Alternate Causes for Pathogenesis of Exfoliation Glaucoma, a Multifactorial Elastotic Disorder: A Literature Review.

Exfoliation glaucoma (XFG) is the most recognizable form of secondary open-angle glaucoma associated with a high risk of blindness. This disease is characterized by white flaky granular deposits in the anterior chamber that leads to the elevation of intraocular pressure (IOP) and subsequent glaucomatous optic nerve damage. Conventionally, XFG is known to respond poorly to medical therapy, and surgical intervention is the only management option in most cases. Various genetic and nongenetic factors are known to be linked to the development of XFG. Despite decades of research on the genetic factors in exfoliation syndrome (XFS) by study groups and global consortia involving different ethnic populations, the pathogenesis of XFS and the mechanism of onset of glaucoma still remains an unsolved mystery. The key lies in understanding how the function of a gene (or set of genes) is altered by environmental triggers, along with other molecular events that underlie the key disease attributes, namely, oxidative stress and the disruption of the blood-aqueous barrier (BAB). It remains a challenge to evolve a theory encompassing all factions of molecular events occurring independently or parallelly that determine the disease manifestation (phenotype) or the stage of the disease in the eye (or in any tissue) in exfoliation. Our enhanced understanding of the underlying molecular pathophysiology of XFG, beyond the known genes or polymorphisms involved in the disease, will lead to improved diagnosis and management and the ability to recognize how the environment influences these key events that lead to the disease phenotype or disease progression. This review summarizes the recent observations and discoveries of four key factors that may hold the answers to the non-lysyl oxidase-like 1 (