Advancing optic disc drusen

Stanford scientists provide hope

When Joyce Liao, MD, PhD, associate professor of ophthalmology and of neurology, came to Stanford in 2006, she began seeing patients with optic disc drusen (ODD), a condition that effects vision and the optic nerve, and was frustrated with how little she could offer them.

In ODD, calcium-containing deposits at the optic nerve head are associated with damaged optic nerve axons. These deposits are present in about 2-4% of the general population, and can lead to irreversible vision loss that can be slowly progressive or sudden in onset.

“ODD typically causes peripheral vision damage in patients, and sometimes it also damages the central vision,” Liao said. “It is common enough, but people may not realize they have it until they are seen by an eye doctor.”

ODD, which affects both children and adults, also has a genetic component. There is a 50% chance someone with ODD will pass it onto their offspring—but studies on what genes cause the disease have been lacking.

“ODD typically causes peripheral vision damage in patients, and sometimes it also damages the central vision. It is common enough, but people may not realize they have it until they are seen by an eye doctor.

“There is an urgent need to advance our understanding of optic disc drusen,” Liao said. “Today, more than 150 years after the first description of this disease, we do not know what causes it, or the pathophysiology of how it leads to vision loss.”

Over the years, the number of ODD patients seen by Liao continued to increase, until finally the evidence became overwhelming: there was a great unmet need to deepen the understanding of the disease, and to start specifically studying its causes and potential for treatments. In 2019 that need was met when a visionary donor provided a $10 million gift to establish the Stanford Center for Optic Disc Drusen at the Byers Eye Institute.

Joyce Liao, MD, PhD, serves as the director of the recently established Stanford Center for Optic Disc Drusen (ODD) at the Byers Eye Institute. ODD is a condition that damages the optic nerve and decreases vision. Photo by Steve Fisch.

The Stanford Center for Optic Disc Drusen at the Byers Eye Institute

The newly established Center helped unite a premier group of faculty dedicated to investigating optic nerve damage, with the goal of preserving and restoring vision in patients with ODD. These include investigators who specialize in studies of the retina, optic nerve, and brain, as well as experts in clinical trial design who can help translate findings into novel clinical studies.

“While a number of us had been doing clinical research on conditions related to ODD for some time, establishing the ODD Center has allowed my colleagues and me to significantly deepen our investigation of ODD,” Liao said.

The formative Center gift has allowed Stanford faculty to pursue critical research in human patients and in animal models in parallel. Generating the first ever animal models of ODD is a key step to investigate the pathogenesis of disease and discover effective therapeutic candidates.

Patient studies will leverage advanced noninvasive imaging and innovative functional measurements invented at Stanford to run a first-of-its-kind comprehensive study of the natural history of the disease, and search for new biomarkers to use in therapeutic trials.

The ODD Center is comprised of a premier group of faculty dedicated to investigating optic nerve damage. The clinical human research group includes: Front row (L to R): Justin Gardner, PhD; and Anthony Norcia, PhD. Back row (L to R): Quan Dong Nguyen, MD, MSc; Yasir Sepah, MBBS; Alfredo Dubra, PhD; Joyce Liao, MD, PhD; Heather Moss, MD, PhD; Tawna Roberts, OD, PhD; Jeffrey Goldberg, MD, PhD; Diana Do, MD; and Brian Wandell, PhD. Not pictured: Shannon Beres, MD; Jonathan Lin, MD, PhD; and Edward Wood, MD.

The basic science research group includes: Front  row (L to R): Jeffrey Goldberg, MD, PhD; and Vinit Mahajan, MD, PhD. Back row (L to R): David Myung, MD, PhD; Alfredo Dubra, PhD; Yang Hu, MD, PhD; Michael Kapiloff, MD, PhD; Joyce Liao, MD, PhD; Yang Sun, MD, PhD; and Albert Wu, MD, PhD, FACS. Not pictured: Andrew Huberman, PhD; Jonathan Lin, MD, PhD.

 The inaugural Optic Disc Drusen Virtual Conference

With a dual goal of increasing patient outreach for these trials, and for convening worldwide science on ODD, the ODD Center hosted the first international ODD conference on May 11, 2020. It was initially planned as an in-person event, but then converted to virtual, because of the coronavirus (COVID-19) pandemic.

“I am encouraged by what we have accomplished since opening the ODD Center. Our hope for the Center is to merge education, rigorous research, and above all provide better treatments for our patients.

The conference featured nearly 450 participants from 35 countries. It helped galvanize the scientific community’s focus on ODD as attendees explored and shared laboratory and clinical advances, seeded collaborative opportunities, and strategized to further advance the field.

 “With the inadequacy of current treatment options for ODD, this conference provided a platform to leapfrog research towards greater understanding and better treatment options,” Liao said. The conference also included ODD patients and their families. “We gave patients a forum to voice the urgency of their experiences with vision loss, and to hear our hope for the future of this research.”

Patients from all over the world will benefit from the research ongoing at the ODD Center.

A patient’s perspective: Seeking hope in the ODD journey

Wendy, a patient who shared her personal story during the conference, was diagnosed with ODD nearly seven years ago when in her early 60’s.

While in the process of moving from one side of the Twin Cities, Minnesota, to the other, she transferred her care to a new ophthalmologist. During her routine checkup she learned for the first time the shocking news that she had had glaucoma and ODD for some years.

Up until that point, she had never even heard of ODD. Wendy had worn glasses and contacts, and had undergone cataract surgery years prior, and yet had never been diagnosed with ODD. Wendy’s new doctor shared that she had the worst case of optic disc drusen he had ever seen. She left that appointment with eye drops for glaucoma, but still seeking a deeper understanding of ODD and a doctor who could help treat her conditions.

“No one could give me any indication about what my future held,” Wendy said. “There was no research and no known cause, and that left me frustrated and worried.”

Wendy had led an active life of swimming, biking, and hiking regularly, but things began to change. Finding her balance became more difficult. She began bumping into people and became more prone to falling. Her vision worsened and although she can still drive today, the hardest part was giving up driving her grandchildren.

Determined to find a cure, Wendy began researching physician scientists across the country, until she came across Jeffrey Goldberg, MD, PhD, the Blumenkranz Smead professor and chair of ophthalmology at the Byers Eye Institute at Stanford, who at the time was a professor at UC San Diego and directing laboratory and clinical optic nerve research while treating patients.

“I have had quite the medical journey,” Wendy said. “I have had cancer treatment, multiple surgeries, back surgery, open heart surgery, and with each one I bounced back quickly, but with my vision it has been tougher. Perhaps it is because my vision is especially precious to me and I had taken it for granted, so when I understood what Dr. Goldberg was doing with optic nerve research, I became a willing participant—his commitment gave me the hope I was looking for.”

She continued to receive care from Goldberg when he came to Stanford. Wendy noted that attending the ODD conference was exceptionally informative and it was helpful to hear about the experiences of other patients with the disease.  

“I am encouraged by what we have accomplished since opening the ODD Center,” Liao said. “Our hope for the Center is to merge education, rigorous research, and above all provide better treatments for our patients.”

To learn more about ODD, visit the Stanford Center for Optic Disc Drusen at the Byers Eye Institute website at https://med.stanford.edu/optic-disc-drusen.html.



By KATHRYN SILL

Kathryn Sill is a web and communications specialist for the Byers Eye Institute in the Department of Ophthalmology, at Stanford University School of Medicine. Email her at ksill@stanford.edu.