New clues about why the eye's iris sheds in pigmentary glaucoma

by Isabella Backman, Yale University

edited by Lisa Lock, reviewed by Andrew Zinin

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Yale School of Medicine researchers have discovered new genetic risk factors associated with a subtype of the eye condition glaucoma. The findings highlight a novel mechanism that may contribute to the onset of the disease.

Doctors sometimes refer to glaucoma as the "silent killer of sight" because patients often don't show symptoms until irreversible damage to the optic nerve has already taken place. Pigmentary glaucoma—in which tiny pigment granules break free from the iris (the colored part of the eye) and block the eye's drainage system—is a subtype that primarily affects younger adults. Previous research has shown that mutations in genes that control pigment production are associated with this form of glaucoma.

Now, in a new study published in Ophthalmology Glaucoma, researchers have uncovered further genetic differences linked to pigmentary glaucoma. These include variations near a gene called EPHA7, which helps control how cells move and attach to neighboring cells.

The findings suggest changes in the way cells detach and spread from the iris may contribute to the disease. Understanding these mechanisms could help researchers design new diagnostic tools and more effective treatments, the team says.

"We were able to identify a novel genetic predisposition to pigmentary glaucoma," says Mathieu Bakhoum, M.D., Ph.D., assistant professor of ophthalmology and visual science at Yale School of Medicine and the study's principal investigator. "These genetic risk factors point at a plausible mechanism related to where or how cells hold onto their neighbors."

The study was led by Bakhoum and first author Mark Dibbs, a medical student at Yale School of Medicine.

What is pigmentary glaucoma?

Imagine the eye as a sink with a drain. Our eyes continuously produce fluid that helps maintain their spherical shape and supply them with nutrients. This fluid then drains out through a spongy tissue. However, if this drain clogs, fluid buildup creates pressure within the eye that can damage the optic nerve, the hallmark of glaucoma.

There are several ways the drainage system can become blocked. In some cases, excess pressure in the eye stems from a condition called pigment dispersion syndrome, in which granules of pigment detach from the iris. Over time, the condition can progress into glaucoma (referred to as pigmentary glaucoma) and cause severe vision loss or blindness.

Pigment dispersion syndrome can arise due to abnormal anatomy. However, some individuals with this anatomy will never develop the condition, while others with normal eye anatomy do. "Anatomy explains part of the disease—it is a very well-established mechanism," Bakhoum says. "But it doesn't explain everything about it."

Uncovering novel genetic variants

For the study, the researchers utilized the All of Us research program, an initiative led by the National Institutes of Health to collect health data from a million or more Americans. The database allows scientists to access both information about participants' genomes and their electronic health records. The program has enrolled nearly 750,000 participants from different racial and ethnic backgrounds, making it the largest database of its kind.

The researchers identified more than 500 participants with pigmentary glaucoma or pigment dispersion syndrome and obtained eye health data from more than 30,000 healthy individuals. Then, they analyzed the genomes of both groups in search of genetic variants that differed significantly between them.

The team conducted two types of genetic analyses. First, they used DNA microarrays, a tool that checks for many specific genetic variants at once. They investigated nearly 900,000 genetic variants, which is more comprehensive than previous studies. They also ran whole genome sequencing, which looks for variants across the entire genome, examining nearly 13 million variants in total.

The analyses identified the same pigment-related gene variants that had been shown by previous research to be associated with pigmentary glaucoma. But they also uncovered novel genetic variants not described in existing studies, including near EPHA7. Additional analyses confirmed that the variant near EPHA7 reduced its expression.

"This supports our hypothesis that the reduction of this gene could be leading to the sloughing off of cells from the iris," Bakhoum says.

Improving glaucoma diagnosis and treatment

Glaucoma affects millions of people around the world. Identifying genetic profiles that might predispose individuals to the disease could help researchers develop tools that identify at-risk patients and enable doctors to catch glaucoma before irreversible damage has taken place.

"If we can identify people at risk of developing this condition, we already have monitoring tools and interventions to prevent them from going blind," Bakhoum says.

For patients with pigmentary glaucoma, available therapies can help prevent damage to the optic nerve by lowering pressure in the eye. But there aren't yet any treatments that stop the release of pigment from the iris. Understanding the underlying mechanisms contributing to pigmentary glaucoma could help researchers develop better therapies that target its specific disease processes.

The study also points to changes in how cells are tethered together as another possible process that contributes to pigmentary glaucoma. In future research, Bakhoum's laboratory plans to confirm if this mechanism indeed plays a role in the disease.

This study would not have been possible, Bakhoum adds, without the All of Us database. "Before, if we wanted to take on such a study, it would have taken millions of dollars, a lot of recruitment and multiple institutions," he explains. "But the fact that this resource is available allowed students to be involved in scientific discovery."

More information

Mark Dibbs et al., Multi-Ancestry Genome-Wide Association with Fine-Mapping Identifies Novel Loci for Pigment Dispersion Syndrome and Pigmentary Glaucoma, Ophthalmology Glaucoma (2026). DOI: 10.1016/j.ogla.2026.07.008

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OphthalmologyClinical genetics Provided by Yale University Who's behind this story?

Lisa Lock

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Citation: New clues about why the eye's iris sheds in pigmentary glaucoma (2026, November 3) retrieved 3 November 2026 from https://medicalxpress.com/news/2026-11-clues-eye-iris-pigmentary-glaucoma.html This document is subject to copyright. Apart from any fair dealing for the purpose of private study or research, no part may be reproduced without the written permission. The content is provided for information purposes only.