New evidence emerging on XFS development, progression

By Cheryl Guttman Krader

Exfoliation syndrome (XFS) was first described nearly a century ago and represents the most common, recognizable cause of secondary open-angle glaucoma. Only recently has XFS received the level of attention it deserves, and now a new concept about XFS development and progression has emerged that may provide targets for intervention, reports Terri Pickering, MD.

Terri Pickering, MD, provided an overview of EXS and its changing role as a disease of environmental risk factors in the progression of secondary open-angle glaucoma.

“XFS is now considered a disease of environmental risk factors among genetically pre-disposed people,” said Dr. Pickering, in private practice, Glaucoma Center of San Francisco, San Francisco. “We know that age and variants of the lysyl oxidase-like 1 (LOXL1) gene may be involved. However, other genes have also been associated with XFS, and the common denominator seems to be an association with extracellular matrix and trabecular function.

Dr. Pickering added that there is evidence that increased ultraviolet (UV) exposure, altitude, and lower ambient temperature have a role in disease onset, while disease progression is affected by oxidative stress and the actions of profibrotic growth factors and matrix metalloproteinases.

Epidemiology

Dr. Pickering pointed out that XFS is more common than many people realize. According to some studies, exfoliative deposits can be found in the anterior portion of the eye in up to 30% of people over age 60, and XFS accounts for between 5% and 25% of all open-angle glaucoma worldwide, depending on the population.

“Although first described in Finland, exfoliation glaucoma occurs in populations in all continents that have been studied,” she said.

Observational studies on XFS showed that it was prevalent among people who spend a lot of time outdoors, including the Navajo, Aborigines, Bantu, fisherman, and farmers in the Adriatic islands. A recent study conducted in the United States and Israel showed an association with history of sun exposure and residential latitude with the risk being higher the further north from the equator.

The study, reported by Pasquale et al. [JAMA Ophthalmol. 2014;132(12):1439-1445], investigated a population comprised of white adults over age 60. It found that the risk of XFS increased by 4% for each hour, per week spent outdoors during the summer averaged over a lifetime and decreased by 2% for every 1% of lifetime sunglass-use during the summer between peak sun hours (10 a.m. to 4 p.m.). Increased time spent outdoors during youth also seemed to be associated with an increased risk of XFS.

Looking at latitude of residence, the researchers found the risk of XFS increased by 11% for every degree of latitude lived away from the equator. The information on time spent outdoors and sunglasses points to a role for UV exposure, and that is further supported by data showing that individuals who worked over water or snow had a four-fold increased risk of XFS.

“Wearing a hat in those conditions was not protective because it does not prevent exposure from the reflected UV rays,” Dr. Pickering said.

Another study analyzed data from participants in the Nurses’ Health Study and the Health Professionals Follow-up Study, focusing on individuals who lived in the same geographic tier of the United States their entire life [Ophthalmology. 2012;119(1):27-35]. Using persons dwelling in northern-tier states as a reference group, that study found the population risk of XFS was nearly 50% lower among people living in the middle latitudes of the United States and about 75% lower for residents of southern-tier states.

Clinical consequences

In the eye, cells of the iris, epithelium, and endothelium make exfoliative material. In addition to causing glaucoma, which tends to be a severe form, XFS has been associated with breakdown of the blood-aqueous barrier and damage to the retinal vasculature and optic nerve. However, XFS is a systemic condition, and exfoliative material is found in many organs of the body in addition to the eye.

“XFS has been associated with hearing loss, renal artery stenosis, hypertension, stroke, angina, myocardial infarction, and Alzheimer’s Disease among other extraocular conditions,” Dr. Pickering said. “So far, there is no clear evidence that it increases the risk for mortality.”