%). No radiation retinopathy was observed. A larger phase III expansion of this trial, the MERITAGE II, is currently underway.

Similarly, a phase I, open-label, multidose safety trial was initiated at the Associacion Para Evitar La Ceguera (A.P.E.C., Mexico City, Distrito Federale, Mexico) to test the combination of the IRay device and IVR. In total, three radiation doses and four treatment strategies were employed:

–Ranibizumab at day 0, 16 Gy IRay treatment between days 1–14, ranibizumab at day 30, and then monthly evaluation with OCT and quarterly fluorescein angiography.

–Ranibizumab at day 0, 24 Gy IRay treatment between days 1–14, ranibizumab at day 30, and then monthly evaluation with OCT and quarterly fluorescein angiography.

–Ranibizumab at day 0, 11 Gy IRay treatment between days 1–14, ranibizumab at day 30, and then monthly evaluation with OCT and quarterly fluorescein angiography.

–16 Gy IRay treatment followed by monthly evaluation with OCT and quarterly fluorescein angiography.

Data has not yet been published, but no adverse

effects – specifically no optic neuropathy, retinopathy, or cataract, have been seen to date. Presently, a prospective multicenter, double-masked, sham-controlled trial for previously treated patients is enrolling patients in Europe evaluating both 16and 24-Gy IRay irradiation in conjunction with ranibizumab therapy.

Overall, radiation therapy provides a promising, yet largely unproven treatment modality for exudative AMD. Particularly, the combination of targeted radiation therapy with anti-VEGF treatment, while still in its infancy, has shown the potential to reach similar levels of vision preservation, with fewer injections, as the gold standard of monthly ranibizumab injections [37, 38]. Long-term safety and outcomes data in larger trials are needed to verify these initial findings, especially as the risk of radiation retinopathy and other complications has not yet been entirely eliminated by current delivery strategies. More precise delivery of radiation (with or without the addition of pharmacotherapies to

further enhance treatment outcomes) has the potential to increase the benefit-to-risk ratio of this therapeutic modality. Several ongoing clinical trials involving advanced delivery systems will provide critical insight.

Summary for the Clinician

›Worldwide prevalence of exudative AMD is predicted to increase as life expectancy continues to improve.

›Choroidal neovascularization found in exudative AMD appears to be a multifactorial process involving inflammatory, vascular, and angiogenic components. Commercially available treatments primarily target a solitary component of this disease.

›Combining various treatment modalities for exudative AMD targets multiple components of choroidal neovascularization and has the potential for similar and perhaps synergistic effects while reducing treatment frequency.

›A move toward combination therapy in the treatment of AMD (e.g., verteporfin photodynamic therapy and anti-VEGF agents, or radiation therapy and anti-VEGF agents) would mirror successful combination treatment regimens currently utilized in other areas of medicine.

›Ongoing clinical trials will aim to clarify optimal combination regimens.

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