Now, a novel clinical trial offers hope for patients with advanced “dry” age-related macular degeneration. Dry age-related macular degeneration is the most common form of the disease.

Researchers at the USC Roski Eye Institute, part of Keck Medicine of USC, are launching a phase 2b clinical trial examining if stem cells bioengineered to replace failing cells in the retina damaged by macular degeneration could restore eyesight. The cells are attached to an implant — an ultra-thin patch, thinner than a strand of hair — which holds the cells in place.

“We are hoping to determine if the stem-cell based retinal implant can not only stop the progression of dry age-related macular degeneration, but actually improve patients’ vision,” said Sun Young Lee, MD, PhD, a retinal surgeon with Keck Medicine and principal investigator of the Keck Medicine study site. “The findings could be groundbreaking because while there are a few treatments available that delay the progress of macular degeneration, there are none able to reverse the damage already done.”

The clinical trial follows early research conducted by USC Roski Eye Institute experts on a small patient population that showed the implant was well-tolerated, stayed put in the eye and was successfully absorbed into the tissue of the retina. Additionally, 27% of patients had some improved vision.

“The earlier phase of the clinical trial showed the treatment to be safe with the potential to benefit patients’ vision; this next phase will investigate whether the therapy can achieve clinically significant improvements in vision,” said Lee, who is also an associate professor of ophthalmology and physiology & neuroscience at the Keck School of Medicine of USC. 

Click here for five tips to help prevent macular degeneration.

How the retinal implant works

Approximately 20 million Americans live with age-related macular degeneration. This number also includes cases of wet macular degeneration, which is a less common but more serious form of the disease.

Age-related macular degeneration affects the eye’s macula, which is located in the center of the retina and is responsible for central vision. In advanced cases, the retinal pigment epithelium (RPE) cells, which line the macula and are key in helping the retina produce clear vision, become damaged or destroyed, which leads to vision loss.

The retinal implant used in the clinical trial is derived from embryonic stem cells grown into RPE cells in a lab. During an outpatient surgical procedure, Keck Medicine eye surgeons will implant a tiny layer of the lab-produced RPE cells into the retina.

“The study will explore if the lab-engineered implant will take over for the damaged cells, function as normal RPE cells would, and improve vision for patients who may currently have no other options for improvement,” said Rodrigo Antonio Brant Fernandes, MD, PhD, an ophthalmologist with Keck Medicine and the study surgeon. He is also an associate professor of clinical ophthalmology at the Keck School. 

Details of the clinical trial

Keck Medicine is one of five locations in the nation enrolling patients in the clinical trial. The study is masked — some of the enrolled participants will receive the implant, while others receive a simulated implant.

Eligible patients must be between ages 55-90 with advanced dry age-related macular degeneration and a diagnosis of geographic atrophy, meaning their RPE cells are damaged or not functioning.

Patients will be monitored for at least one year to determine how the implant is tolerated and for any changes in vision. The trial is hoping to enroll 24 patients.

Those interested in learning more about the trial can contact Mariana Edwards at mariana.edwards@med.usc.edu or Kimberly Rodriguez at kimberly.rodriguez2@med.usc.edu.

"The USC Roski Eye Institute is dedicated to furthering innovative treatments to help improve lives by restoring vision,” said Mark S. Humayun, MD, PhD, co-director of the USC Roski Eye Institute, director of the USC Ginsberg Institute for Biomedical Therapeutics and the Dennis and Michele Slivinski Chair in Macular Degeneration Research at the Keck School. “Stem cell-derived retinal implants may offer one of the greatest possibilities for helping patients with dry age-related macular degeneration and one day, may offer a cure.”

“Current wearable low vision technologies using virtual reality are limited and can be difficult to use or require patients to undergo extensive training,” said Mark Humayun, MD, PhD, director of the USC Dr. Allen and Charlotte Ginsburg Institute for Biomedical Therapeutics, co-director of the USC Roski Eye Institute and University Professor of Ophthalmology at the Keck School.

“Using a different approach — employing assistive technology to enhance, not replace, natural senses — our team adapted AR glasses that project bright colors onto patients’ retinas, corresponding to nearby obstacles,” Humayun said.

Patients with retinitis pigmentosa wore adapted AR glasses as they navigated through an obstacle course based on a U.S. Food and Drug Administration–validated functional test. Using video of each test, researchers recorded the number of times patients collided with obstacles, as well as the time taken to complete the course. Patients averaged 50% fewer collisions with the adapted AR glasses.

Patients also were asked to grasp a wooden peg against a black background — located behind four other wooden pegs — without touching the front items. Patients demonstrated a 70% increase in grasp performance with the AR glasses.

“Patients with retinitis pigmentosa have decreased peripheral vision and trouble seeing in low light, which makes it difficult to identify obstacles and grasp objects. They often require mobility aids to navigate, especially in dark environments,” said Anastasios N. Angelopoulos, study project lead in Humayun’s research laboratory at the Keck School.

“Through the use of AR, we aim to improve the quality of life for low vision patients by increasing their confidence in performing basic tasks, ultimately allowing them to live more independent lives,” Angelopoulos said.
 
How the AR system works
The AR system overlays objects within a 6-foot wireframe with four bright, distinct colors. In doing so, the glasses provide visual color cues that help people with constricted peripheral vision interpret complex environments, such as avoiding obstacles in dimly lit environments.

To accomplish this, researchers used a process called simultaneous location and mapping, allowing the AR glasses to fully render the 3-D structure of a room in real time. The glasses then translated this information into a semitransparent colored visual overlay, which highlighted potential obstacles with bright colors to help patients with spatial understanding and depth perception. This technology can work on commercially available devices.

According to Humayun, while major cost and technical issues remain, this type of assistive technology could eventually become more practical for everyday use in the near future.

— Wendy Wolfson

The treatment, which consists of a layer of human embryonic stem cell–derived retinal pigment epithelium cells on an ultrathin supportive structure, was implanted in the retina of four patients by a USC Roski Eye Institute surgeon. The patients were followed for up to one year to assess its safety. There were no severe adverse events related to the implant or the surgical procedure, indicating that the treatment was well-tolerated. There was also evidence that the implant integrated with the patients’ retinal tissue, which is essential for the treatment to be able to improve visual function.

This is the first human trial of this novel stem cell–based implant, which is designed to replace a single-cell layer that degenerates in patients with dry age-related macular degeneration,” says lead author and surgeon for the study Amir H. Kashani, MD, PhD, assistant professor of clinical ophthalmology at the Keck School of Medicine of USC. “This implant has the potential to stop the progression of the disease or even improve patients’ vision. Proving its safety in humans is the first step in accomplishing that goal.”

A scanning electron microscope image of retinal pigment epithelial cells derived from stem cells.(Photo/USC Roski Eye Institute)

Dry age-related macular degeneration is the most common type of age-related macular degeneration. Over time, it can lead to loss of central vision, which can diminish people’s ability to perform daily tasks like reading, writing, driving and seeing faces. Age-related macular degeneration affects approximately 1.7 million Americans and is projected to rise to almost 3 million by 2020. It is a leading cause of severe visual impairment in adults older than 65.

As part of the study, the research team also performed a preliminary assessment of the therapy’s efficacy. One patient had improvement in visual acuity, which was measured by how many letters they could read on an eye chart, and two patients had gains in visual function, which was measured by how well they could use the area of the retina treated by the implant. None of the patients showed evidence of progression in vision loss.

“Our study shows that this unique stem cell–based retinal implant thus far is well-tolerated, and preliminary results suggest it may help people with advanced dry age-related macular degeneration,” says coauthor and lead inventor of the implant Mark S. Humayun, MD, PhD, director of the USC Institute for Biomedical Therapeutics, co-director of the USC Roski Eye Institute, affiliate principal investigator with the Eli and Edythe Broad Center for Regenerative Medicine and Stem Cell Research at USC and University Professor of Ophthalmology at the Keck School. “CIRM has provided a conducive environment for stem cell research at the USC Roski Eye Institute and the Keck School of Medicine by providing funding for our clinical trial, along with a generous gift to the Eli and Edythe Broad Center for Regenerative Medicine.”

Humayun, David R. Hinton, MD, professor of pathology at the Keck School, and Dennis O. Clegg, PhD, University of California, Santa Barbara Wilcox Family Chair in BioMedicine and co-director of the campus’ Center for Stem Cell Biology and Engineering, co-invented the implant.
Collaborating institutions for the study include Regenerative Patch Technologies LLC, which also contributed to the funding of the study, as well as Camtek LLC, the California Institute of Technology, Retina Vitreous Associates Medical Group, California Retina Consultants, Atlantis Eyecare, City of Hope, University of California, Santa Barbara and Denney Research Center. Additional sources of funding for the study include Lori Mars gift, William K. Bowes Foundation, Vermont Community Foundation, Breaux Foundation, Wilcox Family Foundation and Research to Prevent Blindness.

For more information about the study, visit https://clinicaltrials.gov/ct2/show/NCT02590692?term=nct02590692&rank=1. To participate in the study, please call (323) 442-6335.

— Erica Rheinschild

“Dr. Rao’s research achievements have placed him at the top of his specialty,” said Laura Mosqueda, MD, interim dean of the Keck School. “He has received continuous grant funding from the National Institutes of Health since 1979 and has authored nearly 500 peer-reviewed publications and six books on ophthalmic diseases. He has been a valued faculty member for more than three decades, and I have no doubt that the Department of Ophthalmology will flourish under his leadership.”

Rao has received a number of awards for his research and contributions to ophthalmology, including honors from the National Institutes of Health, U.S. Department of Veterans Affairs, American Academy of Ophthalmology and International Council of Ophthalmology. He has also served as president of the American Uveitis Society, International Society for Ophthalmic Pathology and International Ocular Inflammation Society, among other professional societies.

“It is a great pleasure to lead the Department of Ophthalmology and continue its important mission of ending vision loss and blindness,” Rao said. “I’m looking forward to working with the department’s exceptionally talented physicians, scientists, staff and students to make that goal a reality.”
The founder and first editor-in-chief of the Journal of Ophthalmic Inflammation and Infections, Rao earned a medical degree from Osmania University in Hyderabad, India, completed residencies in pathology and ophthalmology at Georgetown University and completed a fellowship in ophthalmic pathology at the Armed Forces Institute of Pathology.

— Erica Rheinschild