Diane McCoy Lackey knew something was wrong with her right eye.
“Something just happened, and it seemed that I couldn’t see,” the North Philadelphia resident said.
Her ophthalmologist offered a sobering diagnosis: glaucoma, a class of eye conditions that damage the nerve that connects the eye to the brain. In 5% of patients, it leads to blindness.
Black people such as Lackey are five times more likely to develop glaucoma than white people, and the disease tends to strike Black patients a decade earlier and progress faster. Yet, most glaucoma research — as with many other medical studies — has focused on white patients.
A team of scientists and doctors at Penn’s Scheie Eye Institute aims to change that. Led by Joan O’Brien, professor of ophthalmology and director of Scheie, the Primary Open-Angle African American Glaucoma Genetics Study has recruited more than 10,000 Black Philadelphians for one of the largest genetic studies of the disease in this population.
Other researchers are now trying to replicate their success at recruiting a group that scientists often think don’t want to participate in research. “We’ve gotten so many calls and inquiries from other genetic studies asking us … ‘What’s your secret?’” said Marquis Vaughn, director of community outreach for the project.
A race against blindness
Scheie Eye Institute sits in West Philadelphia where three-quarters of residents are Black, according to the most recent census data. Eydie Miller-Ellis, professor of clinical ophthalmology at Penn and chief of the glaucoma service at Scheie, estimates that more than half of her patients are Black.
The researchers leading the study — many of whom are Black — are drawing on personal experiences. Ahmara Ross, assistant professor of ophthalmology and neurology at Penn and a physician-scientist at Scheie, remembers her grandmother — who never visited an ophthalmologist — slowly losing her vision.
Miller-Ellis’ great-grandmother and grandfather had glaucoma, as did Vaughn’s grandfather and uncle. Learning in medical school about glaucoma’s disproportionate impact on the Black community motivated Miller-Ellis to specialize in ophthalmology.
“Once I learned that glaucoma was the number-one cause of preventable blindness in the Black community, that’s really what sold me on it,” Miller-Ellis said. “The word preventable is key.”
The Penn team is focusing on the more chronic form of glaucoma called primary open-angle glaucoma, or POAG, which slowly develops over a patient’s lifetime and is the most common type of glaucoma seen at Scheie. It develops stealthily: Bruce Thompson, of Lawncrest, hadn’t noticed any symptoms when he was first diagnosed with early-stage glaucoma around age 50 at a routine ophthalmologist visit.
Doctors use prescription eye drops, lasers, or surgery to reduce pressure in the eye before it causes irreversible damage to the optic nerve. Lackey says medications have maintained her vision. But not all glaucoma cases respond to treatment.
Moreover, patients who develop POAG while still, say, in their 40s, may think that vision problems are temporary and related to natural aging, not a sign of a progressive disease. By the time they consult a doctor, their vision loss can be permanent.
Combating distrust of research
At Scheie, “There was a rapid rate of people coming in being blind,” Vaughn said. It was clear that they needed to identify cases earlier.
O’Brien, a geneticist by training, wondered whether there might be clues in the genome that could predict risk of developing glaucoma. Because people’s DNA sequence is mostly with them from birth, this could be a way to intervene even before vision loss began. The problem was that, with so much glaucoma research done in white or Asian patients, the same genetic anomalies may not be relevant in people of African ancestry. They needed to do their own study in the Black population.
They set out in July 2010 to recruit thousands of study participants, but it was slow going.
Past research that mistreated Black participants is a well-known factor discouraging trust in medical research, as are many Black Americans’ own negative experiences with medical providers. Lackey is among many potential participants who mentioned the Tuskegee Syphilis study, and also worried about sharing her genetic material. She cited Henrietta Lacks, a Black cancer patient at Johns Hopkins University in the 1950s whose cells were taken and used without her consent in research, and live on to this day. “My DNA is me,” Lackey said.
Vaughn said some people worried that their DNA samples could be used as evidence to accuse them falsely of a crime.
“These types of hesitations and reservations have the negative effect of people of color not participating in very important research,” Vaughn said. “It takes away the chance for them to be a part of cutting-edge treatments.”
Born and raised in North Philadelphia, Vaughn was very familiar with how information spread through the Black community. So she helped design a multimedia glaucoma awareness campaign to encourage people to get screened. She placed informational fliers and postcards at strategic locations including hair salons, barber shops, and bus stops.
By 2014, efforts were intensified with the help of an $11 million grant from the National Institutes of Health.
The team hosted screenings at churches, community centers, health fairs, and in a specially outfitted van. There, clinical coordinators invited people to join the study. A patient diagnosed with glaucoma was referred for eye care. Many who hadn’t previously sought such help because they lacked health insurance or didn’t know they needed it have remained patients at Scheie, Ross said. The researchers provided transportation and lunch vouchers, though not only to study participants.
“We can’t just take, we have to give back, as well,” Vaughn said.
Vaughn convinced her father and uncle to get screened for the study. Although neither ended up being eligible, her father found out that he is at high risk of developing glaucoma — one of many people screened for the study who now receive eye care at Scheie.
Many of the doctors screening patients were themselves Black, and that helped build trust, Ross said.
“I would say, ‘Glaucoma is really the number-one blinding disease in our community and it affects us,’” Miller-Ellis said. “I think that since I could include myself in the ‘us’ that they felt that I was invested in it.”
Spreading the WURD
O’Brien then turned to an institution well-respected in the community: WURD Radio, a Black-owned and -operated talk station founded by Walter Lomax, a well-known Black physician.
His daughter Sara Lomax-Reese, president and CEO of the station, brought on Miller-Ellis and Ross to talk about free glaucoma screenings and participating in the study, and answer listeners’ questions. They also ran ads and testimonials from study participants. Listeners could call a phone number to enroll.
One survey showed that, ultimately, up to 75% of the the study participants recruited from the community heard about it through WURD.
“People assume that Black folks won’t participate in clinical trials because of the history of medical racism — which is real,” Lomax-Reese said. “Our collaboration with Scheie really upended that myth. If you do have trusted messengers, if you take really good care when people come into the institution, you can actually have very profound outcomes.”
After hearing the segment on WURD Radio, Thompson — still reeling from an unexpected glaucoma diagnosis after a routine checkup — decided to get a second opinion at Scheie. When a staff member in the waiting room invited him to join the study, he quickly agreed.
“I just felt it was the right thing to do,” Thompson said. “This is going to wake up some other folks, Black or white.”
The first time Lackey heard about the glaucoma study on WURD, she had reservations. But when she heard about it a second time, she started to imagine the role she could play in helping someone else avoid glaucoma complications.
This was a major motivation, the team found in follow-up interviews. Half of the participants interviewed said they wanted to help others.
“I’m praying that it’ll make a difference so future people don’t have to suffer glaucoma,” Lackey said.
Based on these interviews, the Penn researchers have since published papers to help other studies successfully recruit participants from underrepresented groups.
After initial recruitment was completed in 2019, the researchers began looking for genes that might play a role in glaucoma. These genes might have mutations that increase a person’s risk of optic nerve damage. If the researchers can find such genes, they might be a good target for gene therapy that provides the eye with a corrected copy of the gene, and perhaps become less dependent on medication.
“A lot of the genes that we know about in glaucoma don’t represent my population,” Ross said. “I want to make sure that they’re brought to the forefront and that, when we’re coming up with these targeted therapies, it’s targeted against their disease.”
This year, the Penn team published preliminary studies of genomic sequences — including some that are most often seen in people of African descent — that correlate with glaucoma risk in their Philadelphia cohort. Their recent work even found specific genetic mutations associated with individual eye measurements characteristic of POAG, such as pressure and the thickness of the nerves. This finding might suggest that POAG is a collection of different diseases with distinct genetic drivers, O’Brien said, and could ultimately improve patient care.
Their studies also highlight ways that ophthalmology tools fall short for Black patients. For example, Victoria Addis, an assistant professor of clinical ophthalmology at Scheie, found that the standard optic nerve database built into an eye-imaging machine didn’t match what she saw in healthy Black patients. Although many doctors don’t rely on the database to make their diagnoses, Ross said, it still has the potential to mislead physicians about their Black patients’ risk of glaucoma.
Since joining the study, Thompson continues taking eye drops regularly and hasn’t noticed a decline in his vision.
Lackey said being in the study has reinforced the importance of staying on her medication, something she already knew: A friend went blind from glaucoma without regular treatment.
It has also changed Lackey’s opinion about medical studies. Though still not completely convinced that her DNA is in safe hands, she said, “I’m cautiously optimistic that they can make a difference, and I’m willing to try to help.”
Take COVID-19 vaccine trials, for example: Lackey said she wouldn’t personally volunteer for a trial, but she respects people who did. “That is something they’re doing for all of us,” she said. “Maybe my contribution to glaucoma will be like that.”