From epidemiology to lysyl oxidase like one (LOXL1) polymorphisms discovery: phenotyping and genotyping exfoliation syndrome and exfoliation glaucoma in Iceland.

The first Icelandic articles on exfoliation syndrome (XFS) and exfoliation glaucoma (XFG) appeared some 35 years ago in 1974. Articles since then have included epidemiology, pedigree-based and twin-studies as well as investigations into XFG response to medical therapy and XFS/XFG genetics. All studies found XFS/XFG to be common in Iceland and to be age-related. The Reykjavik Eye Study (RES), a population-based epidemiological study, was first conducted in 1996. The RES found that XFS and XFG prevalence in patients aged 50 years and older was 11% and that XFS/XFG was more common in women than in men. These results were confirmed in 5- and 12-year incidence studies that also suggested that detailed characterization of the phenotype is important, including pupil dilation. In the RES, eyes with XFS were found to be clinically unilateral in about half of cases and to have higher mean intraocular pressure (IOP) than non-XFS eyes. However, XFS was not found to be associated with central corneal thickness, corneal curvature, anterior chamber depth, lens thickness, lens opacification or optic disc morphology. About 15% of persons with XFS had XFG, and XFG eyes had higher risk of developing visual impairment and blindness than eyes with primary open-angle glaucoma. The first genetic studies on Icelanders, conducted about 12 years ago, were linkage studies and were unsuccessful in discovering the genetics behind XFS/XFG. However, in 2007 a genome-wide association study in Iceland using more than 300 000 markers [single nucleotide polymorphisms (SNPs)] on a relatively small number of patients did discover that lysyl oxidase like 1 (LOXL1) on chromosome 15q24 is a major gene for XFS/XFG. These results have now largely been replicated world-wide.