National clinical trials will test innovative amblyopia treatment for children using virtual reality headsets
The first mention of amblyopia, the pediatric eye disease more commonly known as lazy eye, dates back to Hippocrates and ancient Greece. And the oldest, most common way to treat the condition goes way back, too.
For nearly 3,000 years, eye patch therapy — a daily regimen of covering the so-called “good” eye to force the weaker eye to work harder to catch up — has been the go-to treatment for improving vision for millions of children worldwide.
Now, UND researchers are recruiting families for a pair of Pediatric Eye Disease Investigator Group clinical trials that could change that standard of care for the first time in centuries. The PEDIG studies are funded through the National Eye Institute of the National Institutes of Health.
One of 400-plus amblyopia treatment testing sites
“A clinical trial of this scope and scale represents a huge opportunity for the University of North Dakota,” said vision scientist and Psychology Professor Dmitri Poltavski, who’s partnering on the research with retired longtime Grand Forks optometrist Dr. David Biberdorf.
“We’ve been doing vision research together for quite some time, and we’re familiar with what type of treatments, so to speak, are hot and being tried out right now,” Poltavski said. “As the only clinical site selected in the state, we’re super excited to be part of this research for two reasons. No. 1, of course, is because it has the potential to change lives.
“Just for starters, we’re going to be able to give kids in North Dakota and Minnesota treatment that may be more effective than what’s currently available to them. And No. 2, we hope to boost UND’s prominence as a clinical research facility.”
Each of the two studies will include about 250 children being treated at more than 400 pediatric eye centers throughout North America.
Meet the local amblyopia research team
Biberdorf will serve as the principal investigator for the Grand Forks clinical trials. Poltavski will be the site coordinator responsible for protocol training, equipment setup and grant management. He’ll also be the liaison between UND and the Jaeb Center for Health Research in Tampa, Fla., which is the central data collection site.
Rounding out the team is optometric vision therapist Carolina Praus Poltavski. She happens to be Poltavski’s wife, and she worked alongside Biberdorf at Grand Forks’ Valley Vision Clinic for more than 15 years. For the clinical trials, she’ll be in charge of study-specific examinations and treatment procedures, as well as local data entry.
“Between the three of us, we had all the credentials for a complete team, so it was a no-brainer for us to apply to become a clinical trial site,” Poltavski said. “For us, it’s a win-win because not only can we provide this free service to our community — no insurance is involved, the grant pays for all of it — we’re also opening a new avenue for external research funding.”
And being a PEDIG site positions UND for possible future research funding, he said.
“As a study site, we can introduce new advances that we may have discovered here,” Biberdorf added. “We can approach the rest of the group and say, ‘Hey, we have an idea for a study we think needs exploring.’ We can come up with our own innovative ideas to pitch.”
Biberdorf called PEDIG a pioneer in pediatric eye disease research. Formed by NEI in 1997 as a collaborative network dedicated to clinical research in amblyopia, strabismus (misaligned, or crossed, eyes) and other pediatric eye disorders, PEDIG receives millions of dollars in NIH funding each year, he said, and typically manages several ongoing projects.
What is the cause, impact of amblyopia?
The researchers described amblyopia as a neurodevelopmental disorder that results from inadequate visual stimulation to one eye during the first years of life. When the eyes are not properly aligned — for example, if one eye turns outward or inward — they cannot work together, and critical visual development is thrown off course.
Using an analogy to help explain, Biberdorf said: “I like to think of amblyopia as having an underdeveloped eye. It’s like you have a 6-year-old eye and a 3-month-old eye. And what we need to do is get that 3-month-old eye to catch up to the 6-year-old level.”
Added Poltavski: “It’s almost like visual neglect because the brain will suppress the low-quality information from the eye with poor visual acuity and begin to rely more on the information coming from the ‘good’ eye.”
If treated early, prescription eyeglasses sometimes can be enough to correct the condition. But if left untreated, the brain can begin to ignore visual signals from the poor eye altogether.
The disorder affects 2 percent to 5 percent of the pediatric population, and it’s the leading cause of monocular vision loss in children. Biberdorf says it also can cause “substantial variations in brain activity patterns and cortical thickness, changes in gray and white matter and functional brain activity.”
Further, amblyopia often reduces hand-eye coordination and can lower a child’s reading performance and self-perception. Because it impacts binocular (two-eyed) vision, it also diminishes 3D depth perception and visually guided skills such as the speed and accuracy of reaching and grasping.
Poltavski and Biberdorf say it’s important to begin treating amblyopia early because the success rate with current treatment standards drops significantly after age 8 — a statistic largely attributed to a coinciding decrease in patch compliance rates as children get older.
“They get to age 8, and they just don’t want to do it,” Poltavski said. “They don’t want to be different. They don’t want to be teased for wearing the patch.”
How does the advanced amblyopia treatment work?
And that’s just one reason the high-tech treatment using virtual reality headsets may have an advantage.
“The science is complex, but when we’re talking about improving vision, what we’re really talking about is neuroplasticity and training the brain to overcome the poor circuitry that’s feeding reduced information to the visual cortex,” Biberdorf said.
Added Poltavski: “Once you can tap into that mechanism of cerebral plasticity, the eyes will start to work as a team, and the visual cortex will incorporate input from both eyes. Once the process gets started, it’s almost self-healing.”
So how do these advanced treatments differ from the age-old patching method?
Well, that’s complicated, too, but Biberdorf sums it up this way:
The virtual reality headsets incorporate dichoptic/binocular technology, whereby the child watches shows or plays interactive video games as each eye views a separate and independent screen. Different stimuli are presented to each eye simultaneously.
“Employing the science of perceptual learning and brain plasticity, the object is to degrade the image quality or reduce the luminance to the dominant eye to provide the amblyopic eye with a visual advantage of a computer-generated scene,” Biberdorf said. “The manipulated stimuli are such that many of the important details of the scene will be perceived only by the amblyopic eye. In this way, the visual system can achieve a more balanced binocular view of a scene.
“In contrast to patching — in which the object is to penalize the dominant eye and to stimulate the amblyopic eye passively — the binocular treatment has the objective of progressively balancing both eyes to involve a more attentional interaction on the part of the patient. This simultaneous vision approach is thought to lead to improved binocularity.”
Evidence has shown that some of the high-tech digital devices may improve visual acuity more quickly than patching — with patients showing significantly improved acuity after one to two months compared with the four to six months required to achieve similar improvement through typical patching.
“This could improve patient compliance as well as reduce the cost of visits, travel to appointments and time off work for parents,” Biberdorf said.
The technology also is promising for patients whose progress has plateaued with traditional therapy.
“The clinical trials are so new, but the beauty of an NIH-funded study is that it can be systematized in such a way that the results could change the standard of care,” Biberdorf said.
Imagine that. Research that could change the treatment of a disease as old as Hippocrates — the father of medicine himself — is happening right here at UND.
What are the details for the amblyopia treatment studies?
In one clinical trial, children ages 4 to 7 will be randomly selected via computer to begin the 26-week study either by wearing an eye patch two hours a day, seven days a week or watching children’s shows using a Luminopia virtual reality headset for one hour a day, six days a week.
They also will begin by answering some initial questions and have their vision tested while wearing their regular prescription glasses. Follow-up vision tests and questions come at Weeks 13 and 26.
Children who begin with patching will have the chance to try the Luminopia headset if they still show signs of amblyopia at the end of 26 weeks. They then return for follow-ups at Weeks 39 and 52.
The eye patches and headsets will be provided. If new glasses are needed during the study, they will be provided at no charge.
A second study for children ages 8 to 12 is designed to test whether watching shows wearing the Luminopia headset (one hour per day, six days a week) or playing games using a Vivid Vision headset (25 minutes per day, six days a week) improve vision better than glasses alone.
Again, the testing is random for the 18-week study, and the children begin with initial questions and vision tests while wearing their regular glasses. Follow-up visits come at Weeks 9 and 18.
Children selected for the glasses-alone group will have the opportunity to try one of the headsets for 18 weeks if they still have amblyopia at the end of the first round. In that case, two more follow-ups come at Weeks 27 and 36.
In both studies, parents or guardians will record daily treatment time on a calendar and be asked questions about their child’s eyes.
All headsets must be returned at the completion of the study, but families will get to take something home. To cover travel and other visit-related expenses, families will receive $100 Amazon gift cards (up to a total of $500) after each exam is completed.
>> How do I learn more about the studies or find out if my child is eligible? Leave a voicemail at 701.777.6843 or email UND.eyeclinictrials@UND.edu.
>> Read about more amblyopia research conducted by Poltavski and Biberdorf. “Effectiveness of a Novel Video Game Platform in the Treatment of Pediatric Amblyopia” originally was published in April 2023 in the Journal of Pediatric Ophthalmology & Strabismus.
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