By Philip J Rosenfeld, MD, PhD, as told to Sonya Collins
Dry age-related macular degeneration (AMD) progresses over many years. It’s usually not diagnosed until you’re in your 50s. You start having decreased vision in your 60s or later. At first, you might have difficulty in dim light, with glare, driving at night, making the transition from bright outdoor light to darker indoor light or vice versa, and difficulty seeing people’s faces. You won’t be able to tell if the problem is due to cataracts or AMD. Only a doctor can make the distinction.
Eventually, if you live long enough with AMD, you develop geographic atrophy. That’s a loss of tissue in the retina and supporting structures around the retina that allow you to see. If you think of the eye as a camera, it’s not the lens at the front of the camera that’s getting damaged. That’s a cataract. But rather, it's the film or the digital sensor at the back of the camera. And once that’s damaged, we can’t get it back. We can’t restore vision that’s already been lost, so our goal from here is to prevent further vision loss.
Complement Inhibitors
Until recently, we didn’t have any treatment that would slow the progression of geographic atrophy. But now we have two drugs, known as complement inhibitors, that are approved for geographic atrophy. One is called avacincaptad pegol (Izervay), and it’s injected every month. The other, pegcetacoplan (Syfovre), is injected every 4 to 8 weeks.
It’s important for patients to understand that these drugs will not improve their vision. The drugs only slow further enlargement of the geographic atrophy – they slow the loss of tissue with the hope that vision loss will be slowed as well. The longer you get therapy over an extended period, the more it slows the progression of the disease, so there’s a benefit of continued therapy.
How Long Treatment Lasts
Patients always ask whether they will have to stay on this treatment forever, and the answer is that we don’t know. Studies to determine the long-term benefits are ongoing. In addition, it’s going to be the doctors’ clinical experience treating patients with these medications that informs how long we may need to treat. My advice is that as long as you can tolerate and accept the treatment, stay with it because it’s going to slow down the disease. My hope is to save as much vision as possible until a better treatment comes along.
That’s where we are with complement inhibitors. There are other complement inhibitors in development, but we don’t expect them to be much different than the current complement inhibitors. To summarize, patients will do better than they would otherwise, but these drugs will not improve vision, so they are not providing what patients really want.
Treatments on the Horizon
There’s a wide range of other drugs in development that may improve visual function, but they might not slow the enlargement of geographic atrophy. One day, we could be looking at combination therapy where we take one of these drugs alongside complement inhibitors.
Another interesting strategy that I am cautiously optimistic about is based on the idea that one of the reasons AMD progresses is because there’s just not enough blood getting to the eye. We have evidence of this from past studies that look at anatomic changes in the eye as the disease goes on. Blood flow to the eye appears to be decreased in patients with AMD. Now a group of researchers is looking at increasing blood flow in the ophthalmic artery. The ophthalmic artery is the first artery that branches off the carotid artery. There’s a carotid artery on either side of your neck, and they provide the blood supply to your brain. People can get disease in the carotid arteries that decrease blood flow through them. Currently, surgery can be performed to improve the blood flow in the carotid arteries, and one strategy is to place stents in the artery to increase blood flow to the brain.
Interestingly, researchers have found that there can be narrowing of the ophthalmic artery just as it leaves the carotid artery. Now there’s a phase I clinical trial in Argentina in which they insert a catheter through the groin, and they pass the catheter into the ophthalmic artery to improve blood flow. It’s called balloon angioplasty, and so far, the preliminary data look very encouraging.
GA Treatment Research Continues
As for other research, there’s an FDA-approved clinical trial studying a new pill in intermediate AMD, which is the stage of AMD just before it progresses to geographic atrophy. This is the first clinical trial that’s been accepted for the intermediate stage of AMD before any significant vision loss has happened.
The pill is a repurposed drug made for migraine 25 years ago, but it was never FDA approved and has been sitting on the shelf. Scientists have been studying this drug for neurodegenerative diseases. It seems to block the inflammasome, which is a large protein complex that activates inflammation and can cause cell death and disease.
This pill wasn’t developed to target the inflammasome, but since it does, it’s now being repurposed for that use. We know it to be very safe, and we think it’s going to make a very valuable addition to our treatment toolbox. What I like about a pill is that it’s a systemic therapy that gets to both eyes. It won’t require injections into each eye. There are also other systemic therapies (that go through your whole body) in development in the form of IV infusions and shots under your skin. No matter how you deliver the drug, systemic therapy is attractive because it gets to both eyes.
As for other approaches in the research pipeline, there is some encouraging research coming out around stem cell transplantation. Stem cell therapy has been shown to be safe so far, but we’re not near the point where we can use it in the clinic to restore vision or prevent vision loss. It’s not ready for real-world use. But maybe in the future stem cells will allow patients to see better.
For people who want to get into clinical trials to try some of these new approaches, talk to your retina specialist. This is where you as the patient need to advocate for yourself. Ask your retina specialist which clinical trials you could participate in that might hopefully slow down your disease.
Show Sources
Photo Credit: Westend61/Getty Images
SOURCES:
Philip J Rosenfeld, MD, PhD, professor of ophthalmology, retina specialist, Bascom Palmer Eye Institute, the University of Miami Miller School of Medicine.
American Academy of Ophthalmology: “What to Know About Syfovre and Izervay for Geographic Atrophy."
