Macular Degeneration is a condition in which there is a break down of the tissue in the center seeing area. It is important to realize that even though the macula is important for vision it represents only a small portion of the entire retina. If one imagines the inside of the eye to be the size of an ordinary cereal bowl, the area known as the macula would be only about the size of a quarter sitting in the bottom of the bowl. Macular Degeneration rarely injures the retina outside of this quarter-sized zone and as a result rarely causes total blindness in an eye. To put it another way, the central vision can be significantly impaired by Macular Degeneration, but the remaining peripheral vision is usually sufficient to allow persons to perform ease of movement in traveling or moving about the house or office, and caring for children or grandchildren. Persons with vision impairment from Macular Degeneration, however, may need some type of low vision device for activities of daily living such as shopping, reading mail, writing, or cooking. 

It is important to understand more about the eye and how it works, as well as about structures in the retina and layers of tissue below the retina. A person must become familiar with these terms to more fully understand research findings and more complicated explanations of specific areas of the eye.

HOW THE EYE WORKS

The outer most surface of the eye, or the clear outer structure is called the cornea. This is the only part of the eye that can be transplanted, that is, there is no such thing as an eye transplant. The cornea's primary function is to bend light rays coming into the eye so that it focuses them on the retina. Thus, light rays enter the eye, get partially bent, continue through the pupil (which is a black hole) and then enter the lens of the eye. The lens, a flat, clear structure (in youth) which may become cloudy later in life as a cataract whose primary function is to also continue to bend light rays to focus light on the retina.It should be stated that when you hear of procedures such as RK, cornea transplants (donated tissue from an eye bank), or cataract surgery with lens implants, these are references to structures in the front of the eye which are much different from the retina which is in the back of the eye.

MORE ABOUT THE RETINA

As we stated earlier, the retina is the inner layer of the back of the eye and is much like a relay station. The first area touched by light rays are the rod and cone cells. Cone cells live primarily in the macula while rod cells live in the peripheral retina. Rods and cones are like rabbit ears on a TV set. They help catch the light rays that are focused on the retina. The disease of Macular Degeneration is being studied to determine if there is an abnormality in the rods or cone cells or if the primary problem is in a layer of cells below the rod and cone cells called the RPE cells. These cells called the retinal pigment epithelial cells is a layer of cells like a carpet underneath the rods and cones. The primary purpose of this layer is to hook up with the rods and cone cells to bring nourishment for healthy tissue.

There are also several layers beneath the RPE layer including Bruch's membrane, and a layer known as the choroid which contains the blood vessels of the eye. In order for vision to work properly, think of it as a TV set. The TV antenna must work properly with the right "hook up" as well as the cable to the TV set must also work. In the retina there are other "hook-ups" in different types of cells and cell layers - some called bi-polar cells, some called ganglion cells as well as the optic nerve. Thus, there are many difficult hurdles to overcome for "experimental surgery" or treatments for Macular Degeneration. It is understood that the retina connects like "links in a chain" and many areas hook up in the relay station so that one problem or link may be fixed, but there may also be a weaker link where the problem is not easily solved. 

AGE RELATED Macular Degeneration

The most common type of Macular Degeneration affects individuals over the age of 50 and has come to be known as "age related " Macular Degeneration, or late onset Macular Degeneration. There are also a number of earlier onset forms of Macular Degeneration which will be discussed under the heading of Stargardt's and other Juvenile Macular Dystrophies.

The first hint that there may be macular degeneration in a person's retina starts with the appearance of spots on the retina. These spots are called drusen. These drusen are like age spots and themselves do not usually change vision directly, but may be a sign for the doctor to watch for potential danger. These small yellow spots occur beneath the macular retina and with time, these spots may become more numerous. Over a period of time, the retina overlying these drusen may begin to deteriorate, and in a small percentage of patients the eye reacts to this injury by allowing the growth of new blood vessels from an even deeper layer (the choroid) into the space beneath the retina.

If there is a breakdown of the tissue in the macula which lead to loss of vision that loss will usually start in just one eye. It may affect the other eye, later, or not at all. Sometimes the person is not aware that they have had reduced vision in one eye because the better seeing eye (especially if it is the dominant eye) can see detail and is functioning normally. It is important, however, that in these early stages that the vision should be checked by a doctor as soon as possible.

A simple way to check your vision daily is by using an Amsler grid like the one pictured here.

Amsler Grid Instructions

You may notice changes in your vision using this test that you otherwise may have not been able to catch. To use the grid cover one eye, and with your reading glasses on hold the grid approximately 12 to 16 inches away then, look directly at the center with the uncovered eye. Notice whether all the lines of the grid are straight or if any of the areas seem blurred, distorted, or dark. Repeat this process with the other eye. If you notice an abnormality contact your ophthalmologist immediately.

The early stages of Macular Degeneration may sometimes be hardly noticeable. It can also cause different symptoms in different people. Sometimes only one eye loses vision while the other eye continues with good vision for many years. Others may have symptoms in both eyes in a more "milder form" which may not significantly impair vision for many years. For instance, there are estimates of those in the U.S. that are affected by Macular Degeneration in some form totaling 13 million. Those with severe vision impairment from Macular Degeneration range in estimates from 2 to 3 million.

Other important or frequent symptoms may include distortion where straight lines will look wavy such as lines on the Amsler grid or a door frame or blinds on a window that look bent. Sometimes colors don't look quite right or there may be a purple or gray spot that appears in the center vision. These and other similar symptoms are important and should be attended to by your eye doctor.

Many people with the onset of Macular Degeneration have trouble adjusting quickly between bright sunlight or dim light or shadows. This may be especially dangerous if driving in bright sunlight and then entering the shade of a tree or visa versa. Where the normal retina takes 3 to 5 minutes to adjust from the bright light to a dim light (like entering a movie theater) a person with Macular Degeneration may take 8 to 12 minutes or longer. Many people also begin to show more sensitivity to glare both indoors and outdoors.

There are two common types of late onset Macular Degeneration which have come to be known as the "Dry Type" (you will see it written on a doctor's report - atrophic) and the "Wet Type" (which may appear as exudative Macular Degeneration).

DRY OR ATROPHIC Macular Degeneration

The hallmark of late onset Macular Degeneration is the presence of drusen, mentioned earlier, that occur beneath the macular retina. After a while, having this drusen under the macula may cause the macula to thin and degenerate/atrophy thus referring to it as atrophic Macular Degeneration. This can cause a slow and progressive loss of vision in the central seeing area. Atrophic Macular Degeneration is more common than the wet form and occurs in about 9 out of 10 persons with Macular Degeneration. Over time the atrophy or damaged area can cause a large central blind spot also called a scatoma where there is a loss of detailed vision. This scatoma, usually an irregular shape, is found however in the very center of the retina. The damage done by dry Macular Degeneration is usually not as severe as that of the wet form or exudative form. Because the dry form can sometimes change into the wet form it is important for persons with the dry form to continue recommended ophthalmological visits and watch for new changes in vision, for instance, by using the Amsler grid.

WET OR EXUDATIVE Macular Degeneration

In about 10% of cases of Macular Degeneration the eye develops new blood vessels which grow up from the choroid. These new blood vessels can leak fluid or blood which in turn can cause more damage than the degenerative process itself. This is what is known as the wet or exudative type of Macular Degeneration. You may also see terms of a doctor's report such as subretinal neovascularization which means new vessels growing underneath the retina. Keep this term is mind as you read new research reports to try to understand which type of Macular Degeneration is being studied. The wet form then, which is characterized by subretinal neovascularization can be even more severe than the dry form and occurs in about 1 in 10 of persons with Macular Degeneration. Abnormal blood vessel growth which may leak fluid, blood, or lift up the retina causes more damage the longer it occurs and goes untreated. In cases where the damage is not in the center seeing area directly, laser treatment may be done to stop or minimize loss of vision. Also, attempts to curtail the growth of these new vessels are continuing to occur in research studies to see if there are any types of drugs which may halt this progress. If the abnormal blood vessel growth occurs in one eye there is approximately a 10% chance per year that they will occur in the other eye. New studies are being done to see if a beneficial effect of radiation therapy can be done on this "wet type" of Macular Degeneration. Comparisons of data with the natural history of wet Macular Degeneration suggest a beneficial effect of radiation therapy. To date, no negative side effects have been observed. More studies are being done at this time. 

NUTRITION

Scientists are establishing a strong link between lutein, a carotenoid found in green, leafy vegetables, and reduced occurrence of age-related Macular Degeneration. This dietary link to an eye disease has important implications and a potential to change the entire approach to eye health. While there is no cure for Macular Degeneration, recent studies associate higher consumption of lutein with lower risk for Macular Degeneration. Researchers found that those who consume the most carotenoids had a 43% lower risk for Macular Degeneration that those who ate the least. Of these carotenoids, lutein and zeaxanthin were most strongly associated with a reduced risk for age-related Macular Degeneration. " Increasing the consumption of foods rich in certain carotenoids, in particular dark green, leafy vegetables, may decrease the risk of developing macular degeneration, " reported Johanna M. Seddon, M.D., of the Department of Ophthalmology, Harvard Medical School, echoing the results of seven other studies in the past four years. " The association between carotenoid intake and lower risk for ARMD appears to be accounted for primarily by lutein and zeaxanthin rather than carotenoids with provitamin A activity, " concluded Seddon.

Lutein and its isoner zeaxanthin are the only carotenoids found in the macula portion of the eye. A carotenoid is a powerful antioxident responsible for yellow or red pigments in vegetables. Antioxidents are a group of nutrients that neutralize dangerous free radicals - molecules charged with oxygen - that can damage healthy cells and can trigger cancer development. It is theorized that lutein protects by blocking harmful blue light from reaching the back of the eye. Lutein and zeaxanthin may protect the retina from the light's possible photic and oxidative changes. Because the retina is rich in polyunsaturated fatty acids, it can be adversly affected by oxidation and, in turn, protected by nutrients that block oxidated damage.

Until recently, the only way to keep the eye supplied with lutein was eating large quantities of green, leafy vegetables. There are now vitamin formulas that contain both lutein and zeaxanthin which can help supplement your diet.

GENETIC RESEARCH

It seems that a week does not go by where we do not hear a news report about a certain gene being discovered for some disease. This much publicized area of research called Genetic Research is also important in the study of eyes and eye diseases, and specifically, diseases of the retina. Many of the breakthroughs in eye research over the last several years have been in this area of genetics. You may have heard that a new gene or new gene locus has been identified as a cause of a retinal degeneration.

One of the reasons that this type of breakthrough is so important is that it gives the doctors a precise diagnosis, also known as a definitive diagnosis. Another reason this is so important is that eye diseases that affect the macula and have a precise name may actually be more than one disease. That is, the disease may look exactly the same to the eye doctor and may look exactly the same in taking a photograph of the retina but there may be a different gene causing the same, similar appearing Macular Degeneration. As to the number of genes causing macular degeneration, there may be ten or more. That is one reason why it is so important to discover each individual gene as much as possible as it gives the researchers a definitive diagnosis for that particular type of macular degeneration. Otherwise, it would be difficult to do research on so many different types of Macular Degeneration if you did not know the exact type or cause. So the very first thing is the identification of a gene, thereby obtaining a definitive diagnosis and an exact sample of the disease.

Secondly, once the gene is identified, a study can be done to determine in what way does this gene mutation interfere with the normal functioning of the retina to cause Macular Degeneration. Many times, as these genes are discovered, patients are then asked to come to a research center so that more information can be gathered about the specific disease process and how it affects the eye for that condition.

Also being studied in this arena are the cell or cells involved in and around the macula. Cell biologists begin to study in what ways the cell is affected because of this gene mutation. Also, what type of cell is affected, that is, is it the rods and cone cells, or the layer of cells beneath the rods and cone cells called the RPE cells.

Finally, by learning from what the cell biologists have discovered, and by what the doctors or clinicians have discovered from their patients, a precise story can be developed as to what's gone wrong with this particular degeneration. That is, an educated guess or hypothesis can be put forward as to the cause of this type of Macular Degeneration.

Many patients say, "Will this type of research help me now"? There may not be any immediate results from this type of research for the current patient with Macular Degeneration but it is highly important that the researchers understand the cause of Macular Degeneration before they can ultimately figure out the cure.

Some immediate benefit, however, may be in the information gained in order that some types of Macular Degeneration can be explained to families. That is, if a grandmother has Macular Degeneration, what can you say to the family about whether the daughter may get macular degeneration or the granddaughter. At present, much of this type of information is not available, although we receive calls every week from family members asking about the inheritance patterns of Macular Degeneration and/or questions whether Macular Degeneration can run in families. Also, we receive questions each week about ways to prevent family members from getting Macular Degeneration and would it help to take vitamins, or should I make sure my daughter or my grandson wear UV protection sunglasses so that they do not develop macular degeneration later in their life. Again, these are very important questions and this type of research may give us more exact answers in the future for this type of valuable information for families.

Another potential benefit in the future of this type of research and information for families may be the certainty in which a doctor can tell a particular family member that they will not be affected in their life. At this point in time, there can not be such certainty in information given, but in the near future, the possibility of a doctor being able to be 99% certain that because the person does not have a particular gene, this would then mean that the person would not get Macular Degeneration in their life.

Other important factors about genetic research may help in the future towards treatment of a disease. People often ask, "If there is an abnormal gene, can you replace it with a normal gene?". The answer to this question is currently being studied in many centers throughout the world. There are many questions that arise when researching this type of approach such as that if you could insert a new gene into a cell and make it work would it positively influence the disease? A partial answer of "yes" has been discovered that if in deed you could put a new gene into a cell, the disease may be altered in a positive way.

Has there been any success in transferring a normal gene into an abnormal gene? And if it is transferred successfully will it work for long periods? Other questions also arise such as if the new gene is successfully transferred and if the new gene would exist for a long period, would it then produce the right amount of protein necessary to make the disease go away? This is not yet known. The fact that a gene may be transferred is obviously very encouraging but we don't yet know whether such a gene that is transferred would work for a very long period or whether it would deliver the right amount of protein.

So as you can see there are many encouraging steps being taken in genetic research, but at this time there are many more questions to be answered. We look forward to keeping you abreast of some of the research and some of the successes in the genetics area.

CELL TRANSPLANTATION RESEARCH

Another important area of research being studied is cell transplantation. When we talk about the retina again we are talking about cells and cell layers. We are also talking about the inter-connection between layers of cells.

In cell transplantation, people often ask, "Can the diseased cells be replaced with new cells?" The two main types of cells involved in the retina are the photo-receptor cells and the retinal pigment epithelial cells (RPE cells). Many of the questions being asked in research of cell transplantation are, "Can healthy cells be transferred into the proper area of the retina, and then will the cells survive?" This would apply both for the type of cells for the RPE layer and also for the photo-receptor cells, which are basically two different kinds of cells.

Preliminary research seems to indicate that healthy cells can be transplanted into the proper area of the retina and it seems as though they will survive. The next important question to be answered is, "Will these cells work?" The answer to that question has not been answered as of yet. Also questions regarding whether these cells connect or hook up to the cells surrounding it still remains an important question.

If there were a proper connection of new cells in this layer of the retina, that is, do the signals then from these new cells connect in order to reach the brain? And if these signals were to reach the brain properly, does it actually improve vision; does the person actually see better? The answers to these important questions are uncertain at this time. It is good to know that in one situation in research, that of an animal using what is called an RCS rat, the answer to all the above questions seems to be "yes". That is, in this animal that has a damaged tissue layer of RPE cells, new cells that are transplanted into this area seem to help the retina to survive. Also, optimistic are the preliminary indications that the animal seems to behave as if it sees better from having had their treatment. As much of this type of research continues around the world and seems to be very promising, it does not seem as though that this will render a cure or a partial cure in the near future. After all, what we are truly talking about are the inner connections between the retina and the brain. This is why it has been so difficult to come up with a cure for retina diseases as the inner connection with the brain makes it much more difficult to get the proper signals to hook up. It is not simply like transplanting an organ but making proper connections in the brain.

CLINICAL TRIALS

Another area of research toward a potential treatment for Macular Degeneration is in the area of clinical trials. A clinical trial is a study to evaluate the possible benefits of some type of medical intervention (such as a particular drug or vitamin) as well as a surgical intervention to change the course of the disease of macular degeneration. For instance, in Macular Degeneration, a study would be undertaken to see if a medication would slow down the rate of degeneration of the disease as compared to not treating the disease or comparing it with the natural history of the disease.

So this type of scientific research has a critical element which always compares two different groups of persons - one group who has received the particular treatment verses the second group, often called the control group, which has not received any treatment. This second group is often called the placebo group because instead of receiving the medication being studied in the clinical trial they are receiving a sugar pill or placebo.

Because science does not know the answers and does not know if the particular treatment being studied will work, it is ethical to have one group receiving the treatment and the other group receiving the sugar pill, so that the true benefit or possible benefit can be evaluated. This placebo group would then be a population that would be used for comparison.

Clinical trials are necessary as there are rare times in medicine when a particular substance or drug is found that will make a dramatic impact or change. Often times studies also need large numbers of participants to find a benefit, since many of the benefits are not huge breakthroughs but suttle improvements. For instance, a study was undertaken for 10 years to determine if taking one aspirin a day would help persons avoid heart disease. After working with over 10,000 persons during this period, the answer seems to be yes, that this approach is helpful. A clinical trial for Macular Degeneration may involve 500 people or more and may also take several years in order to determine any subtle benefits.

At the heart of clinical trials is the question - What substance are we going to study? The question is the same in every medical disease - What do you try? Obviously, the substance requires careful thought because many persons are going to be involved in a study, lots of time and effort, lots of money will be spent and you need to have something that's appropriate.

We receive letters each month from persons and families affected by Macular Degeneration, some with advice about different things they have tried that have "seemed to help" or "at least not made the problem worse". If these same substances were used on 500 people or more over a five year period, would there be a significant change in enough people to actually show a benefit? This is what the researchers are up against in trying to determine what areas should be studied in clinical trials.

We want to encourage all our members to continue to send letters and information about ideas they may have or things they may have tried, but whether it will stand up against this kind of scientific test is often uncertain.

TREATMENT PROTOCALS

What are the precise instructions necessary in clinical trials to go forward with a particular study? For instance, how many patients will be involved? How will the drug be administered? In what dose? For how long? How will you measure vision over time to make sure the vision is tested properly and results are not because of a difference in a type of measurement?

Another area of concern in clinical trials is, who is going to watch out for the patient; for instance, who is going to watch out for unknown side-effects? Who is going to make sure the patients are not injured? Finally, when the study is completed there is a lot of data to be analyzed. Who will analyze this data and in what form? All of these questions must be taken into careful account before a study is approached and the ultimate benefit is that whatever results are achieved, we can all believe the results which would show solid evidence.

Another concern for this type of clinical trial research is, who gets included, that is, who is eligible? If we are trying to determine whether vision gets worse or stays the same, subjects would be needed who have fairly good vision in order to determine whether the particular intervention would help. Also because of some side effects, persons would have to be excluded from the study based on potential risks or dangers to some people. For example, you would not want to include someone with severe liver damage when doing a study on vitamin A. And finally, persons need to enroll who have the greatest possibility of staying for the duration of the entire study. If there is a study which will take five years, persons who enroll may have to come back several times a year for the entire five year period without dropping out. It is important that by the end of the study that 95% of the patients are still participating. Sometimes these types of studies can be done at a single university setting, and sometimes greater numbers of participants are needed and several multi-center studies with multiple sites are involved. These studies also involve a special committee to monitor safety of the study, to assure that the study is done well and that the persons participating are well-cared for. The committee also looks at the data as the study unfolds year by year to see whether a major positive benefit is evident. If it is, the study might be stopped early so that people in the placebo group may receive the medication and benefit from it.

JUVENILE MACULAR DYSTROPHIES

It has been known for nearly 100 years that there are some forms of Macular Degeneration that are inherited. These inherited forms may strike young children, teenagers, young adults or persons in their 30's and 40's depending on the type of macular dystrophy. In fact, Best's disease can affect children as young as 1 year of age and has been referred to as juvenile Macular Degeneration. Stargardt macular dystrophy is the most frequently encountered juvenile onset form of macular dystrophy and can affect children as young as 6 years of age, teenagers and persons in their 20's, 30's and 40's. Other conditions known as "dominant drusen," "cuticular drusen," and "pattern dystrophy," are also inherited and can cause visual problems very similar to age related Macular Degeneration. Because inherited conditions can be studied with powerful molecular techniques more easily than non-inherited ones, researchers have been applying such methods to the study of inherited forms of Macular Degeneration in the hope that a better understanding of these conditions will lead to a better treatment for these and the more common age related disorders. Using a technique known as chromosome linkage analysis to look for genes that cause Macular Degeneration, researchers study families with inherited macular degeneration. By taking blood samples and analyzing the DNA, a computer program looks for a relationship between certain markers in the DNA and the presence of the macular disease. A study which began in 1987 with over 2000 patients made 2 major discoveries in families with juvenile macular degeneration. First, the gene that causes Best's disease was mapped to the long arm of chromosome 11. Mutations in the peripherian gene were discovered on chromosome 6, which cause a type of macular disease known as pattern dystrophy. This finding was particularly surprising since mutations elsewhere in the same gene can cause a completely different disease- retinitis pigmentosa.

As with age related Macular Degeneration persons with the juvenile onset form complain of a decrease in central vision. Basically, the degeneration is not caused by abnormal blood vessel growth under the retina as in the wet form, but the degeneration is usually associated with the accumulation of a waste material, referred to as lipofuscin. These lipofuscin accumulate for instance in the retinal pigment epithelial cells (RPE cells) in persons with Stargardt macular dystrophy. The accumulation of this material is likely to be responsible for deterioration of visual cells in the retina, referred to as cone and rod cells. Thus, these diseases would fall into the category of the dry type of Macular Degeneration, although it is not usually called this in the juvenile form.

The changes observed in the retina as well as center vision, tend to be more extensive and worsen over time. Persons with Stargardt disease will experience visual loss of 20/100 to 20/400 often by 30 to 40 years of age. As indicated, peripheral, or side vision tends to remain normal. Problems with glare, both indoors and outdoors and reduced color vision are other common symptoms. Presently the cause, and thus a treatment, for Stargardt disease is not known. Researchers are trying to determine the genetic defect that is responsible for the disorder. Once the gene for Stargardt disease can be isolated, investigators are likely to be able to determine the protein or enzyme that is deficient or defective in the retina of patients with Stargardt disease. Depending on the nature of the defect, it might then be possible to consider some form of therapeutic intervention.

ABCD

ABCD is now part of MDI- a valuable consumer resource gains an opportunity to continue to grow.

American Bioptic Certified Drivers (ABCD) began as a non-profit organization dedicated to promoting the interest of individuals who use bioptic lenses for the purpose of operating a motor vehicle. Originally founded in 1983 when bioptic telescopic driving was at a level of public interest, ABCD provided an avenue that encouraged people with low vision across the nation to participate in forming the laws that many of the current states possess today, as well as a means to communicate on a national basis.
Mr. Marc Sessions, the National Chairman of ABCD from 1983-1996, and his wife Doris Sessions, received the 1996 LVS Distinguished Service Award for their tremendous efforts and dedication to ABCD by the Low Vision Section of the American Optometic Association, at the annual continuing education symposium. The LVS Distinguished Service Award is presented to a non-optometric colleague or organization for major contributions to the advancement of low vision care and exceptional service to the community, the field of low vision and/or the AOA Low Vision Section.

Marc Sessions, now retired, has turned over ABCD to MDI and its new ABCD director, Dr. Terra Barnes, a low vision rehabilitative optometrist in Laguna Hills, California. Dr. Barnes would like ABCD and MDI to continue to serve as a resource to the current or prospective low vision driver, and provide a forum for the exchange of ideas and information between private and public agencies. With new direction, Dr. Barnes has chosen to join Tom Perski and Macular Degeneration International to be the medium in which the ABCD quarterly newsletters will continue to appear. Future issues of MDI will incorporate ABCD information on the current research, as well as the various bioptic laws the affect each state, centers that can prescribe bioptics, and public resources for those that are interested in obtaining more information on driving with bioptics telescopes.

back to the Age-Related index page