Age-Related Macular Degeneration

Overview

Age-related macular degeneration (AMD) is the leading cause of vision loss in people over the age of 50, affecting approximately 1.4 million Canadians. The disease is “macular” because it damages the macula, which is the small, central portion of the retina, the light-sensitive tissue at the back of the eye that facilitates the cellular interactions that make sight possible. The macula is responsible for detailed, central vision, and is important for activities such as reading, driving, and distinguishing faces. While the disease is most commonly associated with ageing—hence “age-related”—there are some forms that can affect younger people and are caused by genetic, environmental, nutritional, and other factors, often simply called “macular degeneration.” In fact, the age-related form of the disease (AMD) involves risk factors outside of age that should be taken into account as well, including smoking, diet/nutrition, race (AMD is more common among Caucasians than African-Americans or Hispanics/Latinos), genetics, and family history of the disease.

There are two kinds of AMD: dry AMD and wet AMD. The dry form is more common and less severe. It occurs when the macula becomes thinner and, as a result, less capable of supporting the retina’s photoreceptors, the cells that convert light into visual signals. Vision loss occurs as these cells die off.

A cross-section of the retina showing its different layers, including the layer of RPE cells. The photoreceptors are the elongated shapes standing vertically at the top, which are nourished by the RPE cells below them.

The wet form of the disease is less common, affecting approximately one in ten people with AMD [1], and is a negative progression from dry AMD—in other words, dry AMD has the potential to develop into wet AMD. In the wet form, blood vessels below the thinning macula swell and begin to grow abnormally; if left untreated, they also begin to leak blood and fluid into the eye (hence “wet”). The cells directly affected by leaking vessels are called retinal pigment epithelial (RPE) cells, which nourish and sustain the sheet of light-sensitive photoreceptors above them. Since RPE cells play such a crucial role, their damage and loss during the advanced stages of wet AMD can entail rapid and severe vision loss. In AMD, such vision loss does not lead to blindness, but in the worst cases it cause significant loss of sight.

The below video provides a basic summary of wet AMD:

Content on this page was written by Dr. Chad Andrews and Dr. Mary Sunderland, and was most recently updated on August 23, 2018.

Symptoms and Diagnosis

In the earliest stages of AMD there may not be any noticeable symptoms. As a result, regular eye tests are essential: an ophthalmologist or optometrist will look for build-up of a yellowish deposit called drusen, which indicates the first stages of the macula’s deterioration. Early stages of AMD may also be accompanied by a slight blurring in the field of central vision. Such blurring can be detected via an eye test, but also at home using an Amsler Grid, a simple visual tool that can help you see distortions in your visual field. Please contact the FFB if you would like us to send you a complimentary Amsler Grid. You can also download a copy here.

Images showing an Amsler Grid comparison: the left image shows how a healthy eye would see an Amsler Grid; the right image shows how an eye affected by the early stages of AMD may see a grid, involving a characteristic distortion with both vertical and horizontal misalignment. Image from the Canadian Association of Optometrists.

Eye care professionals will sometimes use an Amsler Grid as well, since it is a straightforward and reliable way to detect anomalies in central vision. Other tests that may be used during an exam include: a visual acuity test, which uses a chart to measure one’s ability to see at distances; a dilated eye exam, where the pupil is dialated with a drop so that the examiner can see into the eye using a specialized magnifying lens; a fluorescein angiogram, where pictures are taken as dye, injected through the arm, highlights leaking blood vessels and other issues; and optical coherence tomography, which uses light waves to take high-resolution images of the eye.

In patients with wet AMD, visual distortion tends to be more significant and vision loss more rapid, particularly when the disease is left untreated. Ideally, if dry AMD is managed appropriately and steps are taken to adjust lifestyle and other factors, the disease will not turn “wet.”

Existing Treatments and Standard of Care

Early-Stage AMD: Nutrition and Exercise

There is no treatment for the earliest stages of dry AMD, which may not involve any symptoms. It is often recommended that individuals living with AMD at this stage seek eye exams at least once a year to monitor the disease’s progression. It is important for patients to self-monitor as well; in other words, any changes in vision should be reported to an eye care professional immediately. At the same time, nutrition and exercise can help stall or even prevent dry AMD from advancing into later stages: a diet of fish and green vegetables is beneficial, and if you smoke, quitting is the most important thing to do. Regular physical activity is important as well, since many of the approaches to cardiac health apply to vision health.

Intermediate AMD or Late-Stage AMD in One Eye: AREDS and AREDS2

In those with intermediate or late-stage dry AMD in one eye, studies undertaken by the National Institutes of Health (NIH) have indicated that nutritional supplements can slow the disease’s progression. The formula tested in 2001 is called “AREDS” (Age Related Eye Disease Study), and it contains beta-carotene, vitamins C and E, zinc oxide, and cupric oxide, a “cocktail” that can decrease the chances of dry-AMD progressing to wet by 25%.[2]

However, beta-carotene has been linked to higher incidences of lung cancer in smokers and former smokers, so there is a more recent NIH-sponsored analysis, AREDS2, that replaces beta-carotene with the micronutrients lutein and zeaxanthin. The study showed no loss of effectiveness with the replacements for beta-carotene. Since there are multiple formulas and studies and since many of the supplements will include different ingredients and doses, it is essential to consult with an ophthalmologist or family doctor about the appropriate supplements for you, even though these vitamins are available without a prescription.

It is important to note that the AREDS formulas are not a cure. According to the NIH, a supplement “does not help people with early AMD, and will not restore vision already lost from AMD. But it may delay the onset of late AMD. It also may help slow vision loss in people who already have late AMD.”[3]

Wet AMD: Anti-VEGF Treatments

Thanks to modern research, there is now a standard of care treatment for individuals affected by wet AMD called anti-VEGF therapies. Vascular endothelial growth factor (VEGF) is a substance that is normally produced in human bodies and is responsible for telling new blood vessels to form. However, the uncontrolled growth of blood vessels in the eye causes vision loss in wet AMD. Anti-VEGF therapies prevent vision loss—and can even reverse some vision loss—by removing excess VEGF from the eye.

In most Canadian provinces and territories, the commonly used anti-VEGF therapies include Lucentis (ranibizumab) and Eylea (aflibercept). Lucentis requires monthly injections into the eye, while each Eylea injection is designed to last two months (after an initial set of monthly injections); Eylea also removes Placental Growth Factor (PIGF), which causes the growth of new blood vessels. Both of these drugs are widely reimbursed across most jurisdictions, and prevent vision loss by getting rid of VEGF. Avastin (bevacizumab) is an anti-VEGF therapy that was designed as a cancer treatment, and although it is not approved by Health Canada to treat wet AMD, it is commonly used “off-label” because studies have shown that it works similarly to Lucentis and Eylea. Doctors continue to discuss the pros and cons of these different treatments, so it is important that you talk to your doctor about what treatment is be best for you.

Wet AMD: Photodynamic Therapy

Though not commonly prescribed today, some patients used to receive photodynamic therapy as a means of removing abnormal blood vessels. The process involves injecting a drug called visudyne into the bloodstream and then activating the drug using a laser that is sent through the eye. Once activated, the injected visudyne will eliminate the abnormal blood vessels and spare the normal ones. This form of combined drug and laser therapy is sometimes used in conjunction with anti-VEGF for specific types of wet AMD.

Wet AMD: Laser Surgery

Before the development of anti-VEGF and advancements in photodynamics, it was not unusual for individuals with wet AMD to undergo laser surgery to destroy abnormal blood vessel growth. This involved a “hot” laser that actually burned away parts of the affected retina, as opposed to the “cold” and less harmful laser utilized by photodynamic therapy. The use of a “hot” laser could in fact damage parts of the surrounding and healthy tissue, often leaving patients with blind spots in their vision. As a result, it is only under extreme and very unique circumstances that conventional laser surgery will be used today.

[2] https://nei.nih.gov/health/maculardegen/armd_facts
[3] https://nei.nih.gov/health/maculardegen/armd_facts

Clinical Trials

Clinical trials are essential to the scientific process of developing new treatments: they test the viability and safety of experimental drugs and techniques, called “interventions,” on human beings. While there is no guarantee that enrolling in a clinical trial will provide any medical benefit, some patients do experience positive results after receiving an experimental therapy.

Read Our Clinical Trials Guide

The website clinicaltrials.gov is a centralized database of clinical trials that are offered globally. But as the disclaimer on the site’s home page states, there is no guarantee that a listed trial has been evaluated or approved—the National Institutes of Health runs the site but does not vet its content. This means that there could be bogus or dangerous trials listed that are preying on patients. It is essential that you discuss a clinical trial with your ophthalmologist before enrolling, and that you pay close attention to enrollment criteria.

If you are interested in exploring what is available on the site you can click on the button below, which will take you to clinicaltrials.gov and initiate a search for trials relevant for patients living with age-related macular degeneration.

CLINICAL TRIALS FOR AMD

Research Developments and Health Policy

The Foundation Fighting Blindness is committed to advancing the most promising sight-saving research, and has invested over $33 million into cutting-edge science since the organization was founded. Recognizing that science is tied to policy frameworks, the Foundation is also actively involved in health policy activities across Canada.

Many research groups are working to develop treatments and cures for AMD. Experimental treatments can be divided into three broad categories (the FFB is funding vision research into these areas):

  • Protective Therapies
  • Corrective Therapies
  • Sight-Restoring Therapies

Protective therapies aim to stop (or at least slow) the loss of vision. These therapies include treatments to stop the process of photoreceptor death (apoptosis), as well as cell-derived therapies that aim to help photoreceptors survive.  Some protective therapies aim specifically to prevent the death of cone cells in AMD – and thus, the loss of central vision – in later stages of the disease.

Corrective therapies aim to target the symptoms that are causing vision loss. If these therapies are successful they might prevent a person who is treated when first diagnosed, from ever developing vision loss. Corrective therapies might also help slow the disease in people whose vision has already been affected, especially in the earlier stages. Anti-VEGF therapies are an excellent example of therapies that can correct some vision loss and prevent further vision loss – there is much research underway to further improve upon the success of these therapies. Many of the new corrective therapies under development aim to extend the amount of time between anti-VEGF injections and also improve the effectiveness of these treatments by combining anti-VEGF with other drug therapies. Some research teams are also working to develop gene therapies for AMD – these efforts are in the earlier stages of development. The FFB is proud to support this research!

Sight-restoring therapies are also a growing area of research success. These therapies are intended for people who have already lost all, or much, of their vision. Stem cell therapies aim to replace the retina’s lost photoreceptors. There are very promising early results with stem cell trials for age-related macular degeneration! At the FFB, we follow stem cell therapy developments very closely and are also very proud to be funding stem-cell research by exceptional scientists, such as Dr. Andras Nagy (to learn more about these research developments, read the list of research stories that appear along the side of this webpage or along the bottom).

Retinal prosthetics, such as the Argus II or “Bionic Eye,” use computer technology to generate vision. The Foundation Fighting Blindness helped to support the first Canadian trial of the Argus II and continues to work closely with health policy experts across Canada to ensure that patients who could benefit from the Argus II device have access to this innovative treatment. At present, research is underway to test if retinal prosthetics could help to restore vision to people living with AMD. Drug and gene therapies are also being developed that may give non-photoreceptor nerve cells in the retina the capacity to sense light.

Thanks to our generous donors, we are funding ground-breaking research in these areas. Click on the button below to review the full list of FFB-funded projects:

FFB-FUNDED RESEARCH

At the bottom of this webpage, you will find an updating list of stories that detail new research and health policy developments relevant for individuals affected by AMD.

Educational Resources

The page you are now on provides information on achromatopsia, but the Foundation Fighting Blindness has developed additional resources that can be helpful in plotting an optimal path through vision care. Below is a link to our must-read resources, where you will find information on genetic testing, clinical trials, stem cell research, and more as well as a link to Vision Quest (the FFB’s in-person educational events). The list will update as new resources are added.

Must-Read Resources

Vision Quest Educational Series

References