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Introduction

Age-Related Macular Degeneration (AMD) is the leading cause of blindness in people over the age of 50 in developed countries, affecting more than 30 million people worldwide. It is characterized by the loss of central vision due to the gradual deterioration the macula—the part of the eye that allows you to see fine details and where sharp central vision occurs. AMD makes precious daily activities, such as reading, driving, recognizing faces, watching television, and navigating stairs, difficult.

AMD does not cause pain and its progression varies, advancing slowly or quickly, in one eye or both eyes. When AMD develops with a very gradual decline in vision, the brain can initially compensate, and its symptoms may not be easily noticed. When the disease advances rapidly, it may swiftly lead to discernible vision loss. Regardless of how quickly the disease progresses, if left untreated, advanced AMD may lead to permanent loss of vision.

AMD has two forms: Wet and Dry.

Dry AMD

Dry AMD is the most common form of AMD, with early or intermediate stages accounting for approximately 90% of all cases. In these earlier stages of Dry AMD, there is a decline in function of the macula, associated with the accumulation of drusen—yellow deposits in the back of the eye that can vary in size and number, considered part of the normal aging of the eye. In early stage Dry AMD, people have multiple smaller drusen or a few medium-sized drusen, with no vision loss. Early stage Dry AMD can develop into intermediate Dry AMD, as more small drusen or one or more large drusen develop. Symptoms that arise during intermediate stage Dry AMD include wavy or blurred spots in the center of vision, and difficulty reading.

Intermediate Dry AMD can develop into advanced Dry AMD or wet AMD. In advanced Dry AMD, the progressive increase in the number and/or size of drusen is accompanied by the deterioration of the light-sensing cells and surrounding tissue in the macula, which is called “geographic atrophy”. Geographic atrophy causes more significant and irreversible vision problems, such as a larger, darker spot in the center of vision, decreased contrast sensitivity, difficulty adjusting from bright to dim lighting, and challenges in reading small print.

One eye or both eyes may be affected by Dry AMD. When only one eye is affected, vision loss is harder to detect because the “good eye” works harder to make up for the deficiency in the affected eye. That’s why it’s important to have regular eye exams to keep tabs on visual acuity in both eyes.

Wet AMD

Wet AMD is the most serious and severe form of AMD and occurs only as an advanced stage of disease. While all people who develop wet AMD have Dry AMD first, only 10 to 15% of people with Dry AMD progress to the Wet form. Also referred to as “exudative macular degeneration”, wet AMD is characterized by growth and leaking of abnormal blood vessels under the macula.

Unlike Dry AMD, which develops slowly and in stages, wet AMD can rapidly damage the macula and quickly cause a loss of central vision. That’s why periodic eye examinations are very important for patients at high risk of wet AMD.

In wet 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 various spots in the center of their vision. This is due to blood or fluid collecting under the macula.

If wet 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 for wet AMD. These treatments can stabilize or, in some cases, even reverse vision loss, if used before scar tissue forms.

Understanding Angiogenesis

Angiogenesis is the process used by the body to grow blood vessels. In healthy adults, normal angiogenesis occurs in healing wounds and reproduction, but in all other situations, it is abnormal.

Wet AMD is caused by abnormal angiogenesis, when new vessels grow under the macula, disrupting 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, impairing 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.
  • Women are more likely to develop AMD than men.
  • AMD is more common in Caucasians than in people of African descent.
  • 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?

  • Don’t smoke
  • Maintain a normal body weight
  • Control blood pressure
  • A diet high in leafy, dark green vegetables, and fruit, lowers the risk of developing AMD. Regularly eating fish and avoiding other dietary fats also lowers the risk. These foods contain antioxidants and substances that naturally prevent blood vessel growth.
  • Regular exercise may decrease your risk of developing AMD.
Referenceshttp://www.nei.nih.gov

Symptoms

In its early stages, AMD may not cause any noticeable symptoms. Over time, you may notice blurring of vision, particularly difficulty seeing sharp details, both up close and from a distance. Straight lines 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 like 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 “good 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 checkups.


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.

Individuals living with AMD often have difficulty performing daily activities such as reading, dialing telephone numbers, and cooking. Wet AMD is associated with impaired quality of life, social isolation, clinical depression, an increased risk of accidental falls and hip fractures, and premature admission to nursing homes.

The important thing to know is that wet AMD can be treated. You must recognize the signs and symptoms, and take immediate action to seek effective treatment.

Factsheet

The prevalence of AMD:

  • More than 30 million people are affected by AMD, and 15% have the advanced form called wet AMD.
  • Women are more likely than men to develop AMD.
  • AMD is more common in Caucasians than in people of African descent.
  • People of Hispanic and Chinese descent have a lower occurrence than Caucasians but a higher incidence than African Americans.
  • 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, while the risk increases to almost 30% in adults over age 75.
  • Currently, 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.
  • In industrialized nations, AMD accounts for 50% of disease-related blindness.

Cost:

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

  • In 2010, the worldwide financial burden of vision loss due to AMD was estimated at US$343 billion, with US$255 attributed to direct health care expenditures.
  • The worldwide projected cost of vision loss due to AMD in 2020 is predicted to be US$392 billion.
Referenceshttp://www.nei.nih.gov/health/ maculardegen/armd_facts.asp

http://www.vision2020.org/main.cfm?type=WIBAGERELMUSCDEG

Klein et al. Ophthalmology Volume 113, Issue 3, March 2006, Pages 373-380.

The Global Economic Cost of Visual Impairment, Access Economics, prepared for AMD Alliance International, March 2010

Importance of Early Diagnosis

Going to a retinal specialist to be tested for AMD is the most important first step.

Early detection:

Early detection is the key to saving as much vision as possible. Having regular eye exams is an important action to take because in the early stages of AMD, there may be few or only very subtle noticeable symptoms. The signs of AMD vary from individual to individual. 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 wet 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. Even then, vision loss can still get worse (with the gray spot getting darker and expanding). The scar can get bigger if 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 wet AMD?

Yes. New treatments have been found in some individuals to reverse vision loss.

Additional reasons for early diagnosis:

If you have Dry AMD, your condition may progress to wet AMD, which is treatable.

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

Referencesde Jong, N Engl J Med 2006;355:1474-85

Testing for AMD

When you go to a Retinal 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 Retinal Specialist will look for signs of scotomas (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.

What Else To Expect

Initially, your Retinal 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 Wet 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 and where the changes have occurred. For patients with Wet AMD, the location and amount of any abnormal fluid in the eye can be determined. This test can take up to three hours to complete. The injection may cause temporary discomfort in the arm. Fluorescein angiography can help establish the diagnosis and guide the doctor in determining which treatments are required. Generally, this test is done only at diagnosis and not during follow-up visits.
  • 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.