Heavy-metal exposure and ocular diseases: A systematic review integrating exposure biomarkers and mechanistic insights

Heavy metals, including lead, cadmium, mercury, and arsenic, are persistent environmental contaminants whose accumulation in ocular tissues represents an underrecognized pathway to visual impairment. This systematic review synthesizes evidence from 2015 to 2026 on the sources, transport, fate, and toxicological effects of heavy metals in the ocular environment. Epidemiological studies suggest associations between chronic exposure and a spectrum of ocular pathologies, including dry eye syndrome, glaucoma, cataract, age-related macular degeneration, diabetic retinopathy, and toxic optic neuropathy. Following environmental release, metals enter the eye through two primary pathways: direct deposition onto the ocular surface from contaminated air, and systemic translocation across blood-ocular barriers. Within ocular tissues, metals exhibit preferential accumulation in melanin-rich structures (retinal pigment epithelium, uveal tract) and avascular compartments (crystalline lens), where they persist due to limited clearance mechanisms. Toxicologically, metals disrupt ocular homeostasis through interconnected molecular mechanisms: oxidative stress via Fenton chemistry and glutathione depletion, inflammatory cascades, mitochondrial dysfunction, enzyme inhibition through sulfhydryl group binding, and disruption of calcium-mediated signaling. Based on this mechanistic understanding, we discuss the contextual implications of source control, exposure biomarkers, chelation, antioxidant strategies, and clinical management; however, the effectiveness of these interventions was not systematically evaluated. This review highlights the need for integrated approaches bridging environmental monitoring, toxicological risk assessment, and clinical ophthalmology.