Model can predict risk of glaucoma in patients with elevated eye pressure

Investigators at Washington University School of Medicine in St. Louis have developed a model to identify patients at high risk of developing glaucoma. Their research was presented at the annual meeting of the American Academy of Ophthalmology in Las Vegas.

The model that predicts glaucoma risk relies on five key risk factors. It was developed using data from two landmark clinical trials: the Ocular Hypertension Treatment Study (OHTS) and the European Glaucoma Prevention Study (EGPS).

“The Ocular Hypertension Treatment Study was really designed to answer two questions,” says Michael A. Kass, M.D., national chair of the 22-center study and head of the Department of Ophthalmology and Visual Sciences at Washington University School of Medicine. “We wanted to learn whether preventive treatment could reduce the incidence of glaucoma, and we also wanted to learn whether we could determine what risk factors might help us predict which patients will go on to develop glaucoma.”

The first question was answered more than four years ago when the results of the OHTS study were announced. That study had looked at patients at risk for glaucoma because of high pressure in the eyes. Kass and colleagues concluded at that time that treating those people with pressure-lowering eye drops could delay, or possibly even prevent, glaucoma.

Now, using five important risk factors that emerged from closely analyzing data from the OHTS study, the researchers have found that it's possible to predict which patients will benefit most from pressure-lowering treatment and which ones don't have much to gain from the eye drops. The five factors researchers plug into the risk assessment model are age, intraocular pressure, cup/disc ratio (a measure of the appearance of the optic nerve head), thickness of the cornea and pattern standard deviation (a measurement derived from computerized visual field tests).

“When you enter these five factors — and our model is based on the average of these factors between the two eyes — you can determine an individual's risk of developing glaucoma during the next five years,” says Mae O. Gordon, Ph.D., professor in the Department of Ophthalmology and Visual Sciences and the Division of Biostatistics at Washington University School of Medicine and first author of the study validating the risk assessment model that was presented at the Academy meeting.

“We have found that you can assess risk two ways,” she says. “We can enter the raw data, and our model will calculate the risk. We've also put together a simplified points system that assigns a certain number of points to the various risk factors. Adding up those points then provides doctors with an estimate of a patient's risk of progressing from elevated intraocular pressure to glaucoma.”

Open-angle glaucoma is the most common form of glaucoma and one of the leading causes of blindness in the United States. It is the number one cause of blindness among African Americans and the second leading cause of blindness in the world, affecting approximately 70 million people.

Fluid regularly flows into and out of the eye. High pressure results when that fluid drains too slowly. Between 4 and 8 percent of Americans over 40 have elevated intraocular pressure, putting them at increased risk for open-angle glaucoma.

In the OHTS study, patients who received treatment were given commercially available, pressure-lowering eye drops. Eye specialists examined them every six months for a minimum of five years. The drops reduced pressure in the eye by approximately 20 percent and the risk of open-angle glaucoma by more than 50 percent.

The EPGS study included people from four European countries. All had elevated intraocular pressure. The patients were followed for an average of 4.8 years.

Kass, Gordon and the other investigators from Europe and the United States, examined data from the patients in both studies who had not received pressure-lowering eye drops. They hoped to learn whether they could identify risk patterns to predict which patients would go on to develop glaucoma. Studying the five factors that eventually emerged from the data analysis changed the way the investigators look at glaucoma risk factors.

“When we first looked at the predictive factors one at a time, race showed up as clearly predictive of risk, particularly for people of African American ancestry,” Kass says. “However, when you put the other factors into the model — particularly cup/disc ratio and corneal thickness — race drops out. It turns out that African Americans tend to have thinner corneas and larger cup/disc ratios, and those factors seem to contribute, at least partly, to the increased prevalence of glaucoma in African Americans.”

Kass believes the new risk assessment model not only will help physicians decide which patients to treat aggressively but will arm patients with information to help them decide whether to go through with treatment. For example, an 80-year-old patient with a 50 percent risk of developing glaucoma in the next five years might be inclined to go in a different direction than a 45-year-old patient with the same level of risk.

Because some eye drops cause harmful side effects and daily treatment can be inconvenient and expensive, Kass believes some patients at low risk may opt for close observation rather than treatment. He recommends doctors use the risk assessment model as only one of several factors to consider when designing a treatment strategy for an individual patient.

“We hope this information will be used to help doctors and patients make good decisions about testing, examination and the possibility of preventive treatment,” he says.

Kass views this model as “version 1.1,” and he expects it will be improved as more is learned about genetic risks and other factors related to glaucoma. He says scientists should view the risk assessment model as a “work in progress” and the best that science can do right now. But just as models of cardiovascular disease risk have improved over the last few decades, he expects this glaucoma risk model will improve and become even more useful in future years.

The risk assessment test will be freely available on-line at http://ohts.wustl.edu/risk. Risk factor numbers can be plugged in and five-year risk estimated, but Kass cautions the web page is designed for use by physicians rather than patients.

“This is not a test that should be done by laypeople because they won't have the detailed information needed to enter into the model,” he says. “Most wouldn't know things about themselves such as pattern standard deviation or cup/disc ratio. Those factors have to be determined by an eye doctor.”

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