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Causes: Unclear; possibly aging, genetic factors, nutrition, smoking, sunlight exposure

Symptoms: Dependent on form; can include blurred or distorted central vision, bleeding within and beneath retina, development of scar tissue, eventual blindness

Duration: Typically long-term

Treatments: Vision aids (e.g., magnifying glasses, special lenses, electronic systems); laser photocoagulation; surgery; low-level radiation; injection of photosensitive chemicals into bloodstream

Magill's Medical Guide 4th rev. ed.
Macular Degeneration

Anatomy or System Affected: Eyes

Specialties and Related Fields: Ophthalmology

Definition: A degenerative disease of the central portion of the retina that results primarily in loss of central vision.

Causes and Symptoms
The macula is located in the center of the retina, the light-sensitive tissue at the back of the eye. The retina instantly converts light, or an image, into electrical impulses. The retina then sends these impulses, or nerve signals, to the brain. One of the earliest signs of age-related macular degeneration (ARMD) seen by physicians during a dilated eye examination is deposits of tiny, bright yellow material called drusen, which is harder as a result of aging or softer and larger if associated with ARMD and vision loss. As parts of the eye in the retina and choroid become thinner or lose tissue, central vision and/or peripheral vision is affected, depending on the area of damage. Central vision is needed to see clearly and to perform everyday activities such as reading, writing, driving, and recognizing people and things. Peripheral vision, needed for walking, is much less commonly affected.

There are two forms of ARMD: early and advanced. About 90 percent of cases are early ARMD, although the advanced type affects 7 percent of those seventy-five years or older. Advanced ARMD is further categorized into two distinct types based on their clinical features: dry and wet. The dry form involves thinning of the macular tissues and disturbances in its pigmentation. About 70 percent of patients have the dry form. The remaining 30 percent have the wet form, which can involve bleeding within and beneath the retina, opaque deposits, and eventually scar tissue. The wet form accounts for 90 percent of all cases of legal blindness in macular degeneration patients.

Neither dry nor wet macular degeneration causes pain. The most common early sign of dry macular degeneration is blurring vision that prevents people from seeing details clearly that are in front of them, such as faces or words in a book. In the early stages of wet macular degeneration, straight lines appear wavy or crooked. This is the result of fluid leaking from blood vessels and lifting the macula, distorting vision.

A number of risk factors can affect the initial development of ARMD: age, smoking, genetic predisposition, and ethnicity. Two risk factors have also been studied and suggested in causing a progression of ARMD: nutrition and high blood pressure. Age is the most important risk factor for macular degeneration: The older the patient, the higher the risk. Studies have shown that having a family with a history of macular degeneration raises the risk factor. Because macular degeneration affects most patients later in life, however, it has proven difficult to study cases in successive generations of a family. Heavy smoking, at least a pack of cigarettes a day, can double a person's risk of developing ARMD. The more a person smokes, the higher the risk of macular degeneration. Moreover, the adverse effects of smoking persist, even fifteen to twenty years after quitting. Those with a family history of ARMD are more likely to develop the disease due to a genetic mutation of part of a gene called the complement factor H gene. With a family history of the disease, the risk is greater for developing the wet type than the dry type of ARMD. Studies have shown that non-Hispanic Caucasians have a greater risk of developing ARMD than do African Americans or Hispanics.

Poor dietary habits contribute to ARMD as well. A diet high in saturated fats may clog the vessels leading to the eyes, thus reducing the flow of nutrient-rich blood. Excess fat may deposit itself directly in the membrane behind the retina. In this case, nutrients might not be able to reach the cells that nourish the retina. High blood pressure has also been shown to increase the risk of developing ARMD in the second eye in those having ARMD in one eye.

An effective test to determine if a person has wet macular degeneration is fluorescent angiography. A special dye is injected into a vein in the patient's arm and then flows to the blood vessels in the eye. Photographs are taken of the retina. The dye highlights any problems in the blood vessels and allows the doctor to determine if they can be treated. Annual eye examinations that include dilation of the pupils are also useful in early detection. Early detection is important because a person destined to develop macular degeneration can sometimes be treated before symptoms appear, which may delay or reduce the severity of the disease. Anyone who notices a change in vision should contact an ophthalmologist immediately.

Treatment and Therapy
New and exciting treatments are in development for ARMD as extensive research is being done. Currently, there is no cure, and no treatment recommendations exist for those with dry type ARMD, the type that is much less threatening to vision. Some treatments, however, can slow the progression of wet type ARMD. Research has shown that stopping smoking is the most effective preventive measure in regard to developing ARMD and slowing its progression.

Antioxidants have proved promising in recent studies which show that they can lower the risk of progression to more advanced ARMD in those who have moderate or advanced disease. In a major clinical trial called the Age-Related Disease Study (AREDS), it was shown that patients with moderate or severe ARMD taking antioxidants vitamin C, vitamin E, and beta carotene plus zinc and copper had a lower risk of progression among both nonsmokers and smokers. Since the group of smokers who took zinc alone had the same lowered risk of progression as those smokers taking antioxidants plus zinc and copper, it was recommended that smokers with ARMD take zinc alone, as some antioxidants have shown to increase the risk of lung cancer and coronary heart disease when used at high doses.

Although no treatments can reverse the actual pathologic process of the disease of wet type ARMD, some treatments used by ophthalmologists are aimed at containing the damaged vessels that cause the loss of vision. They include laser photocoagulation, photodynamic therapy, intravitreous injections, and, as a last resort, macular translocation surgery.

Laser photocoagulation involves using a high-intensity thermal laser to burn off the blood supply to abnormal choroidal membranes. The benefits of this treatment are that it is done in the outpatient setting using only topic anesthetic drops and that it prevents the formation of new abnormal vessels associated with ARMD for two or three years. It is limited, however, to only those patients with well-defined abnormal areas (only about 15 percent of patients with ARMD). It cannot restore lost vision and may actually destroy normal retinal tissue along with the neovascular formation that is targeted.

Photodynamic therapy involves the injection of a dye called verteporfin which, when activated by a photo laser, forms substances that destroy the abnormal newly formed vessels associated with wet type ARMD. Thus, by the use of this dye and laser combination, the normal vessels are protected and the abnormal vessels are destroyed. It has also been shown that this treatment can be repeated safely.

The vascular endothelial growth factor (VEGF) inhibitors are a class of agents that block a factor involved in the disease process of ARMD. VEGF is essential for the formation of the new abnormal vessels that cause the loss of vision and the anatomic destruction associated with ARMD. The VEGF inhibitors block this factor, thereby limiting those destructive effects. Studies involving these agents have shown that a majority of patients showed improvement in their vision and marked anatomic improvement of their retinas.

Macular translocation surgery involves surgically removing the macula from a diseased area and attaching it to a healthier area of the retina. Although currently an experimental therapy and not well studied, it can be used for those patients in which no other treatment options are left. If performed successfully, macular translocation surgery can improve central vision and allow a majority of patients to read. Great risks are associated with this type of treatment, however, including detachment of the retina and the development of double vision. In addition, use of a steroid injection into the vitreous and/or the posterior sub-Tenon's space has shown short-term improvement in vision.

Many visual aids have been developed for patients with ARMD to make the most of their remaining vision, including magnifying glasses, powerful special lenses, and large-print books and reading materials. Voice synthesizers in electronic devices such as calculators, clocks, and phones are also very helpful. Maximizing room lighting by the use of stronger lights, opening windows, and painting walls brighter colors can help patients see better at home.

Perspective and Prospects
Blindness or low vision affects 3.3 million Americans aged forty and over, or one in twenty-eight, according to the Eye Disease Prevalence Research Group study, sponsored by the National Eye Institute. This figure is projected to reach 5.5 million by the year 2020. The study reports that low vision and blindness increase significantly with age, particularly in people over age sixty-five. People eighty years of age and older currently make up 8 percent of the population but account for 69 percent of blindness. ARMD affects about 15 percent of the U.S. population by age fifty-five and more than 30 percent by age seventy-five. It is the most common cause of legal blindness in people over the age of sixty-five.

Although there is no cure for ARMD, many treatments are available to curtail progression of the disease. As extensive research continues in this area, advances in the diagnosis and treatment of this debilitating condition are anticipated by many in the field of ophthalmology. Currently, the National Eye Institute is studying the possibility of transplanting healthy cells into a diseased retina, evaluating families with a history of ARMD to understand genetic and hereditary factors that may cause the disease , and looking at certain anti-inflammatory treatments for the wet form of ARMD.

Kenneth Dill, M.D.

See Also
Aging; Blindness; Blurred vision; Cataracts; Eye infections and disorders; Eye surgery; Eyes; Laser use in surgery; Myopia; Ophthalmology; Smoking; Vision disorders.

Further Information
American Macular Degeneration Foundation. http://www.macular.org/. Provides information to clinicians and patients regarding the latest in research regarding ARMD. Offers an award-winning video for helping patients with ARMD cope with this debilitating illness.

D'Amato, Robert, and Joan Snyder. Macular Degeneration: The Latest Scientific Discoveries and Treatments for Preserving Your Sight. New York: Walker, 2000. Ophthalmologist and noted researcher D'Amato teams up with macular degeneration patient Snyder to write a reassuring, hopeful, and informative book providing the facts that sufferers need in order to understand the disorder, handle treatment options, and live successfully with low vision.

Kansai, Jack. Diseases of the Macula. New York: Elsevier, 2002. A clinical text that covers diseases that primarily affect the macula, such as age-related macular degeneration, together with secondary diseases that might have an indirect effect on macular function, such as vascular and inflammatory disorders.

Macular Degeneration Foundation. http://www.eyesight.org/. Describes this charitable educational and research foundation dedicated to discovering the cause of and developing cures for macular degeneration.

MayoClinic.com. Macular Degeneration. http://www.mayoclinic.com/health/macular-degeneration/DS00284. Provides a comprehensive overview of the risk factors, symptoms, and treatment of ARMD.

Sardegna, Jill, et al. Encyclopedia of Blindness and Vision Impairment. 2d ed. New York: Facts On File, 2002. All aspects of vision impairment are covered in five hundred entries, including health and social issues, surgery and medications, adaptive aids, education, and helpful organizations. Twelve appendixes provide myriad resources for research, support, and services.

Sutton, Amy L., ed. Eye Care Sourcebook: Basic Consumer Health Information About Eye Care and Eye Disorders. 2d ed. Detroit: Omnigraphics, 2003. A complete guide to eye care that includes such topics as eye anatomy, preventive vision care, refractive disorders and eye diseases, current research and clinical trials, and a list of organizations.