There’s new hope for people living with geographic atrophy (GA), an advanced form of the eye disease dry age-related macular degeneration (dry AMD). Scientists hope they’re close to new therapies for the condition that’s proven hard to treat in the past.
In dry AMD, small yellow lesions called drusen form under your eye’s retina. If they grow larger, drusen can block nutrients from reaching the retina and cause cell death. Your eyesight becomes blurred, and if AMD advances to GA, you may have trouble seeing from the center part of your vision.
There are two forms of AMD, wet and dry. Dry AMD affects around 90% of all people with AMD and usually gets worse more slowly. Although treatments for wet AMD have evolved quickly in the past few years, innovations in the dry form of the condition have come at a slower pace.
Michael Cooper, OD, an optometrist and director of medical education at Eyes on Eyecare, calls GA “a currently irreversible, visually devastating disease for millions of people.”
“We want to help people with GA take back some control and empower them by identifying GA earlier on, so they can live their life the way they want,” he says. And while vision loss from GA is permanent, future treatments may stop or slow the disease from getting worse over time.
Right now, the only treatments that might reduce the progression of dry AMD are vitamins and supplements. And once the illness advances to GA, there are no therapies – vision loss in these areas is permanent. Recently though, researchers have made exciting breakthroughs in pursuing treatments for GA, including medicines and surgery.
What Is the Role of the Complement System in GA?
Many of the emerging treatments for GA work to control a part of your immune system called the complement system. These two systems team up to protect you from things that can make you sick such as viruses and bacteria. Your complement system enhances your immune system by switching on proteins that help keep you healthy.
About 50 tiny proteins in your blood’s plasma make up your complement system. Normally, these proteins are idle until something triggers them, like when you’re injured or fighting off bacteria. This sets off a protective chain reaction called a cascade, where one protein switches on, followed by another and another.
Sometimes, proteins in your complement system work too hard, and your body triggers them too often. When this happens, it raises your chances of disease, including AMD, which can lead to GA.
What Are Some Promising Treatments for GA?
The most promising treatments for GA target the complement system. Cooper says researchers haven’t had a strong grasp of the science behind GA, but recently, the complement system “has become the marquee area of geographic atrophy research.”
Researchers have homed in on two types of protein in your blood, the C3 and C5 proteins. Usually, these proteins get rid of germs that make you ill, but they can cause inflammation and also attack healthy cells.
Researchers think C3 and C5 play a critical role in whether you’ll get AMD and eventually GA. They’ve been studying treatments that work to keep the complement system in check and slow the growth of GA lesions. While early clinical trials weren’t successful, recent studies have shown more potential.
One possible treatment is an eye injection called a complement inhibitor. It works by slowing C3 and the growth of GA lesions in people with dry AMD. A study of the therapy, named pegcetacoplan (Syfovre), found it can help slow lesion growth in those who have monthly shots and those who get shots every other month.
Based on the results of three studies, The FDA has fast-tracked the drug. The fast-track process speeds up the development and review of important new treatments so they can get to people sooner. The FDA considers whether the drug will fill an “unmet medical need,” meaning there’s currently no treatment for a specific medical condition, like geographic atrophy.
Another complement inhibitor, called avacincaptad pegol (Zimura), slows GA from getting worse by targeting the C5 protein. One study found that people who took the drug, given as an eye injection, slowed GA by around 27% over 12 months.
In late 2022, the FDA named the treatment a breakthrough therapy. Like fast track, this process also speeds the development and review of certain drugs. A breakthrough therapy aims to treat a serious condition, and early evidence may show that the drug has an advantage over an available treatment.
Besides shots, researchers are also studying complement inhibitors in tablet form. These clinical trials are not as far along as the ones for treatments you take as a shot.
Gene Therapy Surgery
One possible downside of eye injections is that you may need them once a month or every 2 months for life. But researchers are looking at another option for GA that you would need just one time.
It’s a gene therapy designed to help the eye make a protein called complement factor I (CFI). CFI keeps complement in check, and boosting it with a one-time shot delivered beneath the retina can balance out an overactive complement system.
Cooper says gene therapy is the next wave of treatments for GA. “As time progresses, we get more sophisticated with our ability to formulate these medications, and I think we’ll see more of this type of delivery.”
Early study data found most people who had the treatment showed higher CFI levels. Some saw these results more than a year post-treatment. Researchers continue to study gene therapy for GA in ongoing clinical trials.
Modified Vitamin A
Vitamin A is essential for vision but can turn toxic and form what scientists call “dimers.” Researchers have long thought that dimers play a role in whether you’ll get dry AMD. Now, they’re studying a chemically modified form of vitamin A that could ward off and treat dry AMD.
The drug, a capsule called ALK-001, replaces your body’s natural vitamin A with a version that slows the dimer-making process. Scientists are currently investigating how well the drug works to slow GA.