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Stereotactic radiotherapy (SRT) for neovascular age-related macular degeneration (nAMD) reduced the use of anti-vascular endothelial growth factor (VEGF) medications without significantly affecting visual acuity, a randomized trial showed.

Patients assigned to SRT received an average of 10.7 doses of ranibizumab (Lucentis) over 2 years as compared with 13.3 for patients assigned to sham SRT. Best-corrected visual acuity (BCVA) did not differ significantly between groups at the end of the trial. Adverse events (AEs) occurred in a similar proportion of patients in each group, but microvascular abnormalities were detected more often in patients randomized to SRT.

The reduction in anti-VEGF injections more than offset the cost of SRT, resulting in an average savings of £565 (~$725) per patient, reported Timothy L. Jackson, MBChB, PhD, of King's College Hospital in London, and co-authors in .

"If widely implemented, SRT could reduce the burden of nAMD treatment for patients, and the global cost of delivering nAMD treatment," the authors wrote. "SRT could potentially avoid 1.8 million anti-VEGF injections per year globally across all high-income countries."

The authors of an lauded the findings but cautioned that "additional gaps in knowledge need to be addressed before the widespread adoption of this therapy."

First, investigators administered ranibizumab on an as-needed basis for patients who had already received anti-VEGF injections. How the findings translate into management of untreated nAMD remains to be seen, said Gui-shuang Ying, PhD, and Brian L. VanderBeek, MD, both of the University of Pennsylvania Perelman School of Medicine in Philadelphia. Also uncertain is the ability of SRT to reduce anti-VEGF injections when used in conjunction with longer-acting agents.

Second, the trial did not assess the risk of geographic atrophy with SRT. A of a higher dose of SRT for nAMD showed geographic atrophy in half of the treated eyes after 6.2 years.

Finally, nearly all participating clinics reported high rates of missed visits and potential treatments during the trial, which was conducted during the COVID-19 pandemic, Ying and VanderBeek noted. Sensitivity analyses showed results similar to the overall analysis, but a more detailed accounting of missed visits could show a larger impact.

"If the reduction in anti-VEGF injection rate, noninferior visual acuity results, and acceptable safety profile of SRT remain through future studies, the will be a foundational piece in advancing a promising adjunctive therapy forward," Ying and VanderBeek concluded.

Intravitreal anti-VEGF injections have become standard of care for nAMD, but are costly, with an for treatment and monitoring in the U.S. alone. As practiced in many countries, anti-VEGF therapy can impose a considerable treatment burden on patients, Jackson and co-authors said. Though generally safe, each injection does carry a from infectious endophthalmitis. A study of patient priority-setting showed a need for a noninvasive treatment that avoided or at least reduced intravitreal injections.

More than 30 years ago, for nAMD suggested a biologic effect but not one that would be sufficient during the emergence of anti-VEGF agents, the authors explained. About 20 years later, the , which looked at a radiation device specifically for nAMD, showed that SRT significantly reduced use of ranibizumab. During 2 years of follow-up, 13% of 140 participants developed retinal microvascular abnormalities attributed to SRT, two of which "might have affected vision."

To address an ongoing need for alternatives to anti-VEGF therapy, Jackson and colleagues conducted a randomized, sham-controlled trial to evaluate the impact of SRT on use of anti-VEGF therapy. They enrolled 411 patients who were randomized 2:1 to 16-Gy SRT or to sham SRT, in addition to existing treatment with ranibizumab. Data analysis included 359 patients for efficacy and 409 for safety.

During 2 years of follow-up, patients treated with SRT had a statistically significant reduction of 2.9 anti-VEGF injections per patient (95% CI -4.2 to -1.6, P<0.0001). BCVA decreased by 1.7 letters, which met prespecified parameters for noninferiority of SRT versus sham.

Microvascular abnormalities detected by central review occurred in 35% of SRT-treated patients versus 12% of sham-treated eyes. Overall, eyes with microvascular abnormalities had better BCVA than those without, the authors noted.

"The between-group difference in the number of injections increased over time," the authors wrote in their discussion of the findings. "This benefit occurred without sacrificing BCVA, which was relatively stable following SRT and noninferior to anti-VEGF monotherapy."

"Assuming noninferior vision and acceptable safety, it seems probable that many patients would prefer a treatment that reduces intravitreal injections," they added.

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