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In the news: Environmental Factors in Exfoliation Syndrome

Exfoliation Syndrome: Background

Exfoliation syndrome (XFS) is the most common cause of secondary open angle glaucoma. Patients with this syndrome are also predisposed to develop angle-closure glaucoma, and XFS can lead to retinal vein occlusion and increased cataract formation. XFS is also suspected to be a systemic disorder and has been preliminarily associated with transient ischemic attacks, stroke, hypertension, and heart attack.

The underlying mechanism of XFS is believed to involve abnormal extracellular matrix metabolism, which produces elastic fiber components that clump and accumulate in many ocular tissues. Deposits of white material on the anterior lens surface are the most consistent, important diagnostic feature of XFS.

Genetics play a role in XFS. The enzyme lysyl oxidase-like 1 (LOXL1) is pivotal in bolstering the tensile strength of collagen and elastin in extracellular matrices. Common gene variants in LOXL1 have been found in approximately 99% of XFS cases in Scandinavian populations. However, about 80% of controls also had disease-associated LOXL1 gene variants. Similar findings were seen in cases and controls from Australia. These observations suggest that other factors in addition to genetics contribute to XFS. Harvard researchers recently reviewed findings on factors that may influence the development of XFS (1).

Environmental Factors: Recent Findings

The review identified and discussed non-genetic factors associated with increased risk of XFS, including:

Diet

Low serum folate levels are linked with increased risk of XFS. Low levels of serum folate can lead to elevated homocysteine, and homocysteine levels are higher in the serum, aqueous humor and tear samples of XFS patients compared with controls. Elevated homocysteine may increase exfoliation material formation by contributing to vascular damage, oxidative stress, and changes in the extracellular matrix.

Coffee consumption may be another factor that alters XFS, as heavy consumption is associated with increased risk. It may be that drinking too much coffee causes homocysteine levels to rise. The exact mechanism by which homocysteine enhances the formation of exfoliation material remains unclear, but it may involve extracellular matrix metalloproteinase regulation.

Climate
Colder temperatures in the summer and winter months appear to be independent risk factors for XFS. In fact, many countries with cold mean temperatures such as Iceland, Norway and Sweden have a high prevalence of the syndrome. One possible explanation for this observation is that extracellular deposits of XFS are the result of a precipitation reaction that develops at colder temperatures.

Sun Exposure
Cold can’t be the only factor involved in XFS, however, since the Arctic-dwelling Inuit people are relatively immune to developing the syndrome. A number of studies have linked outdoor occupations or time spent outdoors during summer months with greater XFS risk. UV-light exposure has been found to up-regulate the expression of LOXL1 and major elastic fiber proteins found in the exfoliation extracellular deposits.

Additionally, longer exposure to reflective surfaces such as water or snow increases the odds of developing XFS. Snow reflects as much as 80% of UV-B during midday, suggesting that ocular exposure to light from reflective surfaces may be an important UV source in the pathogenesis of XFS.

The authors conclude that a better understanding of the environmental components associated with XFS could lead to lifestyle changes that help prevent the syndrome and its consequences.

Reference

1. Dewundara S & Pasquale LR. Review: Exfoliation syndrome: A disease with an environmental component. Curr Opin Ophthalmol 26:78–81, 2015.