Anne Lynch, MD, distinctly remembers the day the Sue Anschutz-Rodgers Eye Center’s age-related macular degeneration (AMD) registry enrolled its first patient.
“We were just so delighted. I started working here at the beginning of that year, so we had about six months of organizing and planning to get everything ready, and on July 9, 2014, we took in our first patient,” recalls Lynch, a professor of ophthalmology and director of the Division of Ophthalmic Epidemiology at the University of Colorado School of Medicine.
“Since that day we’ve had so many motivated patients enroll that realize how important this registry is and how it enables research that helps us understand the condition,” she says.
The registry holds repositories of electronic data, imaging data, and blood samples for biomarker studies that allow researchers to further investigate the disease. By 2040, it’s projected that AMD will impact an estimated 288 million people worldwide.
Damage to the macula progressively diminishes central vision. In dry AMD, which accounts for about 80% of cases, parts of the macula thin as small clumps of protein called drusen form. In wet AMD, which is rarer, new blood vessels grow under the retina and leak blood and fluid. Wet AMD leads to faster vision loss.
Now in its 10th year of operation, the registry includes close to 2,000 patients. It’s also been the foundation for 29 published manuscripts and nearly 50 presentations at various meetings and conferences around the world.
“We are proud that all of our retinal specialists and the registry team have worked together to create this rich, highly curated registry of patients over the last decade,” says AMD specialist Naresh Mandava, MD, professor and chair of the Department of Ophthalmology.
“There is tremendous value of the large datasets created from the registry,” Mandava, who is also the Sue Anschutz-Rodgers Chair in Retinal Diseases, continues. “We can mine the data and find associations with biomarkers in the blood, genetics, images of the retina, and our deep understanding of the health of our patients. We have discovered associations of biomarkers with imaging findings as well as the identification of higher risk biomarkers indicative of the greater risk of developing advanced AMD.”
The work that’s made possible by the registry may lead to drug discoveries that target new pathways also identified through the registry and help find patients who may be a good fit for clinical trials because they have the highest risk of progression to advanced disease.
Going the distance
Other AMD registries across the country and the globe exist, but few of them capture longitudinal data.
When a Sue Anschutz-Rodgers Eye Center patient is first recruited into the registry, they give enrollment samples of their blood and complete multimodal imaging. Physicians analyze these images and classify the case into early AMD, intermediate AMD, and advanced types of AMD, which include geographic atrophy (GA) and neovascular AMD.
Then, each year after that, the registry team collects another blood sample from each patient on the registry and connects it to their imaging. This allows the researchers to study changes over time.
“It’s quite novel to collect longitudinal measures of certain biomarkers,” Lynch says. “It makes our registry unique.”
It can also be a challenge. Most of the people in the registry are elderly, as the disease mainly affects older populations. Sometimes they become too feeble or frail or cognitively impaired to continue to participate in the registry. Other times, they develop other comorbidities that hinder their inclusion in the registry.
In 2019, an analysis of the registry found that 20% of participants died within a 52.5-month average follow-up time. Better general health and the ability to drive were each separately associated with significantly lower risk of death individuals with AMD.
“Longitudinal studies are difficult because they require deep commitment and large investments to retain the confidentiality, quality, and integrity of the data collected,” Mandava says. “They also require teams that stay together for many years with a deep commitment to discovery and I am proud that we have that here at the Sue Anschutz-Rodgers Eye Center.”
Studying disease trajectory and building risk scores
AMD researchers in the department have used the registry for several investigations on the epidemiology of AMD, the complement system, proteomics, inflammation, and imaging.
In 2021, the group received its first grant from the National Institutes of Health (NIH), totaling $1.6 million, to study inflammatory biomarkers and create patient risk profiles that aim to offer earlier intervention and treatment options.
Lynch says developing an AMD progression risk score that combines known AMD risk factors, new systemic inflammatory profiles, imaging, and genetics can improve intervention timing.
The NIH funding has helped the researchers make significant progress on their goal. As a part of that work in 2022 a study confirmed an association between vision loss from AMD and depression.
What’s ahead for AMD researchers
Lynch, Mandava, and the team of registry researchers and staff say the first decade is just the beginning for the registry.
“We are committed to continuing to collect patient information and as technology advances, we are able to interrogate our datasets and create algorithms that can be used on all patients even outside of the registry,” Mandava says.
Recently, the department’s artificial intelligence team developed a clinical tool to visualize the growth of geographic atrophy, an advanced form of AMD.
“With this tool, our researchers are publishing new discoveries on how these atrophic areas grow over time. This has implications for clinical trial design as well as current therapies,” Mandava says.
Biologic discoveries also continue to improve each year. Having biobank specimens that the researchers can test with new technologies allows them to go back and study a biopsy of time in the lifecycle of a patient’s macular degeneration.
“This opens the door for even more discoveries,” Mandava says.
Of course, the patients willing to participate in the registry make it all possible.
“Our team is grateful for the dedication and commitment these patients have to the registry,” Lynch says. “We have to keep working for them toward new interventions and slowing the progression of this terrible disease.”
