Recent advances and future perspectives of long-acting ophthalmic preparations (LAOPs) in clinical applications

The intricate structure of ocular barriers significantly impedes drug penetration, leading to suboptimal efficacy of conventional ophthalmic formulations. Sustained/controlled-release long-acting ophthalmic preparations (LAOPs) address these limitations by prolonging drug retention, reducing dosing frequency, and enhancing therapeutic precision. This review categorizes clinically validated LAOPs by administration route, highlighting both market-approved products and investigational candidates in ongoing clinical trials. We detail mechanistic principles governing sustained-release systems while critically evaluating their translational challenges, including interspecies prediction gaps, long-term biocompatibility risks, and manufacturing reproducibility issues. The review concludes with a strategic roadmap to accelerate clinical translation of LAOPs, emphasizing molecular-level decoding of ocular disease pathways, computational modeling frameworks, bioengineered organoid models, and artificial intelligence (AI)-augmented manufacturing processes. These multidisciplinary advances position LAOPs to transform ophthalmic care through efficient, safe and personalized therapeutic paradigms. This targeted review aims to provide clinically relevant insights to guide future therapeutic development of LAOPs.