Advances in dry eye disease: from immunopathological mechanisms to emerging ophthalmic drug delivery systems

Dry eye disease (DED) is a multifactorial disorder of the lacrimal functional unit and ocular surface that leads to ocular discomfort, visual disturbance, and tear film instability. It affects a substantial proportion of the global population and is driven by a complex interplay of immune dysregulation, environmental stressors, and systemic factors. Accumulating evidence indicates that immune-mediated inflammation is central to DED pathogenesis and is closely intertwined with oxidative stress, autophagy imbalance, pyroptosis, apoptosis, ferroptosis, viral infection, and alterations in the ocular surface microbiota, ultimately disrupting ocular surface homeostasis. Despite the availability of multiple therapeutic options, current treatments often fail to achieve sustained symptom relief, largely due to short ocular residence time, limited bioavailability, and insufficient targeting of underlying inflammatory mechanisms. In recent years, innovative ophthalmic drug delivery systems–including nanoparticles, hydrogels, liposomes, microspheres, and emerging gene-based platforms–have been developed to enhance drug retention, improve ocular bioavailability, and enable controlled and targeted therapy. This review provides an updated and integrative overview of the immunopathological mechanisms underlying DED and critically summarizes recent advances in ophthalmic drug delivery technologies. By linking disease mechanisms with translational delivery strategies, we highlight how emerging delivery systems may overcome the limitations of conventional therapies and facilitate precision, long-acting, and patient-centered treatment for DED. These insights may inform future therapeutic development and guide the clinical translation of innovative treatment strategies for this increasingly prevalent ocular surface disease.