Two-year results of a large, UK-based randomized clinical trial suggest that a single treatment with 16-Gray stereotactic radiotherapy (SRT) may significantly reduce the number of ranibizumab injections required in patients with chronic neovascular AMD (nAMD) without affecting long-term visual acuity or safety outcomes.
Study Design
This was a randomized, double-masked, sham-controlled trial evaluating the therapeutic potential of 16-Gray SRT for the treatment of nAMD. Four hundred eleven patients (≥50 years of age) with active, chronic nAMD from 50 hospitals across the United Kingdom were randomized 2:1 to receive a single treatment with either 16-Gray SRT or sham SRT. All patients had received at least 3 anti-VEGF injections (ranibizumab), with at least 1 occurring within the previous 4 months. Treatment followed the Comparison of Age-Related Macular Degeneration Treatments Trials pro re nata (PRN) treatment regimen. Primary clinical outcomes were final BCVA and the number of intravitreal injections required over 2 years, and adverse events were closely tracked.
Outcomes
By the 96-week primary endpoint, there was a 22% decrease in the total number of ranibizumab injections required in SRT-treated eyes vs in sham-treated eyes (mean 10.7 injections vs 13.3 injections, respectfully), with a greater difference seen in the second year of the study than in the first. Between groups there was no statistically significant difference in BCVA, and vision remained stable in each group overall. Both groups also had similar rates of adverse events (e.g., cataract/cataract surgery, conjunctival/subconjunctival hemorrhage, endophthalmitis), although there was a higher rate of retinal microvascular abnormalities (e.g., cotton wool spots, retinal hemorrhage) in the SRT group (35%) than in the sham group (12%).
Limitations
This study was likely somewhat affected by taking place during the COVID-19 pandemic. Ranibizumab was chosen as the study medication based on its marketing authorization for PRN use since its PRN treatment allowed for more flexibility in the number of injection over time than treat-and-extend protocols (enabling the best chances of detecting between-group differences in injection frequency), but PRN treatment strategies are limited by the treatment burden of coming into the office monthly. Other anti-VEGF medications may have had different effects.
Clinical Significance
In this study, a single treatment with 16-Gray SRT significantly decreased the injection burden for patients undergoing treatment for nAMD while maintaining visual acuity and having a reasonable side-effect profile. Given that many patients with nAMD are undertreated, incorporating SRT treatment may help to better stabilize the disease. In addition, considering intravitreal injections and increasing indications for their use, requiring fewer injections to treat nAMD may subsequently open opportunities to treat other conditions. More stable disease over time may also lead to better visual acuity in the long term, although the 2-year data at this point does not point to a statistically significant difference in visual acuity associated with SRT treatment, and the use of this treatment would need to be compared to newer anti-VEGF agents which themselves may allow larger intervals between dosing for some patients.
Financial Disclosures: Dr. Jessica Randolph discloses financial relationships with Apellis Pharmaceuticals (Lecture Fees/Speakers Bureau); Astellas, Genentech (Consultant/Advisor).