What’s Next for Geographic Atrophy

By Neil M. Bressler, MD, as told to Keri Wiginton

Age-related macular degeneration (AMD) is the leading cause of vision loss for people over 65. We have excellent treatments for the wet form of AMD. But until recently, we haven’t had any therapeutics to target the root cause of geographic atrophy, an advanced form of dry AMD.

The pegcetacoplan (Syfovre) injection is the first-ever FDA-approved drug to slow the progression of GA. It’s a shot you get in your eye every month or every other month. We expect to see the approval of a second, similar drug called avacincaptad pegol (Zimura) soon. 

These breakthrough medications offer hope to people with late-stage dry AMD, but they’re just the beginning of advances in treatment for geographic atrophy. 

What Is the New Treatment for Geographic Atrophy?

To understand why we need more interventions for GA, it’s 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 shot can’t stop atrophy or reverse vision loss. That means your eyesight won’t get better with this treatment. 

Another issue is that while the shot is generally considered safe, it does come with certain risks. In clinical trials, only 3% of people who didn’t get the medication got 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 the current treatment, let’s talk about where GA therapies are headed. 

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It’s always harder to talk about the future than the present or the past because there are a lot of unknowns. But there are some promising medical therapies in the pipeline. And we hope they’ll do more than the current drug to improve vision and stop the growth of lesions.

In the next few years, we may see big progress in the following areas:  

Complement inhibitors. The complement pathway is a part of the immune system. You have about 50 proteins in this system. Viruses, bacteria, or injury can trigger one protein to activate another. This complement cascade usually helps you ward off illness or repair tissue. 

But large studies by the National Eye Institute and other great researchers around the world discovered that an overactive complement system likely plays a key role in the development of dry AMD and progression to GA. 

That brings us back to the newly approved drug. Pegcetacoplan is an anti-complement drug that targets the C3 pathway. The forthcoming drug avacincaptad pegol is a C5 inhibitor. These drugs block some of the complement proteins thought to cause GA. 

Future therapies will likely target similar pathways to these two drugs but may work in a slightly different and better way. More effective complement inhibitors might do a better job of stopping cell loss and have more of a functional effect on vision. That’s the hope, anyway. 

I tell people with GA to think of atrophy like the size of a football field. And maybe these first drugs only slow growth by 20 yards over 2 years. But maybe the next round of complement inhibitors will cut down on cell loss by 60 or 80 yards.

Modified vitamin A. Based off research on other eye disease, scientists think a chemically modified form of vitamin A may slow the growth of GA lesions and protect the light-sensitive cells in the retina. 

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Specifically, researchers are studying if 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 anything more than give you extra vitamin A, just in a different form. 

Can Artificial Intelligence Help People Who Have GA?

We can’t predict who with early-stage dry AMD will progress to advanced disease. But many ongoing studies are using artificial intelligence (AI) to scan retina images to try to find out. The goal is to train computers to recognize early signs of GA before the loss of retina cells.

What kind of biological biomarkers might an AI algorithm find? And can the computer pinpoint who is more likely to develop GA years before the atrophy sets in? Those are questions we don’t have the answers to yet.

But if a computer program can look at a picture of someone’s drusen early on and know whether they’ll develop atrophy 5 or 10 years down the road, we may be able to use the medication 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 may be a way to stop vision loss from GA without brand-new treatments.

What Might Be Possible One Day for GA Treatment?

Geographic atrophy is a complex disease, and there’s still a lot we don’t know about what causes it and how best to treat it. But we may see a number of exciting new therapies within the next decade or beyond. 

Some areas of ongoing research include: 

Cell replacement therapy. The retina is just an extension of the central nervous system. And just like we can’t replace brain cells if they’re lost, retinal cells don’t grow back when they die. But there’s some evidence that we may one day be able to repair or replace tissue damaged by GA. 

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One possible way to do this is through cell replacement therapy. And scientists are studying how to create healthy retinal cells from a person’s own tissue. Once they grow the cells in a lab, 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 injured retinal cells. And maybe one day, these therapies will help some cells regrow or live longer. But we’re not there yet.

While cell replacement therapy is promising, we need more research to know if this kind of treatment is safe, effective, or possible for large groups of people with GA. 

Retinal implants. With GA, the general idea is to connect an electronic receptor to the back part of the eye so it can transmit visual signals from the retina to the brain. 

Right now, so-called optogenetic therapy can help someone with no vision at all tell the difference between light and dark. It’s amazing that scientists can do that, but that’s not helpful for someone with vision loss due to macular degeneration. 

But just because a technology doesn’t exist right now doesn’t mean it won’t in the future. 

If you have GA, stay in touch with your doctor. And never give up hope. There’s always the possibility that a new treatment or breakthrough will come through at any time. It’s already happened once in our lifetime. 

Source: https://www.webmd.com/eye-health/macular-degeneration/features/future-treatment-geographic-atrophy?src=RSS_PUBLIC