Exfoliation syndrome is a common condition in which a flaky white material is deposited in many tissues of the eye (the lens, the cornea, and the drainage structures) and throughout the body. Exfoliation syndrome is an important cause of glaucoma as up to half of those with exfoliation syndrome eventually develop a secondary glaucoma (exfoliation glaucoma).
An animal model of exfoliation syndrome was recently reported in collaboration with our colleague Michael Anderson, PhD. and his mouse genetics laboratory at the Iowa Glaucoma Center (Trantow et al., 2009). Several features of human exfoliation syndrome were identified in mice with a genetic defect in the Lyst gene. These mice have deposition of exfoliation material in their eyes and they have a classic iris defect (Marcel iris trans-illumination defects) that closely mimic what is seen in human patients with exfoliation syndrome (Figure 2).
Figure 2. Iris defects and exfoliation syndrome. Top Panel. Human eyes with XFS exhibit a distinct iris trans-illumination defect. Infrared video images of (A) normal and (B) XFS eyes showing a unique pattern of concentric periodic iris trans-illumination defects. Bottom Panel. Similar trans-illumination of the iris in (A) control C57BL/6 mice and in (B) the mouse model of exfoliation syndrome (B6-Lystbg-J). Images from Trantow et al., 2009.
We had noticed that many of our patients with exfoliation syndrome had a typical pattern of iris defects (Figure 2). However, until recently, this type of iris defect (Marcel iris trans-illumination defect) had not been prospectively tested to see if it is a specific clinical sign for exfoliation syndrome. The Glaucoma Genetics Laboratory and colleagues from the Glaucoma Service at the University of Iowa has carried out a prospective masked study of iris appearance in exfoliation syndrome that has shown a strong association (p=0.000069) with iris trans-illumination defects (Figure 3). The identification of a new clinical sign for exfoliation syndrome may provide patients and their doctors with a powerful and benign predictive test for exfoliation syndrome that can help with diagnosis and management of this important eye disease.
Figure 3. Typical iris defect seen in exfoliation patients in the masked prospective study.
Recently, a large association study by Thorleifsson et al. identified an important genetic factor for exfoliation syndrome on chromosome 15. This study suggested that genetic variations in a chromosome 15 gene, lysyl oxidase like-1 (LOXL1), confer high risk for the development of exfoliation syndrome. The Glaucoma Genetics Lab was the first research group to confirm this discovery (Fingert et al., 2007) with studies of exfoliation syndrome patients and controls from Iowa.
The Glaucoma Genetics Lab is currently searching for other genes than along with the LOXL1 gene lead to the development of exfoliation syndrome and exfoliation glaucoma.