Pelvic organ prolapse may be clue to presence of exfoliation syndrome

Reviewed by Barbara M. Wirostko, MD

Researchers have identified a link between exfoliation syndrome, an inherited systemic disorder of elastin and extracellular matrix (ECM) associated with the LOXL1 gene locus, and pelvic organ prolapse, a commonly diagnosed connective tissue disorder in women. The identified association was highly statistically significant and thus, unlikely to be a chance finding.

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The recent investigation found that women in the study population with a history of pelvic organ prolapse had an increased risk of about 50% of receiving a diagnosis of exfoliation syndrome.

In exfoliation syndrome, noted Barbara M. Wirostko, MD, lead author of the Utah Project on Exfoliation Syndrome Study, exfoliative material is deposited in the anterior ocular segment (which can result in exfoliation glaucoma) as well as in the heart, brain, lungs, and skin, with the potential for the development of cardiovascular and cerebrovascular diseases and hearing loss, among other conditions.

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Pelvic organ prolapse is considered a major health issue for women, noted Dr. Wirostko, clinical adjunct associate professor, Department of Ophthalmology and Visual Sciences, John A. Moran Eye Center, University of Utah School of Medicine, Moran Eye Center, Salt Lake City.

Study investigators noted the prevalence estimates of symptomatic pelvic organ prolapse have been reported to range between 3% and 11%. In addition, 11% to 19% of women have been reported to need surgical intervention to repair the pelvic organ prolapse during their lifetimes.

“Pelvic organ prolapse is believed to be associated with defects produced by elastin and connective tissue injury in conjunction with abnormalities in pathways for ECM tissue repair,” the investigators said.

The study team explained in their report (JAMA Ophthalmol 2016;134:1-8; doi:10.1001/jamaophthalmol.2016.3411; published online Sept. 15, 2016) that “because both exfoliation syndrome and pelvic organ prolapse are characterized by changes in elastin-containing ECM tissue, we hypothesized that women with pelvic organ prolapse are more likely to develop exfoliation syndrome during their lifetime.”

Study design and results

Using the Utah Population Database-a research resource at the University of Utah that contains medical, demographic, and genealogical records-a two-pronged approach of a cross-sectional analysis in Medicare patients and a retrospective cohort study in patients in the University of Utah Healthcare system of hospitals and clinics was employed.

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Investigators first performed a cross-sectional analysis (substudy A) of 132,772 Utah women aged more than 65 years who were Medicare recipients for more than 3 consecutive years from 1992 to 2009 to determine the association between pelvic organ prolapse and the exfoliation syndrome.

Then, investigators estimated the longitudinal risk of an incident diagnosis of exfoliation syndrome from Jan. 1, 1995, to Dec. 31, 2014, in 5,130 women aged between 30 and 65 years at baseline who had been diagnosed with pelvic organ prolapse compared with 15,338 age-matched female controls-women who had not ever received a diagnosis of pelvic organ prolapse (substudy B), Dr. Wirostko noted.

The mean age of the women in substudy A was 82 years during the last year of follow-up in the respective Medicare record. In substudy A, investigators reported that pelvic organ prolapse was associated with a 56% increased risk of a diagnosis history of exfoliation syndrome in Medicare beneficiaries (odds ratio, 1.56; 95% confidence interval [CI], 1.4-1.7)

In substudy B, the results showed a 48% increased incident risk of receiving a subsequent exfoliation syndrome diagnosis in women who were aged 30 to 65 years at baseline when they had been diagnosed with a pelvic organ prolapse compared with age-matched controls during 20 years of follow-up (hazard ratio, 1.48; 95% CI, 1.1-1.9).

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“Systemic conditions with altered ECM metabolism, such as pelvic organ prolapse, might share common biological pathways with the exfoliation syndrome,” Dr. Wirostko said. “It is possible that the LOXL1 dysregulation, thought to occur in the exfoliation syndrome, is a common contributing factor.”

She added that a better understanding of the shared pathways will ultimately impact clinical diagnosis, management, and treatments.

Barbara M. Wirostko, MD

E: barbara.wirostko@gmail.com

Dr. Wirostko has no financial interest in any aspect of this report. She was joined in this study by Karen Curtin, PhD, Samuel Thomas, MD, Kristina Allen-Brady, PhD, Gregory S. Hageman, PhD, and Ken R. Smith, PhD, from the University of Utah, Salt Lake City; Robert Ritch, MD, New York Eye and Ear Infirmary of Mount Sinai, NY, and R. Rand Allingham MD, Duke University, Durham, NC.