What You Need to Know
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Geographic atrophy (GA) is a chronic, progressive degeneration of the macula that can occur in some people with dry macular degeneration. GA is a late, or advanced, stage of the disease.
The people who develop geographic atrophy have areas in the retina where there’s a loss of photoreceptors and their support cells, says Margaret Greven, MD, an ophthalmologist with Wake Forest Baptist Health in Winston-Salem, North Carolina.
“Those are the cells that are responsible for taking the picture so that you can have a visual image. When you lose areas of the photoreceptors and support cells, then you basically develop a blind spot in the area where geographic atrophy is,” she explains.
Some people with geographic atrophy may not have any symptoms or may not notice the blind spot if it’s a small area far away from the center part of the vision, says Dr. Greven.
“But if it’s in the center, or closer to the center part of the vision, it can cause severe vision loss. You can lose your ability to recognize faces when you are looking straight ahead,” she says.
New Treatments Bring New Hope
The approval of Syfovre (pegcetacoplan injection) and Izervay (avacincaptad pegol intravitreal solution) in 2023 means that for the first time in history, there are treatments available for geographic atrophy.
“There are so many people who are affected by dry macular degeneration, and there are a lot of people who have geographic atrophy. Prior to these approvals, there’s been a huge gap in our armamentarium of how we treat our patients,” says Greven.
Still, these drugs may not be the right fit for everyone. Here’s what you need to know about new treatments for geographic atrophy.
How Do the New Geographic Atrophy Treatments Work?
Both new treatments target the complement system, which is a series of more than 20 proteins that circulate in the blood and fluid tissues that protect against pathogens. But the complement can be activated and cause damage to eye tissue, called a “complement cascade,” which is an inflammatory process. These drugs target the complement and reduce inflammation, and that’s thought to reduce the progression of the geographic atrophy.
Although we are making progress in understanding this disease, the scientific community still doesn’t fully understand exactly what precedes and causes GA, says Greven. “We suspect that it has to do with inflammation, and there are a few reasons for that. One is that geographic atrophy tends to get a lot worse in people who smoke cigarettes and use tobacco products, which is a pro-inflammatory process,” she says.
And then, there have been signals in preclinical and clinical studies that show that blocking complement slows the progression of the atrophy. By decreasing the inflammation in geographic atrophy, the hope is that it can prevent progression.
Do the New Treatments Repair Existing Damage to the Retina?
The new treatments don’t restore vision that’s already been lost from geographic atrophy or even completely stop its progression, says Greven.
Nor do the drugs improve visual acuity, or sharpness of vision.
“Patients on these treatments will continue to have growth of the areas of blind spots in their retinas, but the drugs reduce the rate of progression: Compared to no treatment, they reduce the amount the blind spots are growing by about 20 to 30 percent,” she says.
In Syfovre clinical trials, the drug slowed the growth of lesions (blind spots) by an average of 20 percent in people who had monthly injections, and 17.5 percent when injections were given every other month.
In clinical trials for Izervay, participants were given monthly injections, and at the end of 12 months, there was 35 percent slower progression than in people who received no treatment, and in the second trial, the progression drop was 18 percent.
Can These Treatments Be Used to Prevent Geographic Atrophy?
Syfovre and Izervay are currently only recommended for use in people who already have geographic atrophy that’s a certain size in their retina, says Greven.
“Some people have wondered if the treatments could be used preventively in people who have dry macular degeneration but have not yet developed geographic atrophy, but so far it hasn’t been established that there’s any benefit to doing that,” she says.
Who Is a Candidate for the New GA Treatments?
“Patients who would be very good candidates for this treatment would be those who have already lost vision in one eye from the progression of geographic atrophy and who also have areas of GA in the other eye that haven’t yet affected the center of the vision,” says Greven.
How Are the New GA Treatments Administered?
The treatments are administered by intravitreal injection, which is an injection of medicine into the eye, performed in the doctor’s office, says Greven. “It goes through the sclera, which is the white part of the eye. During the procedure, we numb the eye so that patients don’t feel pain. Even though that sounds quite uncomfortable, believe it or not, you can make it so the eyes are numb, and you don’t feel the injection,” she says.
Everybody’s experience is a little bit different with intravitreal injections, says Greven. “Some people will have some blurry vision and an increase in floaters initially after the injection just from the medicine going into the eye,” she says.
The surface of the eye is cleaned to prevent infection, and sometimes that can cause a little irritation or blurry vision, but that typically doesn’t last long, says Greven.
“Usually if people’s vision is good enough to drive to the appointment, they are able to drive home without any issues,” she says.
RELATED: What’s It Like to Get Anti-VEGF Injections for Wet Macular Degeneration?
How Frequently Are the Injections Given?
Injections are typically given monthly or every other month, says Greven. “In the clinical trials, they had groups of patients who received the injections monthly or every other month, and there was a stronger effect of the medication for the people getting monthly injections; they had more reduction in the growth of their GA compared with the patients who got it every other month,” she says.
But sometimes it can be challenging for patients to get an injection every month, especially if they can no longer drive themselves, says Greven. “For those people, we might decide to do injections every other month. There can be a few factors that go into how often to do the injections, and ideally, your ophthalmologist can tailor a plan that works for you,” she says.
How Do You Know if the Treatment Is Working?
Unlike some other eye treatments, it’s hard to know if these treatments for GA are working, says Greven. “Geographic atrophy progresses in everyone, but the rate at which it’s going to get worse is different for different patients,” she says.
That means that even when you’re receiving these treatments, the geographic atrophy will grow. “We’ll still be able to document that those areas where the photoreceptors and their support cells have died off are enlarging over time. And you can’t really show a patient what it would have looked like if we didn’t do the treatment; we just don’t know,” she says.
It’s a very different situation from injections for wet macular degeneration, says Greven. “With those injections, if a patient has fluid in the retina and they have blurred vision, when we give them an injection, the fluid gets better, and their vision improves. We can tell it’s doing something,” she says.
Do the Injections Need to Be Continued for Life?
“Once you start treatment, you need to continue for the benefit to persist. That said, you can always stop the injections at any time once you’ve started them, but you wouldn’t expect the benefit of the treatment to persist if you’re no longer doing the injections,” says Greven.
In general, if you’re doing the treatment to slow the progression of geographic atrophy, then you would want to continue getting the injections as long as there are some areas of the retina that are not affected by the geographic atrophy.
“If you were doing the treatments and a patient had progressed to the point where they have geographic atrophy involving the entire center part of their vision and they’ve lost that central vision, there wouldn’t really be a reason to continue doing them,” she says.
What Are the Main Side Effects of These Drugs?
There really aren’t any common potential side effects for these treatments, but they can occur, says Greven. “Though rare, the most serious risk that I worry about whenever I’m doing an injection is an infection. We try to limit the risk of infection by using Betadine on the eye prior to the shot, but even if you do everything correctly, an infection is still possible,” she says.
The rate of infection from these injections is low, somewhere between 1 in every 2,000 injections to 1 in every 10,000 depending on the study, says Greven.
Another potential risk that’s been observed is that patients with GA who are treated with these injections have higher rates of wet macular degeneration, she says.
“We don’t know exactly why that is, but in the clinical trials, patients who received the injections developed wet macular degeneration at a statistically significant higher rate than the group not getting the injections,” says Greven.
Recently, there have also been reports of rare but serious side effects in patients receiving Syfovre. “It’s called retinal vasculitis, which is severe inflammation that can cause permanent vision loss. The rate is about 1 in 10,000 injections from the information that we have so far,” says Greven.
Right now, that’s only been observed in people getting Syfovre, which has been on the market a little longer, and there’s more data on this treatment.
New Therapies Are a Step in the Right Direction
“These treatments give us reason to be hopeful: We have gone from having no treatments to two approved treatments in the last year,” says Greven. “Hopefully this is the first step toward treatments that will not only slow down but actually halt the progression of geographic atrophy,” she says.
With a better understanding of how geographic atrophy works and how these drugs slow its progression, more new therapies may be developed that work even better, says Greven.
“Someday — I hope — we can even have treatments that could restore vision in patients who have lost it due to geographic atrophy,” she says.
Talk to Your Ophthalmologist About the Pros and Cons
These therapies have benefits for many patients, but they do come with some risks, says Greven. “I don’t think these treatments are necessarily for everyone, but for some patients who understand what’s involved and what the potential risks are, I think it’s a great option,” she says.
People with geographic atrophy should talk to their ophthalmologist about these treatments so they can be educated and make informed decisions about what’s best for them, says Greven.
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