The enigma of exfoliation syndrome
Article first published online: 25 JUL 2007
© 2007 The Author
Acta Ophthalmologica Scandinavica
Volume 85, Issue 5, pages 470–471, August 2007
How to Cite
Bruce Shields, M. and Ritch, R. (2007), The enigma of exfoliation syndrome. Acta Ophthalmologica Scandinavica, 85: 470–471. doi: 10.1111/j.1600-0420.2007.00951.x
- Issue published online: 25 JUL 2007
- Article first published online: 25 JUL 2007
Although exfoliation syndrome (XFS) is the most common identifiable cause of open-angle glaucoma (OAG) worldwide (Ritch 1994), it continues to elude our understanding at many levels. In fact, there is even a lack of universal consensus as to what it should be called.
In 1987, the Sigrid Juselius Foundation sponsored an International Workshop in Espoo, Finland to consider this global condition (Tarkkanen & Forsius 1988). The first order of business was to agree on a preferred term: the majority favoured ‘exfoliation syndrome’ over the alternative, ‘pseudoexfoliation syndrome’. Today, both terms are commonly found in the world literature, although we prefer the term adopted by the International Workshop.
With rare exceptions, XFS is found in all parts of the world and yet there are not only marked geographic differences in prevalence, but gender and ethnic influences differ strikingly between locations. What does this tell us about the aetiology of XFS? Is it infectious or genetic? Is it influenced by environmental factors, such as altitude, temperature or exposure to ultraviolet light? What is its association with systemic disease, and does that increase the mortality rate? The answers to these questions will come from many disciplines of research, but continued epidemiological studies will always comprise the basis for our understanding of XFS.
Åström et al. (2007) have advanced our knowledge of the prevalence and incidence of XFS with a landmark study carried out in northern Sweden. In 1981, these authors performed a population-based study on 339 persons, aged 66 years, in a single municipality and found a rate of prevalence of XFS of 23%. Over the next 21 years, the authors followed these individuals at 7-year intervals and found that, by 87 years of age, the prevalence of XFS among them had risen to 61%, which represents an annual incidence of 1.81%. The prevalence of OAG in this population rose from 2.1% at 66 years of age to 25% at 87 years, with XFS accounting for 59% of glaucoma cases in the latter age group. Additional observations of interest include a two-fold prevalence in women and the lack of a significant difference in mortality between individuals with and without XFS.
Although these prevalence figures are high, they are consistent with the well established observation that XFS increases steadily and dramatically with age. In addition, its prevalence varies considerably between countries and even within regions or between ethnic groups within some countries (Taylor et al. 1977; Kozobolis et al. 1997; Shakya et al. 2004; Åström et al. 2007). Exfoliation syndrome is especially prevalent in Scandinavian countries and, with some exceptions, rates tend to be higher in the northern regions of those countries (Krause et al. 1988; Hirvelä et al. 1995; Åström et al. 2007). High prevalence rates have also recently been reported in populations in which XFS was previously thought to be extremely rare (Rotchford et al. 2003; Teshome & Regassa 2004).
The reported influences of gender and ethnicity also differ among geographic populations. For example, prevalence rates of XFS in Black and White persons with OAG were reported to be 20% and 1.4%, respectively, in South Africa (Luntz 1972), compared with 0.3% and 2.0%, respectively, in southern Louisiana (Ball et al. 1989). These differences in reported prevalence undoubtedly represent a combination of true population differences and variations in study design. For example, dilated and undilated examinations are likely to give different results. In addition, some cases may be subclinical and are recognizable only by histological examination of the lens or other tissues of the eye and body.
The main observations of clinical interest in the study by Åström et al. (2007) concern the fact that, in a high-risk population for XFS, and especially in older age groups, the prevalence of OAG may be unusually high and half or more such OAG cases may be associated with XFS. However, we are still left with questions concerning the aetiology of XFS and its association with systemic disease, which will ultimately tell us what we need to know about optimum treatment modalities for these patients. Multiple two-generation families have now been identified, and preliminary analysis of these pedigrees suggests an autosomal dominant inheritance for XFS (Orr et al. 2001). If genetic factors are confirmed, will there be associated environmental influences in the aetiology? It is unlikely that exposure to ultraviolet light is a major factor, as some XFS material is found in parts of the body that are not typically exposed, whereas the influence of temperature and altitude continue to be evaluated (Forsius 1988).
The knowledge that XFS is found throughout the body suggests that this is a systemic disease (Ritch & Schlotzer-Schrehardt 2001) and raises the issue of increased mortality rates in these patients. Although some studies have suggested increased vascular morbidity (Mitchell et al. 1997; Akarsu & Unal 2005; Visontai et al. 2006; Yuksel et al. 2006), none have shown an increase in total mortality, which is consistent with the study by Åström et al. (2007). Thus, there is yet much to learn about the ocular morbidity of XFS, particularly with regard to glaucoma and cataracts, as well as its influence on general health. Nonetheless, Åström et al. (2007) have significantly advanced our understanding of this enigmatic disorder, for which they are to be sincerely congratulated and thanked.
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