Test may predict eye disease outcome

UNC-CHAPEL HILL (US) — A new study is the foundation for a promising stem cell blood test that may detect the progression of macular degeneration to its more serious form, which can lead to blindness.

Age-related macular degeneration (ARMD) is the most common cause of central vision loss in the western world. Those affected find daily activities such as driving, reading, and watching TV increasingly difficult.

In the United States as many as 11 million Americans have some form of macular degeneration, including both early and later stages of the “dry” and “wet” forms. The eye condition deteriorates the macula, the central area of the retina, causing blind spots and blurred or distorted vision.


“People with macular degeneration start out with the dry type, which we can detect with a simple dilated eye exam,” says Sai H. Chavala, assistant professor of ophthalmology and cell biology and physiology at the University of North Carolina at Chapel Hill.

“But about 20 percent of patients at some time in their life will develop wet macular degeneration, which is characterized by blood vessels that grow under the surface of the retina. These abnormal vessels can leak blood and fluid, which causes irreversible damage to the cells of the retina leading to irreversible vision loss.

“Since we don’t have a way to predict the precise timing of this event, we have no way of preventing it.”

Currently, no test is available to predict the conversion from dry to wet ARMD. But a new paper, published in the journal PLoS One, describes how it could be accomplished.

‘Most coveted achievement’

The ability to predict the conversion from dry to wet age-related macular degeneration is one of the most coveted achievements in vision science, according to Chavala. “A clinical test that predicts impending conversion is the first step in developing treatments to prevent the switch to wet macular degeneration.”

In the study, the researchers used the cell search system, an FDA-approved technology for automated rare cell analysis (ARCA), which Chavala and colleagues applied to the identification and analysis of endothelial progenitor cells (EPCs). These cell types are rare compared to other blood cells.

EPCs are a stem cell subset that give rise to the endothelium found in the inner lining of blood vessels. EPCs are liberated from the bone marrow and circulate in the blood in response to signals for new blood vessel growth.

Previous studies using fluorescence activated cell sorting (FACS), or flow cytometry, have demonstrated that EPCs are elevated in patients with wet macular degeneration compared to patients with the dry type. However, FACS measurements are subject to substantial variability between observers, along with an element of subjectivity when measuring rare cell populations challenging its clinical use.

Chavala and colleagues thought that ARCA, a new technology capable of measuring rare cell populations reliably, was better suited as a diagnostic blood test. This technology is currently being used in clinical practice for cancer patients so the technology can be readily adopted for macular degeneration patients.

The study compared traditional FACS and ARCA in 23 subjects with age-related macular degeneration, both dry and wet. The samples were “masked” so that no one involved in the sample assessments at the two labs where the analyses were done knew the type of macular degeneration the patients had.

A promising trend

“We found a promising trend favoring the ARCA technology in detecting a higher number of EPCs in the wet macular degeneration group compared to the dry. And that trend was not observed with traditional FACS,” Chavala says. “We were surprised that we needed to analyze relatively few patients to detect this trend.

“Our ‘proof of concept study’ suggests that the ARCA technology could be a powerful tool for monitoring progression in macular degeneration. Further study is required to validate this test for detecting and preventing the conversion from dry to wet macular degeneration,” Chavala says.

“The next step is to do a prospective study in a greater number of subjects having the known criteria that puts them at higher risk of progressing from dry to wet macular degeneration.”

Emil Anthony T. Say at UNC Kittner Eye Center is the study’s first author. Researchers from Duke University and the Retina Group of Washington contributed to the study, which was funded by the Adler Foundation, Hope for Vision, and Research to Prevent Blindness.

Chavala has filed a patent surrounding this technology and is founder of Serrata, LLC, a company that plans to market diagnostic testing for ocular disease.

Source: UNC-Chapel Hill