Next-Generation Drug Delivery for Age-related Macular Degeneration: Promise of Controlled Release Formulations

OBJECTIVE: To review emerging long-acting drug delivery and implantable systems developed to overcome the limitations of conventional intravitreal anti-vascular endothelial growth factor (anti-VEGF) therapy for neovascular age-related macular degeneration (nAMD). SIGNIFICANCE OF REVIEW: nAMD is a leading cause of irreversible vision loss worldwide. Although intravitreal anti-VEGF injections are clinically effective, their short intraocular half-life necessitates frequent administration, resulting in high treatment burden, poor patient compliance, and increased risk of procedure-related complications. Long-acting injectable and implantable drug delivery systems offer a promising approach to maintain therapeutic drug levels while reducing injection frequency and healthcare burden. KEY FINDINGS: Recent advances in controlled-release technologies, including electrospun nanofibers, injectable microcapsules, core-shell nanofibers, 3D-printed implants, dip-cast tubular devices, nanostructured thin-film systems, suprachoroidal implants, encapsulated cell technologies, and gene therapy-based approaches, demonstrate sustained drug release ranging from several weeks to over 1 year. These platforms provide improved drug stability, higher payload capacity, tunable release kinetics, and favorable biocompatibility. Clinically validated refillable implants, such as Susvimo™, confirm the feasibility of long-term intraocular anti-VEGF delivery. CONCLUSIONS: Next-generation long-acting ocular drug delivery systems have the potential to transform nAMD management by reducing invasive procedures, improving patient adherence, and maintaining durable therapeutic efficacy. Continued optimization and clinical translation of these technologies are essential for their successful integration into routine ophthalmic care.