Abstract
Exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) represent a complex matrix of ocular age-related neurodegenerative changes. Numerous decades of research on this disease entity have highlighted the unique clinical features of ocular protein-complex aggregates, which lead to tissue dysfunction of the ocular outflow channels, leading to irreversible optic nerve damage and glaucoma. While genetic studies have reported several genes associated with XFS and XFG, numerous studies have shown their association with common systemic diseases such as ischemic heart disease, cerebrovascular accidents, and hypertension. Environmental factors are also reported to play a role in the disease pathogenesis by epigenetic control of gene expression and partly explain the difference in the prevalence rates of the disease process. Despite the identification of possible triggers for the disease onset or for the development of glaucoma, the exact mechanisms or the role of several reported risk factors in disease pathogenesis remain a mystery. This review comprehensively evaluated the several risk factors in XFS and XFG while discussing the interactive interplay between the risk factors that determine the disease onset or phenotype in XFS and XFG.