Anti-vascular endothelial growth factor therapy for posterior segment diseases: Progress, challenges, and the road ahead.

The emergence of anti-vascular endothelial growth factor (anti-VEGF) therapy has marked a paradigm shift in the treatment of retinal and choroidal vascular diseases. Following the identification of VEGF as a central mediator of pathological angiogenesis and vascular permeability, anti-VEGF molecules have undergone significant evolution with increasing molecular sophistication and efficacy. Landmark clinical trials have defined contemporary treatment paradigms, along with established and emerging therapeutic indications related to anti-VEGF injections. This comprehensive review outlines the progression of anti-VEGF agents across successive generations, highlighting their mechanisms of action, pharmacokinetic and pharmacodynamic properties, and complications associated with and challenges related to anti-VEGF therapy, including the financial implications of long-term treatment in routine clinical practice. Recent advances in injection techniques, sustained drug-delivery systems, alternative delivery routes, growing availability of biosimilars, and gene-based therapies offer promising strategies to reduce treatment burden and improve cost-effectiveness. In addition to the conventional intravitreal route, alternate routes of anti-VEGF injections, like subretinal, supra-choroidal, and topical therapies, are being explored in various phases of the ongoing clinical trials. However, safety issues are vital for the clinical adaptability of the newer injection regimens, especially sustained drug deliveries and gene therapies. Furthermore, emerging technologies such as artificial intelligence-assisted home optical coherence tomography monitoring are poised to transform disease surveillance and personalized care. Collectively, these developments are expected to reshape the future landscape of anti-VEGF therapy and improve global retinal disease outcomes.