For more than a decade, ophthalmologists have treated wet age-related macular degeneration (AMD) with periodic eye injections and dry AMD with antioxidant vitamins. These treatments were groundbreaking, offering hope for the first time that this sight-threatening disease could be slowed, and in some cases stopped or even reversed. This revolution is undergoing an intriguing evolution. So, what will the next decade hold for the nearly 20 million Americans with some form of AMD?
In short, the latest research is varied, vibrant, and suggests a future in which ophthalmologists will have more effective options to protect people from going legally blind from AMD. Here's a rundown of the most promising AMD treatments on the horizon.
New Treatments for Wet AMD
Wet AMD develops when new, abnormal blood vessels grow under the retina and leak blood or other fluids. You lose vision faster with wet AMD than with dry AMD.
In the early 2000s, scientists began creating drugs that interfere with this process. These drugs block a protein called vascular endothelial growth factor (VEGF). Before the creation of these so-called anti-VEGF drugs, people with wet AMD were almost certain to develop severe vision loss or blindness.
Then, in 2005, anti-VEGF drugs broke ground by saving the sight of patients with wet AMD. These drugs — including aflibercept (Eylea), ranibizumab (Lucentis), faricimab (Vabysmo) and bevacizumab (Avastin) — stabilize or improve vision in the vast majority of patients. But they must be injected into the eye on a regular basis.
"Today, more durable therapies are coming out, and treatments that may even cure the disease are in the works. There’s a lot of hope for people with AMD,” Sridhar says.
While clinical trials show that anti-VEGF injections have allowed more than 90% of patients to maintain their level of vision, in the real world the percentage is closer to 50%. That’s because people aren’t being treated as regularly as they should. The problem is most people have needed an injection every month or two to keep their vision. This can be a difficult schedule to maintain for many elderly patients struggling with other maladies and reliant on others to get them to their ophthalmology visits.
Some of the most exciting research today explores alternatives to frequent injections. It’s not just about convenience; the hope is that a more consistent treatment will also help people keep more of their vision.
Longer-lasting drugs for wet AMD
A new, higher-dose version of well-established anti-VEGF medicine Eylea may allow patients to go longer in between injections. Eylea HD quadruples the dose of the traditional treatment and can last up to 3 to 4 months as compared to the standard-dose version.
Another new drug that targets two underlying causes of AMD has been FDA approved for both AMD and diabetic macular edema. Faricimab (Vabysmo), targets both VEGF and the protein angiopoietin-2. It’s injected into the eye like a typical anti-VEGF treatment, and it may last longer than earlier types of treatments. The latest research suggests most patients can go 3 to 4 months between treatments with Vabysmo.
It may also be possible to combine two drugs and hit wet AMD with a double punch. These combos could further improve vision and make injections last longer. Opthea’s OPT-302 (Sozinibercept) is currently in clinical trials and has been shown to have better outcomes than anti-VEGF treatments alone.
Gene therapy for wet AMD
Gene therapy is a promising alternative to ongoing eye injections of drugs such as Eylea, Lucentis, Vabysmo and Avastin. The goal of gene therapy is to provide a ‘one-and-done’ treatment by helping the eye make its own anti-VEGF medicine. Two different methods are under investigation. One injects the gene therapy underneath the retina in a surgical procedure; the other injects it into the eye just like a routine anti-VEGF treatment and is done in the ophthalmologist’s office.
Despite the promise of gene therapy, the long-term effectiveness remains to be seen. Such a treatment is likely to be very expensive and may not be suitable for everyone with wet AMD.
New Treatments for Dry AMD
About 8 out of 10 of people with AMD have the dry form. Dry AMD occurs when parts of the macula thin with age and/or tiny clumps of protein called drusen grow. Patients can slowly lose central vision making it more difficult to retain independence. Depending on severity, dry AMD is considered early, intermediate or late stage.
For people with intermediate disease, a formulation of antioxidant vitamins called the AREDS2 formula can help reduce the risk of vision loss. People with late-stage AMD, also called geographic atrophy (GA), did not have any treatments available until recently. Today, two new therapies are accessible for patients with GA. They are offering some hope to patients who previously had none. However, these therapies have special considerations that should be discussed with your retinal specialist.
Dry AMD treatments that target the immune system
A part of the immune system called the “complement cascade” has long been identified as a culprit in AMD. Two new drugs that target the complement cascade and stop it from attacking the retina have recently been approved by the FDA: Pegcetacoplan (SYFOVRE) and avacincaptad pegol (Izervay). Like currently available treatments for wet AMD, these drugs are injected directly into the patient’s eye. While they have been shown to slow the development of geographic atrophy by up to 20%, they do not improve vision.
Additionally, these therapies can cause side effects or complications ranging from mild to severe. Your retinal specialist will discuss these tradeoffs with you and help you determine the best course of treatment.
Replacing vision cells in people with dry AMD
Another concept under investigation is the possibility of replacing some cells that begin to die in late-stage dry AMD. Stem cells may be able to replace the retinal cells that are killed off by this disease. Doctors are devising ways to transplant these stem cells into the eye. One strategy is to layer the stem cells on thin scaffolds. Another tactic is to put the cells into a fluid suspension that can be injected under the retina. Stem cells have been tested in small clinical trials and they do not have unexpected side effects. It may take about 10 to 15 years for these therapies to be fine-tuned and proven effective in humans.