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Age-related Macular Degeneration (AMD)
Dr. Dunaief is Assistant Professor of Ophthalmology, and Dr. Charkoudian is a resident, F.M. Kirby Center for Molecular Ophthalmology, Scheie Eye Institute, University of Pennsylvania, Philadelphia, PA.
If you are past your mid-fifties and you are having vision problems, you may be worried about developing age-related macular degeneration, or AMD. AMD is the leading cause of adult visual impairment and blindness in the world's developed nations. While there is no surefire way to prevent or to cure this disease, medical science has made great strides in understanding who gets the disease and why, as well as developing several promising new treatments.
Signs and SymptomsAs its name implies, the disease causes a gradual loss of function in the part of the eye called the macula. Located near the center of the retina, the macula plays a key role in sharply focused and central, as opposed to peripheral, vision. When AMD causes the macula to degenerate, the result is blurring or darkness at the center of a person's field of vision. While the degeneration usually takes years, there may be a sudden change in vision over a period of days. It also causes loss of the fine vision needed for reading, driving and recognizing other people's faces. To those in the later stages of AMD, printed words may appear blurry and straight lines may appear wavy. Peripheral vision usually remains unaffected by AMD and the disease almost never causes total blindness. Other classic signs of the disease are the development of drusen, or small spots on the eye, and color changes in the macula (see Figure 1 on next page).
Advanced AMD takes two forms: "wet" AMD, in which many small blood vessels grow into the cornea, leak and destroy photoreceptors, a phenomenon known technically as neovascularization; and "dry" AMD, which causes the loss of photoreceptors by a different process.
Who Gets AMD and WhyRight now, an estimated 7 million individuals in the U.S. have intermediate AMD and 1.75 million have advanced AMD.(1) Although 80% of these have the non-neovascular, or "dry," form, the neovascular, or "wet," form is responsible for most cases of severe visual loss.(2) As its name implies, age-related macular degeneration becomes more common with age and is very rare in people younger than 55.(3) For some reason, advanced AMD is significantly more prevalent in white people than among African-Americans or Hispanics.(4)(5)(6)
The exact cause of AMD is not clear, but — like many age-related diseases — it most probably results from a combination of oxidative damage to bodily tissues, cardiovascular disease and genetic predisposition.
OxidationOxidation occurs when oxygen molecules interact with other substances, including human tissue. Oxidation can be destructive, as when it causes iron to rust. Its exact effects depend on the amount of oxygen present and the nature of the material it touches. True oxidation happens on a molecular level. Within our bodies, for example, oxidation and so-called oxidative stress can damage certain cells and contribute to various diseases, including AMD.
We know that oxidation is associated with drusen formation.(7)(8)(9) Research showing that antioxidants — certain vitamins and minerals taken in through our diet or in the form of nutritional supplements that combat oxidation — slow the progression of AMD further supports this idea.(11) The presence of drusen is thought to lead to inflammation and a condition called oxidative stress. Oxidative damage accumulates over time, which is consistent with the age-related nature of the disease, as well as the gradual increase in number and size of drusen that characterizes AMD. Oxidative stress seems also to stimulate neovascularization.
Cardiovascular diseases such as hypertension and atherosclerotic (characterized by the buildup of plaque in the arteries) heart disease, are associated with an increased likelihood of developing AMD.(12)(13)(14) Epidemiological surveys have also found higher rates of disease within families and among twins than in the general population, which suggests that there is a genetic aspect to the disease.(15)(16)
Research has also found evidence of a connection between AMD and overactivity of the immune system, which is known to cause inflammation and cellular damage.(17)(18)(19)(20)
Risk FactorsThe main risk factors for AMD are:
AgeLarge epidemiologic studies show that AMD becomes more common with age. The prevalence of AMD in individuals aged 75-85 years is more than three times that of individuals aged 43 to 54 years.
EthnicityAdvanced disease is significantly more prevalent in white than in African-American or Hispanic populations. It may also be higher among Asians.
SmokingHeavy smoking can double a person's risk for AMD.(21) Stopping smoking reduces the odds of AMD reaching the advanced stage.
Genetic FactorsThese have been shown to significantly increase the risk of disease.(22)
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