Precision Medicine Method May Reduce Glaucoma-Related Blindness

Researchers at The Ohio State University Wexner Medical Center are creating a precision medicine method to determine patients’ genetic risk of developing glaucoma, with the goal of reducing glaucoma-related blindness in the future.

Glaucoma is a major cause of blindness both in the US and worldwide. Globally, glaucoma-related blindness in one eye is reported to be as high as 42 percent, researchers said. While new treatments are available to slow the progression of glaucoma, they can be expensive and still don’t offer a cure.

“As clinicians, we use a trial-and-error approach to treating patients with glaucoma,” said Sayoko Moroi, MD, PhD, an ophthalmologist and chair of the Department of Ophthalmology and Visual Sciences at the Ohio State Wexner Medical Center.

“At this point, the only treatment that has shown to be effective in slowing down the advancement of glaucoma is lowering eye pressure.”

Eye pressure is a known risk factor of glaucoma, but eye pressure can fluctuate significantly in an individual and change from one patient to another.

“It’s challenging to sample enough eye pressures in an individual to capture enough data to identify those people at risk for glaucoma,” Moroi said. “Pressure screening is not a good way to identify patients at risk because of the variability in a person and between individuals.”

The research team will study the genetic architecture of eye pressure and develop genetic risk prediction models. The group expects that their discoveries will provide new opportunities for eye pressure evaluation.

“The application of genetic risk models is being applied with the goal to improve outcomes for a variety of conditions, such as obesity, heart disease, type 2 diabetes and breast cancer. We hypothesize that a combination of genes that have already been linked to eye pressure will also predict individuals who will have pressure spikes versus those who have a more flat pressure profile,” said Moroi.

“In our research, we’re moving beyond clinical risk factors of glaucoma, such as eye pressure, older age and a thin cornea, to include these genetic models that may improve our ability to diagnose patients earlier and to know which patients have a risk for large pressure fluctuations and who we need to treat more aggressively to flatten their eye pressure profile.”

Ophthalmologists currently assess eye pressure by gathering data during their office hours, usually between 8 am and 5 pm. However, researchers noted that a patient’s eye pressure can fluctuate throughout the day, and clinicians aren’t capturing this data outside of office hours.

The team will study the measure of the factors that determine eye pressure and fluctuation. Clinicians can determine eye pressure by the eye’s fluid production, fluid drainage, and blood pressure.

“We can measure these factors by measuring the inflow of fluid, drainage of fluid and venous pressure of the eye,” said Moroi. “In individuals, we can parse out the relative contributions of inflow, outflow and blood pressure factors that determine the eye pressure and eye pressure fluctuation. The measurement of these basic factors of eye pressure is called aqueous humor dynamics.”

The group will study 200 patients from Ohio State, the Mayo Clinic, and the University of Nebraska, who have either glaucoma or ocular hypertension.

“We have excellent clinical team members at those sites. We will build upon our database of these same measures in individuals who have healthy eyes without glaucoma,” said Moroi.

In addition to studying these factors without medication, researchers will examine these factors under treatment with commonly used glaucoma drugs. Patients will be randomized to the order of treatment starting timolol treatment for one week, then the patient will wash out the therapy and switch to latanoprost treatment for one week. The other group of patients will start with latanoprost treatment for one week and then switch to timolol treatment.

Under each treated condition, researchers will measure the inflow and outflow of fluid and eye pressure and venous pressure to see if there’s a pattern of individual physiological factors that relate to being a poor responder or super responder to therapy.

In the second part of the study, the team will train participants to use a new technology that allows them to measure their own eye pressure without the use of eye drops.

“There’s a huge added value to understanding eye pressure fluctuation in a real-world environment,” said Moroi.

After collecting blood samples from each of the research subjects, the group will look at the variation between genes, called single nucleotide polymorphisms (SNPs), linked to eye pressure. The team will then determine if a certain genetic architecture relates to eye pressure fluctuations and glaucoma drug responses, paving the way for precision medicine treatments.

“That will take at least another five years, since we are just embarking upon this study now, but we are very excited about studying genetics and glaucoma pharmacology,” Moroi said.

“We hope the study will guide us to improve upon our current clinical approach so that we can improve glaucoma outcomes. We hope it will take the guesswork out of deciding which therapy to use for patients. Additionally, we expect that this combined genetic and clinical risk approach will result in time-saving measures for patients and doctors, so that patients don’t have to return to the office for unnecessary office visits for eye pressure checks.”