Is Epimacular Brachytherapy Superior to Anti-VEGF in Treating Age-Related Macular Degeneration?

Epimacular brachytherapy (EMB) does not reduce the number of ranibizumab injections required by patients with chronic, active neovascular age-related macular degeneration (ARMD), and it is associated with worse visual acuity compared with anti-vascular endothelial growth factor (VEGF) treatment alone, according to a study published in JAMA Ophthalmology.

In European and North American nations, ARMD is the leading cause of blindness, and anti-VEGF agents are the main treatments for the disease. However, the treatment requires regular hospital visits and repeated injections, which can be burdensome to patients. In addition, “long-term follow-up reports of pivotal anti-VEGF clinical trials showed that after initial visual acuity (VA) gains in the first 2 years, participants experienced a decline from baseline.”

EMB, a form of radiotherapy, was developed as an alternative treatment for ARMD. EMB delivers radiation to lesions through an endoscopic probe containing a strontium-90 source. The device was tested in the Macular Epiretinal Brachytherapy in Treated Age-Related Macular Degeneration (MERITAGE) study. Results showed “a loss of less than 15 Early Treatment Diabetic Retinopathy Study (ETDRS) letters in 81% of participants after 12 months and in 68% after 24 months, despite participants’ receipt of fewer anti-VEGF injections than before the administration of EMB.”

In a 24-month randomized clinical trial, researchers tested the efficacy and safety of EMB in 363 patients with active, chronic ARMD. The Macular Epiretinal Brachytherapy vs Ranibizumab [Lucentis] Only Treatment (MERLOT) trial recruited participants from 24 National Health Service hospitals in the United Kingdom between November 2009 and January 2012.

Individuals were randomized 2:1 and categorized based on lens status and angiographic lesion type. In total, 244 participants received EMB plus as-needed ranibizumab or as-needed ranibizumab monotherapy (n = 119), the latter serving as the control group. Assessments of best-corrected visual acuity (BCVA) and imaging were masked. In the months following treatment, refraction, BCVA testing, ocular examinations, and optical coherence tomography (OCT) were carried out at screenings.

Of the 363 participants, 329 completed 24-month follow up visits (222 in the EMB group and 107 in the ranibizumab group).

Analyses after 24 months revealed:

• Average (SD) number of as-needed ranibizumab injections from month 1 to month 24 inclusive was 9.3 (6.7) in the EMB group (n = 244) and 8.3 (4.5) in the ranibizumab group (n = 119), with a difference of 1.0 injection (95% CI, —0.3 to 2.3; P = .13)
• Average change in BCVA from baseline was —11.2 (15.7) ETDRS letters in the EMB group (n = 243) and –1.4 (10.9) ETDRS letters in the ranibizumab group (n = 119), with a difference of 9.8 ETDRS letters (95% CI, –6.7 to –12.9) (1 participant in EMB group was excluded)
• Percentage of participants gaining 0 or more ETDRS letters was 28.3% (69 of 244) in the EMB group and 51.3% (61 of 119) in the ranibizumab group, with a difference of 23% (95% CI, 12.4%-33.6%; P&thinsp;<&thinsp;.001)
• Average foveal thickness increased by 7.0 (193) μm in the EMB group (n&thinsp;=&thinsp;213) and decreased by —20.0 (130) μm in the ranibizumab group (n&thinsp;=&thinsp;100), with a difference of 27 μm (95% CI, –14.8 μm to 68.8 μm; P&thinsp;=&thinsp;.19)
• Clinically significant cataract was the most frequent adverse event, occurring in 66.0% of eyes (161 of 244) in the EMB group and 20.2% (24 of 119) in the ranibizumab group
• Microvascular abnormalities were present in 20 of 207 eyes (9.7%) in the EMB group and 1 of 97 eyes (1.0%) in the ranibizumab group

Despite the unfavorable results of the MERLOT trial for EMB, radiotherapy delivered by other means has produced more positive outcomes, authors note. For example, the INTREPID study, testing stereotactic radiotherapy, “reported that significantly fewer ranibizumab retreatments were required in the active group and those with small (<4 mm), actively leaking lesions had significantly better BCVA compared with sham despite 55% fewer injections.”

This may be due to the fact that different devices were used to deliver radiation to the eyes.

“The use of EMB as a second-line therapy for chronic neovascular ARMD was not supported by the data,” researchers conclude. “Despite having marketing authorization in Europe, we believe that the EMB device tested in this study should not be used as part of standard clinical care in patients with chronic, active neovascular ARMD.”

Reference

Jackson TL, Soare C, Petrarca C, et al. Evaluation of month-24 efficacy and safety of epimacular brachytherapy for previously treated neovascular age-related macular degeneration. JAMA Opthalmol. Published online July 9, 2020. doi:10.1001/jamaophthalmol.2020.2309