Radiation, injections reduce treatment burden

March 1, 2010

Patients with neovascular AMD maintain visual acuity.

A preliminary study of epimacular brachytherapy showed that radiation and anti-vascular endothelial growth factor (VEGF) injections reduced the treatment burden and maintained the visual acuity (VA) in patients with neovascular age-related macular degeneration (AMD).

Surprisingly, 63% of patients had increased VA even though numerous injections of anti-VEGF drugs previously had not accomplished that, said Dr Pravin U. Dugel. He reported the results of the 6-month MERITAGE I Study (Macular Epiretinal Brachytherapy in Treated Age-related Macular Degeneration Patients) during retina subspecialty day at the annual meeting of the American Academy of Ophthalmology.

"Angiogenesis is the result of a long and complicated cascade involving hundreds of chemical agents," said Dr. Dugel, managing partner, Retinal Consultants of Arizona, and founding partner, Spectra Eye Institute, Phoenix. "Vascular endothelial growth factor (VEGF) is the most important one, but not the only one.

Combination therapy composed of radiation and anti-VEGF inhibition was reported to be greater than either treatment alone for inhibiting angiogenesis, he said. This experimental approach now is being used clinically to treat solid tumors, such as breast and colon cancers.

In support of combination therapy, Dr. Dugel said that the current anti-VEGF monotherapy treatment may have to be administered indefinitely.

"With this in mind, the goal is to harness the beneficial effects of radiation and, at the same time, minimiz[e] the side effects. "It makes sense to use an isotope that has a rapid energy drop-off, such as strontium, and apply it locally and directly exactly to the point of pathology in one dose."

Epimacular brachytherapy can deliver a controlled dose of beta radiation to a choroidal neovascularization (CNV) lesion. This therapy addresses CNV with increased oxygenation due to the vitrectomy, directly targets the lesion, and has the benefits of anti-VEGF therapy, according to Dr. Dugel.

The study was designed to address the treatment burden of 50 patients with persistent retinal fluid despite having received numerous anti-VEGF injections while maintaining the VA improvement.

Two phases were required for patient participation, the first of which was a loading phase that consisted of three consecutive anti-VEGF injections given monthly. The second phase required that patients had to have received a minimum of five additional injections during the 12 months before they enrolled in the study or they had to have received a minimum of three additional injections in the 6 months before they enrolled in the trial, Dr. Dugel said.

The re-treatment criteria consisted of changes in the VA (loss of greater than five letters from baseline on two consecutive visits within 7 days without lesion activity), fluorescein angiography (new or an increase from the last visit in subretinal blood confirmed by red-free photos and/or fluorescein angiography and new neovascularization), and changes on optical coherence tomography (new or increased subretinal, intra-retinal, or subretinal pigment epithelium persistent fluid).

"The most common criterion was a change in the central retinal thickness of 50 μm or more from the visit at which the central retinal thickness was previously thinner," he said.

In this patient population the mean number of previous anti-VEGF injections was 12 and the baseline VA was 20/100, both of which he described as "remarkable."

The safety data showed no evidence of radiation retinopathy in the more than 400 cases treated thus far.

"The cumulative data showed that the number of injections decreased from a mean of 12 before epimacular brachytherapy to two injections after epimacular brachytherapy," Dr. Dugel said. "A look at the 6-month interval before epimacular brachytherapy compared with the 6-month period after epimacular brachytherapy shows a 50% decrease in the number of injections."

More data are forthcoming from the fully enrolled CABERNET and MERITAGE studies. The former study will test the efficacy of epimacular brachytherapy in 450 patients with newly diagnosed AMD or who have never been treated for neovascular AMD; the latter study will evaluate the treatment in 340 patients who require frequent numerous anti-VEGF injections.

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