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Introduction

Age-related macular degeneration (AMD) is one of the world’s leading causes of blindness, particularly among people aged 65 and older. In the United States, an estimated 2.1 million people aged 50 and older have advanced or late-stage AMD (with loss of visual function) and another 9.1 million have early or intermediate AMD (with minimal to significant vision loss). The number of people around the world with diagnosed AMD is expected to reach 196 million by the year 2020, as life expectancies rise and populations age.

AMD is characterized by the loss of central vision due to the gradual deterioration of the macula—the part of the eye that allows you to see fine details and where sharp central vision occurs. AMD makes daily activities, such as reading, driving, recognizing faces, watching television, and navigating stairs difficult or impossible. AMD is not painful. The speed of its progression varies (advancing slowly or quickly) and it can occur in one eye or both eyes. When the disease advances rapidly, it may swiftly lead to discernible vision loss. The advanced stages of AMD may lead to permanent loss of vision if left untreated. To reduce risk of dry AMD rapidly advancing, make use of available at home tests, such as the Amsler Grid (download here) and at home monitoring devices, such as the ForeseeHome device (learn more here). If only one eye is affected, vision loss is harder to detect because the unaffected eye works harder to make up for the deficiency in the affected eye. It is important to have regular eye exams to keep tabs on visual acuity and macular function in both eyes. healthyretina AMD has three forms: early, intermediate, and advanced. Early and intermediate AMD are the most common of the phases. Usually AMD progresses linearly (from early to intermediate to advanced), but most people with intermediate AMD do not progress to an advanced form. Only about 10% to 15% of adults with early and intermediate AMD will progress to advanced AMD, which can be “wet” (also known as exudative or neovascular AMD) or “atrophic” (known as “geographic atrophy”).

Early AMD

Early and intermediate AMD are the most common forms of AMD, accounting for approximately 90% of all cases. Early AMD and intermediate AMD are both considered “dry” forms of the disease. Early AMD is generally very mild and asymptomatic. Eye care professionals characterize early AMD by the presence, size and amount of drusen found in the eye.

 

Drusen are yellow deposits in the back of the eye that can build up and affect vision. People in their 30s and 40s can have drusen, but the presence of drusen alone does not indicate early AMD. You must be over the age of 50 for an eye care professional to diagnose you with early AMD.

Intermediate AMD

Intermediate AMD is more advanced than the early form of AMD and it is characterized by larger drusen, many drusen, or pigmentary changes in the macula.

 

Many people with intermediate AMD have no symptoms at all. One of the first things you may notice is a problem adjusting from light to dark environments. For example, you may notice you have trouble reading a menu when you go into a dimly lit restaurant, or you may notice problems when you are driving and enter a dark tunnel. This is called “prolonged photo stress recovery” or “delayed dark adaptation.” You may also experience difficulty reading and sensitivity to bright light. These symptoms are not normal signs of aging and you should talk to your doctor about any changes in vision right away. There are currently no treatments for the early and intermediate forms of AMD. You are only eligible for treatment if your AMD progresses to the advanced, “wet” form of AMD (also called exudative or neovascular AMD).

 

Daily monitoring of intermediate AMD is important to detect the visual changes that may occur when advanced AMD develops. You can track the progression of intermediate AMD at home by using an Amsler Grid (available for download here). You can track changes in your vision by noting whether the straight lines become wavy or distorted by looking at this grid daily. If you notice changes in the lines, talk to your doctor right away. There are also new at home-monitoring devices that facilitate the early detection of macular changes in intermediate AMD. ForeseeHome is a non-invasive monitoring device that can be used at home daily (learn more click here).   If you have intermediate AMD, talk to your doctor about the AREDS or AREDS2 vitamin formulas.

 

These vitamin formulas are a combination of antioxidants and zinc, and have been shown to effectively reduce the risk of the progression of intermediate AMD to the more advanced forms. AREDS vitamins were shown to reduce the relative risk of advanced AMD by 25 percent in studies of those with intermediate AMD. This large-scale study was conducted by the National Eye Institute (a part of the National Institutes of Health). The AREDS or AREDS2 vitamin formulas are available over-the-counter at the pharmacy or for purchase online.

Advanced AMD (Also Known as Exudative, Neovascular or Wet AMD)

Once AMD progresses from an early or intermediate case it is considered advanced AMD. Advanced AMD is split into two categories: atrophic AMD (also known as geographic atrophy) and exudative AMD (also known as neovascular or commonly ‘wet’ AMD). Exudative AMD or geographic atrophy can result in significant loss of visual function over time. Exudative AMD often causes scarring of the macula and retina, producing rapid and permanent loss of central vision in as little as three months if not treated promptly.

People living with advanced AMD can have many visual problems that profoundly affect their quality of life. Daily activities like dialing the telephone, reading, driving, preparing food, and doing laundry can be very difficult or impossible due to vision loss. It can also be difficult to read and recognize faces. Talk to your doctor about how AMD is impacting your life and whether they can refer you to support services in your community that can help.

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Exudative AMD is the most serious and severe form of AMD. All people who develop exudative AMD once had intermediate AMD, but only 10 to 15% of people with intermediate AMD will progress to the exudative form. Exudative AMD is characterized by the growth and leaking of abnormal blood vessels under the macula. Exudative AMD can rapidly damage the macula and quickly cause a loss of central vision. Routine eye examinations are very important for patients at a higher risk of developing exudative AMD.

In exudative AMD, blood vessels grow abnormally beneath the macula, through a process called angiogenesis. These abnormal vessels leak fluid and blood, which may cause a blister-like pocket to form beneath the macula. These blisters distort vision in the affected eye, making straight lines appear wavy. The patient may see a dark spot or spots in the center of their vision due to blood or fluid collecting under the macula. You can monitor changes in vision at home using the Amsler Grid (downloadable here) and other at-home monitoring tools.

If exudative AMD is left untreated, bleeding in the eye can cause scar tissue to form, leading to irreversible vision loss. The good news is that there are several effective treatment options, known as anti-VEGF therapies, for exudative AMD. Anti-VEGF treatments can stabilize or, in some cases, reverse vision loss if used before scar tissue forms.

Anti-VEGF treatments are administered as injections in the eye by a trained retina specialist. These injections can be slightly uncomfortable, but you can talk with your doctor about minimizing discomfort during the procedure. Most people notice that injections help them maintain the vision they have, and in some cases, the vision can even improve. If the first anti-VEGF treatment you try isn’t working, you still have options. Talk to your doctor about trying another anti-VEGF therapy that could be better for you.

A diagnosis of wet AMD meant certain vision loss before anti-VEGF treatments became available in 2006. Now people are able to prevent vision loss, especially when treated early.

Once you are receiving anti-VEGF treatment, it’s important to stay on the treatment schedule recommended by your doctor.

Eye care professionals once thought intermediate AMD (dry) went away once it progressed to exudative AMD (wet), but the advent of anti-VEGF treatments have shown that dry AMD remains even after someone is diagnosed with exudative AMD. This may explain why AMD cannot be completely reversed even with effective anti-VEGF treatments.

Atrophic AMD or Geographic Atrophy

Atrophic AMD or geographic atrophy (GA) is the most advanced form of dry AMD. GA is a leading cause of visual impairment among elderly people. GA affects 5 million people worldwide, including 22% of people over 90 years old. While there are no approved treatments currently available, recent advances in our understanding of AMD mechanisms and risk factors provide a host of potential targets for drug development. GA progression causes a gradual loss of visual function in patients. Symptoms include the presence of scotomas (large dark or blind spots in the visual field), difficulty recognizing faces, decreased reading speed, problems adjusting to dark rooms, impaired contrast sensitivity, and difficulty driving at night.

Treatments

There was no treatment available for people diagnosed with AMD up until 2006.

Today, neovascular AMD (also known as exudative or wet AMD) is treatable with groundbreaking medicines called anti-VEGF therapies. These include ranibizumab (Lucentis®) and aflibercept (Eyelea®). A third treatment called bevacizumab (Avastin®) can also be used to treat AMD but is considered an “off-label” approach, meaning the FDA has approved the drug for a different use than what the doctor is prescribing it.

These anti-VEGF treatments work by blocking molecules that cause abnormal blood vessel growth in the eye and drive the progression of wet AMD. Anti-VEGF treatments have dramatically changed wet AMD patient outcomes by helping to prevent and even reverse vision loss in some cases.

It’s important to stay on a regular treatment schedule and not miss appointments while receiving anti-VEGF treatment. Missing even just one or two injections can lead to vision loss.

Understanding Angiogenesis

Angiogenesis is the process by which the body grows new blood vessels. In healthy adults, normal angiogenesis occurs in healing wounds and during reproduction, but in all other situations, it is abnormal.

Exudative AMD is caused by abnormal angiogenesis. New vessels grow under the macula and disrupt the central region of the retina. These new blood vessels bleed and leak fluid, causing the macula to bulge or lift up from its normally flat position and impair central vision. If left untreated, scar tissue can form and central vision is irreversibly lost.

The process of angiogenesis has been studied by researchers for more than 40 years. Here’s how it happens:

  • New blood vessels are stimulated to grow by special proteins called “growth factors”.
  • One protein called Vascular Endothelial Growth Factor (VEGF) is made in high amounts in the retina of people with wet AMD.
  • Excess VEGF causes new blood vessels to sprout from pre-existing blood vessels under the macula.
  • The new, sprouting blood vessels that grow because of the excess VEGF are very fragile and leak fluid, causing edema, and may bleed.
  • New vessels form loops.
  • Special cells called pericytes are recruited to the newly forming blood vessels, and these pericytes wrap around the vessels to stabilize their structure.
  • Other cells called “endothelial progenitor cells” are also recruited to the new vessels. These are special stem cells that normally reside in the bone marrow but respond to signals from growing blood vessels.

Risk Factors

There are various factors that can put you at risk for AMD:

  • Age is the greatest risk factor. People over 60 are at greatest risk.
  • If you have immediate family members who have been diagnosed with AMD, you are at a higher risk of developing the disease.
  • If you have AMD in one eye, you are at high risk of developing AMD in the other eye.
  • Smokers are two to three times more likely to develop AMD. The more you smoke, the higher the risk.
    Quitting smoking can decrease the risk of developing AMD by 300%!
  • Women are more likely to develop AMD than men.
  • AMD tends to be more common in Caucasians. Those with lighter irises (i.e., blue or green eyes) may have increased risk.
  • Obesity increases the progression of early and intermediate stage AMD to advanced AMD.
  • Uncontrolled high blood pressure increases the risk of developing AMD.

What can I do to decrease my risk?

  • Avoid smoking.
  • Eat a healthy diet rich in oily fish (like salmon) and green leafy vegetables (like spinach and kale).
  • Control your blood pressure and cholesterol
  • Regular exercise may decrease your risk of developing AMD.
  • Get a yearly, dilated eye exam!

Symptoms

Many people think the symptoms of AMD are just a normal sign of aging, but this isn’t true! Talk to your doctor as soon as you experience symptoms and make sure to get a yearly, dilated eye exam. If you have AMD, you may notice blurring of vision and have particular difficulty seeing sharp details up close and from a distance. Straight lines may appear wavy or fractured in parts of the visual field. You may notice distortions of lines and shapes in everyday objects, such as crooked doorframes. Here are some other warning signs:

  • A blurry or dark spot may appear in the central part of your vision.
  • Faces may begin to blur.
  • It becomes difficult to distinguish colors.
  • Contrast sensitivity decreases.
  • Adjusting from bright to dim lighting becomes challenging.
  • Depth perception is impaired.
  • Sensitivity to bright lights increases.
  • Vision improves at night.
  • Close work (such as threading a needle) becomes impossible.

These symptoms may be inconsistent and may change from day to day. Sometimes only one eye loses vision while the other eye continues to see fairly well for a long period of time. The unaffected eye will take over to compensate for vision loss in the affected one, so you may not notice the problem until both eyes are affected. This is why it is important to go to your eye doctor for regular, dilated eye exams.

The rate of progression of AMD and the onset of symptoms will vary from person to person. Some people may experience rapid deterioration of central vision, while others may have gradual vision loss. In most cases, peripheral vision remains. People living with AMD often have difficulty performing daily activities such as reading, dialing the telephone, driving, and cooking. The important thing to know is that wet AMD can be treated and there are low vision support services that can help.

Importance of Early Diagnosis

Visiting a retina specialist to be tested for AMD is an important first step.

Early detection:

Early detection can be the key to saving as much vision as possible. Having yearly, dilated eye exams is important because in the early stages of AMD there may be few or only very subtle noticeable symptoms. The signs of AMD vary from person to person. Some may experience sudden and rapid deterioration of central vision, while others may experience only a gradual onset of vision problems.


The danger of scar tissue:

If AMD is left untreated, irreversible vision loss can occur. In advanced AMD, fluid and blood leaking from abnormally growing blood vessels accumulate under the macula and damage the light-sensing nerve layers that are responsible for vision. If left untreated, the accumulation of fluid and blood can lead to the development of scar tissue in the macula, resulting in permanent loss of central vision. Vision loss can still get worse (with the gray spot getting darker and expanding) if the scar gets bigger and the leaking and bleeding continues. Treatment can still help, even if there is irreversible damage.

Prompt diagnosis and early treatment can preserve as much vision as possible by stabilizing the disease and preventing further decline of vision. In some cases, effective treatments can even reverse the lost vision.

Is it possible to reverse vision loss due to advanced AMD?

In some cases it may be possible. Most people, however, notice that anti-VEGF treatments help them maintain their current level of vision so the disease doesn’t get worse.

Additional reasons for early diagnosis:

If you have early or intermediate AMD, your condition may progress to advanced AMD, which is treatable.

If you have advanced AMD in one eye, the other eye can become affected and needs to be carefully monitored.

Testing for AMD

When you go to a Retina Specialist with symptoms, you will be tested for AMD. The vision in each eye is examined separately.

Distortions in vision are detected through a simple test using the Amsler grid. The retina specialist will look for signs of scotoma (blind spots) and visual distortions, which may appear as breaks, blurry areas, black spots, waviness, missing portions of the lines of the grid, or wavy or crooked lines when viewing the grid. Proper use of the Amsler grid allows for detection of very subtle changes in your vision, which occur even when there is a small amount of fluid under your macula.

The Amsler grid can also be used at home. To perform the Amsler grid test yourself, follow these steps:

  • Wear your reading glasses. If you wear bifocals, use the bottom reading portion.
  • Attach the Amsler grid to a wall at eye level and stand at a comfortable reading distance away from it.
  • Cover one eye. With the other eye, look at the center dot on the Amsler grid.
  • The first time you observe the grid, mark any gray, blurry, or blank spots, or any distorted areas.
  • Every morning, look at the same center dot. If you notice any new areas of distortion, wavy lines, or enlargement of the blank spots toward the center, instead of straight lines, call your Retinal Specialist to make an urgent appointment. The reason it’s urgent is because you don’t want to risk having new blood vessels that might bleed and cause scarring and permanent vision loss.

At-Home Monitoring

For over 50 years, the Amsler Grid has been used for the at-home monitoring of intermediate AMD, yet new technologies are available that remove the need for people to objectively determine whether they have suffered vision loss.

 

There is an FDA-approved at-home monitoring device called the ForeseeHome AMD Monitoring Program. foresee This device tracks the progression of intermediate AMD, can detect the earliest changes of progression to advanced AMD, and sends the results to an Independent Diagnostic Testing Facility (IDTF). If an alert occurs, the IDTF will notify your doctor immediately. Your doctor can then determine if you have progressed from intermediate to advanced AMD and are eligible to receive treatment. This device may be covered by your insurance. Talk to your doctor and learn more by visiting this link: https://www.foreseehome.com/

 

There is also an app called myVisionTrack that can be downloaded on your phone and used to track the progression of AMD. This app is FDA cleared and requires a prescription from your eyecare provider to activate. To learn more visit: https://www.myvisiontrack.com

 

What Does My Doctor See? Initially, your retina specialist will look at the retina in the back of your eye with an instrument called an ophthalmoscope to see if any abnormalities are present in the macula. If any damage is seen, additional tests are performed using highly specialized equipment to photograph the retina. These photographic techniques can reveal whether there is any fluid leaking under the retina and if there are changes in the amount of accumulated fluid. When a patient is being treated for exudative AMD, these photographic tests can measure the amount of fluid to determine if the treatment is working and when retreatment is needed. Some additional testing might include:

  • Fluorescein Angiography: In this procedure, a colored dye is injected into the patient’s arm. When the dye reaches the eye, a special camera is used to photograph the blood vessels in the retina. The photographs will reveal any changes in the retina. For patients with exudative AMD, the location and amount of any abnormal fluid in the eye can be determined. Fluorescein Angiography can help establish the diagnosis and guide the doctor in determining which treatments are required. Generally, this test is done at diagnosis but may be repeated periodically to monitor progression of the disease.
  • Fundus Camera and Autofluorescence (AF): The fundus camera is a low-powered microscope with an attached camera. Special filters attached to the fundus camera can detect naturally occurring fluorescence (Autofluorescence, AF) in the eye to reveal damaged retinal pigment epithelium cells (RPE). AF is noninvasive and does not require any dye injections.
  • Ocular Coherence Tomography (OCT): OCT uses light to scan the retina, allowing the doctor to visualize the different layers of the retina and ocular tissues. OCT only takes a few minutes to perform. It is noninvasive and no instruments touch the eye. No injections or exposure to intense light is necessary. The OCT is used to monitor the structure of the eye, to evaluate how well different therapies are working.

Factsheet

Age-related macular degeneration is a leading cause of blindness in the world, particularly among people aged 65 and older.

In the United States, an estimated 2.1 million people aged 50 and older have advanced or late-stage AMD (with loss of visual function) and another 9.1 million have early intermediate AMD (with minimal to significant vision loss).

The number of people around the world with diagnosed AMD is expected to reach 196 million by the year 2020, as life expectancies rise and populations age.

Women are more likely than men to develop AMD.

AMD is more common in Caucasians.

If an immediate family member has AMD, you are at a higher risk of developing the disease.

AMD is twice as prevalent as Alzheimer’s disease in people over the age of 60.

Middle-aged adults have about a 2% risk of developing AMD, which increases to almost 30% in adults over age 75.

AMD is responsible for almost 8.7% of all blindness due to diseases of the eye, varying from 0% in Sub-Saharan Africa to 50% in industrialized nations.

AMD accounts for 50% of disease-related blindness in industrialized nations.

Cost:

In terms of financial burden, the cost of AMD treatment and care is substantial.

Worldwide, the financial burden of vision loss due to AMD is estimated to exceed US $343 billion, with US $255 attributed to direct costs. In the United States alone, the annual economic burden of vision loss and eye disorders is estimated to be US $66.8 billion in direct costs and US $72.2 billion in indirect costs. Only three chronic diseases – cancer, heart disease, and hypertension impose higher economic burdens.