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Conventional ophthalmic formulation is hindered by ocular physiological barriers, leading to low bioavailability and necessitating frequent administration. To overcome these limitations, novel microenvironment\u2010responsive drug delivery systems (MR\u2010DDSs), have emerged as a highly promising strategy. This review aims to systematically summarize recent advances in MR\u2010DDSs for treating ocular diseases, providing insights for clinicians and researchers. Firstly, we elucidated the characteristics of the ocular microenvironment under normal and pathological conditions, including factors such as temperature, pH, and the levels of ions, reactive oxygen species (ROS), and enzymes. Subsequently, we introduced the categories, properties, and molecular mechanisms of stimulus\u2010responsive polymers, followed by a summary of preparation methods, characterization techniques and performance metrics for major systems. Then, we summarized the application and therapeutic efficacy of MR\u2010DDSs in managing a range of common ocular surface diseases, including dry eye disease, infectious keratitis, and corneal neovascularization. Finally, we critically analyzed the obstacles to clinical translation and propose promising avenues for future research. 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