January-February 2020


Research Highlight
Exfoliation syndrome, COPD most common among tobacco users

by Vanessa Caceres Contributing Writer

“It certainly would not hurt to discuss smoking cessation with XFS patients, if applicable.”
—Natasha Nayak Kolomeyer, MD

Exfoliation syndrome (XFS) is the most recognizable cause of open-angle glaucoma and is associated with systemic comorbidities such as cardiovascular disease, abdominal aortic aneurysms, hernias, cardiac arrhythmias, and other conditions. There is also a possible association between chronic obstructive pulmonary disease (COPD) and XFS that Samuel Taylor, BS, and coauthors analyzed in a study published in Ophthalmology Glaucoma.1
The case-case and case-control comparison found that patients with XFS may have an increased risk of a COPD diagnosis compared with those who do not have XFS, particularly among tobacco users. However, they did not find an increased risk of XFS in patients with COPD.
Exfoliation syndrome is strongly associated with genetic variants of the lysyl oxidase-like gene (LOXL1), according to the authors. The presence of LOXL1 provides the link to both the ophthalmic and systemic effects.

Study details

The researchers used a dataset of Utah Healthcare Medicare beneficiaries, all of whom were 50 years or older and had three consecutive years of records connected to the Utah Population Database, a research resource housed at the University of Utah, Salt Lake City, Utah. Among the 2.2 million University of Utah Healthcare patients over a 20-year period through 2015, researchers identified two cohorts: 2,943 patients for an XFS cohort and 20,589 patients for a COPD cohort. Codes from the International Classification of Diseases, Ninth Revision, were used to determine which patients had XFS and/or COPD. There also was a comparison group of age- and sex-matched controls in a 5:1 ratio who did not have a history of XFS (n=14,713), as well as a comparison group of patients with no history of COPD who were selected and matched 5:1 to COPD patients (n=102,939).
There were no major differences in race, age at diagnosis, and years of follow-up between women and men in the groups. Sixty- eight percent of the XFS patients and 44% of the COPD patients were female. At diagnosis, the mean age was 75 years and 67 years for XFS and COPD, respectively.
Patients with XFS were more likely to be living at the end of the study period than their respective controls; conversely, COPD patients were less likely to be alive compared with matched controls.
Patients with COPD were more likely to have a history of using tobacco compared with controls.
Among those with XFS, it was somewhat more likely that they would have a history of COPD than respective controls (5.5% vs. 4.4%, respectively). However, those with COPD did not significantly differ regarding an XFS history compared with matched controls.
When delving in further, there was a higher risk of COPD in a subset of 190 XFS patients who used tobacco. In that subset, COPD was associated with a 2.2-fold risk of XFS, and the risk was consistent both with patients with onset before or after 70 years old.
Although XFS is associated with certain systemic comorbidities, those with a history of XFS had better survival overall than patients who did not have XFS. Although survival was lower with those who had COPD, having both XFS and COPD seemed to have a protective effect.

Research and clinical implications

The researchers concluded that if there is a genetic disposition to LOXL1-related XFS, in those who use tobacco, “ ... perhaps the elastin repair processes called into action are thus altered such that there is an increase in subsequent risk of COPD in this subset,” they wrote. More research is needed, they added.
When it comes to further study, Lauren Goodman, MD, would like to know whether COPD diagnoses were made by spirometry, or if the diagnosis codes reflect clinical suspicion for COPD. If COPD was not officially diagnosed, the ideal next step would be to perform screening spirometry on XFS patients and matched controls to compare incidence and physiologic severity of obstruction, controlling for tobacco use history.
The results may lead to some small steps in the management of patients with XFS. “The study is probably compelling enough to suggest that physicians caring for XFS patients should ask about tobacco use and urge cessation,” Dr. Goodman said. They also could refer for spirometry when appropriate. This same patient group should be advised to stop smoking because they have an increased risk for emphysema, said Roger Maxfield, MD.
“It certainly would not hurt to discuss smoking cessation with XFS patients, if applicable,” said Natasha Nayak Kolomeyer, MD. However, the state-specific database used in the study and the lack of diversity, as well as the reliance on billing code data, limit extrapolation of the findings, she thinks.
“Further studies along this path do have the opportunity to change clinical management, depending on the findings,” Dr. Kolomeyer said.
Another future avenue for research could be looking for a correlation between XFS and emphysema specifically, Dr. Maxfield said.
Although XFS has primarily been viewed as an ophthalmic disorder, further research in this area and the ability to study larger populations may force a change in this perception, the researchers noted. “It will become increasingly important to have a broader appreciation of XFS as a systemic condition that may require increasing medical attention and be amenable to targeted therapy,” they wrote.

About the doctors

Lauren Goodman, MD
Pulmonary disease and critical care medicine
The Ohio State University
Wexler Medical Center
Columbus, Ohio

Natasha Nayak Kolomeyer, MD
Department of Glaucoma
Wills Eye Hospital
Philadelphia, Pennsylvania

Roger Maxfield, MD
Professor of medicine
Columbia University
Medical Center
New York, New York


1. Taylor SC, et al. Association between chronic obstruction pulmonary disease and exfoliation syndrome. Ophthalmology
Glaucoma. 2019;2:3–10.

Relevant disclosures

Goodman: None
Kolomeyer: None
Maxfield: None


Goodman: Amy.Colgan@osumc.edu
Kolomeyer: nkolomeyer@willseye.org
Maxfield: jr3674@cumc.columbia.edu

Exfoliation syndrome, COPD most common among tobacco users Exfoliation syndrome, COPD most common among tobacco users
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