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Eye Conditions » Macular Degeneration
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What is Macular Degeneration?


What is age-related macular degeneration?

Age-related macular degeneration (AMD) is a retinal degenerative disease that causes a progressive loss of central vision. AMD is the most common cause of vision loss in individuals over 55. An estimated 10 million people in the U.S. either have AMD or are at substantial risk of developing it.

Illustrated cross section of an eye

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What are the symptoms?

The macula is a small region in the center of the retina, which enables a person to see fine detail. Light sensing cells in the macula, known as photoreceptors, convert light from the visual field into electrical impulses and then transfer the impulses to the brain via the optic nerve. Central vision loss from AMD occurs when photoreceptor cells in the macula degenerate.

People with AMD may first notice a blurring of central vision, especially during tasks such as reading or sewing. Also, straight lines may appear distorted or warped. As the disease progresses, blind spots may form within the central visual field. In most cases, if one eye has AMD, the other eye will develop the disease. The extent of central vision loss varies depending on the type of AMD — dry or wet.

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A simulated image of normal vision
Normal vision
A simulated image what someone with macular degeneration sees
Picture as seen by someone who has macular degeneration

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What is dry AMD?

Dry AMD accounts for about 90 percent of all cases, and normally affects vision less than wet AMD. Dry AMD is sometimes called atrophic, nonexudative, or drusenoid macular degeneration. A characteristic of dry AMD is the accumulation of tiny protein and fat-containing “drusen” deposits in a thin layer of cells beneath the photoreceptors in the retina called Bruch's membrane. The origin of drusen is unknown, but they may be from waste products of various cells and tissues of the retina. Drusen may interfere with the health of the macula, causing progressive degeneration of the photoreceptor cells. Drusen deposits can, however, be present without vision loss.

Reduction in central vision from dry AMD occurs gradually over many years. Vision may even remain stable between eye examinations. People with dry AMD do not usually experience a total loss of central vision but tasks that require finely focused vision may become more difficult.

Research suggests that medium- and large-sized drusen present a greater risk for the progression of dry AMD to wet AMD. Wet AMD causes more severe vision loss. Although no standard therapies currently exist to treat dry AMD, several clinical research trials are evaluating methods, including laser treatments, to reduce their size.

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What is wet AMD?

Wet AMD accounts for about 10 percent of all cases of macular degeneration. Wet AMD is also called choroidal neovascularization (CNV), subretinal neovascularization, or exudative or disciform degeneration. In wet AMD, abnormal blood vessels grow beneath the macula. These vessels leak blood and fluid into the macula that damage photoreceptor cells. Wet AMD often progresses rapidly and can cause substantial loss of central vision.

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What treatments are available for wet AMD?


Current AMD Treatments

AREDS formulation — The Age-Related Eye Disease Study (AREDS) — a landmark investigation conducted by the National Eye Institute (NEI) — determined that antioxidant supplementation can slow the progression of AMD. The AREDS formulation is an over-the-counter antioxidant supplement recommended for people who are at risk of developing more advanced forms of either dry or wet AMD.

The AREDS formulation includes the antioxidants beta carotene, vitamin E, and vitamin C, as well as the nutrients zinc and copper. The AREDS formulation contains specific amounts and forms of antioxidants nutrients; do not try to substitute multivitamins or dietary nutrients for the AREDS formulation.

The NEI has initiated a second AREDS study (AREDS2) to evaluate the potential benefits of the antioxidants lutein and zeaxanthin and the omega-3 fatty acids docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA). For more information on the second AREDS study, visit www.areds2.org.

EYLEA™ (alflibercept)
— Regeneron’s wet AMD treatment, Eylea, blocks the development of unhealthy blood vessels underneath the retina.  Regeneron reports that in clinical trials, Eylea treated wet AMD as effectively as Lucentis, but with fewer intraocular injections. Typically, patients are treated monthly with Eylea for three months and every other month thereafter.  Eylea was FDA approved in 2011.

Lucentis (ranibizumab)
— Developed by Genentech, Lucentis is effective in reducing the risk of losing vision from the abnormal blood vessel growth under the retina associated with wet AMD. The treatment was approved by the FDA and made available in 2006. A two-year study showed that 95 percent of people with wet AMD who received monthly injections of Lucentis experienced no significant loss in visual acuity. Genentech also reported moderate visual improvement in 24.8 percent of participants treated with a 0.3 mg dose of Lucentis and 33.8 percent of participants treated with a 0.5 mg dose.

A colorectal-cancer drug called Avastin® — a drug similar to Lucentis — has been used “off-label” by some ophthalmologists to treat wet AMD. A few small clinical studies of short duration (e.g., three months) have shown Avastin to be safe and effective. The NEI is currently conducting a clinical study of Avastin for the treatment of wet AMD to better determine the drug’s long-term safety and effectiveness. In this study, Avastin is being compared to Lucentis. Interim, one-year results of the study showed that the drugs were similar in safety and efficacy.

Macugen® (pegaptanib)
— Available since 2004, Macugen has been effective in reducing the risk of vision loss in people with wet AMD by inhibiting the growth of abnormal blood vessels under the retina. Typically, Macugen is administered every six weeks through an injection into the eye. In clinical studies, approximately 70 percent of patients treated with Macugen experienced no significant vision loss.

Visudyne® (verteporfin) Photodynamic Therapy (PDT)
— Visudyne PDT involves the use of a light-activated drug that targets and destroys the blood vessels that cause vision loss in wet AMD. In this treatment, Visudyne is injected intravenously. When the drug reaches the eye, a low-intensity laser is directed to the region of blood vessel growth, activating the drug, which destroys the unhealthy vessels. PDT treatments are usually repeated, and may be performed in combination with other treatments such as Macugen or Lucentis. Visudyne became available in 2000.

Vision-Enhancing Implantable Telescope
— The FDA has approved the use of an implantable miniature telescope (IMT) for enhancing the central vision of people with end-stage, untreatable age-related macular degeneration (AMD). The IMT provides improved central and detailed vision by focusing and magnifying images onto the functional, outer regions of the recipient’s retina. People with advanced AMD normally experience degeneration of the macula or central region of the retina. The IMT was developed by VisionCare Ophthalmic Technologies.

Emerging AMD Treatments Currently in Clinical Trials

RetinoStat® — Oxford Biomedica, a gene therapy company in the United Kingdom, has launched a Phase I clinical trial of its gene therapy for the treatment of wet AMD. Known as RetinoStat, the treatment works by blocking the growth of leaky, unhealthy blood vessels under the retina that cause vision loss in wet AMD. The study is taking place at the Wilmer Eye Institute at Johns Hopkins.

Advanced Cell Technology (ACT)
— The biopharmaceutical company ACT has launched a Phase I/II clinical trial of its cell-based therapy for people with dry AMD.  Participants in the study are receiving transplants of retinal pigment epithelial cells derived from stem cells. The company believes the treatment may slow the progress of the disease, saving and potentially restoring vision. The Foundation funded earlier lab studies of this treatment approach, which made ACT’s clinical trial possible.

Encapsulated Cell Technology (ECT)
— Developed by Neurotech, the ECT is a tiny capsule — the size of a rice grain — implanted into the eye. The capsule contains retinal cells that produce a vision-preserving protein called Ciliary Neurotrophic Factor (CNTF). The protein helps keep photoreceptors alive and healthy, thereby preserving vision. In spring 2009, Neurotech reported that the device stabilized vision in people with dry AMD (geographic atrophy) participating in a Phase II human clinical trial. FFB funded earlier, preclinical studies of this therapy.

Fenretinide
— In both clinical and preclinical studies, fenretinide has reduced the accumulation of vision-robbing toxins in the retina that are associated with dry AMD. Developed by ReVision Therapeutics, the drug slowed the growth of vision-robbing lesions associated with dry AMD (geographic atrophy) by 45 percent for people participating in an ongoing Phase II clinical trial. Fenretinide also reduced the incidence of wet AMD by 50 percent in a Phase IIB clinical trial. FFB funded earlier, preclinical studies of this therapy.

Other Emerging Treatments in Clinical Trials
— Dozens of potential AMD treatments are in clinical trials in the U.S. and around the world. Many were made possible by preclinical research funded by FFB. These therapies include: eye drops, ocular injections, gene therapy, and pharmaceutical agents. To learn more about  these studies, visit www.FightBlindness.org, click on Resources, and from the pull-down menu, select Clinical Trials.

Other Key AMD-Related Research Initiatives

Complement Factor H (CFH) gene — In early 2005, FFB-funded researchers identified variations in a gene known as CFH, which are implicated in as many as 50 percent of all cases of AMD. In early 2006, these same investigators found that variations in CFH along with variations in two other newly identified genes, factor B (BF) and complement component (C2), are present in 74 percent of AMD cases.

Though the environmental and genetic causes of AMD are complex and not completely understood, these landmark findings confirm a genetic influence on the development of AMD. And, these genes give a clear target for the development of future, more effective therapies. Specifically, the CFH finding strongly suggests that the immune system and related inflammatory responses are key factors in the development of AMD. Future therapies may be directed toward stopping the effects of CFH variations and other related genes.

Scientists have identified other genes that are related to AMD risk and believe more AMD–related genes will be found in the future.

FFB continues to fund genetic research for AMD, because the identification of genetic risk factors will give experts the best targets for treatments that will prevent AMD-related vision loss before it occurs.

FFB does not endorse specific treatments for AMD or other retinal degenerative diseases. Consult an ophthalmologist to determine what treatment is optimal for you.

This document may not reference every available AMD clinical trial or treatment.

For the latest information on AMD treatments, research, and clinical trials, please visit the Web site of the Foundation Fighting Blindness at www.FightBlindness.org.

Comprehensive AMD clinical trial information is also available at www.clinicaltrials.gov.

 

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What are the risk factors?

 

The exact causes of AMD are not completely understood. However, genetics, diet, cigarette smoking, bright sunlight, cardiovascular disease and hypertension are risk factors for AMD.

 

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Is AMD an inherited disease?

 

Researchers are discovering that genetics appears to be a major factor in more than half of AMD cases. Three research groups have discovered a gene called Complement Factor H (CFH) that appears to be linked to at least 50 percent of all cases of AMD. Prior to this landmark discovery, Foundation-funded researchers discovered other genes that appeared to be linked to AMD, though these genes were implicated in a smaller number of cases than CFH.

 

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What is the Amsler grid?

Along with regular examinations by an eye doctor, people can evaluate their eyesight for possible symptoms of AMD using a simple home testing device known as the Amsler grid. The Amsler grid, consisting of parallel and perpendicular lines, looks much like a sheet of graph paper. By focusing on a marked spot in the middle of the grid, it is quite easy to detect blurred or distorted vision. While the Amsler Grid is not a substitute for an expert medical diagnosis, it does allow people to check their eyesight regularly for possible symptoms of AMD.  Click here to complete a short form to gain instant access to a free, printable Amsler grid and instructions for use.

An amsler grid depicting normal vision
Normal vision
An amsler grid depicting macular degeneration
Picture as seen by someone who has macular degeneration

 

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What low-vision aids are available?

As central vision declines, people with AMD may benefit from low-vision aids like magnifying glasses and special lenses, screens that enlarge small print, text-to-speech and speech-to-text computer software programs, and any number of other specialized technologies. Low-vision experts can also help individuals adapt daily living skills. Low-vision specialists are available through ophthalmology centers and physician referrals.

Related Links: www.maculardegeneration.org
Related Diseases: Stargardt Disease

*Images courtesy of the National Eye Institute, NIH

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