Innovative Iteration of Anti-Inflammatory Therapies and Delivery Technologies for Dry Eye: A Multidimensional Perspective.

PURPOSE: To investigate the effect of anti-inflammatory drug classes, delivery methods, and personalized regimens on ocular surface health in dry eye patients, providing evidence-based support for optimizing medication regimens.

METHOD: We systematically reviewed 127 studies (2013-2023; 368 datasets). Multiple linear regression analyzed tear film breakup time (TBUT) predictors. Four pharmacokinetic models (zero-order, first-order, Higuchi, Ritger-Peppas) fitted drug release; robustness and subtype heterogeneity were evaluated. Compared to NSAIDs, targeted anti-inflammatory drugs, glucocorticoids, and calcineurin inhibitors increased TBUT by 1.84s, 1.58s, and 0.97s (all P < 0.01). Compared to eye drops, implants/contact lenses, in situ gels, liposomes/nanocapsules, and nanoemulsions increased TBUT by 1.96s, 1.51s, 1.27s, and 0.83s (all P < 0.01). Personalized dosing added 0.76s (P < 0.01). Eye drops showed first-order release with burst effect ( R 2 R 2 = 0.984); nanoemulsions and liposomes/nanocapsules followed Higuchi ( R 2 R 2 = 0.972) and Ritger-Peppas ( R 2 R 2 = 0.992) models; in situ gels and implants maintained zero-order release ( R 2 R 2 = 0.968, 0.992). Subtype analysis revealed aqueous-deficient dry eye responded best to calcineurin inhibitor gels, evaporative dry eye to glucocorticoid nanoemulsions, and moderate-to-severe mixed dry eye to targeted drug implants, confirmed by robustness tests. Advanced delivery technologies and subtype-tailored therapy improve patient outcomes, with zero-order release systems carrying targeted anti-inflammatory drugs offering a promising future approach.