Xiaodong Sun, Guanran Zhang, Xinting Feng, Zhe Hong, Yanlin Qu, Mengda Li, Ziyao Xia, Jiayu Xu, Jovine Bachwenkizi, Hubert Lam, Yaxing Wang, Yasushi Honda, Masahiro Hashizume, Renjie Chen, Zhenyu Wu, John S Ji, Donghai Liang, Yuming Guo, Haidong Kan, Huixun Jia, Tien Yin Wong
The exposome, defined as the totality of external exposures individuals experience throughout the lifespan and the internal biological responses they trigger, is increasingly recognized as a major, modifiable determinant of health. The eye is uniquely vulnerable to exposome risk factors because it comprises an external interface directly exposed to the environment, a transparent lens highly sensitive to cumulative oxidative injury, and metabolically active retina prone to inflammation and vascular dysregulation. Research linking ocular diseases to air pollution, climate and weather factors, heavy metals, persistent organic pollutants, and emerging threats such as micro-/nanoplastics has expanded rapidly, yet the evidence remains fragmented and lacks systematic integration. In this review, we propose an anatomy-informed ocular exposome atlas along the visual axis to comprehensively evaluate evidence from clinical studies, pathological mechanisms, and intervention strategies across major disease groups-including ocular surface diseases, cataract, refractive errors, glaucoma, and retinal diseases. We further integrate cross-disease mechanistic pathways (oxidative stress, cellular responses, inflammation, immune reactions) and discuss causality. Finally, we identify priority research directions and provide actionable recommendations for prevention and policy.