The role of pseudoexfoliation in open‐angle glaucoma

S tudies on pseudoexfoliation (PEX), or pseudoexfoliation syndrome (XFS), and capsular glaucoma have a long tradition in the Nordic countries. PEX was first described by the Finnish ophthalmologist John Lindberg in his thesis 1917 (See Tarkannen & Kivelä 2002). Icelandic colleagues (Thorleifsson et al. 2007) recently published the first report of the association between PEX and single-nucleotide polymorphism in the lysyl oxidase-like 1 (LOXL1) gene. Clinical research focused on PEX is also in progress in the Nordic countries and it is fitting that Acta Ophthalmologica has given priority to publish many of these studies. Openangle glaucoma (OAG) is in most cases a slowly progressing disease and the long-term studies we have recently seen published are of particular interest. One of them is the cohort study in Tierp that has been going on for more than 20 years. This issue of Acta reports on epidemiological studies of OAG and PEX in the Tierp population, all of which were based on automated perimetry (Ekström 2008; Ekström & Alm 2008). It provides a good reason to comment on these and earlier reports from Tierp. The Tierp Glaucoma Survey was conducted in 1984–86. The prevalence of definite OAG in people 65–74 years of age, 5.3% (Ekström & Alm 2008), was almost identical to that of the Reykjavik Eye Study (Jonasson et al. 2003). These estimates were higher than that reported for other comparable studies undertaken on Caucasians. The populations in Tierp and Reykjavik both had high prevalence rates for PEX, emphasizing the significance of PEX as a risk factor for OAG. Interestingly, if individuals with previously diagnosed disease were excluded, PEX was not identified as a risk factor for prevalent OAG (Ekström & Alm 2008). This finding is likely to be explained by a selection procedure, in which capsular glaucoma patients are diagnosed more frequently in eye health care services, compared to patients with primary open angle glaucoma (POAG). The incidence of definite OAG in the Tierp population was high, 7.1 per 1000 person-years in people 65– 94 years of age (Ekström 2008). The follow-up of the Dalby population in southern Sweden (Bengtsson 1989) revealed an incidence of 2.4 per 1000 person-years in people aged 65– 80 years. This estimate was considerably lower than the rate of 6.4 per 1000 calculated for participants of the same age in the Tierp cohort. The difference is likely to be explained by capsular glaucoma. Three of 27 cases in Dalby had capsular glaucoma, compared with 18 of 31 cases in Tierp. Whether the difference between Dalby and Tierp reflects a genetic difference between the two populations remains to be investigated. Studies on geographic differences in the prevalence of LOXL1 polymorphism are now ongoing but there is yet no information on differences between the southern and central parts of Sweden. Still, geographical differences within the Nordic countries can be expected; a histopathological study on eyes with absolute glaucoma or melanoma showed that PEX was almost 10 times as frequent in Finland as in Denmark (Alyahya et al. 2005). Intraocular pressure (IOP) is an established risk factor both for the development of OAG (Nemesure et al. 2007) and for its progression (Leske et al. 2007). Still, OAG can develop and progress at normal levels of IOP and other factors have been much debated. In particular some form of vascular dysregulation has been proposed as a factor in the pathogenesis of OAG. Gottanka et al. (2005) examined the optic nerves obtained at autopsy from 36 eyes with POAG and 15 with capsular glaucoma. They noted a difference between eyes with POAG and eyes with capsular glaucoma. The density of capillaries in the optic nerve was reduced in eyes with POAG, but not in eyes with capsular glaucoma, and they concluded that other factors than elevated IOP are involved in the development of optic nerve damage in POAG. Should we conclude then that elevated IOP is the dominating factor in capsular glaucoma? PEX is a strong risk factor for the development of OAG, as documented in a 5-year follow-up of the population survey in Tierp (Ekström 1993), and IOP is higher in eyes with PEX than in eyes without (Arnarsson et al. 2007). This is true even if the two eyes are compared in cases with unilateral PEX (Åström & Lindén 2007). In the Tierp study PEX was at least as strong a risk factor as elevated IOP. Ekström (1993) reported that individuals with an IOP of ‡21 mmHg at baseline had a 3.4-fold increased adjusted risk of developing OAG, while the same figure for those with PEX was 9.8. More over, exposure to both risk factors increased the risk 67-fold, Acta Ophthalmologica 2008