SELECTED CONTEMPORARY THERAPEUTIC STRATEGIES FOR AGE-RELATED MACULAR DEGENERATION: EFFICACY, SAFETY, AND FUTURE DIRECTIONS

Abstract

Age-related macular degeneration (AMD) is one of the leading causes of irreversible central vision impairment in older adults. The introduction of intravitreal vascular endothelial growth factor (VEGF) inhibitors has fundamentally changed the prognosis of neovascular AMD (nAMD). Contemporary research focuses both on maintaining functional efficacy while reducing treatment burden and on developing effective therapies for geographic atrophy (GA).

The aim of this review is to critically evaluate selected contemporary therapeutic strategies used or investigated in AMD, with particular emphasis on efficacy, safety, durability of treatment effect, and the quality of available evidence. The evidence evaluated primarily comprised randomized controlled trials, systematic reviews, and meta-analyses, supplemented by early-phase clinical trials for experimental technologies and post-marketing data when relevant safety signals were identified.

The most mature body of evidence demonstrating preservation or improvement of visual function in nAMD concerns anti-VEGF therapy. The PULSAR and TENAYA/LUCERNE trials demonstrated that aflibercept 8 mg and faricimab, respectively, can be administered at extended treatment intervals while maintaining non-inferior functional efficacy compared with active comparators [8–11]. The ranibizumab Port Delivery System (PDS) represents an alternative strategy for reducing the frequency of intravitreal injections but requires surgical implantation [17,18].

In GA, the complement inhibitors pegcetacoplan and avacincaptad pegol have demonstrated modest reductions in the rate of anatomical disease progression [32–34]. These effects should not be interpreted as retinal regeneration or as necessarily translating into improved visual function. For pegcetacoplan, post-marketing safety signals are also clinically relevant [41]. The European Medicines Agency (EMA) did not grant marketing authorization for Syfovre in the European Union, concluding that the demonstrated reduction in GA lesion growth did not translate into a sufficiently meaningful clinical benefit for patients to establish a positive benefit-risk balance [42].

Photobiomodulation demonstrated statistically significant functional outcomes in the LIGHTSITE III program; however, its evidence base remains substantially smaller than that supporting anti-VEGF therapy [35,36]. Gene therapies represent a promising investigational approach, but current evidence is derived predominantly from early-phase studies and is insufficient to establish these treatments as equivalent or superior alternatives to standard anti-VEGF therapy [37,38].