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Epimacular brachytherapy does not look promising as a treatment for previously-treated neovascular age-related macular degeneration (AMD), investigators say.
Nice, France-Epimacular brachytherapy does not look promising as a treatment for previously-treated neovascular age-related macular degeneration (AMD), investigators say.
Timothy L Jackson of King’s College London, who presented a study on the therapy at the European Society of Retina Specialists 15th EURETINA Congress, expressed his disappointment at the results. “In visual acuity we didn’t establish non-inferiority, in fact the visual acuity in the radiation arm was slightly worse than that in the control arm,” he said.
Although anti-vascular endothelial growth factor (anti-VEGF) therapy helps most patients with neovascular AMD, not all patients benefit. The frequent injections required can be both a financial and practical burden. Researchers are therefore looking for alternative and supplementary treatments.
In epimacular brachytherapy, patients undergo a pars plana vitrectomy before an endoscopic probe (Vidion Anti-Neovascular Therapy System, NeoVista Inc) is passed into the cavity and held over the macula, delivering a dose of 24 grays of beta radiation from a strontium-90/yttrium-90 source to the centre of the lesion for 3 to 4 minutes. The radiation tails off exponentially as you get farther from the probe.
In this phase 3 trial across multiple sites in the United Kingdom, Dr Jackson and colleagues randomly assigned 363 people with previously treated wet AMD to this therapy in combination with the anti-VEGF drug ranibizumab, or ranibizumab alone as required (pro re nata). All patients had previously received treatment with ranibizumab. Those who had previously received treatment other than anti-VEGF, prior radiation to the head or neck or who had subfoveal scarring, diabetes or lens opacity were excluded. To be eligible, patients had to have received three consecutive monthly ranibizumab injections. In the period running up to the study they had to have two injections in the 6 months or four injections in the 12 months prior to enrolment. Patients were retreated if they had a loss of more than five letters from baseline due to wet AMD, an increase of more than 50µm in central retinal thickness from the lowest optical coherence tomography reading, new or increased haemorrhage or new neovascularisation visible on fluorescein angiography.
Next: 'Results fell short of researchers' hopes'
The results fell short of researchers’ hopes. Of the 363 patients recruited, investigators were able to obtain data on 350 at month 12: 234 in the brachytherapy group and 116 in the control group. The brachytherapy group lost a mean of 4.8 Early Treatment Diabetic Retinopathy Study letters, while the ranibizumab group lost a mean of 0.9.n“There were slightly more injections in the brachytherapy arm, so disappointing on both counts,” Dr Jackson said.
The investigators also looked for subgroups who might have responded especially well to the experimental treatment. They looked at such baseline variables as phakic versus pseudophakic lens status, visual acuity, lesion times and lesion sizes. Some of these groups responded better than others to brachytherapy. Lesions under 3.5 disc areas in size were more affected than larger ones, and classic lesions were more affected than minimally classic or occult lesions. None of the subgroups responded significantly better to brachytherapy than to ranibizumab alone.
Dr Jackson contrasted this finding to the results of a trial of stereotactic radiotherapy in which he was the principle investigator. (Ophthalmology. 2015 Jan;122(1):138-45, http://www.aaojournal.org/article/S0161-6420(14)00687-3/fulltext). The robotically-controlled device (Nvidia IRay, Oraya Therapeutics International) delivers X-rays and does not involve vitrectomy. Radiation reduced the number of intravitreal injections over 2 years and there was a trend toward an improvement in visual acuity in the treatment group versus control group, though this was not statistically significant, Dr Jackson said.
“So what we can conclude from this is that our mode of delivery of radiation is critical,” said Dr Jackson. He also pointed out that the dose might be important. “I think the other issue to consider is that the vitrectomy may reduce the drug half-life such that you therefore have to fight harder to maintain the effectiveness of this drug which doesn’t last long in the vitreous cavity,” he added.
Less than 1% of the patients experienced retinopathy, according to Dr Jackson. While some patients showed signs of microvascular changes, these patients tended to have better visual acuity than those without the changes. “My personal hypothesis is that there are some people who are more sensitive to radiation, so you get more vascular changes, but paradoxically they may sometimes respond better,” he said.
Session moderator Guy Donati, MD, of the Clinique la Colline, told Ophthalmology Times Europe that the research answered an important question. He said he was, however, concerned that research on stereotactic radiation has not included long enough follow-up times. “All of these studies are 1 to 2 years,” he said. “The problems may come in 3 to 5 years.”