Age-Related Macular Degeneration: Current Treatments and Future Therapies

Posted By SHL Librarian

Presented by Diana V. Do, MD
Professor of Ophthalmology
June 22, 2017

For most people, vision is one of the most important parts of their health. Yet as we age, the risk rises that we could lose eyesight from a condition called age-related macular degeneration.

“The eye and the sense of vision is so important to all of us,” said Diana V. Do, MD, professor of ophthalmology at Stanford’s Byers Eye Institute, at a recent lecture for the Stanford Health Library.  “When we encounter the outside world, to see the beautiful flowers or to see our friends or to read books, we depend on our vision.”

To prevent macular degeneration, it’s important to see an eye doctor to get treatment before any damage is done, Dr. Do said.

“It’s an eye condition that probably affects someone you know,” she said “It’s a disease of aging. And our population is living longer.”

In the United States, age-related macular degeneration is the leading cause of blindness in people over age 50, Dr. Do said.

Higher risk

Some people are more prone to developing age-related macular degeneration than others because they have certain risk factors:

  • Genetics play a key role in who develops age-related macular degeneration, according to multiple scientific studies.
  • People of Caucasian race have a higher risk of potentially developing age-related macular degeneration than someone of a different race, Dr. Do said.
  • Advancing age increases the risk for macular degeneration.

These risk factors can’t be changed. So the best way to preserve your vision is to see an eye doctor, called an ophthalmologist, who can diagnose and treat the condition early.

How the eye works

To avoid macular degeneration, it helps to understand how the eye works.

  • The front of the eye is the clear part called the cornea.
  • The colored part of your eye, the iris, gives you either blue-colored eyes, brown, or hazel-colored eyes.
  • Behind the iris sits the lens of the eye. With aging, you can develop a cloudiness of the lens, which is called a cataract. Some people get cataract surgery to remove the cloudy lens.
  • Behind the lens lies the area of the retina—a thin film of tissue that coats the back wall of the eye. This is the area that can be affected by macular degeneration.

Genetic marker

Within the last 5 years, scientists identified a genetic marker that is linked to a person’s risk for developing age-related macular degeneration. The genetic marker is called complement factor H (CFH). When the marker has a specific form (Y402H), that gives someone a higher risk for developing macular degeneration, Dr. Do said.

CFH is located on chromosome 1. An alteration in this gene can make the body more likely to have inflammation. Scientists think this plays a role in age-related macular degeneration, Dr. Do said.

People who have this higher-risk alteration in both copies of their CFH gene have a 7-fold higher risk of developing age-related macular degeneration. “That’s significant,” Dr. Do said.

Reducing risk

What can people do to prevent macular degeneration? Some of the causes—each person’s race, genetics, age—can’t be changed. “That’s what we were born with,” Dr. Do said.

There are other steps people can take to decrease their risk:

  • Stop smoking. “Smoking is very dangerous,” Dr. Do said. It increases the risk of lung cancer as well as the risk of developing age-related macular degeneration.
  • Keep a healthy weight. Studies have found that a higher waist-to-hip ratio is linked to macular degeneration. “Being overweight can cause numerous problems,” Dr. Do said. “It can also increase the risk of age-related macular degeneration.”

Apart from these 2 risks, the best way people can guard against age-related macular degeneration is to see an eye doctor called an ophthalmologist, Dr. Do said. Ophthalmologists are trained to evaluate eye diseases.

If an ophthalmologist sees signs of macular degeneration in a patient, he or she may send the patient to a specific type of ophthalmologist—a retinal specialist–who specializes in the eye retina.

“A retina specialist is the ideal type of eye doctor you should see if you’re concerned about age-related macular degeneration,” Dr. Do said.

The retina

The retina is a complex tissue in the back of the eye. It has different cellular layers to it. Underneath the retina is a basement membrane and a tissue called the RPE, or retinal pigment epithelium.

“All of these layers have to be healthy in order for you to have ideal perfect vision,” Dr. Do said.

In the early stages of age-related macular degeneration, a person develops tiny yellow-colored deposits beneath the retina, called drusen.

“They appear as these little yellow dots on examination,” Dr. Do said.

If the eye doctor sees drusen, he or she may do more tests. Another telltale sign of age-related macular degeneration is when the retina’s basement membrane appears to be thickened.

Stages of disease

Treatment for age-related macular degeneration depends on how far the condition has progressed, Dr. Do said. Ophthalmologists classify the condition into to several stages:

  • No signs of disease: patients who have only a few small drusen and good vision.
  • Early stage disease: many drusen that are small (less than 63 microns), or a few medium-size drusen (63 to 125 microns). “We can only see that under high magnification with a trained ophthalmologist’s eyes,” Dr. Do said.
  • Intermediate stage disease: many medium-size drusen, or one large drusen.
  • Advanced disease: atrophy (shriveling) of the retina or the retinal pigment epithelium.
  • Advanced disease: bleeding and swelling in the back of the eye, which are signs of “wet” macular degeneration. That occurs when abnormal blood vessels grow under the retina.

Catching disease early

“Advanced AMD, when untreated, will lead to irreversible loss of your central vision. We want to prevent that,” said Dr. Do.

People with early age-related macular degeneration have a very low risk of losing central vision within 5 to 10 years, Dr. Do said. Those with intermediate disease have a 12 percent risk of developing advanced macular degeneration or severe vision loss within 5 years.

Before people reach the advanced stages of age-related macular degeneration, what can they do to avoid losing their vision? Studies have found that taking a specific combination of antioxidant vitamins can help, Dr. Do said. The combination of antioxidants—vitamin C, vitamin E, zinc, cupric oxide, beta-carotene and zeaxanthin—is available as the AREDS 2 Preservision vitamins. These vitamins are sold over the counter.

Antioxidant vitamins

People with intermediate-stage disease or advanced AMD in one eye should take these antioxidant vitamins to reduce their risk of progression to advanced AMD, Dr. Do said. Individuals who took the vitamins had a small reduction in the risk of getting worse.

“So there was a small risk reduction in patients who had intermediate macular degeneration, if they took these supplements every day,” Dr. Do said.

Taking the antioxidant combination has become a standard recommendation for people with intermediate age-related macular degeneration.

Apart from the antioxidants, people should continue to see an ophthalmologist if they have signs of age-related macular degeneration. For those with early disease, once a year is enough. Those with intermediate disease should go to see a retinal specialist at least every 6 months, Dr. Do said. Anyone with new symptoms should go more often.

Advanced disease

Advanced macular degeneration requires a different kind of treatment. Advanced disease can lead to severe vision loss if untreated, Dr. Do said.

In advanced disease, someone might notice that they have lost in their central vision, or a dark spot–a scotoma–in their central field of view. Sometimes patients complain of distorted vision.

“Their friend’s face looks irregular or warped,” Dr. Do said. Other people may have trouble reading or seeing different colors, especially in low light.

Wet and dry

There are 2 kinds of advanced age-related macular degeneration that can lead to severe vision loss: wet and dry. About 20 percent of people with age-related macular degeneration have the wet form, while 80 percent have the dry form, Dr. Do said. Although the wet form is less common, it is most often the cause of severe vision loss.

Wet macular degeneration is caused by abnormal blood vessels, called choroidal neovascularization, that grow underneath the retina. These blood vessels distort or damage the retina, and they can bleed. And that’s why someone may lose some of their central vision, Dr. Do said.

Some signs are swelling in the retina with fluid, or elevation of the retinal pigment epithelium (the layer of tissue underneath the retina).  Those are very suspicious signs of wet macular degeneration, Dr. Do said.

Those kinds of symptoms must be confirmed by more tests before diagnosing wet macular degeneration. A retinal specialist can:

  • Take color photos of the retina to detect changes over time.
  • Get a 2-dimensional view of the retina with optical coherence tomography (OCT).
  • Run a test called fluorescein angiography that uses dye to show any abnormal blood vessels.
  • Use OCT angiography, available at Stanford, to see normal and abnormal blood vessels.

Treating advanced disease

Treatment for advanced wet macular degeneration is different than for dry macular degeneration. Medicine is injected to halt the swelling and bleeding of the wet form of the disease.

The treatment blocks excess levels of a protein, called vascular endothelial growth factor (VEGF). The medicine is injected in the eye (with an anesthetic) in the clinic.

“It’s effective because it delivers the medicine right into the area where it’s needed, without having the medicine go through out your entire body,” said Dr. Do. “It might sound scary to you,” she said. People might say, “I don’t want an injection of medicine in my eye.”

But she added, “This is done in the office under topical anesthesia, and actually can be a very comfortable procedure.” The medicine is effective for about 1 to 2 months. So the injections must be repeated every 1 to 2 months, depending on whether the wet macular degeneration has become active again, to keep the eye protected.

These injections can improve some of the vision lost in people with advanced wet macular degeneration, Dr. Do said. On average, patients who received injections consistently for 2 years were able to read an additional 5 to 8 letters on an eye chart.

It’s important to administer a treatment as soon as the doctor detects swelling or bleeding, Dr. Do said. Without it, those abnormal blood vessels continue to grow and are harder to treat. Over time, scar tissue forms.

“That’s a bad sign,” Dr. Do said. “Unfortunately there is no effective treatment to remove scar tissue. That area with the scar will not improve and your vision will have a permanent reduction in that area.”

Severe dry disease

In addition to wet macular degeneration, there’s a second cause of advanced disease: severe dry macular degeneration. When the dry form is accompanied by thinning and atrophy of the retina and loss of pigmentation, it’s called geographic atrophy.

“That can cause irreversible vision loss,” said Dr. Do.

Geographic atrophy is more difficult to diagnosis because doctors must look for subtle signs in the retina and loss of pigmentation. They use special photography machines called fundus autofluorescence.

Unfortunately, there is no treatment yet for geographic atrophy, Dr. Do said. Stanford doctors are conducting clinical studies of potential new treatments.

Other research studies are also exploring better treatments for wet and dry macular degeneration. A longer-acting medicine might mean patients need fewer injections or trips to the doctor, Dr. Do said. Stem cell therapy or gene therapy might also be useful.

The bottom line is that people should get regular eye examinations and see an ophthalmologist and retina specialist at the first sign of potential macular degeneration.

“Early detection and treatment is so vital to keeping and preserving your eyesight,” said Dr. Do.

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Diana V. Do, MD

Byers Eye Institute at Stanford