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AGE-RELATED MACULAR DEGENERATION
RESEARCH PROGRAM


AGE-RELATED MACULAR DEGENERATION
An Epidemic of Blindness

Age-related macular degeneration (AMD) is a complex eye disease that affects the macula, the central portion of the retina at the back of the eye. Both genetic and environmental factors may be involved in its development.

While AMD doesn’t cause total blindness, it destroys central vision so reading, watching TV, driving and many other activities are impossible. AMD also steals the ability to see fine detail, colors and the faces of loved ones.

AMD is the leading cause of irreversible blindness and vision impairment in people over age 50 in the United States and the western world.

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About 13 million Americans have evidence of AMD, according to Prevent Blindness America.

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AMD has caused visual impairment in an estimated 1.7 million of the 34 million Americans over age 65, according to the National Eye Institute.

Research indicates that AMD could reach epidemic proportions in the next decade due to the general aging of the population. While AMD is most common in people over age 60, symptoms can develop in the 40s and 50s.

AMD is particularly prevalent in the Southwest, with its large retired population. More than 1 million Arizonans were age 50 or older in 2000, and by 2010 they will number more than 2 million, according to the Arizona Department of Economic Security.

In 2002, AMD was responsible for visual impairment in 29,352 Arizona residents (Prevalence of Adult Vision Impairment and Age-Related Eye Diseases in America--2002. National Eye Institute, 2002). The incidence of AMD within the Arizona population is similar to that in the United States as a whole. The percentage of Americans affected by AMD increases dramatically with increasing age. AMD causes significant visual impairment in 7.1% of those between 60-69 years old, 14.4% of those 70-79 years old, 35.4% of those over 80 years of age (Prevalence of Age-Related Macular Degeneration in the United States. Archives of Ophthalmology 2004;122:564-72).

Currently, there is no cure for AMD, and treatments are very limited. Finding the cause of AMD is our challenge, and research is the only hope for the future.

AMD Research Program

Established in September 2000, by the Department of Ophthalmology and Vision Science at the University of Arizona College of Medicine in Tucson, the Southwest AMD Research Program is dedicated to retinal disease, specifically the elimination of AMD. With the demographics of our state, the program’s combination of research and clinical care will positively impact our friends, neighbors and colleagues. This venture, led by the UA Department of Ophthalmology and Vision Science and its Lions partners, promises results in the fight against AMD.

The Program’s goals include:

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develop better surgical and nonsurgical treatments for AMD

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understand the molecular and cellular mechanisms of AMD

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develop new techniques for early diagnosis of AMD

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bring new ideas into AMD research through collaborations with UA colleagues

The Department of Ophthalmology and Vision Science is well-positioned for success in its effort to eliminate AMD. The Department has a strong commitment to research and clinical care. Our researchers collaborate with UA molecular geneticists and biologists and with laser scientists in the UA optical sciences program. A program for research and clinical treatment of AMD satisfies all three goals of the UA mission statement: service, education and research.

Dissemination of Technology

The Southwest AMD Research Program is committed to disseminating any developed technologies to the Arizona medical community. As new technologies and techniques are developed, community physicians will be given access to the equipment and training to enable them to implement more advances.

The Program’s mission also includes establishing a research training program for clinical and postdoctoral fellows, graduate medical students and undergraduate students.

Advisory Group

The Southwest AMD Research Program is organizing an Advisory Group to assist in guiding research programs. The Advisory Group will include local and national physicians and scientists who may offer fresh perspectives on developing technology.

Program Endowment

Stemming the tide of the AMD epidemic requires building a world class research team. The Southwest AMD Research Program already has recruited several experts, including specialists in retinal cell biology, ophthalmic optics, engineering and ophthalmology. Our goal is to create an endowment to sustain funding and permit long-range planning.

To acquire the staff and equipment needed to make AMD treatments possible, the Department has initiated a $10 million campaign to fund the development of the Southwest AMD Research Program. The necessary funds will be raised from private sources, in particular, those most likely to benefit from the development of new treatments.

With Your Help, We Can Overcome This Blinding Condition

There are many ways in which you can help further this important research. Donations of all sizes, including planned gifts, major gifts, restricted and unrestricted gifts, will be utilized to increase knowledge of AMD and to provide the best possible vision care.

To make a tax-deductible contribution, please make your check payable to: UA Foundation, Ophthalmology Department. Please write “AMD Research” on the “For” line of your check.

Research Team

  Dr. Marmorstein Photo

Alan Marmorstein, PhD
Associate Professor, UA Department of Ophthalmology and Vision Science and UA College of Optical Sciences

A cell biologist, Dr. Alan Marmorstein’s research interests include identifying the metabolic processes that lead to inherited and age-related forms of macular degeneration and developing new medications for treatment and prevention. He also is developing new diagnostic techniques, including a non-invasive imaging device to diagnose AMD. Prior to joining the UA in 2003, he was an assistant staff member with the Cleveland Clinic Cole Eye Institute Department of Ophthalmic Research in Cleveland, Ohio, with a secondary appointment in the Cleveland Clinic Lerner Research Institute Department of Cell Biology. Prior to joining that, he was a senior research biochemist at Merck Research Laboratories in West Point, Pa., where he began studying the protein bestrophin, which is mutated in individuals with Best macular dystrophy, an inherited form of macular degeneration. He received his doctorate from the State University of New York Health Science Center in Brooklyn. As a postdoctoral fellow at Cornell University Medical College in New York City, he introduced and defined cell culture systems for studying the function of proteins in the RPE and pioneered a new method of studying the molecular physiology of retinal pigment epithelium (RPE) cells.

  Dr. Marmorstein Photo

Lihua Y. Marmorstein, PhD
Assistant Professor, UA Department of Ophthalmology
and Vision Science and UA Physiology

A cell biologist, Dr. Lihua Marmorstein’s research focuses on genetics and the development of age-related macular degeneration (AMD), as well as developing and testing new diagnostic, treatment and prevention strategies. Her current research, which is funded by the National Institutes of Health (NIH), is investigating the molecular basis of malattia leventinese (ML), an inherited macular degenerative disease similar to AMD, and its associated gene EFEMP1. She has demonstrated that in both ML and AMD, mutant EFEMP1 is abnormally accumulated beneath theRPE, a layer of cells behind the retina. Her work for the first time links defective proteins and the translation of genetic information to the development of AMD. Prior to joining the UA in 2003, she was an assistant staff member with the Cleveland Clinic Cole Eye Institute, Department of Ophthalmic Research, in Cleveland, Ohio. She received her doctorate from the State University of New York Health Science Center in Brooklyn and her postdoctoral training at the Mount Sinai School of Medicine in New York and the University of Pennsylvania in Philadelphia.

  Dr. McKay Photo

Brian S. McKay, PhD
Assistant Professor, UA Department of Ophthalmology
and Vision Science

A retinal cell biology specialist, Dr. McKay has developed a new method for culturing RPE cells in the laboratory that has overcome many of the problems that have plagued other researchers. He has an NIH grant to test the suitability of his discovery for RPE cell transplantation. His process for growing RPE cells also has applications in other fields; he is collaborating with the UA Department of Neurology to develop a technique for implanting RPE cells into the brain for treatment of Parkinson’s disease. Prior to joining the UA in 2002, he was an assistant professor in the Departments of Ophthalmology and Cell Biology at Duke University in Durham, N.C. He received his bachelor’s degree in biology from the University of Wisconsin and his doctorate from the Medical College of Wisconsin in Milwaukee. He received his postdoctoral training at The Scripps Research Institute in La Jolla, Calif.

Anatomy

AMD is a complex eye disease that affects light-sensitive photoreceptor cells in the macula, the central portion of the retina at the back of the eye, where light-sensitive cells send visual signals to the brain. While it doesn’t cause total blindness, the diseases destroys central vision so reading, watching TV and driving are impossible.

A review of the anatomy of the eye is crucial in understanding AMD. The eye functions much like a camera. The cornea and lens (see figure at right) act as a focusing system. The iris acts as an aperture, controlling light entering the eye. The retina, a thin fragile layer of nerve tissue lining the back of the eye, functions like the film in a camera, converting light to an electrical signal which is transmitted through the optic nerve to the brain.

Camera Lens Illustration
 

Human eye (above) and photographic camera (right). The human eye functions very much like a camera. (Illustrations courtesy of the American Academy of Ophthalmology.)

 

The macula is the central portion of the retina. It is the most sensitive part of the retina and is responsible for our ability to read and to see faces and fine details. The macula is the portion of the eye affected in AMD.

The retina is composed of a number of layers of cells. AMD affects a deep layer of cells in the retina called the retinal pigment epithelium (RPE). Damage or loss of the RPE cells results in loss of vision.

Disease Categories

AMD is divided into two types: dry and wet. According to the National Eye Institute, approximately 90 percent of people with AMD have the dry type and about 10 percent have wet AMD, however, wet AMD causes 90 percent of all cases of blindness from AMD.


Normal


Dry AMD

Wet (or Exudative) AMD

 

Normal IVFA Photo

Dry AMD Photo

Wet ARMD Photo

 

 

Patients with dry AMD have yellow deposits called drusen under the RPE or may have loss of RPE cells (called geographic atrophy). Drusen contain complex lipids (fats) and calcium and can accumulate with age. Patients with drusen may retain good vision. Patients with macular degeneration develop a central blind spot.

Patients with wet AMD may experience a rapid deterioration in vision, caused by the growth of new blood vessels under the retina. The new vessels may leak fluid or blood under the retina, causing vision loss.

 

Symptoms

Symptoms of both types of AMD include a central blind area and blurred or distorted vision. As a rule, symptoms develop slowly and gradually affect one’s ability to drive, read, recognize faces and do close work, such as sewing.

Risk Factors

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Age.

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Family history of the disease.

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Gender. Women have a greater risk of developing AMD, according to several studies. Women over age 75 have more than twice the risk as that of men in the same age group.

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Smoking. Smoking has been associated with an increased risk of developing the changes associated with AMD.

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Eye color. Studies indicate that people with light eyes and skin are at higher risk for AMD than those with darker irises. This may be related to sunlight transmission or to low macular pigment density.

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Cardiovascular disease. Cardiovascular disease may be a factor, although the correlation demonstrated in some studies may be due to other related risk factors.

Current and Experimental Treatments

Several new treatments for wet AMD recently have been introduced, and others are in development and soon will be available. Treatment options for dry AMD, the most common form of the disease, are unavailable.

Wet AMD

Thermal Laser Treatment. A high-temperature laser is used to destroy the new vessels. However, the laser destroys healthy as well as diseased tissue, leaving a black spot in the patient’s visual field. The treatment is used only in certain types of wet AMD.

Ocular Photodynamic Therapy (PDT). A dye is injected into an arm vein and a laser is shined into the eye in the region of the new vessels. The laser does not burn the vessels, but caues a change in the dye within the vessels, ultimately destroying them without damaging surrounding tissue. PDT is used to treat specific types of wet AMD.

Transpupillary Thermal Therapy (TTT). A laser is used to slightly raise the temperature of wet AMD vessels for a prescribed period of time to stop further growth.

Radiation Therapy. Low-dose radiation therapy to stop or slow the growth of new vessels is being studied as an alternative treatment for the vast majority of patients who are not eligible for laser treatment.

Surgical Removal of New Vessels. The results of surgically removing new vessels have been limited by the loss of retinal pigment epithelium (RPE) cells (a layer of cells behind the retina) during the procedure.

Pharmacologic Therapy. Vascular endothelial growth factor (VEGF) inhibitors are a new class of medicines that are injected directly into the eye. Macugen is FDA approved and is being used at the University of Arizona. Lucentis is a second VEGF inhibitor and is currently in clinical trials at the University of Arizona.

Macular Translocation Surgery. The macula is relocated to an area of the eye with healthier RPE. This experimental surgical technique has had success. However, it is a difficult and very risky procedure that involves producing a complete retinal detachment.

Dry AMD

Laser Treatment of Drusen. A low-intensity laser is used to treat and remove drusen, yellow deposits containing complex lipids (fats) and calcium under the RPE. The effectiveness of this procedure is under evaluation in a large clinical trial.

Retinal Pigment Epithelial (RPE) Cell Transplantation. A patient’s own healthy RPE cells are transplanted beneath the macula. To date, this procedure has had very limited success due to changes in the RPE cells during the implantation process.

The Southwest Age-Related Macular Degeneration (AMD) Research Program, established in September, 2000, by the Department of Ophthalmology and Vision Science at the University of Arizona College of Medicine in Tucson, is dedicated to retinal disease, specifically the elimination of AMD. Program goals include developing better surgical and nonsurgical treatments for AMD, understanding the molecular and cellular mechanisms of AMD, and bringing new ideas into AMD research through collaborations with UA colleagues. For more information about AMD, contact Ryan Winet at (520) 626-0716 or email at rwinet@eyes.arizona.edu.

 

With Your Help, We Can Overcome

This Blinding Condition

   
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Become an eye donor: Groundbreaking discoveries on glaucoma depend upon research using donated eyes.

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Write to your Congressional representative: As a taxpayer, your representative needs to know that research on glaucoma is important to you.

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Monetary gifts: Donations of all sizes, including planned giving, major gifts, restricted and unrestricted gifts, support glaucoma research in Arizona. Every bit helps. Your gift will truly be a “gift of sight.”

 

LINKS

University of Arizona Department of Ophthalmology Clinical Studies

Facts about Age-Related Macular Degeneration

Are You at Risk for Age-Related Macular Degeneration?

Results--Age-Related Eye Disease Study

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National Eye Institute, National Institutes of Health