**Background:** Oxidative stress arises from an imbalance between the generation of reactive oxygen species (ROS) and the antioxidant defense mechanisms of cells. The eye is particularly vulnerable due to its constant exposure to light, high metabolic activity, and high oxygen consumption. ROS can damage cellular macromolecules, including DNA, proteins, and lipids, contributing to the pathogenesis of numerous ocular diseases. This review aims to summarize the mechanisms of oxidative stress in ocular diseases affecting the anterior and posterior segments of the eye and discuss potential therapeutic approaches.
**Methods:** This is a narrative review of the literature on oxidative stress in ocular diseases. The authors synthesized findings from preclinical and clinical studies, meta-analyses, and reviews to describe the sources of ROS, antioxidant defense systems, and molecular mechanisms of oxidative damage in the eye. They focused on diseases of the ocular surface (dry eye disease, pterygium), cornea (keratoconus, Fuchs endothelial corneal dystrophy, diabetic keratopathy), lens (cataract), retina (age-related macular degeneration, diabetic retinopathy, retinal vascular occlusion, retinitis pigmentosa, retinopathy of prematurity), and optic nerve (glaucoma, Leber's hereditary optic neuropathy, anterior ischemic optic neuropathy).
**Key Results:** The review reports that in dry eye disease, oxidative stress markers such as lipid peroxide, myeloperoxidase, 4-HNE, and MDA are elevated in tear fluid, while antioxidant enzymes like CAT, GPX, and SOD are reduced. In pterygium, serum total oxidant status is higher, and antioxidant enzyme activity (CAT, SOD, GPX) is significantly reduced. For keratoconus, a meta-analysis showed significant decreases in total antioxidant status, aldehyde/NADPH dehydrogenase, lactoferrin/transferrin/albumin, and selenium/zinc. In Fuchs endothelial corneal dystrophy, increased levels of 8-OHdG, a marker for oxidative DNA damage, have been observed. In cataract, reduced glutathione (GSH) synthesis decreases with age, leading to protein thiolation and formation of large protein conglomerates. In age-related macular degeneration, aging, UV/blue light exposure, and smoking promote ROS generation, and the AREDS study reported a reduced risk of progression with daily supplementation of 500 mg vitamin C, 400 IU vitamin E, 2 mg cupric oxide, 80 mg zinc, and 15 mg β-carotene. In diabetic retinopathy, hyperglycemia activates the polyol, hexosamine, AGE, and PKC pathways, increasing ROS. In glaucoma, elevated oxidative stress markers (8-OHdG, MDA) are found in serum, aqueous humor, and trabecular meshwork, and are correlated with advanced visual field defects and elevated IOP. In Leber's hereditary optic neuropathy, idebenone (a synthetic CoQ10 analogue) is the only disease-specific medication, approved by the European Medicine Agency in 2015 at a dose of 300 mg three times daily.
**Clinical Implications:** Oxidative stress is a central pathogenic mechanism in a wide range of ocular diseases. Therapeutic strategies include antioxidant supplementation (e.g., vitamins C, E, A, lutein, zeaxanthin), activation of the Nrf2 pathway, inhibition of ROS-generating enzymes (e.g., NOX inhibitors), and use of agents like idebenone for LHON. However, many antioxidant therapies have shown contradictory results in clinical trials, and further research is needed to develop effective treatments that balance ROS scavenging with preservation of physiological ROS functions. The review emphasizes the need for improved drug delivery systems and clinical trial designs to translate promising preclinical findings into clinical practice.