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Background: Ferroptosis, an iron-dependent form of regulated cell death characterized by lipid peroxidation and oxidative stress, has emerged as a critical mechanism in the pathophysiology of multiple ophthalmological diseases. Increasing experimental evidence implicates ferroptosis in retinal and ocular surface disorders, including age-related macular degeneration, diabetic retinopathy, glaucoma, retinal ischemia–reperfusion injury, retinitis pigmentosa, cataracts, and dry eye disease. Despite substantial mechanistic insights, its clinical relevance remains incompletely defined.

Methods: This review synthesizes current literature published between 2012 and 2026, encompassing mechanistic studies, in vitro and in vivo experiments, and emerging translational research on ferroptosis in ophthalmology. A structured analysis of recent systematic reviews and experimental studies was conducted to evaluate the role of ferroptosis in disease pathogenesis and to assess the therapeutic potential of ferroptosis-targeting interventions.

Results: The evidence base demonstrates that ferroptosis contributes significantly to retinal pigment epithelium dysfunction, photoreceptor degeneration, and retinal ganglion cell loss through iron accumulation, glutathione depletion, and impaired activity of glutathione peroxidase 4 (GPX4). Multiple preclinical studies have identified ferroptosis inhibitors, such as ferrostatin-1 and iron chelators, as effective in mitigating retinal damage and preserving visual function in animal models. Approximately 20 ferroptosis-targeting compounds have shown therapeutic efficacy in experimental settings. However, clinical translation remains limited, with a paucity of human trials and no approved ferroptosis-based therapies for ophthalmic indications to date.

Conclusions: Ferroptosis represents a promising but still largely preclinical therapeutic target in ophthalmology. While mechanistic and experimental data strongly support its role in disease progression, a substantial gap persists between laboratory findings and clinical application. Future research should prioritize well-designed clinical trials, biomarker development, and targeted drug delivery strategies to fully elucidate the clinical impact of ferroptosis modulation in ocular diseases.