Aug. 28, 2024 – Recent evidence has shown that a specific combo of vitamins and minerals may slow the progression of disease in people with the later stages of dry age-related macular degeneration.
Age-related macular degeneration (AMD) is a common eye disease — often seen in people 50 or older — that leads to vision loss due to damage to the macula, the central part of the eye responsible for visual clarity. The disease affects about 20 million people in the U.S. and nearly 200 million people worldwide.
And by 2040, the disease may affect nearly 300 million people worldwide as the average life expectancy continues to rise and diagnostic methods improve.
Two forms exist: “dry” and “wet.”
Late stage dry age-related macular degeneration, also known as geographic atrophy, leads to a gradual loss of the retinal pigment epithelium, a single layer of cells in the eye essential for health and function of the eye. It is a progressive and irreversible condition that can cause a dark or dim area in the center of your vision, surrounding blind spots, and potentially complete loss of central vision.
The other late-stage form of AMD is wet AMD. With wet AMD, abnormal blood vessels grow behind the macula, the small, rounded area at the back of the eye responsible for central vision, color vision, and fine detail. These vessels can leak blood and other fluids, scarring the macula and causing a rapid deterioration of central vision.
However, dry age-related macular degeneration is the much more common form, accounting for around 85%-90% of cases. Though it’s less severe than wet AMD, it can cause substantial vision loss in advanced stages.
The supplement in question, called AREDS 2, is composed of antioxidant vitamins and minerals, namely vitamins C and E, lutein, zeaxanthin, zinc, and copper. This formula can be bought over the counter mixed together in ready-made tablets.
The new study, spearheaded by Tiarnan Keenan, MD, PhD, staff clinician in retinal disease at the National Eye Institute, was published in the journal Ophthalmology in July. The study reinvestigated the original retinal scans of participants who developed dry AMD in earlier studies.
“The purpose of those original trials wasn't really to study geographic atrophy or expansion rates. They did take all these retinal images, which meant we were able to study geographic atrophy expansion,” Keenan said.
This has profound implications for the treatment of dry age-related macular degeneration going forward and may inform future clinical trials, he said.
Reinvestigating an Old Study
Keenan and other authors of the new study reviewed data from the original studies and found that, of those who hadn’t yet had their central vision overcome by geographic atrophy, the supplement slowed the rate of expansion by about 55% over an average of 3 years.
Geographic atrophy starts around the perifoveal region of the eye, an area just outside the more central foveal region. The perifoveal region gets its name from the fovea, which is the central part of the macula. After it begins to spread around the perifoveal region of the eye, geographic atrophy then expands inward into the fovea, where it can cause the most damage.
Before Keenan’s study, it was widely assumed that the formula had little to no benefit in treating advanced dry age-related macular degeneration. They found micronutrient supplements slowed geographic atrophy through a natural phenomenon called “foveal sparing.” As its name implies, foveal sparing occurs when geographic atrophy surrounds the fovea but does not affect the fovea itself, effectively sparing it from atrophy.
Foveal sparing wasn’t accounted for in the original studies, published in 2001 and 2013.
“If you've got a patch of geographic atrophy a little bit off-center, it will expand upwards and downwards, but not into the very center. So you start to get these funny configurations of atrophy, like a horseshoe, where it's wrapping around the center but not involving it ... where its growth into the centers for some reason is much slower,” Keenan said.
According to Keenan, his study was able to separate the components of the supplement and then compare how each fared against different aspects of age-related macular degeneration. Zinc seemed to be effective at reducing the risk of dry AMD progressing to wet AMD, in which abnormal vessels grow into the back of the eye and damage the macula.
However, zinc didn’t seem to have much of a positive effect against geographic atrophy. Meanwhile, vitamins C and E showed the most effectiveness against atrophy expansion, probably due to their antioxidant properties.
How Findings Changed Over Time
Subtle changes toward the center of the retina could be missed in studies that don’t specifically focus on center-directed progression of geographic atrophy, according to David A. Merle, MD, a retinal expert at University College London’s Institute of Ophthalmology. Center-directed progression simply refers to the way in which geographic atrophy progresses through the retinal cells, such as from outward to inward, or to the center of the retina in the eye.
“It was not known that [the supplements] had an effect on geographic atrophy,” he said. “And the main reason for that probably is the way these the readouts were constructed in the new trial because they were looking to center-directed progression as opposed to overall growth of lesions.”
The findings are “impressive” and encouraging, according to Merle, especially for those who want to avoid using more invasive therapies, such as the recently US-approved complement inhibitors Syforvre and Izervay.
Both Syfovre and Izervay must be injected directly into the eye once per month, or every other month, on an ongoing basis. They prevent damage to retinal cells by calming the immune response and can slow the development of geographic atrophy by about 14-20%. However, complement inhibitors like Syfovre and Izervay can cause inflammation, bleeding beneath the clear lining of the eye, blurred vision, and an increase of fluid pressure in the eye. Some patients have even developed wet AMD after taking the drugs.
Though complement inhibitors can slow the growth of geographic atrophy by around 14%-20% vs. about 55% for the antioxidant supplements, the relevant studies for both courses of treatment report the difference in overall atrophy growth, and don’t focus on how growth slowed toward the center of eye.
The large reduction in overall lesion growth with the antioxidant supplements is still relevant, but one has to see how it directly compares with complement inhibitors. Still, there’s little to no risk with supplements.
“Given the fact that those complement inhibitors are not available outside of the US, bring some risks and have to be injected on a regular basis, [these] supplements may depict a good and immediately available treatment option. They're relatively safe. You can take them without any major side effects, and if they prove to be that efficient, then these supplements may become the future gold standard for geographic atrophy," Merle said.
Merle was quick to point out that although he is very encouraged by these new findings, there hasn't been a large-scale clinical trial, which is something Keenan hopes to do in the future.
“You have to keep in mind, these trials were not specifically designed for this endpoint,” Merle said. But doctors shouldn’t be concerned about prescribing supplements for their patients, even those with advanced forms of the disease.
“There's no real risk we're taking if we advise patients to take those medications. So why not give it a try?” Merle said.
Disease Prognosis and Patient Response
In clinical practice, it’s difficult to assess the progression of the disease in patients who take the supplements versus if they had not. Without a control group in a clinical routine, there’s no direct measurement of the size of atrophy.
“It's more down to a case-to-case basis,” Merle said.
Prognosis can vary widely on a case-by-base basis as well, as age-related macular degeneration is a complex disease. Lucky patients may see their partially compromised vision stay relatively the same after some degree of loss, with very slow progression, whereas some will see the disease progress into the center of the retina where the fovea is. Protecting the fovea is the most important goal of treatment.
Though the supplements cannot prevent the development of age-related macular degeneration or cataracts, researchers in earlier clinical trials have found the formula to slow the progression from intermediate to later stage by around 25% in those at a higher risk of developing advanced age-related macular degeneration.
They also can’t prevent wet AMD. However, research suggests the supplements could help at least delay the onset of wet AMD.
