Exfoliation syndrome (XFS) is a common age-related disorder of the extracellular matrix that is frequently associated with severe chronic secondary open-angle glaucoma and cataract. XFS syndrome may affect up to 30% of people over 60 years of age ... Exfoliation syndrome (XFS) is a common age-related disorder of the extracellular matrix that is frequently associated with severe chronic secondary open-angle glaucoma and cataract. XFS syndrome may affect up to 30% of people over 60 years of age worldwide and is biomicroscopically diagnosed by abnormal microfibrillar deposits on ocular structures that line the aqueous-bathed surfaces of the anterior segment (Schlotzer-Schrehardt and Naumann, 2006).
Forsius (1981) considered the exfoliation syndrome to be a disorder of the suspensory ligament. Secondary glaucoma results from effects of exfoliated lens material ('capsular glaucoma'). The disorder was first described by Lindberg (1917), Forsius's teacher. Forsius himself had ... Forsius (1981) considered the exfoliation syndrome to be a disorder of the suspensory ligament. Secondary glaucoma results from effects of exfoliated lens material ('capsular glaucoma'). The disorder was first described by Lindberg (1917), Forsius's teacher. Forsius himself had the disorder. Yuksel et al. (2001) described the ocular hemodynamics in pseudoexfoliation syndrome and pseudoexfoliation glaucoma. They found that the hemodynamic parameters in the retrobulbar vessels were altered in patients with pseudoexfoliation syndrome and pseudoexfoliation glaucoma and that these alterations were more prominent in the glaucoma patients. Specifically, they found decreases in the mean peak systolic velocity of the central retinal artery and decreases in the end diastolic velocities of the central retinal artery and the short posterior temporal ciliary arteries. However, the resistive indices were increased in the ophthalmic artery. Gasch et al. (2003) concluded that XFS caused abnormalities in the zonules, ciliary body, iris, trabecular meshwork, and corneal endothelium, which could lead to significant clinical problems, including cataract surgery complications and glaucoma. Konstas et al. (2004) performed a retrospective analysis of 167 patients with exfoliation glaucoma in Greece, Spain, Russia, and Hungary. They found that intraocular pressure reduction helped to prevent glaucoma progression in patients with exfoliation glaucoma, although it did not guarantee the prevention or worsening of the disease. Grodum et al. (2005) found that pseudoexfoliation was a strong independent risk factor for glaucoma in patients with ocular hypertension. Schlotzer-Schrehardt and Naumann (2006) reviewed the ocular and systemic manifestations and pathophysiology of pseudoexfoliation syndrome.
Thorleifsson et al. (2007) performed a genomewide search which yielded multiple SNPs in the chromosome 15q24.1 region associated with glaucoma. Further investigation revealed that the association was confined to exfoliation glaucoma (XFG). Two nonsynonymous SNPs in exon 1 ... Thorleifsson et al. (2007) performed a genomewide search which yielded multiple SNPs in the chromosome 15q24.1 region associated with glaucoma. Further investigation revealed that the association was confined to exfoliation glaucoma (XFG). Two nonsynonymous SNPs in exon 1 of the LOXL1 gene, dbSNP rs1048661 (153456.0001) and dbSNP rs3825942 (153456.0002), explained the association, and the data suggested that they confer risk of XFG mainly through exfoliation syndrome (XFS). About 25% of the general population is homozygous for the highest risk haplotype, and their risk of suffering from XFG is more than 100 times that of individuals carrying only low risk haplotypes. The population-attributable risk of the 2 higher risk haplotypes is more than 99% . The product of LOXL1 catalyzes the formation of elastin fibers found to be a major component of the lesions in XFG. In a Caucasian Australian population-based cohort of 2,508 individuals, 86 (3.4%) of whom were diagnosed with pseudoexfoliation syndrome, Hewitt et al. (2008) confirmed that 2 previously identified nonsynonymous variants in exon 1 of LOXL1, R141L (dbSNP rs1048661) and G153D (dbSNP rs3825942), were strongly associated with pseudoexfoliation: 2 copies of the high-risk haplotype at these SNPs conferred a risk of 7.20 (95% CI, 3.04 to 20.75) compared to no copies of the high-risk haplotype. Hewitt et al. (2008) noted that their Caucasian population had a 9-fold lower lifetime incidence of pseudoexfoliation syndrome compared to the Nordic populations studied by Thorleifsson et al. (2007) despite having similar allelic architecture at the LOXL1 locus, and suggested that genetic or environmental factors independent of LOXL1 strongly influence the phenotypic expression of the syndrome. In a case-control study of 59 Finnish patients with XFS, 82 with XFG, 71 patients with primary open-angle glaucoma (see POAG, 137760), and 26 unaffected individuals, and in a family study of 28 patients with XFS or XFG and 92 unaffected relatives from an extended Finnish family, Lemmela et al. (2009) analyzed 3 SNPs in the LOXL1 gene, the 2 previously studied exonic SNPs dbSNP rs1048661 and dbSNP rs3825942, and a SNP in intron 1, dbSNP rs2165241 (153456.0003). In both studies, the strongest association was with the intronic SNP dbSNP rs2165241 (p = 2.62 x 10(-13) and p less than 0.0001, respectively); however, no linkage was observed for LOXL1 risk alleles. The corresponding 3-locus haplotype GGT increased the risk of XFS/XFG nearly 15-fold relative to the low-risk GAC haplotype (p = 1.6 x 10(-16)).
In light of its peculiar population distribution, this disorder seems to have an important genetic basis (Forsius, 1981). In Finland and elsewhere in Scandinavia, it may have a frequency of as high as 20% in persons over age ... In light of its peculiar population distribution, this disorder seems to have an important genetic basis (Forsius, 1981). In Finland and elsewhere in Scandinavia, it may have a frequency of as high as 20% in persons over age 80 years. It is frequent in Lapps and northern-living Russians, but Forsius (1981) found it totally lacking in Eskimos. It has been found in Canada, but in persons of Scandinavian extraction. It is rare in Germany and in the United Kingdom, but frequent in Amerindians, in Greece, and in the African Bantu. Gasch et al. (2003) reported the high prevalence of exfoliation syndrome (XFS) in Azerbaijan; patients were designated as having XFS if exfoliation material was apparent on the anterior lens capsule and/or at the pupillary border during routine postdilation biomicroscopy. The youngest patient with XFS was 46 years old. XFS was present in 32% of those over 60 years of age. The prevalence increased with age. XFS was bilateral in 48% of those affected. The reported prevalence among individuals older than 60 years ranged from 0% among Eskimos to 38% among the Navajo of New Mexico. Krishnadas et al. (2003) determined the prevalence and risk factors for pseudoexfoliation in a rural population of southern India. The prevalence was 6.0%, increased with age, and was greater in males. Prevalence of glaucoma among patients with pseudoexfoliation was 7.5%; exfoliation was present in 26.7% of patients with primary open-angle glaucoma. Pseudoexfoliation also increased the risks of operative complications during cataract surgery. Rotchford et al. (2003) determined the prevalence and clinical features of XFS among black South Africans. They examined 1,840 individuals, 40 years of age or older, from Hlabisa and Temba. Prevalence of XFS was 7.7% in Hlabisa and 6.0% in Temba. Prevalence increased with age, with 18.9% (Hlabisa) and 16.5% (Temba) of those aged 70 years or older affected. Clinical appearance was similar to that reported in other ethnic groups. Exfoliative glaucoma accounted for approximately one-fourth of open-angle glaucoma (OAG) cases. Among patients with XFS and OAG, 16 of 18 were blind in 1 or both eyes. Rotchford et al. (2003) concluded that open-angle glaucoma associated with XFS appeared to be associated with a poor prognosis.