Macular Degeneration: Treatments Seek to Limit or Stop Vision Loss

Age-related macular degeneration, which can lead to distorted vision and blindness, affects 20 million Americans.

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Age-related macular degeneration (AMD), a progressive eye disease affecting close to 20 million Americans, is the leading cause of vision loss in people over 50. While existing treatments help many patients, others experience vision loss or even blindness. New therapies and improvements in the current standard of care aim to prevent disease progression and vision loss.

AMD affects the macula, an area in the back of the eye responsible for sharp vision. AMD symptoms include distorted vision, central vision loss (“blind spots”), or difficulty seeing in low light.

There are two types of age-related macular degeneration. Dry AMD—also referred to as geographic atrophy—is caused by drusen, or fat and protein deposits whose accumulation causes the macula to shrink. While some drusen is fine, having a lot of it causes gradual loss of central vision and the inability to read, drive, or recognize faces.

Wet AMD, which is less common, occurs when blood vessels in the back of the eye leak and damage the macula, causing AMD’s characteristic central vision loss.

Heredity is a risk factor for AMD, but the risk may be lowered through lifestyle changes like quitting smoking, eating a healthy diet, maintaining recommended blood pressure and cholesterol levels, and taking nutritional supplements.

What Are the Current Treatments for AMD?

Wet AMD treatment involves eye injections of anti-vascular endothelial growth factor (anti-VEGF) drugs, which prevent the formation of new blood vessels. Patients receive these “intravitreal” injections as frequently as monthly and, typically, for life.

“This is not ideal for the patient experience and may cause some to stop or miss treatments,” said Dr. Tiarnán Keenan, a clinician and clinical researcher at the National Eye Institute, via email.

Anti-VEGF drugs help about 90 percent of wet AMD patients in clinical trials, but real-world numbers are closer to 50 percent due to several factors. Eye injections cause discomfort and pain, involve regular doctor visits, and may not be fully covered by the patient’s insurance.

The U.S. Food and Drug Administration (FDA) has approved three injected anti-VEGF therapies for wet AMD: ranibizumab (brand name Lucentis) in 2006, aflibercept (Eylea) in 2011, and brolucizumab (Beovu) in 2019. In 2021, the FDA approved Susvimo, which contains the same active ingredient as Lucentis, but the ranibizumab is delivered slowly through a refillable device implanted in the eye.

Aside from minor side effects related to the injection, Lucentis is associated with increased eye pressure, inner eye inflammation, and rare, serious allergic reactions. The drug has no known adverse interactions with foods, supplements, or other drugs.

Several improvements in anti-VEGF treatments are being studied, including anti-VEGF eye drops or tablets, port delivery systems, and controlled-release dosing. Researchers are also looking into repurposing drugs already approved for other illnesses.

All these approaches reduce or eliminate the discomfort of injections and frequent doctor visits.

Repurposing already approved drugs is attractive because these medications have already passed human safety tests. One strategy for finding them is to search for drugs known to interact with one or more genes involved in AMD and to test them in laboratory and animal models.

University of Chicago researchers, for example, found several candidates among antioxidants and medicines approved to treat high cholesterol and diabetes. Among the most promising were curcumin, the antioxidant and anti-inflammatory agent in turmeric, and metformin, a Type 2 diabetes drug.

Already approved drugs may work for wet AMD, but developers will likely need to show equivalence or superiority to current treatments. “Intravitreal anti-VEGF therapy will be a high bar to pass,” Dr. Keenan said.

Delivering anti-VEGF medicines as drops instead of injections would eliminate most of the treatment’s negatives. This development is still years away, but not for lack of trying.

Some preparations using drugs similar to Lucentis were effective in animals but failed in people. “Anti-VEGF eye drops would be amazing, but their bioavailability issues have been very challenging,” Dr. Keenan told The Epoch Times.

Bioavailability refers to getting drugs into affected tissues or organs at the right dosage. Anti-VEGF drops do not easily penetrate the eye.

Another standard treatment for wet AMD is photodynamic therapy (PTD), which uses a laser to activate a light-sensitive medicine that causes blood vessels in or near the macula to stop leaking. PTD has been seen less frequently since the advent of anti-VEGF injections, but a doctor may prescribe it alongside the injections. Side effects include pain, sun sensitivity, loss of sharp vision, and blind spots.

Fewer Treatment Options for Dry AMD

Far less is known about the causes of dry AMD, making treatment innovations less likely. The first treatments specifically for dry AMD were approved by the FDA in 2023.

In February 2023, the FDA approved Syfovre, a repurposed form of Empaveli, a drug previously approved to treat paroxysmal nocturnal hemoglobinuria, a rare, life-threatening blood disease. Then, in August 2023, the FDA approved Izervay, a novel drug formerly known as Zimura. Both drugs require periodic intravitreal injection.

“These drugs appear to slow geographic atrophy but are only modestly effective and do not affect visual acuity,” Dr. Keenan said. Both medicines are expensive, carry the usual drawbacks of eye injections, and pose a significant risk to patients of developing wet AMD. “In my opinion, their risk–benefit balance does not favor their widespread use,” Dr. Keenan added.

While existing treatments cannot stop vision loss for people with advanced AMD, research on treatment options is ongoing.

Next-Level Strategies

Two experimental treatments for dry AMD offer the potential for long-term control over its progression.

Autologous stem cell treatments use cells harvested from the patient with AMD to replace dead or damaged cells in the macula. In a typical protocol, doctors collect ordinary blood cells and convert them to induced pluripotent stem cells (iPSCs), which have the capability to become any cell type.

The iPSCs are programmed to become retinal pigment epithelial (RPE) cells (the ones destroyed by dry AMD), grown into sheets, and implanted inside the retina, where they are expected to replace the damaged RPE and preserve whatever photoreceptor cells remain.

Stem cell therapies are promising, but safety concerns have forced stakeholders to proceed slowly, which is why these treatments for dry AMD are not expected before 2030.

The other approach involves gene therapy.

“Geographic atrophy involves multiple biological pathways,” said Shankar Musunuri, who holds a doctorate in pharmaceutical sciences and is CEO of Ocugen, a gene therapy company. Ocugen’s clinical target, the RORA gene, is a “master switch”  that turns all these underlying processes on and off, according to Mr. Musunuri. “Current drugs target just one or two processes, but since none alone stop vision loss, they inevitably fail.”

Ocugen hopes its therapy product, which entered Phase 1/2 clinical study in December 2023, will halt the progression of dry AMD through a single treatment and possibly restore some lost vision. One big drawback will be its price tag, as currently approved gene therapies cost between $1 million and $3 million per dose.

Gene therapy is also being studied as a one-time treatment for wet macular degeneration.

Until safe, effective drugs based on new discoveries emerge for dry AMD, patients can take the widely used AREDS 2 oral supplements. “AREDS 2 are highly effective in slowing geographic atrophy and appear to preserve vision in ways no existing treatments have done,” said Dr. Keenan. “They are also low cost and have minimal side effects.”