For millions of people with macular degeneration, treatment options are slim. The disease causes loss of central vision, which allows us to see straight ahead, and is highly dependent on age, with people over 75 at approximately 30% risk of developing the disorder. The BrightFocus Foundation estimates 11 million people in the U.S. currently have one of three forms of the disease.
Recently, ophthalmologists including Daniel Palanker at Stanford University published research showing advances in the PRIMA retinal implant, which could help people with advanced, age-related macular degeneration regain some of their sight. In a feasibility study, five patients had a pixelated chip implanted behind the retina, and three were able to see using their remaining peripheral vision and—thanks to the implant—their partially restored central vision at the same time.
Should people with macular degeneration be excited about these results?
“Every week, if not every day, patients come to me with this question because it's devastating when they lose their central vision,” says retinal surgeon Lynn Huang. About 40% of her patients have macular degeneration. Huang tells them that these implants, along with new medications and stem cell therapies, could be useful in the coming years.
“The goal here is to replace the missing photoreceptors with photovoltaic pixels, basically like little solar panels,” Palanker says.
That implant, a pixelated chip, works together with a tiny video camera on a specially designed pair of eyeglasses, which can be adjusted for each patient’s prescription. The video camera relays processed images to the chip, which electrically stimulates inner retinal neurons. These neurons, in turn, relay information to the brain’s visual cortex through the optic nerve. The chip restores patients’ central sight, but not completely. The artificial vision is basically monochromatic (whitish-yellowish) and fairly blurry; patients were still legally blind even after the implant, except when using a zoom function on the camera, but those with proper chip placement could make out large letters.
“The goal here is to replace the missing photoreceptors with photovoltaic pixels, basically like little solar panels,” Palanker says. These pixels, located on the implanted chip, convert light into pulsed electrical currents that stimulate retinal neurons. In time, Palanker hopes to improve the chips, resulting in bigger boosts to visual acuity.
The pixelated chips are surgically implanted during a process Palanker admits is still “a surgical learning curve.” In the study, three chips were implanted correctly, one was placed incorrectly, and another patient’s chip moved after the procedure; he did not follow post-surgical recommendations. One patient passed away during the study for unrelated reasons.
University of Maryland retinal specialist Kenneth Taubenslag, who was not involved in the study, said that subretinal surgeries have become less common in recent years, but expects implants to spur improvements in these techniques. “I think as people get more experience, [they’ll] probably get more reliable placement of the implant,” he said, pointing out that even the patient with the misplaced chip was able to gain some light perception, if not the same visual acuity as other patients.
Retinal implants have come under scrutiny lately. IEEE Spectrum reported that Second Sight, manufacturer of the Argus II implant used for people with retinitis pigmentosa, a genetic disease that causes vision loss, would no longer support the product. After selling hundreds of the implants at $150,000 apiece, company leaders announced they’d “decided to pursue an orderly wind down” of Second Sight in March 2020 in the wake of financial issues. Last month, the company announced a merger, shifting its focus to a new retinal implant, raising questions for patients who have Argus II implants.
Retinal surgeon Eugene de Juan of the University of California, San Francisco, was involved with early studies of the Argus implants, though his participation ended over a decade ago, before the device was marketed by Second Sight. He says he would consider recommending future implants to patients with macular degeneration, given the promise of the technology and the lack of other alternatives.
“I tell my patients that this is an area of active research and development, and it's getting better and better, so let's not give up hope,” de Juan says. He believes cautious optimism for Palanker’s implant is appropriate: “It's not the first, it's not the only, but it's a good approach with a good team.”
At age 52, Glen Rouse suffered from arm weakness and a lot of muscle twitches. “I first thought something was wrong when I could not throw a 50-pound bag of dog food over the tailgate of my truck—something I use to do effortlessly,” said the 54-year-old resident of Anderson, California, about three hours north of San Francisco.
In August, Rouse retired as a forester for a private timber company, a job he had held for 31 years. The impetus: amyotrophic lateral sclerosis, or ALS, a progressive neuromuscular disease that is commonly known as Lou Gehrig’s disease, named after the New York Yankees’ first baseman who succumbed to it less than a month shy of his 40th birthday in 1941. ALS eventually robs an individual of the ability to talk, walk, chew, swallow and breathe.
Rouse is now dependent on ventilation through a nasal mask and uses a powerchair to get around. “I can no longer walk or use my arms very well,” he said. “I can still move my wrists and fingers. I can also transfer from my chair to the toilet if I have two of my friends help me.”
It’s “shocking” that modern medicine has very little to offer to people with this devastating condition, Rouse said. But there is hope on the horizon. Yesterday, the U.S. Food and Drug Administration approved Relyvrio, a drug made up of two parts, sodium phenylbutyrate and taurursodiol, to treat patients with ALS.
“This approval provides another important treatment option for ALS, a life-threatening disease that currently has no cure,” said Billy Dunn, director of the Office of Neuroscience in the FDA’s Center for Drug Evaluation and Research, in a statement. “The FDA remains committed to facilitating the development of additional ALS treatments.”
Until this point, the FDA had approved only two other medications—Riluzole (rilutek) in 1995 and Radicava (edaravone) in 2017—to extend life in patients with ALS, which typically kills within two to five years after diagnosis. That’s why earlier this week, Rouse was optimistic about the FDA’s likely approval of a controversial new drug for ALS.
When Relyvrio is taken in addition to Riluzole, it appears to slow functional decline by an additional 25 percent and extend life by another 6 to 10 months, said Richard Bedlak, director of the Duke ALS Clinic. “It is not a cure, but it is definitely a step forward.”
“The whole ALS community is extremely excited about it,” he said the day before Relyvrio’s expected approval. “We are very hopeful. We’re on pins and needles.”
A study of 137 ALS patients did not result in “substantial evidence” that Relyvrio was effective, the agency’s Peripheral and Central Nervous System Drugs Advisory Committee concluded in March. However, after some persuasion from FDA officials, patients and their families, the committee met again and decided to recommend approving the drug.
In January 2019, following an ALS diagnosis in October the previous year, Jeff Sarnacki, of Chester, Maryland, was accepted into a trial for Relyvrio. “Because of the trial, we did experience hope and a greater sense of help than had we not had that opportunity,” said Juliet Taylor, his wife and caregiver. They both believed the drug “worked for him in giving him more time.”
In June 2019, Sarnacki chose an open-label extension, offered to patients by drug researchers after a study ends, and took the active drug until he died peacefully at home under hospice care in May 2020, five days after his 60th birthday. A retired agent with the federal Bureau of Alcohol, Tobacco, Firearms and Explosives who later worked as a security consultant, Sarnacki lived about 19 months after diagnosis, which is shorter than the typical prognosis.
His symptoms had begun with leg cramps and foot drop in late fall 2017. At the end of life, he could only move a few fingers on his left hand and could not speak or eat by mouth; a feeding tube became necessary, Taylor said. He also took Radicava and Riluzole, the two previously approved drugs, for his ALS. “We were both incredulous that, so many years after Lou Gehrig’s own diagnosis, there were so few treatments available,” she said.
The dearth of successful treatments for ALS is “certainly not for lack of trying,” said Karen Raley Steffens, a registered nurse and ALS support services coordinator at the Les Turner ALS Foundation in Skokie, Ill. “There are thousands of researchers and scientists all over the world working tirelessly to try to develop treatments for ALS.”
Unfortunately, she adds, research takes time and exorbitant amounts of funding, while bureaucratic challenges persist. The rare disease also manifests and progresses in many different ways, so many treatments are needed.
As of 2017, the Centers for Disease Control and Prevention estimated that more than 31,000 people in the U.S. live with ALS, and an average of 5,000 people are newly diagnosed every year.
Most cases of ALS are sporadic, meaning that doctors don’t know the cause. There is about a one-year interval between symptom onset and an ALS diagnosis for most patients, so many motor neurons are lost by the time individuals can enroll in a clinical trial, said Richard Bedlack, professor of neurology and director of the Duke ALS Clinic in Durham, North Carolina.
Bedlack found the new drug, Relyvrio, to be “very promising,” which is why he testified to the FDA in favor of approval. (He’s a consultant and disease state speaker for multiple companies including Amylyx, manufacturer of Relyvrio.)
The “drug has different mechanisms of action than the currently approved treatments,” said Bedlack, who is also chief of neurology at the Durham Veterans Affairs Medical Center. He adds that, when Relyvrio is taken in addition to Riluzole, it appears to slow functional decline by an additional 25 percent and extend life by another 6 to 10 months. “It is not a cure, but it is definitely a step forward.”
T. Scott Diesing, a neurohospitalist and director of general neurology at the University of Nebraska Medical Center in Omaha, said he hopes the drug is “as good as people anticipated it should be, because there are not too many options for these patients.”
So far, Rouse's voice is holding up, but he knows the day will come when ALS will steal that and much more from him.
ALS is 100 percent fatal, with some patients dying as soon as a year after diagnosis. A few have lasted as long as 15 years, but those are the exceptions, Diesing said.
“If this drug can provide even months of additional life, or would maintain quality of life, that’s a big deal,” he notes, adding that “the patients are saying, ‘I know it’s not proven conclusively, but what do we have to lose?’ So, they would like to try it while additional studies are ongoing.” The drug has already been approved in Canada.
As his disease progresses, Rouse hopes to get a speech-to-text voice-generating computer that he can control with his eyes. So far, his voice is holding up, but he knows the day will come when ALS will steal that and much more from him. He works at I AM ALS, a patient-led community, and six of his friends have already died of the disease.
“Every time I lose a friend to ALS, I grieve and am sad but I resolve myself to keep working harder for them, myself and others,” Rouse said. “People living with ALS find great purpose in life advocating and trying to make a difference.”
The Friday Five covers important stories in health and science research that you may have missed - usually over the previous week, but today's episode is a lookback on important studies over the month of September.
Most recently, on September 27, pharmaceuticals Biogen and Eisai announced that a clinical trial showed their drug, lecanemab, can slow the rate of Alzheimer's disease. There are plenty of controversies and troubling ethical issues in science – and we get into many of them in our online magazine – but this news roundup focuses on scientific creativity and progress to give you a therapeutic dose of inspiration headed into the weekend and the new month.
This Friday Five episode covers the following studies published and announced over the past month:
- A new drug is shown to slow the rate of Alzheimer's disease
- The need for speed if you want to reduce your risk of dementia
- How to refreeze the north and south poles
- Ancient wisdom about Neti pots could pay off for Covid
- Two women, one man and a baby