Eyeworld

EW GLAUCOMA 76 February 2015 by Tony Realini, MD, MPH, EyeWorld Contributing Writer Is sun exposure to blame for exfoliation? P seudoexfoliation was a term coined by the ocular pathologist Georgiana Dvorak-Theobald, MD, in 1954 to differentiate this condition from the true exfoliative lens changes caused by infrared ex- posure and commonly seen in glass- blowers of the time. In recent years, this distinction has waned, and the preferred term for the constellation of findings that includes a bull's-eye pattern of fluffy material on the an- terior lens capsule, peripupillary iris transillumination defects, pigment clumping along Schwalbe's line, poor iris dilation, and lax zonules is once again exfoliation syndrome. For a long time, exfoliation syn- drome was thought of as a disease of Scandinavians and their descen- dants. But in recent years, epidemio- logic studies have demonstrated that exfoliation can be found all over the world. Interestingly, there is signif- icant geographic variability in the prevalence of exfoliation. Within that variability may lay a clue to the etiology of this common condition. Sun exposure and exfoliation prevalence "The etiology of exfoliation syn- drome, which can lead to exfoliation glaucoma, is unclear," said Jae Hee Kang, ScD, Harvard University. The LOXL1 gene, recently discovered, is present in virtually all patients with exfoliation but also in the majority of control subjects, suggesting that the gene alone is not sufficient to cause disease. A gene-environment interaction has been proposed, but the environmental triggers have not been established. "Given the higher prevalence of exfoliation syndrome in non-equa- torial regions, climatic factors may play a role," Prof. Kang said. Specifically, Prof. Kang and colleagues hypothesized that "cli- mate factors such as greater ocular ultraviolet (UV) exposure may play a role and more time spent outdoors may represent greater exposure to climatic factors." To test this hypothesis, the research group utilized the rich databases from the Nurses' Health Study (NHS) comprising nearly 50,000 U.S. women (all of whom are nurses) who have been followed since 1980 and the Health Profes- sionals Follow-Up Study (HPFS) comprising more than 20,000 American men (primarily dentists, pharmacists, and optometrists with no medical doctors) who have been followed since 1986. Only partic- ipants over the age of 60 were in- cluded in this analysis. Participants in both studies regularly complete exhaustive questionnaires to charac- terize exposure to a huge variety of potential risk factors and to report new diagnoses of glaucoma, which are confirmed with medical record review. Among the exposures queried was solar exposure. Specifically, each participant was asked to report the time spent outdoors in direct sunlight at mid-day during 3 differ- ent times in their lives: from high school to age 24; from ages 25–35; and from ages 36–59. Incident cases of exfoliation glaucoma (manifest or suspect) in both the male and female cohorts were established by medical record review. Overall, 223 women and 38 men were diagnosed with exfoli- ation glaucoma or suspect status during the follow-up period from baseline to 2010. The only age range for which a relationship between sun expo- sure and exfoliation glaucoma was observed was in the earliest period from high school through age 25. In this group, pooling both men and women, there was a statistically significant increase in risk of exfolia- tion glaucoma with increasing time spent outdoors (p=0.001). Compared to those who reported spending 5 or less hours per week outside at mid-day during this period of their lives, those reporting 6–10 hours of sun exposure had a 40% higher risk of developing exfoliation glauco- ma. For those reporting 11 or more hours per week of sun exposure at mid-day, their risk of developing exfoliation increased a full 100%— a doubling of the risk. "In this U.S. study, greater time spent outdoors in young adulthood was associated with exfoliation glau- coma and suspect status, supporting P seudoexfoliation is a fascinating condition. It can be dramatic in its presentation at the slit lamp as well as in its impact on the patient—and the surgeon. Even its name is controversial, as we learn in this month's "Glaucoma editor's corner of the world" where Aliya Jiwani, MD, and Jae Hee Kang, ScD, share their insights on the latest theories of the etiology of exfoliation. Exfoliation is so common, so obvious at the slit lamp, and so pervasive in its ef- fects in the eye that it seems as though the etiology should not be difficult to determine. But the opposite has been true, and it has defied attempts to elucidate why it develops most commonly in certain ethnic groups and in certain locations. Genetic associa- tions also have been considered, but so far they are not the full story either. Dr. Jiwani and Prof. Kang highlight studies that show the risk of exfoliation increases the farther away people live from the equator. They also cite studies showing that sun exposure during the first 25 years of life increases the risk. They connect these dots by speculating that it might be angulated sunlight and sunlight reflected off snow or water that are the missing links. I applaud the investigators in trying to figure out the mystery of exfoliation. This group has also found a relationship between heavier coffee consumption and exfoliation. 1 So the associations are piling up. But the etiology is complex because we have patients all over the world who develop exfoliation and who don't work on snow or water and who don't drink coffee. This means that other components of the etiology remain to be found. Hopefully the Harvard group will continue its march toward a fuller understanding of cause and effect in exfoliation. Reay H. Brown, MD, glaucoma editor Reference 1. Pasquale LR, Wiggs JL, Willett WC, Kang JH. The relationship between caffeine and coffee consumption and exfoliation glaucoma or glaucoma suspect: a prospective study among two cohorts. Inv Ophthalmol Vis Sci 2012; 53:6427–6433. Glaucoma editor's corner of the world

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