Two-year data do not support epimacular brachytherapy for wet AMD
Two-year results of the MERLOT trial showed no benefit of epimacular brachytherapy as an adjunct to anti-VEGF injections. In fact, the combined therapy group had worse results overall compared with the ranibizumab monotherapy group.
The attempt to combine anti-VEGF injections with epimacular brachytherapy (EMB) was driven by the hypothesis that targeted radiation might help reduce the overall number of injections without sacrificing visual acuity outcomes.
One-year results did not support the use of EMB. However, because the full effect of radiation and radiation damage takes time to manifest, the 12-month results were not judged to be sufficient to establish the safety and efficacy of this method.
The MERLOT study enrolled 363 participants with active neovascular age-related macular degeneration in 24 NHS hospitals in the U.K. They were randomly assigned 2:1 to receive either EMB plus ranibizumab as needed or ranibizumab as needed as monotherapy; 329 patients (90.6%) completed the 24-month follow-up.
At month 24, visual acuity outcomes were significantly worse in the EMB group, with a mean change in best corrected visual acuity of –11.2 letters from baseline as compared with –1.4 letters in the ranibizumab monotherapy group. Anatomic outcomes mirrored the decline in vision, with an increase of 7 µm in foveal thickness in the EMB group as compared with a decrease of –20 µm in the ranibizumab group, as well as an increase of 4.1 mm2 in total lesion size in the EMB group vs. 2.1 mm2 in the ranibizumab monotherapy group.
Adverse events were also more frequent in the EMB group but consistent with the known effects of vitrectomy, with more than a threefold greater incidence of cataract. Microvascular abnormalities were reported in 9.7% of the EMB group vs. 1% of the ranibizumab monotherapy group, but these were often subtle, and none involved the foveal center.
Interestingly, the goal of reducing the number of injections by combining ranibizumab with radiation was not achieved. The total number of injections from month 1 to month 24 inclusive was 9.3 in the EMB group vs. 8.3 in the ranibizumab group.
“These results do not support the use of epimacular brachytherapy for chronic, active wet AMD, as it did not reduce the number of anti-VEGF injections that patients required, and vision was worse,” Timothy Jackson, PhD, FRCOphth, first author of the study, told Healio/OSN.
Although the EMB device used in the study has marketing authorization in Europe, he does not see a role for EMB in the emerging treatment landscape. An alternative could be stereotactic radiotherapy (SRT), which used a robotically controlled system in the randomized, double-masked, sham-controlled INTREPID study.
“We used SRT in combination with ranibizumab as needed in patients with wet AMD and found very different results. Participants required significantly fewer anti-VEGF injections than the control group, with better vision in selected subgroups,” Jackson said. “This may be because radiation delivery was very precise using eye tracking software, and patients did not require vitrectomy, which reduces the half-life of intravitreal anti-VEGF drugs.”
Accordingly, the U.K.’s National Institute for Health Research is funding the STAR trial, in which 411 patients are randomly assigned to receive SRT or placebo. They will be followed up regularly for 2 years and again checked for safety at the end of 3 and 4 years. Results are expected in the first half of 2022.