Review explores immunopathology of dry eye disease and emerging drug delivery systemsWhy do dry eye treatments often fail? A new review points to inflammation

Frontiers in Medicine Published April 1, 2026 DOI ↗ Editorial oversight: Dr. Amelia Tan, PhD · Internal Medicine & Chronic Disease

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Key Takeaway

Consider this review a summary of DED mechanisms and theoretical drug delivery advances, not new clinical evidence.

This systematic review examines the immunopathological mechanisms underlying dry eye disease (DED) and recent advances in ophthalmic drug delivery systems. The review focuses on the global population affected by DED, though specific sample size, study setting, and intervention details are not reported. The authors describe immune-mediated inflammation as central to DED pathogenesis, intertwined with oxidative stress, autophagy imbalance, pyroptosis, apoptosis, ferroptosis, viral infection, and alterations in ocular surface microbiota.

The review identifies limitations of current treatments, including short ocular residence time, limited bioavailability, and insufficient targeting of inflammatory mechanisms, which often result in failure to achieve sustained symptom relief. In response, the authors discuss innovative drug delivery systems such as nanoparticles, hydrogels, liposomes, microspheres, and gene-based platforms designed to enhance drug retention, improve ocular bioavailability, and enable controlled, targeted therapy.

No safety, tolerability, or adverse event data from specific interventions are reported, as this is a review of existing literature rather than primary clinical research. Key limitations include the absence of new primary data, direct clinical trial results, or comparisons between specific delivery systems. The practice relevance is restrained, as the evidence presented is theoretical and preclinical; clinicians should interpret these findings as a summary of potential future directions rather than established clinical options.

If you've ever used eye drops for dry eye, you know the frustration: the relief often doesn't last. A new scientific review digs into why that happens for so many people. It concludes that dry eye isn't just about a lack of moisture—it's a complex inflammatory disease where the body's own immune response damages the eye's surface. This inflammation is tangled up with other processes like oxidative stress and changes to the eye's natural microbiome.

The review explains that many current treatments, like standard eye drops, have a hard time fixing this core problem. They wash out quickly, don't get absorbed well, and often fail to target the inflammatory mechanisms directly. This helps explain why symptoms like burning, grittiness, and blurry vision can persist.

Researchers are exploring a new generation of delivery systems to overcome these hurdles. These include nanoparticles, tiny gels, and other platforms designed to keep medicine on the eye longer, deliver it more effectively, and target inflammation precisely. It's important to remember this is a review of existing science, not a report on new clinical trials. These advanced systems are still in development and are not yet available to patients. The analysis maps out the scientific challenge and potential future paths, but it doesn't prove any new treatment works.

What this means for you:

Dry eye is an inflammatory disease, and many current treatments don't last long enough to tackle it.

Study Details

Study typeSystematic review

EvidenceLevel 1

PublishedApr 2026

View Original Abstract ↓

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.

Review explores immunopathology of dry eye disease and emerging drug delivery systemsWhy do dry eye treatments often fail? A new review points to inflammation

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Review explores immunopathology of dry eye disease and emerging drug delivery systemsWhy do dry eye treatments often fail? A new review points to inflammation

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