Age-related macular degeneration

Definition

Age-related macular degeneration (ARMD) is a chronic, painless eye disease occurring in people over age 50 that causes irreversible loss of central vision; peripheral (side) vision is not affected.

Description

The macula is the central part of the retina, the layer of nerves lining the back of the eye that sense light and transmit the information to the brain. The macula is very sensitive to light and is the part of the eye that allows people to see sharp, crisp details. In ARMD, central vision becomes blurry and may be completely lost. Peripheral vision (seeing “out of the corner of your eye”) is not affected, so although people with ARMD may become legally blind (visual acuity of 20/200 or worse), ARMD does not lead to a complete absence of sight. Damage done to the retina by ARMD cannot be repaired. Vision cannot be restored to normal levels, but vision loss can often be slowed, especially if the disease is diagnosed early.

Dry ARMD

There are two forms of ARMD. All ARMD begins with the dry form of the disease, also called non-neovascular or nonexudative ARMD. Eighty-five to ninety percent of people with ARMD have the dry form. Many people have mild dry ARMD for a long time without noticing any serious symptoms because vision deteriorates slowly. Dry ARMD usually affects both eyes, it may occur in only one eye. In this case, the unaffected eye usually compensates for any vision loss and daily activities remain unaffected.

Dry ARMD develops because waste products build up in the retina. The outermost layer of the retina is called the retinal pigment epithelium (RPE). Under this is a layer of blood vessels called the choroid. Nutrients for the retina pass from the choroid blood vessels into the RPE. Waste products from the retina pass in the opposite direction, enter the bloodstream, and are removed. As individuals age, the RPE begins to break down and thin out (atrophy). The waste-disposal system slows down, and waste begins

to accumulate faster than it can be removed. Waste build-up causes clumps of yellow pigment, called drusen, to develop under the retina. Drusen are common in people over age 60. Ultimately this failure to dispose of retinal waste causes cells in the macula to become damaged, leading to a loss of central vision.

Wet ARMD

Wet ARMD affects 10–15% of people with ARMD. People who develop wet ARMD start by having dry ARMD. They can have dry ARMD for a long time, and in most people, it never progresses to wet ARMD. However, some people can progress to wet ARMD within days or weeks. Wet ARMD causes rapid deterioration of vision. Wet ARMD usually develops first only in one eye, although the chance of developing it in the other eye within five years is quite high. Early on in the disease, objects with straight lines in the central field of vision appear wavy. Severe vision loss (20/200 or worse) that affects daily activities can develop quickly.

Wet ARMD develops because new blood vessels suddenly grow in the choroid layer. These are called choroidal neovascularizations (CNVs). They appear to grow in response to an accumulation of waste or lack of nutrition in the retina when the RPE begins to break down. The CNVs leak blood and fluid into the retina (thus the name “wet”) causing disruption of the nutrition system and damaging the cells of the macula

Another less common form of wet ARMD called retinal pigment epithelial detachment occurs when the choroid layer does not grow any CNVs, but fluid from the blood vessels already present leaks and collects under the RPE. Symptoms are the same as for other wet ARMD, but vision deteriorates much more slowly (months or years instead of days or weeks). Eventually, new CNVs develop and this form of wet ARMD progresses to the more common form of wet ARMD.

Demographics

ARMD is a disease of the elderly; it is not diagnosed in people under age 50. In the industrialized world, the disease is most common in Caucasians and least common among people of African ancestry. It occurs more often in women than in men, and occurs among all socioeconomic groups. Estimates of the rate of ARMD vary considerably depending on the conditions used to define the disease, but it is believed that about 20% of Americans over age 60 show some sign of retinal changes (but not necessarily vision loss) associated with ARMD. About 2% of the population over age 70 have either wet ARMD or advanced dry ARMD; this increases to 6% of those over age 80. In 2004 it was estimated that 8 million Americans had ARMD and that 1.75 million were severely affected. This number is expected to increase as more people live to a greater age.

Causes and symptoms

The root cause of ARMD is not known, but scientists have found multiple genes that appear to be associated with the disease. As of 2008, there is no genetic test for ARMD. Advanced age, cigarette smoking, obesity , family history of ARMD, and poor diet all increase the risk of developing ARMD. Cigarette smoking doubles the risk and is the single most preventable cause of the disease.

Symptoms of dry and wet ARMD differ. Often dry ARMD shows no symptoms, and neither wet nor dry ARMD causes pain . In other cases, individuals with dry ARMD may:

• need more light for reading.
• find that colors look more pale or washed out.
• have difficulty doing detailed work, such as needlepoint or model-making.
• have slightly hazy vision.
• take longer for their vision to adapt to low lighting.
• develop a blurry or blind spot in the center of their field of vision.

The main symptoms of wet ARMD are that straight lines appear distorted and central vision deteriorates rapidly.

A few people with ARMD develop visual hallucinations. They may see patterns, animals, faces, or other objects. This is called Charles Bonnet syndrome, and it is a neurological side effect of ARMD. Although these hallucinations can be upsetting they are not a sign of mental illness.

Diagnosis

Diagnosis begins with a complete dilated eye examination . If drusen are detected, other tests may be ordered to diagnose ARMD. These include:

• fluorescein angiography. In this test dye is injected into a vein in the arm. The dye rapidly travels through the circulatory system and passes through the blood vessels in the retina. Photographs are taken that show drusen and CNVs.
• indocyanine green angiography. Similar to fluorescein angiography only using a different dye, this test provides additional photographic evidence of ARMD.
• Optical coherence tomography (OCT). This test scans the retina in order to measure its thickness and detect the presence of fluid.

Treatment

ARMD cannot be reversed or cured. The goal of treatment is to slow vision loss. Treatment depends on the type, location, and stage of ARMD. For mild (early-stage) dry ARMD, often the process only involves watchful waiting. Individuals should have regular eye examinations and see their eye care professional immediately if they notice any vision changes. They can monitor their vision at home for signs that dry ARMD is converting to wet ARMD using an Amsler grid obtainable from their physician. This is a simple checkerboard line grid with a dot in the middle. While staring at the dot, individuals with ARMD may notice that some of the lines appear to be missing. If the lines appear wavy, wet ARMD may be developing.

Treatment for wet ARMD involves procedures and drug therapy. Not every procedure is appropriate for every patient. Many clinical trials are underway to test new drugs and treatments for ARMD.

Photocoagulation is an outpatient procedure in which a doctor uses a laser to burn the CNVs and seal or destroy them so that they will not leak fluid. This procedure is often unsuccessful or produces less than the desired results.

Photodynamic therapy (PDT) involves injection of the drug verteporfin (Visudyne) followed by laser treatment. The drug accumulates in the CNVs and is activated by laser light. Once activated, the drug destroys the CNVs. PDT is not particularly painful. The procedure takes about half an hour and can be performed in the doctor's office.

Drug injections can be given to stop the growth of CNVs and to reduce fluid leakage. These drugs are called anti-vascular endothelial growth factor (anti-VEGF) medications or anti-angiogenesis drugs. These include:

• pegaptanib (Macugen). This drug is approved for use in wet ARMD. It requires a series of injections.
• ranibizumab (Lucentis). This drug is approved for use in ARMD. It destroys new blood vessels and decreases leakage. It has shown some signs of improving vision. In 2008, Lucentis was very expensive (about $2,000 per treatment) and was not covered by all insurance carriers.
• bevacizumab (Avastin). This drug is approved for treatment of colorectal cancer. Its use in treating ARMD is an off-label use, but it appears to have some of the benefits of Lucentis at a much lower price.

Kenalog is a steroid drug used to treat inflammation. Using it to treat ARMD is an off-label use, however, it appears to be somewhat effective in reducing fluid, especially if used in combination with photodynamic therapy.

Nutrition/Dietetic concerns

A large research study called the Age-Related Eye Disease Study (ARED) found that certain dietary supplements slowed the progression of vision loss by up to 25% in cases of moderate to advanced ARMD. The question of preventing ARMD was not addressed. The ARED supplements included the antioxidants vitamin C, vitamin E , beta-carotene (which is converted in the body to vitamin A), and the minerals zinc and copper. More recent studies have suggested lutein and zeaxanthin may also be beneficial.

The ARED supplements are to be taken in specific amounts that are often at higher levels than can be acquired through diet alone or than are found in standard multivitamin tablets. Individuals should not begin taking these dietary supplements on their own. They should consult their physicians about whether they would benefit from ARED supplementation and review with their physicians all medications they are taking in order to prevent harmful interactions.

QUESTIONS TO ASK YOUR DOCTOR

• What kind of ARMD do I have?
• What type of treatment is best for my ARMD?
• Are both eyes affected?
• Can I drive safely?
• Where can I get more information about lowvision aids?
• Should I be taking ARED supplements?
• Are there clinical trials of new drugs or procedures that would benefit me?

Prognosis

ARMD is not reversible. Dry ARMD often progresses slowly and necessitates few changes in daily activities such as reading or driving. About 15% of people with dry ARMD develop wet ARMD. Wet ARMD can progress rapidly and result in legal blindness, thus limiting daily activities.

Prevention

Preventive measures include stopping smoking, and eating a healthy diet high in fruits and vegetables and low in animal fats. Regular eye examinations aid in early diagnosis, which is important in slowing vision loss.

Caregiver concerns

Caregivers should be alert to the fact that dry ARMD develops slowly and may gradually make it unsafe for individuals to drive. They should also be aware that people with ARMD may be more prone to falling and tripping over objects on the floor. Caregivers can help people with moderate to severe ARMD by providing low-vision aids such as excellent direct lighting, large-print books, large-number telephones, color-coded pillboxes, and similar aids. Legally blind individuals with ARMD may qualify for free mobility and orientation training or for a guide dog.

KEY TERMS

Antioxidant —A molecule that prevents oxidation. In the body antioxidants attach to other molecules called free radicals and prevent the free radicals from causing damage to cell walls, DNA, and other parts of the cell.

Dietary supplement —A product, such as a vitamin, mineral, herb, amino acid, or enzyme, that is intended to be consumed in addition to an individual's diet with the expectation that it will improve health.

Drusen —Clumps of pigment that accumulate under the retina when wastes build up faster than they can be removed. Drusen are a sign of dry age-related macular degeneration.

Fluorescein dye —An orange dye used to illuminate the blood vessels of the retina in fluorescein angiography.

Macula —The sensitive center of the retina that is responsible for detailed central vision.

Off-label use —Use of a drug in the United States to treat a condition other than one for which the drug was approved by the U.S. Food and Drug Administration (FDA).

Retina —Light-sensitive tissue on the back of the eye that receives images and converts them into nerve impulses to be sent to the brain by way of the optic nerve.

Resources

BOOKS

Gilbert, Patricia. Coping with Macular Degeneration. London: Sheldon Press, 2006.

Roberts, Daniel L. The First Year: Age-Related Macular Degeneration: An Essential Guide for the Newly Diagnosed. New York: Marlowe & Co., 2006.

Accupuncture for Age-related Macular Degeneration. EyeCare America Foundation of the American Academy of Opthamology. March 26, 2007 [cited February 4, 2008]. http://www.eyecareamerica.org/eyecare/treatment/alternative-therapies/acupuntureamd.cfm.

Antioxidant Supplements and Age-related Macular Degeneration (AMD). EyeCare America Foundation of the American Academy of Opthamology. March 26, 2007 [cited February 4, 2008]. http://www.eyecareamerica.org/eyecare/treatment/alternative-therapies/antioxidant-supplements-amd.cfm.

“Macular Degeneration.” MayoClinic.com. August 14, 2006 [cited February 4, 2008]. Mayo Clinic. http://www.mayoclinic.com/health/macular-degeneration/DS00284. National Eye Institute. http://www.nlm.nih.gov/medlineplus/maculardegeneration.html.

“Nutrition's Role” AMD.org January 2007 [cited February 4, 2008]. Macular Degeneration Partnership. http://www.amd.org/site/PageServer?pagename=Nutrition.

ORGANIZATIONS

EyeCare America Foundation of the American Academy of Opthamology, P. O. Box 429098, San Francisco, CA, 94142-9098, (877) 887-6327, (800) 324-EYES (3937), (415) 561-8567, http://www.eyecareamerica.orgpubserv@aao.org, http://www.eyecareamerica.org.

National Eye Institute, 2020 Vision Place, Bethesda, MD, 20992-3655, (301) 496-5248, 2020@nei.nih.gov, http://www.nei.nih.gov.

The Macular Degeneration Partnership, 8733 Beverly Blvd. #201, Los Angeles, CA, 90048, (888) 430-9898, (301) 623-1837, http://www.amd.org.

Tish Davidson A.M.