AMD RADIOTHERAPY

Stereotactic radiotherapy (SRT) seems to offer a safe and efficacious treatment for neovascular age-related macular degeneration (AMD), with patients achieving a statistically significant reduction in ranibizumab retreatment after 24 months, according to Timothy L Jackson PhD, FRCOphth.

“Our study showed that stereotactic radiotherapy produced a 25 per cent reduction in the anti-VEGF injection frequency over the course of two years. With appropriate case selection we can bring that reduction down to 45 per cent with the possibility of better visual acuity, in particular treating lesions that are within the 4.0mm treatment zone, those with active leakage and those with limited fibrosis,” he told delegates attending the 13th EURETINA Congress in Hamburg.

Wet AMD treatment

Dr Jackson presented the results of the INTREPID study, the first shamcontrolled double-masked trial to evaluate the effectiveness and safety of a one-time radiation therapy (IRay™, Oraya Therapy) in conjunction with as-needed anti-VEGF injections for the treatment of wet AMD. A total of 21 sites in five European countries participated in the trial with a total enrolment of 226 patients.

The aim of the study was to demonstrate the safety and efficacy of the Oraya Therapy IRay system at two dose levels for the treatment of choroidal neovascularisation (CNV) secondary to neovascular AMD, said Dr Jackson. The primary end point was not visual acuity, but rather the reduction in the number of as-needed 0.5mg ranibizumab (Lucentis, Roche) anti-VEGF injections over the course of 12 months. Secondary outcomes included ETDRS visual acuity and independent assessment of total lesion size and CNV lesion size based on fluorescein angiography to determine the correlation, if any, between the functional changes and the morphology of the lesions.

The study was randomised, doublemasked and sham-controlled, with patients assigned to one of four treatment groups: 16 Gy IRay radiotherapy and PRN ranibizumab (sham 16 Gy radiotherapy and PRN ranibizumab, 24 Gy radiotherapy and PRN ranibizumab and sham 24 Gy radiotherapy and PRN ranibizumab. Inclusion criteria included patients of 50 years or older with CNV due to AMD diagnosed within the year preceding the study enrolment who had received at least three anti-VEGF injections, and who were without serious systemic illness such as diabetes.

Exclusion criteria included intraocular surgery within the preceding six months, prior vitrectomy, contraindication to radiation or suction-coupled contact lens and the presence of retinal vascular anomalies other than neovascular AMD, such as those associated with diabetes mellitus. All patients received an anti-VEGF injection within 14 days prior to radiotherapy and returned every four weeks thereafter to be assessed on the need for anti-VEGF retreatment. The retreatment criteria were a 100-micron increase in central subfield thickness from best prior OCT scan, evidence of new or increased macular haemorrhage or a loss of more than five letters of visual acuity.

Fewer injections

After 12 months, the data conclusively showed that the trial achieved its primary end point demonstrating a statistically significant reduction in as-needed injections. The actively treated patients required approximately 35 per cent fewer injections than the sham group with similar or in some cases better visual acuity outcomes. Twenty-five per cent of Oraya Therapy patients needed no further injections.

Vision benefit

A defined population sub-group comprised of roughly half of the study participants experienced even lower injection rates while exhibiting meaningful vision benefit compared to sham. A post hoc analysis of this subgroup found that patients with more fluid on the macula whose lesions were confined within a designated 4.0mm central zone of the macula seemed to derive most benefit from the Oraya Therapy.

Reported adverse events were very low over the two-year follow-up period, said Dr Jackson, with no particular pattern emerging comparing the treatment arms and the control arms, except for one case where the investigator identified radiation-related retinopathy within the 24 Gy treatment arm. Detailed images were also sent off to an independent central reading centre to try to identify any microvascular abnormalities such as cotton-wool spots or retinal haemorrhages which might arise due to the radiation treatment, said Dr Jackson.

“Overall there were up to nine cases where the microvascular changes could be attributable to radiation and two of these where it may have had a possible impact on their vision. However, these were in patients where the disease was very advanced and it was extremely difficult to discriminate whether or not it was radiation or the advanced AMD itself that may have affected the vision,” he said.

Summing up, Dr Jackson said that overall the two-year results of the INTREPID trial are very encouraging for people with wet AMD. The prospect of fewer eye injections will appeal to all those receiving anti-VEGF therapy, and for certain subsets there is the added advantage of an improved visual outcome, he said.

Timothy L Jackson: timljackson@doctors.org.uk