Macular degeneration age-related (AMD) is one of the most common causes of vision loss among adults over age 55 living in developed countries. It is caused by the breakdown of the macula, a small spot located in the back of the eye. The macula allows people to see objects directly in front of them (called central vision), as well as fine visual details. People with AMD usually have blurred central vision, difficulty seeing details and colors, and they may notice distortion of straight lines.
In order to understand how the macula normally functions and how it is affected by AMD, it is important to first understand how the eye works. The eye is made up of many different types of cells and tissues that all work together to send images from the environment to the brain, similar to the way a camera records images. When light enters the eye, it passes through the lens and lands on the retina, which is a very thin tissue that lines the inside of the eye. The retina is actually made up of 10 different layers of specialized cells, which allow the retina to function similarly to film in a camera, by recording images. The macula is a small, yellow-pigmented area located at the back of the eye, in the central part of the retina. The retina contains many specialized cells called photoreceptors that sense light coming into the eye and convert it into electrical messages that are then sent to the brain through the optic nerve. This allows the brain to "see" the environment.
The retina contains two types of photoreceptor cells: rod cells and cone cells. The rod cells are located primarily outside of the macula and they allow for peripheral (side) and night vision. Most of the photoreceptor cells inside of the macula, however, are the cone cells, which are responsible for perceiving color and for viewing objects directly in front of the eye (central vision). If the macula is diseased, as in AMD, color vision and central vision are altered. There are actually two different types of AMD: Dry AMD and Wet AMD.
Approximately 90% of individuals with AMD have dry AMD. This condition is sometimes referred to as nonexudative, atrophic, or drusenoid macular degeneration. In this form of AMD, some of the layers of retinal cells (called retinal pigment epithelium, or RPE cells) near the macula begin to degenerate, or breakdown. These RPE cells normally help remove waste products from the cone and rod cells. When the RPE cells are no longer able to provide this "clean-up" function, fatty deposits called drusen begin to accumulate, enlarge and increase in number underneath the macula. The drusen formation can disrupt the cones and rods in the macula, causing them to degenerate or die (atrophy). This usually leads to central and color vision problems for people with dry AMD. However, some people with drusen deposits have minimal or no vision loss, and although they may never develop AMD, they should have regular eye examinations to check for this possibility. Dry AMD is sometimes called "nonexudative", because even though fatty drusen deposits form in the eye, people do not have leakage of blood or other fluid (often called exudate) in the eye. In some cases, dry AMD symptoms remain stable or worsen slowly. In addition, approximately 10% of people with dry AMD eventually develop wet AMD.
Around 10% of patients with AMD have wet AMD. This form of AMD is also called subretinal neovascularization, choroidal neovascularization, exudative form or disciform degeneration. Wet AMD is caused by leakage of fluid and the formation of abnormal blood vessels (called "neovascularization") in a thin tissue layer of the eye called the choroid. The choroid is located underneath the retina and the macula, and it normally supplies them with nutrients and oxygen. When new, delicate blood vessels form, blood and fluid can leak underneath the macula, causing vision loss and distortion as the macula is pushed away from nearby retinal cells. Eventually a scar (called a disciform scar) can develop underneath the macula, resulting in severe and irreversible vision loss.
AMD is considered to be a complex disorder, likely caused by a combination of genetic and environmental factors. This type of disorder is caused by multifactorial inheritance, which means that many factors likely interact with one another and cause the condition to occur. As implied by the words "age-related", the aging process is one of the strongest risk factors for developing AMD. A number of studies have suggested that genetic susceptibility also plays an important role in the development of AMD, and it has been estimated that the brothers and sisters of people with AMD are four times more likely to also develop AMD, compared to other individuals.
Determining the role that genetic factors play in the development of AMD is a complicated task for scientists. Since AMD is not diagnosed until late in life, it is difficult to locate and study large numbers of affected people in the same family. In addition, although AMD seems to run in families, there is no clear inheritance pattern (such as dominant or recessive) observed when examining families. However, many studies have supported the observation that inheritance plays some role in the development of AMD.
One method scientists use to locate genes that may increase a person's chance to develop multifactorial conditions like AMD is to study genes that cause similar conditions. In 1997, this approach helped researchers identify changes (mutations) in the ATP-binding cassette transporter, retina-specific (ABCR) gene in people diagnosed with AMD. The process began after genetic research identified changes in the ABCR gene among people with an autosomal recessive macular disease called Stargardt macular dystrophy. This condition is phenotypically similar to AMD, which means that people with Stargardt macular dystrophy and AMD have similar symptoms, such as yellow deposits in the retina and decreased central vision.
The ABCR gene maps to chromosome 1p22, and people who have Stargardt macular dystrophy have mutations in each of their two alleles (gene copies). However, the researchers who found mutations in the ABCR gene among people with AMD located only one allele with a mutation, which likely created an increased susceptibility to AMD. They concluded that people with an ABCR gene mutation in one allele could have an increased chance to develop AMD during their lifetime if they also had inherited other susceptibility genes, and/or had contact with environmental risk factors. Other scientists tried to repeat this type of genetic research among people with AMD in 1999, and were not able to confirm that the ABCR gene is a strong genetic risk factor for this condition. However, it is possible that the differing research results may have been caused by different research methods, and further studies will be necessary to understand the importance of ABCR gene mutations in the development of susceptibility to AMD.
In 1998, another genetic researcher reported a family in which a unique form of AMD was passed from one generation to the next. Although most families with AMD who are studied do not show an obvious inheritance pattern in their family tree, this particular family's pedigree showed an apparently autosomal dominant form of AMD. Autosomal dominant refers to a specific type of inheritance in which only one copy of a person's gene pair (i.e. one allele) needs to have a mutation in order for it to cause the disease. An affected person with an autosomal dominant condition thus has one allele with a mutation and one allele that functions properly. There is a 50% chance for this individual to pass on the allele with the mutation, and a 50% chance to pass on the working allele, to each of his or her children.
Genetic testing done on the family reported in 1998 showed that the dominant gene causing AMD in affected family members was likely located on chromosome 1q25-q31. Although the gene linked to AMD in this family and the ABCR gene are both on chromosome 1, they are located in different regions of the chromosome. This indicates that there is genetic heterogeneity among different families with AMD, meaning that different genes can lead to the same or similar disease among different families. It is also possible that although one particular gene may be the main cause of susceptibility for AMD, other genes and/or environmental factors may help alter the age of onset of symptoms or types of physical changes seen by examining the eye. Some studies have shown that other medical conditions or certain physical characteristics may be associated with an increased risk for AMD. Some of these include:
However, not all studies have found a strong relationship between these factors and AMD. Further research is needed to decipher the role that both genetic and environmental factors play in the development of this complex condition.
Determining the role that environmental factors play in the development of AMD is an important goal for researchers. Unlike genetic factors that cannot be controlled, people can often find motivation to change their behaviors if they are informed about environmental risk factors that may be within their control. Unfortunately, identifying environmental factors that clearly increase (or decrease) the risk for AMD is a challenging task. Several potential risk factors have been studied. These include:
Although research has identified these possible risk factors, many of the studies have not consistently shown strong associations between these factors and the development of AMD. This makes it difficult to know the true significance of any of these risk factors. One exception, however, is the relationship between smoking and AMD. As of 1999, at least seven studies consistently found that smoking is strongly associated with AMD. This is one more important reason for people to avoid and/or quit smoking, especially if they have a family history of AMD. Further research is needed to clarify the significance of the factors listed above so people may be informed about lifestyle changes that may help decrease their risk for AMD.
Among adults aged 55 and older, AMD is the leading cause of vision loss in developed countries. The chance to develop AMD increases with age, and although it usually affects adults during their sixth and seventh decades of life, it has been seen in some people in their forties. It is estimated that among people living in developed countries, approximately one in 2,000 are affected by AMD. By age 75, approximately 30% of people have early or mild forms of AMD, and roughly 7% have an advanced form of AMD. Since the number of people in the United States aged 65 years or older will likely double between 1999 and 2024, the number of people affected also should increase. Although AMD occurs in both sexes, it is slightly more common in women.
The number of people affected with AMD is different in various parts of the world and it varies between different ethnic groups. Some studies suggest that AMD is more common in Caucasians than in African Americans; however, other reports suggest the numbers of people affected in these two groups are similar. Some studies of AMD among Japanese and other Asian ethnic groups have shown an increasing number of affected individuals. Further studies are needed to examine how often AMD occurs in other ethnic groups as well.
During eye examinations, eye care specialists may notice physical changes in the retina and macula that make them suspect the diagnosis of AMD. However, affected individuals may notice:
The majority of people with AMD maintain their peripheral vision. The severity of symptoms depends upon whether a person has dry or wet AMD. In addition, the degree of vision loss and physical symptoms that can be seen by an eye exam change over time. For example, people with dry AMD usually develop vision loss very slowly over a period of many years. Their vision may change very little from one year to the next, and they usually do not lose central vision completely. However, individuals with wet AMD usually have symptoms that worsen more quickly and they have a greater risk to develop severe central vision loss, sometimes in as little as a two-month period. Since people diagnosed with dry AMD may go on to develop wet AMD, it is important for them to take note of any changes in their symptoms and to report them to their eye care specialist.
The physical symptoms of AMD eventually impact people emotionally. One study published in 1998 reported that people with advanced stages of AMD feel they have a significantly decreased quality of life. In addition, they may have a limited ability to perform basic daily activities due to poor vision, and as a result, they often suffer psychological distress. Hopefully, improved treatment and management will eventually change this trend for affected individuals in the future.
Eye care specialists use a variety of tests and examination techniques to determine if a person has AMD. Some of these include:
As of 2001, there are no genetic tests readily available to help diagnose AMD. Genetic research in the coming years will hopefully help scientists determine the genetic basis of AMD. This could help diagnose people with increased susceptibility before they have symptoms, so they may benefit from early diagnosis, management and/or treatment. This knowledge may also allow people who are at a genetically increased risk for AMD to avoid environmental risk factors and thus preserve or prolong healthy vision.
There is no universal treatment available to cure either wet or dry forms of AMD. However, some people with wet AMD can benefit from laser photocoagulation therapy. This treatment involves the use of light rays from a laser to destroy the abnormal blood vessels that form beneath the retina and macula and prevent further leakage of blood and fluid. Previously lost vision cannot be restored with this treatment, and the laser can unfortunately damage healthy tissue as well, causing further loss of vision.
In April 2000, the FDA approved the use of a light-activated drug called Visudyne to help treat people with wet AMD. Visudyne is a medication that is injected into the bloodstream, and it specifically attaches to the abnormal blood vessels present under the macula in people with AMD. When light rays from a laser land on the blood vessels, the Visudyne is activated and can destroy the abnormal vessels, while causing very little damage to nearby healthy tissues. Although long term studies are needed to determine the safety and usefulness of this medication beyond two years, early reports find it an effective way to reduce further vision loss.
Researchers have been trying to identify useful treatments for dry AMD as well. Laser photocoagulation treatments are not effective for dry AMD since people with this form do not have abnormal blood or fluid leakage. Although many drugs have been tested, most have not improved visual acuity. However, one study published in October 2000, reported that people with dry AMD who received a medication called Iloprost over a six-month period noted improvements in visual acuity, daily living activities and overall quality of life. Followup studies will be needed to determine how safe and useful this medication will be over time.
Although no treatments can cure AMD, a number of special devices can help people make the most of their remaining vision. Some of these include:
People with AMD may also find it useful to meet with low-vision specialists who can help them adapt to new lifestyle changes that may assist with daily living. Eye care specialists can help people locate low-vision specialists. There are also a number of nationwide and international support groups available that provide education and support for individuals and families affected by AMD.
People can live many years with AMD, although the physical symptoms and emotional side effects often change over time. The vision problems caused by dry AMD typically worsen slowly over a period of years, and people often retain the ability to read. However, for people who develop wet AMD, the chance to suddenly develop severe loss of central vision is much greater. Regular monitoring of vision by people with AMD (using an Amsler grid) and by their eye care specialists, may allow for early treatment of leaky blood vessels, therefore reducing the chance for severe vision loss. As physical symptoms worsen, people are more likely to suffer emotionally due to decreasing quality of life and independence. However, many low-vision devices and various support groups can often provide much needed assistance to help maintain and/or improve quality of life.
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AMD Alliance International. PO Box 550385, Atlanta, GA 30355. (877) 263-7171. <http://www.amdalliance.org>.
American Macular Degeneration Foundation. PO Box 515, Northampton, MA 01061-0515. (413) 268-7660. <http://www.macular.org>.
Foundation Fighting Blindness Executive Plaza 1, Suite 800, 11350 McCormick Rd., Hunt Valley, MD 21031. (888) 394-3937. <http://www.blindness.org>.
Macular Degeneration Foundation. PO Box 9752, San Jose, CA 95157. (888) 633-3937. <http://www.eyesight.org>.
Retina International. Ausstellungsstrasse 36, Zürich, CH-8005. Switzerland (+41 1 444 10 77). <http://www.retinainternational.org>.
Pamela J. Nutting, MS, CGC