Systemic Associations of Exfoliation Syndrome

Exfoliation syndrome (XFS) is an age-related disease characterized by the production, deposition, and progressive accumulation of a white, fibrillar, extracellular material in many ocular tissues, most prominent on the anterior lens surface and pupillary border. Its prevalence increases steadily with age in all populations. It is the most common identifiable cause of open-angle glaucoma worldwide and is a potentially reversible or even curable disease. First described in Finland in 1917 by Lindberg, it has long been associated with open-angle glaucoma. However, in recent years, it is being increasingly reported in conjunction with a multiplicity of both ocular and systemic disorders, and the number of these is expected to grow, particularly with investigations based on attempts to associate other diseases with those genes known to be associated with XFS. Despite the focus on XFS as a cause of open-angle glaucoma for nearly a century, in reality it is still only an ocular manifestation of a protean systemic disease. It is a unique disorder with extensive and often serious ocular and systemic manifestations and not, as it has long been termed, a "form" or "type" of glaucoma. This misconception has delayed research into the molecular and cellular processes involved in its development, and the underestimation of its overall importance and its underlying causative mechanisms have largely been long ignored. The purpose of this article is to review the systemic disorders which are becoming increasingly associated with XFS. Reviews of epidemiology, genetics, biomarkers, molecular mechanisms of development, and ocular findings may be found elsewhere.