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AGE-RELATED
UNDERSTANDING MACULAR DEGENERATION


When The Doctor Says “You Have Macular Degeneration” - You Say, “Tell Me The Rest of the Story”

There are many “stages” or sub-categories under the title called Macular Degeneration. It is important to know ALL about your situation, for many reasons, as critical information means more definitive answers as to whether your Macular Degeneration will stay the same or get worse. More on that later, but for now, what you should know and if not told, what you should ask!!

In Macular Degeneration, we are talking about the center portion of the retina. The retina is a very thin sheet of nerve tissue that lines the back inside wall of the eye. Under this thin layer are RPE cells (retinal pigment epithelial cells) and beneath this layer is a layer called the choroid, made up of tiny blood vessels that bring food and oxygen to the retina to keep it healthy.

The macula is the center of the retina which brings fine, detailed vision or central vision - macula from the Latin “spot” - and “small” or “small spot” right in the center of the retina, like a bullseye is in the center of a target. The very center of this macula also has a name and it is called the fovea. The macula only makes up about 5% of the retina, but it is the part of our vision that is responsible for all reading, recognizing faces, driving a car and watching television.

When persons have a disease of the macula, it can be called a degeneration or a dystrophy. A dystrophy is not very common, but can occur from early in childhood, through teen and adult years. The term is used when a person has a hereditary disease, that affects both eyes, is similar in both eyes, and is distinctive in it’s appearance when seen by a specialist (usually someone who has special training not only in retina diseases, but also in inherited retina diseases or dystrophies).

More common is a degeneration, which means the tissues are normal at an early age and adult age, and then later, show a disease. A degeneration is usually not alike in each eye, nor does it progress at the same rate. Some early changes that are noticeable in the retina, sometimes even before Macular Degeneration, are the presence of tiny orange or yellow dots among the RPE cells. The German word “drusen” is the name for these small dots. These dots can be small at first, and very few in number. The drusen, by themselves, do not indicate vision loss will occur. Over time, however, the drusen can become larger and increase in number. This may mean that there is something wrong with the retina, that the retina is sick. The drusen, accumulate waste products, and like small waste cans, can sometimes overflow, get larger, and stop the flow of nutrients to the retina and healthy RPE cells. The RPE cells can get very thin and disappear. When the RPE cells are diseased and die, the overlying retina can lose it’s function and begin to degenerate. This type of degeneration is called dry or atrophic Macular Degeneration - there is no leaking of fluid or blood in this type.

Other features of dry Macular Degeneration
As we mentioned, some people develop more and larger drusen over time. Large drusen (measured by eye doctors and referred to as larger than 65 microns) can be a risk factor for getting wet Macular Degeneration at a later time. Also, within the RPE cells, cells may begin to “clump” together, which is called pigment clumping. This clumping is a healing response in the eye for some.. Pigment clumping may also be a risk factor for getting the wet form.

Super large drusen (more than 500 microns in size) can also occur, and they can cause a small detachment in this area of the drusen which is called a pigment epithelial detachment. Patients are often told they have a blister or bump in their retina. This is important to know, as there is a 30% chance that this bump or blister will convert to the wet form within five years.

Over time, sometimes over many years, the atrophy of the RPE cells gets more prevalent with all of the macula being affected. This degeneration which is called geographic atrophy, may be considered the end stage of the dry form. Geographic atrophy looks like a circle or spot of degeneration, right in the center.

Actually, all persons start with a dry form of macular degeneration. Later, about one in seven, begin to have other problems, which leads to the wet form. Blood vessels from the deeper layer, called the choroid, begin to grow spontaneously, up into the RPE layer and up in between the RPE and the retina, like the weeds growing under the sidewalk. These new blood vessels (called neovascularization - neo for new and vascularization for vessels) are very fragile, and easily leak and bleed. Eventually, this process goes on to form a scar. Once it is stopped and healed, a discaform scar forms, which looks like a disc shaped, grey scar in the middle of vision. This scar may take time to form, sometimes six to eighteen months - and once it does it destroys all retina tissue in that area and a person is left with a large central blind spot. Also, Macular Degeneration cannot be reversed once this has occurred.

So, the progression goes from early drusen, to dry or atrophic, to geographic atrophy. One in seven continue to go to the wet form - (also called exudative), to a discaform scar. The wet form is more damaging as about 85% of those in this category lose all their central vision and are measured in the 20/200 to 20/400 range of vision. (The person can see the big E, or the second line of the eye chart with his/her glasses). Only about 15 to 20% of those with the dry form progress to the geographic atrophy and measure 20/200 to 20/400. Others may have one eye dry, and the other eye wet. The dry form is usually much slower in it’s progression, sometimes taking years, while the wet form may happen suddenly, and cause severe vision loss in several weeks.

This wide spectrum from early drusen to a discaform scar falls under the title Macular Degeneration, the leading cause of vision loss in all developing countries around the world in persons age 65 and older. There is no SPECIFIC definition of Macular Degeneration, so if you are told you have Macular Degeneration, what do you have? Do you have early drusen, many drusen, some very large drusen? Do you have dry or geographic atrophy? The Wet form? A discaform scar?

You see, it’s all very different and you would not have any idea of what you have unless it is described to you, and better yet, put in a letter on your behalf so you have it for your records and for your family. Macular Degeneration can occur early and be very mild, or it can be more severe, or anything in between. We all need to know much more specifics about our particular type of Macular Degeneration.

Some types of Macular Degeneration may also be an indicator of better or worse things to come. That is, the more specific the description of what type of degeneration is seen, the better predictors of the prognosis for the future. Also, when analyzed with known risk factors like smoking, high blood pressure, and high fat diet, an even BETTER predictor can be made for your situation. For example, one famous study showed if a person had small drusen and the dry form, did not smoke, had a good diet and no high blood pressure, they were only at a 4% risk for developing the wet form. For a person with many drusen, some very large, with RPE changes like pigment clumping, and who also smoked, had high blood pressure and high cholesterol, he/she would have a 48% chance of developing a more severe loss of vision and having it turn into the wet form. That’s quite a difference!! So, if the doctor tells you that you have the dry form, it is important to know “the rest of the story”. Finally, other studies clearly show that the problem increases the longer people live, so age is a factor that must be taken into account.

Smoking, by the way, is shown to be a risk factor in both the dry form and the wet form, and is dose dependent - the more one smokes, the higher the risk !!

Who gets Macular Degeneration?
Some studies suggest more women than men will get Macular Degeneration; but, between the ages of 75 and 80, there are more women alive than men, so this may not hold true. Macular Degeneration is very uncommon in native African people and Aboriginal Australians. It is uncommon in the U.S. in African Americans, slightly more common in Hispanic Americans, and quite common in European Americans. It is most common in Australians of British ancestry.

When looking at families in large population studies, people with age related Macular Degeneration were twice as likely to report that they also had someone in their family who had it, when compared to people who had normal vision of the same age. A European study showed that siblings of a person with Macular Degeneration (either early or late, dry or wet forms) had a 4 times greater chance of having Macular Degeneration when compared with those whose relatives did not have it. Also, some families may say a sibling does not have macular degeneration, but in clinical studies the sibling may have early drusen and RPE changes - are they normal or do they have Macular Degeneration? Studies of twins showed that when an identical twin gets Macular Degeneration there is a 100% probability that the second twin will also develop Macular Degeneration. In non-identical twins the probability becomes 40%.

More about the wet form of Macular Degeneration
If a person develops an abnormal blood vessel under the retina, this is called a sub-retinal neovascularization (SRNV) - it is also called choroidal neovascularization (CNV). This denotes the beginning stage of the wet form. No blood vessels grow under the macula at first. These vessels start off to the side of the retina, and grow toward the center. For some, it can take only days to grow under the macula, for others it could take weeks. It is important for people to monitor their vision to try to detect if they are beginning to grow abnormal blood vessels, which can begin even if a person has only had the dry form. Abnormal blood vessels can reoccur after many years of having the wet form (which later turns to a discaform scar). So, no matter what situation you’re in, you can’t give up on testing your own vision.

Amsler Grid Chart
Ask your eye doctor for the best way to test your vision so you both can be on the lookout for changes in your vision due to new CNV or SRNV. Many people can use an amsler grid chart to detect subtle changes in vision. Others, who may have only one good eye, may notice changes without a chart.

Those who notice changes in the grid that were not there previously should alert their doctor immediately, because some abnormal blood vessels only take several days to go from the side of vision to the center. It is urgent that you make an appointment to see the doctor when this occurs. This is especially true with new treatments on the horizon for the early stages of the wet form. This monitoring of vision is crucial and follow up appointments need to be timely. You may want to ask your doctor in advance as to “what do I need to do to make a quick appointment if I see changes in the amsler grid?”.

The location of the vessel is important to the eye doctor, as there have been clear guidelines for many years as when to use the laser to stop a leaky vessel. The angiogram is one test that allows the doctor to see the location of the vessel. A new imaging green dye has proven to be even more effective in some cases in identifying abnormal vessels.

Over the past twenty years, many people have not been candidates for treatment - first of all, about 85% of all people have the dry form, thus no treatment has been available. For those who have the wet form, only about 7 in 100 can have conventional laser treatment, as the blood vessel is far enough away from the macula (the center) to treat - now with this new medical imaging (the green dye ), an additional 14 out of 100 can receive treatment for the wet kind. So, of this group of 100 with the wet form, there is still no treatment option for 79 out of 100 people.

Once the location of the vessel is made, there is one more important factor in determining whether a person is a candidate for treatment There are two types of CNV or SRNV. One is called classic, and it means that the vessel is like a flower with one main stalk; it is clear and is well defined on the angiogram or picture - a well defined leak that one could draw a circle around to show its location. The other type, called occult or an occult vessel, may be growing in many directions all at once and cannot be seen in a clear, well defined manner.

So as we stated earlier, the location of a subretinal neovascular membrane that is leaking is treatable if it is not near the center of vision, or away from the macula. In fact, even with some of these new therapies that will be discussed later, laser surgery (a classic CNV away from the macula) will still be the main method chosen by surgeons to stop a leaky vessel. Follow-up studies, however, also have shown that if a vessel is near the center of vision but not directly in the center (greater than 200 microns from the center), it may still be treated with conventional laser as long as it is of the classic type. What some of the studies have shown regarding this treatment of the extrafoveal or juxtafoveal classic membrane is that 25% of persons treated continue to get worse, while 65% of those untreated continue to get worse over an 18 month period. In some of these cases where the membranes are treatable and caught in time, the patient could regain some vision - for instance going from 20/200 to 20/60 once the hemorrhage is taken care of by the laser.

Other important data learned from the study is that when treated with a laser DIRECTLY under the macula, 20% of patients lost 6 lines of vision compared with 37% who did not receive treatment when measured after a 2 year period. This is a difficult situation for both the patient and the doctor because treating with the laser under the macula causes immediate vision loss. This permanent and immediate loss of vision is a difficult choice to make even though studies show that a much higher percentage of patients will be worse after 2 years if not treated. This is not an easy or satisfying choice for the patient or doctor.

Subsequent studies led to the following - If a patient has a large vessel under the macula and has good vision, the vessel should be left alone (and not treated with laser). If it is a large blood vessel and the patient has poor vision, it probably won’t help to treat it. If a person has a small vessel with good vision, it probably should be left alone. However, if the patient has a small vessel, and has reduced vision in that eye, it should probably be treated with laser because the size of the blind spot or scatoma can be kept from getting larger.

Also studied were patients who had the wet form and then later have another reoccurrence of abnormal blood vessel growth (55% of all patients can have this reoccurrence within 3 years). Many times this reoccurrence of new blood vessels happens within the first six months - the analogy is sometimes used that it is like the weeds in the garden, if you don’t get the roots, they grow back. Again, findings showed that if it was a small membrane in a reoccurring vessel, under the center of vision, it should be treated to keep the blind spot from getting larger.

But, because treating vessels in the center of vision is frustrating for the patient and not so successful for the doctor, this has spurred on new studies and new research to find better answers for patients who have this abnormal blood vessel growth under the macula.

Some of the New Treatments for Wet Macular Degeneration Show Promise
Over the last year there has been a lot of activity surrounding several drugs in a procedure called photodynamic therapy (PDT). This therapy is for the wet form of Macular Degeneration and it holds promise for those who can “catch” the degeneration early and before it reaches the discaform scar stage.

How Does Photodynamic Therapy Work?
Photodynamic Therapy involves using a drug which is injected into the arm and then travels through the body, into the eye, and binds only to the abnormal blood vessels (the drug binds to abnormal LDL proteins expressed in high concentrations in the abnormal blood vessels). This characteristic of binding only to abnormal blood vessels and not to the normal vessels helps it aim its effectiveness at the diseased tissue while not harming the normal tissue.

Once the ingredients of this “smart bomb” have done their job, the process of the therapy continues by shining a low energy ( a non-harmful laser) into the center portion of the retina thereby activating the ingredients in the drug. That is, the light passes through the retina and to the underlying abnormal blood vessel to make the vessel clot or involute, thereby stopping the leakage and sparing the healthy retina from damage. The effectiveness of the treatment works only in the area where the light has been aimed or exposed.

One of the first drugs to be studied and recently approved by the FDA is called Visudyne. In the first year of the Visudyne clinical trials, the studies showed that 61.4% of patients treated remained stable or improved, versus 45.9% who were not treated. (Stable or improved vision was categorized as zero to 3 lines of lost vision on the eye chart).

There were many groups studied in the Visudyne trials, that is, a treated group versus a control group. In each sub-group, those treated with Visudyne always showed a stronger tendency toward stabilizing or improving versus those who were not treated.

Other positive signs were that there were no harmful side effects seen from this treatment, although people must stay out of the sun for several days after the treatment. However, studies showed that patients had to return for treatment approximately every three months as new vessels begin to grow back over time. So as you can see, Visudyne is not a cure, nor does it stop it completely, but it may be an important first step in helping to catch and minimize the effects of the early stages of the wet form of Macular Degeneration.

One negative factor about Visudyne, however, may be its price. A single dose of Visudyne is $1288.00. This indeed is expensive, especially if someone has to have the treatment three or four times per year. Hopefully, Medicare and other insurance companies will see the importance of helping to pay for the Visudyne treatment, but at this point it is still uncertain as to whether it will be covered. On a promising note, some of the new data about Visudyne, beyond the first year of study, shows that patients may not have to be retreated as often the second year as they do the first.

Who is a Candidate for Photodynamic Therapy (PDT)?
Those who are candidates for PDT must have the wet form of Macular Degeneration and be at the early stage of the disease, (i.e., they haven’t formed a discaform scar).

In addition, the new blood vessels must be DIRECTLY under the macula (otherwise, conventional laser would be used if the leaky vessels were off to the side), AND they also must be of the classic CNV type (see above). People who showed primarily occult CNV were not helped by PDT. It is important to understand that the treatment of choice away from the macula will still be the conventional laser therapy. But, those who have blood vessel growth directly under the macula, either as a new vessel or a reoccurring growth of blood vessels, are candidates for PDT. In studies, however, it showed that those with new blood vessel growth did better with photodynamic therapy than those who had a reoccurrence of abnormal blood vessel growth and were then treated with PDT.

There are some new drugs that are being studied that also show promise in the area of photodynamic therapy. One drug called PhotoPoint or Purtlyn by Miravant Pharmaceuticals is currently in phase III clinical trials and is showing much promise. The phase II results showed a little bit better outcome than Visudyne, (perhaps less frequent treatments were needed), although more studies need to be done. PhotoPoint has not yet been approved by the FDA as of June 30, 2000.

Patients treated with Visudyne or with PhotoPoint showed a complete stoppage of the leak after a one week period. This complete occlusion of the vessel with PDT shows promise; however, over time as we mentioned, the blood vessels begin to grow back. For some, the blood vessels did not grow back as large the second time, and after a second treatment the patients could see better. However, for some, the vessel actually grew back larger than the original vessel, causing a drop in vision. This photodynamic therapy is a big area of active research and, actually, there are many more drugs currently being tested in animal models that may prove to be even more effective in years to come.

There may also be a role for other therapies to be used in conjunction with photodynamic therapy. For instance, perhaps radiation therapy could be used after the patient has undergone photodynamic therapy to keep new blood vessels from growing back. This type of approach is new and is currently under investigation. Another ongoing study uses this same approach, in that a patient would receive PDT, and then after the blood vessel leakage was stopped (in a week’s time or so), they would receive a steroid injection called anecortave, ( manufactured by Alcon Pharmaceuticals). This is a specially designed steroid molecule that is fairly potent at stopping abnormal blood vessel growth yet is modified for the eye so it does not cause glaucoma or cataracts.

What About Those With the Occult Form Of CNV?
Despite all of the new optimism regarding photodynamic therapy, there are still over 50% of patients who do not qualify for PDT because of occult vessels and not having classic CNV. There are, however, new studies being done on a procedure called transpupillary thermotherapy or TTT for short.

What Is TTT?
Transpupillary thermotherapy is a very recent idea that is being studied to help people who cannot benefit from laser or photodynamic therapy but who have CNV of the occult type. The concept of how this therapy works is that it uses infrared laser at low energy for a long duration. It is a localized hypothermia or warming in the abnormal blood vessel. That is, it heats the blood vessel but does not cause a thermal injury.

Of the first small group that was studied and treated with TTT, 19% of those eyes treated showed a 2 line or better improvement. 56% were stable, 25% went down 1 line of vision or more. 94% saw reduced leakage and there were no side effects. These TTT studies are currently in Phase II and Phase III clinical trials and would of course be of help to many who fall into this occult CNV category, where there has not been any other treatment available. If the treatment shows promise, it could also be used in conjunction with other therapies such as the new steroid injection, radiation therapy or other treatments that may play a role in attacking these abnormal blood vessels. Thus, patients could gain a long term edge and not lose vision over time. The next several years show great promise in these areas and we look forward to keeping you abreast of the progress that is being made.

Article by Thomas B. Perski, M.A.

Special acknowledgment to the following individuals who contributed:
Henry L. Hudson, MD Retina Centers, P.C., Tucson, AZ
Richard A. Lewis, MD Baylor College of Medicine, Houston, TX


Updated Information About RheoTherapy Now Known as Rheopheresis

OccuLogix Corporation
OccuLogix Corporation is a biomedical technology company that was established in December of 1996 to develop fundamentally new medical therapies for ophthalmologic diseases initially targeting Age-related Macular Degeneration (AMD).

We have written about RheoTherapy in the past and continue to get many inquires about this therapy for the dry form of Macular Degeneration. Until recently, there had not been good scientific studies done in the U.S. about this treatment. This system of filtering the blood is designed to deplete certain high molecular weight plasma proteins and Lipoproteins from the blood, which are believed to contribute to the development of macular degeneration. This treatment process is now called Rheopheresis blood filtration.

A pilot study has recently been completed at the University of Utah's Health Science Center in Salt Lake City, Utah and will be part of a multi-center study known as MIRA-1 (Multi-center Investigation of Rheopheresis for AMD) here in the U.S.. Although patient numbers were small for the pilot study, there were four patients who actually showed vision improvement, and it was shown that these four patients were in the group that received the treatment, not the placebo. In addition to this study, the "MAC-II" clinical trial has recently begun in Europe.

People Affected with Advanced AMD Needed for National Study

Tufts Medical Center and Tufts University are announcing a national study to conduct an important study of age related macular degeneration.

Johanna M. Seddon, MD, ScM and her research team and colleagues are seeking participants with advanced age-related macular degeneration (AMD) for a study to determine the contributions of both nature and nurture to the development and progression of the disease. This study will include participations with or without a family history of AMD. Results could lead to new ways to prevent and treat this disease, and may help to reduce the burden of blindness for future generations. Your help is needed to make this important program a success.

Patients are eligible if they meet the following criteria: have wet or advanced dry macular degeneration in one or both eyes, diagnosed over age 55, and are English speaking and Caucasian. Participants can be seen locally, and do not have to travel.

There is no experimental treatment and no regular follow-up involved. All materials are kept confidential and for research purposes only.

Please call 1-800-219-9157 if you are interested. Thank you for considering to help; it would be very much appreciated. They hope to hear from you soon!!"

it would be a great help to our recruitment process. Please contact me at 1-800-219-9157 with any questions, if there is a problem with changing this information, or if there is someone else I should contact in regards to this matter.

 

For more information on Macular Degeneration,
visit The Foundation Fighting Blindness at www.FightBlindnesss.org
or e-mail us at MDInfo@blindness.org.

Toll Free Helpline 1-800-683-5555