Causes and Risk Factors of Macular Degeneration
Understanding Age-Related Macular Degeneration
AMD is a disease that damages the macula, the small central area of the retina (the light-sensitive tissue at the back of the eye). The macula is responsible for sharp, detailed central vision. You rely on it for reading, driving, recognizing faces, and seeing fine details. When the macula deteriorates, central vision becomes blurry, distorted, or dark. Side vision usually remains intact.
An estimated 11 million people in the United States have some form of AMD (NEI, 2021). More than 1.6 million Americans over age 60 have advanced AMD (NEI, 2015). These numbers are expected to rise as the population ages.
About 85 percent of people with AMD have the dry form (NEI, 2021). Dry AMD develops when the macula thins with age and tiny yellowish deposits called drusen accumulate beneath the retina. Drusen are made up of proteins and fats. Small drusen are common with aging, but larger drusen can signal the beginning of AMD.
Over time, the buildup of drusen and thinning of retinal tissue can lead to gradual central vision loss. In its most advanced stage, dry AMD can progress to geographic atrophy. In this condition, patches of retinal cells in the macula die off completely.
Wet AMD, also called advanced neovascular AMD, affects roughly 15 percent of people with the disease (AAO, 2023). It occurs when abnormal blood vessels grow beneath the macula. This process is known as macular neovascularization. These new vessels are fragile and prone to leaking blood and fluid.
The leaking distorts the structure of the retina and can cause rapid, severe damage to central vision. A protein called vascular endothelial growth factor (VEGF) drives the growth of these abnormal vessels. Although wet AMD is less common than dry AMD, it accounts for a large share of severe vision loss from the disease.
The exact cause of AMD is not fully understood, but the disease develops as the eye ages. In early stages, changes occur in the retina and the choroid (the layer of blood vessels beneath the retina). These changes can include drusen buildup, pigment changes, and thinning of tissue layers.
AMD often starts in one eye and may eventually affect both. Not everyone with early AMD will progress to advanced stages. However, without monitoring, significant vision loss can occur before a person notices symptoms.
Who Is Affected and Risk Factors
Age is the single greatest risk factor for AMD. The disease is rare before age 50 and becomes significantly more common with each decade of life. The biological aging process causes cumulative wear on retinal cells and supporting structures. Over time, the eye's ability to clear waste products and maintain healthy blood flow to the macula declines.
Smoking is the risk factor most consistently linked to AMD. Current smokers face two to three times higher risk of developing AMD compared to nonsmokers (AAO, 2023). The risk increases with heavier smoking. Smoking damages blood vessels, reduces oxygen supply to the retina, and increases oxidative stress on delicate retinal cells.
People with a family history of AMD are at higher risk of developing the disease. Researchers have identified several genes associated with AMD. These include genes related to the complement system, which is part of the body's immune response. If a parent or sibling has AMD, your own risk is significantly elevated. Genetic factors may influence how the body handles inflammation and waste removal in the retina.
AMD is more common among Caucasian and European-descent populations than among other racial groups (NEI, 2021). Women are also at somewhat higher risk, partly because they tend to live longer. However, anyone can develop AMD regardless of race or gender.
Several cardiovascular risk factors also raise the likelihood of developing AMD. These include:
- High blood pressure, which can damage the small blood vessels that nourish the retina
- High cholesterol levels, which may contribute to drusen formation beneath the macula
- Heart disease, which is associated with reduced blood flow to the eye
- Obesity, which increases inflammation throughout the body and in the eye
Managing these conditions through lifestyle changes and medical treatment may help lower AMD risk or slow its progression.
Signs and Symptoms
One of the challenges of AMD is that early stages often produce no noticeable symptoms. Vision may seem normal even as drusen begin to form and subtle changes take place in the macula. This is why regular eye examinations are so important, especially after age 50. A retina specialist or eye doctor can detect AMD before you experience any vision changes.
As AMD advances, several warning signs may appear. Recognizing these changes early is critical because prompt treatment can help slow or stop further vision loss. Common symptoms include:
- Distortion or warping of straight lines, such as doorframes or text on a page
- A dark or blurry area in the center of your vision
- Decrease in the brightness or intensity of colors
- Difficulty reading, even with glasses
- Trouble recognizing faces
- Gradual or sudden loss of central vision
An Amsler grid is a simple tool that looks like graph paper with a dot in the center. By looking at the grid one eye at a time, you can check for wavy, broken, or missing lines. These changes may signal problems in the macula. Retina specialists recommend using an Amsler grid regularly at home, especially if you have been diagnosed with early or intermediate AMD. Any new distortion should be reported to a retina specialist right away.
Diagnosis and Testing
A comprehensive dilated eye exam is the most reliable way to detect AMD. During this exam, drops widen the pupils so a retina specialist can examine the macula and retina in detail. The specialist looks for drusen, pigment changes, fluid, blood, or areas of thinning. This exam can reveal AMD even before symptoms develop.
Optical coherence tomography, or OCT, is an imaging test that creates detailed cross-section pictures of the retina. It allows a retina specialist to see the individual layers of the retina and measure their thickness. OCT can detect fluid buildup, swelling, drusen, and areas of geographic atrophy. It is painless and takes only a few minutes. OCT is used both for initial diagnosis and for monitoring AMD over time.
Fluorescein angiography is a test that helps detect wet AMD. A special dye is injected into a vein in the arm. A camera then takes rapid photographs as the dye travels through the retinal blood vessels. Leaking or abnormal blood vessels beneath the macula show up clearly on these images. This test helps a retina specialist determine whether wet AMD is present and plan treatment.
Treatment Options
Anti-VEGF injections are the standard treatment for wet AMD. These medications block vascular endothelial growth factor, the protein that drives abnormal blood vessel growth beneath the macula. By stopping the growth and leaking of these vessels, anti-VEGF treatment can preserve central vision and, in some cases, improve it.
Several anti-VEGF medications are available. Eylea (aflibercept) is one of the most commonly used, typically given every four to eight weeks after an initial loading phase. Lucentis (ranibizumab) was the first anti-VEGF therapy approved for eye use. Vabysmo (faricimab), a bispecific antibody, targets two pathways and can be given every four to sixteen weeks. Avastin (bevacizumab) is FDA-approved for cancer but is used off-label for AMD treatment. Beovu (brolucizumab) is given every eight to twelve weeks but carries a risk of retinal vasculitis.
For the advanced dry form of AMD known as geographic atrophy, two newer treatments are available. Syfovre (pegcetacoplan), a complement C3 inhibitor, is given as an intravitreal injection (an injection into the eye) monthly or every other month. In clinical trials, Syfovre reduced the growth rate of geographic atrophy by 20 to 29 percent (FDA, 2023). Izervay (avacincaptad pegol), a complement C5 inhibitor, is given monthly. It reduced the growth of geographic atrophy by approximately 27 percent (FDA, 2023).
These complement inhibitors slow the expansion of areas where retinal cells have been lost. Neither drug prevented a decline in visual function compared with untreated groups over two years in clinical trials. They slow the disease but do not reverse damage that has occurred.
The Age-Related Eye Disease Study 2 (AREDS2) found that a specific combination of vitamins and minerals may help slow the progression of intermediate dry AMD to advanced stages. The AREDS2 formula includes vitamin C, vitamin E, lutein, zeaxanthin, zinc, and copper. These supplements are available over the counter. A retina specialist can advise whether AREDS2 supplements are appropriate based on the stage of your AMD.
Supplements are not a treatment for wet AMD and do not reverse vision loss. They are intended as a preventive measure for people at risk of progression.
AMD is a chronic condition that requires regular monitoring. For people with dry AMD, periodic visits to a retina specialist allow for early detection if the disease progresses or converts to wet AMD. For those receiving injections, ongoing appointments are needed to assess response and adjust treatment schedules.
What to Expect
If you are diagnosed with early or intermediate dry AMD, you may not need treatment right away. Your retina specialist will likely recommend regular monitoring, typically every six to twelve months. You may be asked to check your vision at home using an Amsler grid. Many people with early AMD maintain good vision for years.
If you need anti-VEGF or complement inhibitor injections, the procedure is performed in a retina specialist's office. The eye is numbed with drops or a small amount of anesthetic. The injection itself takes only seconds. You may feel pressure or mild discomfort during and after the procedure. Most people resume normal activities the same day.
Treatment outcomes vary from person to person. Anti-VEGF injections for wet AMD are highly effective at stabilizing vision and can improve it in some cases. Results depend on how early treatment begins and how consistently it is continued. Complement inhibitors for geographic atrophy can slow disease progression, but they do not restore vision that has been lost. Working closely with a retina specialist gives you the best opportunity to preserve as much vision as possible.
Living with Age-Related Macular Degeneration
Certain lifestyle changes may reduce your risk of AMD progression. Quitting smoking is the single most impactful step you can take. Other helpful changes include:
- Eating a diet rich in leafy green vegetables, fish, and fruits
- Maintaining a healthy weight
- Exercising regularly
- Managing blood pressure and cholesterol levels
- Wearing sunglasses that block ultraviolet light
If AMD has caused significant central vision loss, low vision rehabilitation can help you make the most of your remaining sight. Low vision specialists can recommend magnifying devices, special lighting, large-print materials, and electronic aids. Many people with AMD continue to live independently and enjoy daily activities with the right support and tools.
A diagnosis of AMD can bring feelings of worry, frustration, or sadness. These reactions are normal. Talking with family, joining a support group, or speaking with a counselor can help. Staying informed about your condition and actively participating in your treatment plan can provide a sense of control.
When to See a Retina Specialist
Because early AMD often has no symptoms, regular comprehensive eye exams are essential after age 50. If you have risk factors such as a family history of AMD, a history of smoking, or cardiovascular disease, more frequent screenings may be recommended. Early detection gives you the best chance of preserving your vision.
Certain vision changes can signal a rapid worsening of AMD or other serious eye conditions. See a retina specialist or go to the emergency room immediately if you experience:
- A sudden increase in floaters (spots or lines drifting across your vision)
- Flashes of light in one or both eyes
- A curtain or shadow moving across your field of vision
- Sudden loss of central vision in one eye
These symptoms may indicate that dry AMD has converted to wet AMD or that another urgent retinal problem is developing. Quick evaluation and treatment can make a significant difference in outcomes.
Questions and Answers
There is no proven way to prevent AMD entirely. However, you can reduce your risk by not smoking, eating a healthy diet, maintaining a healthy weight, exercising regularly, and managing blood pressure and cholesterol. If you have intermediate dry AMD, AREDS2 supplements may help slow progression. Regular eye exams allow for early detection, which can lead to earlier treatment and better outcomes.
AMD affects central vision, not peripheral (side) vision. Most people with AMD do not lose all of their sight. Even in advanced cases, peripheral vision is typically preserved. With current treatments, especially anti-VEGF injections for wet AMD, many people maintain enough central vision for daily activities. Early detection and consistent treatment improve the chances of preserving functional vision.
Drusen are small yellowish deposits that accumulate beneath the retina in the early and intermediate stages of dry AMD. They are a hallmark sign of the disease but do not necessarily mean vision will be severely affected. Geographic atrophy is the advanced stage of dry AMD, where patches of retinal cells in the macula die and cannot be replaced. Geographic atrophy causes more significant and lasting central vision loss than drusen alone.
The frequency of injections depends on the type of AMD and the medication used. For wet AMD, anti-VEGF injections typically start with monthly doses for the first few months. After that, treatments may be given every four to sixteen weeks depending on the medication and your response. For geographic atrophy, complement inhibitors are given monthly or every other month. Your retina specialist will create a treatment schedule and adjust it over time.
Research into AMD is active and ongoing. Scientists are studying new drug therapies, gene therapies, and implantable devices that could deliver medication over longer periods. Longer-acting anti-VEGF formulations and new targets in the complement pathway are also being explored. While no treatment currently reverses AMD, the pace of new developments continues to improve the outlook for people living with this condition.