By Neil M. Bressler, MD, as told to Keri Wiginton
Age-related macular degeneration (AMD) is the leading cause of vision loss in people over 65 years of age. We have excellent treatments for the wet form of AMD. But until recently, we had no therapies that could address the cause of geographic atrophy, an advanced form of dry AMD.
The pegcetacoplan (Syfovre) injection is the very first FDA-approved drug that slows the progression of GA. It is an injection that you receive in your eye every month or every other month. We expect to soon see the approval of a second, similar drug called avacincaptad pegol (Zimura).
These groundbreaking drugs offer hope for people with late-stage dry AMD, but they are just the beginning of advances in the treatment of geographic atrophy.
What is the new treatment for geographic atrophy?
To understand why we need more interventions for GA, it is important to first recognize the limits of this new drug.
Pegcetacoplan can slow the growth of GA lesions, and that’s a great first step. But it falls short in other areas. One weakness is that the injection cannot stop the atrophy or deterioration of vision. This means that your vision will not improve with this treatment.
Another problem is that while the shot is generally considered safe, it carries certain risks. In clinical trials, only 3% of people who did not receive the medication developed wet AMD. But the rates were slightly higher (12% and 7%) for those who got the shot monthly or every other month.
What medical treatments are on the horizon?
Of course, the FDA wouldn’t approve a dangerous drug with no medical use. But now that you know some of the pros and cons of current treatment, we can talk about the direction GA therapies are heading.
It is always more difficult to talk about the future than the present or the past because there are many unknowns. But there are a number of promising medical therapies in the pipeline. And we hope they will do more than the current drug to improve vision and stop the growth of lesions.
In the coming years we can see great progress in the following areas:
Complement inhibitors. The complement pathway is part of the immune system. You have about 50 proteins in this system. Viruses, bacteria or injuries can cause one protein to activate another. This complement cascade usually helps you ward off disease or repair tissue.
But major studies by the National Eye Institute and other major researchers around the world have found that an overactive complement system likely plays a key role in the development of dry AMD and progression to GA.
Which brings us back to the newly approved drug. Pegcetacoplan is an anti-complement drug that targets the C3 pathway. The upcoming drug avacincaptad pegol is a C5 inhibitor. These drugs block some of the complement proteins that are thought to cause GA.
Future therapies will likely target similar pathways as these two drugs, but may work in slightly different and better ways. More effective complement inhibitors could better stop cell loss and have a more functional effect on vision. That’s the hope anyway.
I tell people with GA to think of atrophy as the size of a football field. And perhaps these first drugs only slow growth by 60 feet in two years. But perhaps the next round of complement inhibitors will reduce cell loss by 60 or 80 meters.
Modified vitamin A. Based on research into other eye diseases, scientists believe that a chemically modified form of vitamin A may slow the growth of GA lesions and protect the light-sensitive cells in the retina.
Specifically, researchers are investigating whether an oral drug called ALK-001 can slow GA and improve visual acuity or reading speed. But for now we don’t know if this capsule does more than give you extra vitamin A, just in a different form.
Can artificial intelligence help people who have GA?
We cannot predict who with early-stage dry AMD will progress to an advanced stage of the disease. But many ongoing studies use artificial intelligence (AI) to scan retinal images to find out. The goal is to train computers to recognize early signs of GA before the loss of retinal cells.
What kind of biological biomarkers could an AI algorithm find? And can the computer determine who is more likely to develop GA, years before atrophy begins? These are questions to which we do not yet have an answer.
But if a computer program can look at a picture of a person’s drusen early on and know whether they will develop atrophy in five or 10 years, we might be able to use the drugs we have now at an earlier stage. Drusen are extracellular deposits of lipids, proteins, and debris in the layers of the retina. They look like small, yellow deposits on dilated eye exams. This could be a way to stop vision loss from GA without brand new treatments.
What could one day be possible for GA treatment?
Geographic atrophy is a complex disease, and there is still much we don’t know about what causes it and how best to treat it. But we could see some exciting new therapies within the next decade or beyond.
Some areas of current research include:
Cell replacement therapy. The retina is merely an extension of the central nervous system. And just as we cannot replace brain cells when they are lost, retinal cells do not grow back when they die. But there are indications that we may one day be able to repair or replace tissue damaged by GA.
One possible way to do this is through cell replacement therapy. And scientists are studying how to make healthy retinal cells from a person’s own tissue. Once they grow the cells in a laboratory, the idea is to surgically replace areas of atrophy with a patch of functioning retinal cells.
Researchers are also trying to see if they can transplant healthy cells to trigger the natural repair of damaged retinal cells. And perhaps one day these therapies will allow some cells to grow back or live longer. But we’re not there yet.
Although cell replacement therapy shows promise, we need more research to know whether this type of treatment is safe, effective, or possible for large groups of people with GA.
Retinal implants. In GA, the general idea is to connect an electronic receptor to the back of the eye so that it can transmit visual signals from the retina to the brain.
Currently, so-called optogenetic therapy can help someone without vision see the difference between light and dark. It’s amazing that scientists can do that, but it doesn’t help someone with vision loss due to macular degeneration.
But just because a technology doesn’t exist today doesn’t mean it won’t exist in the future.
If you have GA, contact your doctor. And never give up hope. There is always the possibility that a new treatment or breakthrough will emerge at some point. It’s already happened once in our lives.