Exfoliation syndrome (XFS) is a major risk factor for glaucoma. It is characterized by a pathological accumulation of polymorphic fibrillar material in the anterior segment of the eye. It is likely that the increase in intraocular pressure (IOP) seen in XFS patients is at least in part because of flakes of material clogging up the trabecular meshwork, and thereby increasing the resistance to outflow and increasing IOP. XFS glaucoma progresses more rapidly, is more resistant to medical treatment and has worse prognosis than other glaucomas. The prevalence of XFS has been found to vary greatly between different studies, raising the possibility of racial and/or environmental modulators. XFS has also been linked to other changes in ophthalmological structures such as; changes in central corneal thickness (CCT), steeper corneal curvature (CC) and nuclear lens opacifications. Some studies have found XFS to be associated with systemic diseases, mostly cardiovascular and cerebrovascular. Exposure to ultra-violet (UV) light has also been investigated as a possible culprit, along with several other plausible factors. The aim of the present study was to determine the prevalence and 5-year incidence of XFS, to establish possible risk factors and/or concomitant symptoms and finally to investigate the relationship between XFS and glaucomatous changes. The Reykjavík Eye Study (RES) is a prospective study based on a random sample from the Icelandic national population sample. The baseline examination was performed in the autumn of 1996, when 1045 persons older than 50 years participated. Of these, 846 (88.2% of survivors) participated in a follow-up 5 years later. All participants went through a standard examination protocol, and answered a comprehensive questionnaire on health and life style. In the prevalence study, XFS was found in 10.7% of subjects, more frequently in women and older persons. Five years later, a further 5.2% of those that participated in the follow-up study and had no signs of XFS at baseline were diagnosed having XFS. We found a strong correlation between IOP and XFS. No difference was found in the anterior segment parameters measured, but there was a significant loss of neural tissue in the XFS as demonstrated by measurements of cup/disk ratio. In conclusion, we find XFS to be frequent among Icelanders, increasing with age and more in women. Our diagnostic criteria are reliable over time. We have also identified possible risk factors that point to a role of antioxidants in the development of XFS. We find changes in corneal curvature and thickness more related to age than XFS.