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Leonard M. Miller School of Medicine at the University of Miami

Eye Care

Macular Diseases

What is the Macula?
What is macular degeneration?
What are the symptoms of macular degeneration?
How is macular degeneration diagnosed?
What are the current treatment options for macular degeneration?
Do vitamins have an impact on the development of macular degeneration?
What about macular degeneration research?
What is a macular hole?
What are the symptoms of a macular hole?

How is a macular hole diagnosed?
What are the treatment options for a patient with a macular hole?
What advantage does Bascom Palmer offer for patients with a macular hole?
What research in being conducted in the United States and at Bascom Palmer Eye Institute on macular holes?
Who are the Macular Specialists at Bascom Palmer Eye Institute?
Other Macular Disease Resources

What is the macula?

The macula is an oval area in the retina on the back of the eye where the photoreceptors are most dense and where the light is focused. The center of the macula is called the fovea. The macula is responsible for the central (or reading) vision. The macula has the greatest concentration of photoreceptor cells, and when the eye is directed at an object, the part of the image that is focused on the fovea is the image most accurately seen.

What is macular degeneration?

In the western world, age-related macular degeneration (AMD) is the leading cause of legal, irreversible blindness among people 50 years of age and older.

  • Dry macular degeneration (atrophic AMD) is the most common form of macular degeneration and can progress to cause severe central vision loss. This disease progresses slowly and most people usually maintain some central vision in at least one eye. The condition always starts as "dry" AMD. "Dry" AMD refers to the slow degenerative process that occurs without any formation of abnormal blood vessels. The recent Age-Related Eye Disease Study (AREDS) demonstrated that the progression of "dry" AMD could be slowed with vitamin supplementation. This study demonstrated the benefits of taking Vitamin C, Vitamin E, beta carotene, and zinc along with copper. Several vitamin preparations containing the appropriate amounts of these vitamins are currently available and we encourage patients with AMD to discuss these various vitamin preparations with their eye care specialist. Previous studies have also suggested that green leafy vegetables may be beneficial and smoking may be detrimental to patients with AMD.
  • "Wet" macular degeneration (exudative or neovascular AMD) is caused by blood vessels growing under the retina in the macula. "Wet" AMD always arises from pre-existing "dry" AMD. These blood vessels leak fluid, protein, lipid and blood. Eventually, if untreated scar tissue forms under the macula and central vision is destroyed. Current treatments approved for "wet" macular degeneration include thermal laser therapy and photodynamic therapy with VisudyneŽ.

Dry Macular Degeneration

Wet Macular Degeneration

Normal Retina

What are the symptoms of macular degeneration?

There is no pain associated with dry or wet AMD. The most common symptom of dry AMD is slightly blurred or fuzzy vision requiring greater illumination to see greater details. Also, an inability to recognize faces at a distance may develop.

As dry AMD progresses, a blurred spot develops in the center of vision. With time, the spot may get bigger and darker, reducing central vision. Often, when dry AMD is limited to one eye patients do not complain of visual changes because of the ability of the other healthy eye to see clearly, allowing for driving, reading, recognizing faces and seeing fine details.

Symptoms of wet AMD may be that straight lines, such as sentences on a page, appear wavy; rapid loss of central vision; and a blurred or blind spot in the center of vision.

How is macular degeneration diagnosed?

If an ophthalmologist suspects a patient of having AMD, he or she may:

  • perform a visual acuity test to measure vision at a distance
  • perform a dilated pupil examination to see the inside of the eye with an ophthalmoscope to check for drusen (tiny yellow deposits on the retina which are the most common early signs of AMD)
  • ask the patient to look at an Amsler grid with a pattern of straight horizontal and vertical lines. To the person with AMD, the lines appear wavy, distorted or missing or a black spot may appear in the center of the grid.
  • perform a fluorescein angiography. During this test, a dye is injected into the arm and quickly travels throughout the blood system. Once the dye reaches the blood vessels in the back of the eye, photographs are taken of the eye. The dye allows the ophthalmologist to detect blood vessels that are abnormal and leaking dye.

What are the current treatment options for macular degeneration?

Currently, treatments for macular degeneration are rapidly advancing and changing approximately every three months. It is anticipated that for the next three to five years, the treatment will be changing all the time. Various treatments are currently available, but most of these treatments are directed at the early stage of wet AMD. Regardless of the treatment therapy followed, patients with advanced dry macular degeneration should check the vision in each eye, one at a time, at least once a day. By staring at the central point on an Amsler grid, patients can help monitor their vision regularly and can detect distortions in vision. These distortions represent the earliest stages of wet macular degeneration.

One treatment for wet AMD is a drug recently approved by the FDA, Macugen (pegaptanib sodium injection).  Patients with wet AMD have high levels of the vascular endothelial growth factor (VEGF) protein in their affected eyes.  VEGF is a protein that causes the abnormal blood vessels to grow, leak, bleed, and damage a part of the retina known as the macula resulting in loss of central vision and interfering with driving, reading and other everyday tasks. Studies published in the New England Journal of Medicine showed that levels of VEGF protein were increased in eyes that developed abnormal new blood vessels, and that VEGF-blocking drugs (Macugen) were able to prevent the growth of these abnormal blood vessels.  Macugen, manufactured by Eyetech Pharmaceuticals, Inc. and Pfizer Inc., is administered by injection into the eye every six weeks in an ophthalmologist's office.  It is the first drug to be approved in a new class of ophthalmic drugs that specifically target the VEGF protein explains Bascom Palmer retina specialist, Philip J. Rosenfeld, M.D., Ph.D.  Rosenfeld, associate professor of ophthalmology, is the principal investigator at Bascom Palmer for the national Macugen Collaborative Trial in which nearly 1,200 patients were enrolled at 117 sites throughout the world for two years.

Another treatment for wet AMD is thermal laser photocoagulation of the abnormal blood vessels. Only 15 percent of patients with wet AMD are eligible for this therapy. Among those treated, the blood vessels continue to grow in about 50 percent of the cases. Overall, this means that laser photocoagulation is really only helpful in about 7-8 percent of patients with wet AMD. When successfully treated, wet macular degeneration is converted back to dry macular degeneration. Over time, there will be continued vision loss, but the outcome is far better than the outcome if the wet AMD was untreated. Laser photocoagulation isn't useful for most cases of wet AMD because the blood vessels are under the center of the macula. If these blood vessels are treated with the hot laser, the center of the macula would be burned and immediate vision loss would result. This has limited the usefulness of laser photocoagulation.

Co-developed by Novartis Ophthalmics, Inc. and QLT Inc., photodynamic therapy, like Macugen, was investigated here at the University of Miami Miller School of Medicine's Bascom Palmer Eye Institute, as well as at other international centers of ophthalmology. The clinical trials designed to establish the therapy's effectiveness have involved more than 900 patients and resulted in FDA approval for this therapy.

Visudyne therapy is based on the platform of technology, photodynamic therapy. It entails a two-step approach designed to affect the abnormal blood vessels in wet AMD:

First, a photosensitizing agent, a new type of drug, is injected into a vein in the arm. The drug circulates throughout the body’s blood vessels, including the abnormal vessels under the macula.

Next, a "non-burning" laser is shined on the abnormal blood vessels, activating the drug.

Step 1
Step 2

The activated drug then selectively affects the abnormal blood vessels without damaging the surrounding retinal tissue. In some cases the therapy stops growth of the abnormal blood vessels and halts the corresponding vision loss.

Despite all these advances, we still do not have effective therapies for the vast majority of patients with dry or wet AMD. For this reason, the best option for many of our patients is to receive low vision training. Whether it is vision loss for conditions such as AMD, glaucoma or diabetes, low vision aids help patients perform normal activities of daily living and lead independent lives. To help facilitate this training, Bascom Palmer Eye Institute has a Low Vision Clinic to assess patients' remaining vision and prescribe appropriate low vision aids.

Do vitamins have an impact on the development of macular degeneration?

The National Eye Institute, one of the federal governments National Institutes of Health, sponsored a major clinical trial called the Age-Related Eye Disease Study whose results were published in the October 2001 issue of Archives of Ophthalmology. Scientists found that high levels of antioxidants and zinc may reduce the risk of losing vision in the future from age-related macular degeneration. Click here for greater details, including the dosage formulation and information for smokers.

What about macular degeneration research?

There is much more that needs to be done to slow the progression of both dry and wet AMD, and even restore vision in patients with this disease. For those patients with wet AMD, there is significant hope in the very near future. Ongoing clinical research is investigating new treatment strategies using photodynamic therapy in the hope of saving much more vision in many more patients. These studies are underway and the preliminary results are very encouraging.

One of the newest strategies that holds promise is the use of new drugs that stop blood vessels in wet AMD and can cause existing blood vessels to regress. This new class of drugs is known as anti-angiogenic agents. At Bascom Palmer Eye Institute, we are currently investigating six such drugs. Three drugs are being investigated for the treatment of AMD and three drugs are being investigated for the treatment of diabetes.

The most promising anti-angiogenic drugs are being investigated in patients with wet AMD. These drugs are injected either around or into the eye. The names of these drugs are rhuFab V2 (Genentech, Inc.), Avastin (Genentech, Inc.) and Anecortave acetate (Alcon Research Ltd.). Ophthalmologists are optimistic about the preliminary results using these drugs, but it is important to understand that these drugs are only available to patients participating in a clinical study.

Recently, Bascom Palmer announced early results from the Systemic Avastin™ for Neovascular Age-Related Macular Degeneration (SANA) Study. Avastin™ was shown to substantially reduce the leakage from abnormal blood vessels in eyes of patients with neovascular (wet) age-related macular degeneration (AMD).  Within 1 week, vision improvement occurred in patients treated with Avastin™, a drug designed to inhibit angiogenesis, the body’s process of making new blood vessels. Avastin™ is given through an intravenous infusion.

The SANA study results were presented at the Macula Society meeting in Key Biscayne, Florida.  The Macula Society is an international association of retinal specialists dedicated to the dissemination of the most advanced scientific information in retinal vascular and macular diseases. The presentation highlighted the outcomes in the first 9 patients treated with Avastin™ through 3 months. Overall, average vision improved in both eyes since most of the patients had wet AMD in both eyes.  At the beginning of the study, one eye of each patient was designated as the “study eye” and the other eye as the “fellow eye”.  At 3 months, the average vision improved just over 2 lines in the “study eyes” (p=0.008) and just over 3 lines in the “fellow eyes” (p=0.001)as measured by the number of letters used on a standard eye chart  The improvement in vision correlated with a decrease in the leakage of fluid from the abnormal blood vessels in these eyes.

“A potential advantage of Avastin™ over other therapies for wet AMD is that vision improvement can occur within 1 week of treatment,” said Philip J. Rosenfeld, M.D., Ph.D., associate professor of ophthalmology at Bascom Palmer Eye Institute and the principal investigator of this Bascom Palmer clinical trial.  “In addition to the improved vision, Avastin™ causes a reduction in leakage from the abnormal blood vessels, and we observed a restoration of normal macular anatomy.” Avastin™, also known as bevacizumab, is manufactured by Genentech Inc., and presently approved by the FDA for the treatment of patients with metastatic cancer of the colon or rectum when used in conjunction with 5-FU based chemotherapy.

Patients with macular degeneration are thought to have elevated levels of vascular endothelial growth factor (VEGF) in their affected eyes.  VEGF is a protein that causes abnormal blood vessels to grow, leak, bleed, and damage the macula resulting in vision loss.  New anti-VEGF drugs work by blocking this protein and the formation of abnormal blood vessels that grow in the eye.

“We’ve been injecting anti-VEGF drugs into the eye for the past 3 years with very encouraging results.  It’s not surprising to us that a drug with the same mechanism of action would work when given as an intravenous infusion,” said Rosenfeld.

“This isn’t a cure and it’s not the right treatment for everyone with wet AMD.  Some people would rather have an injection in the eye than worry about the risks from a systemic drug.  What this offers us is a new potential option for patients with wet AMD.  It also provides us with additional evidence that VEGF is the major factor responsible for blood vessel growth and vision loss in wet AMD.”

Treatment for AMD traditionally included thermal laser photocoagulation therapy and photodynamic therapy.  Although neither treatment is a cure for wet AMD each treatment may slow the progression of vision decline or stop future vision loss.  While these therapies are effective for certain types of wet AMD, pharmacotherapy (drug therapies) represents the new era in macular degeneration treatment.

While Avastin™, approved by the FDA in February 2004, was the first drug that targets the VEGF protein, the FDA approval was for the treatment of metastatic colorectal cancer. Avastin™ is not approved for the treatment of macular degeneration. Macugen®, approved by the FDA in December 2004, is the first ophthalmic drug approved for the treatment of macular degeneration that specifically targets the VEGF protein.

“Funded by the Macular Degeneration Research Fund at the Bascom Palmer Eye Institute, the SANA study would not have been possible without the generosity and financial support of grateful patients,” said Rosenfeld. At this time, only 18 patients have been treated, but all the patients have done very well and, at this time, their wet AMD is resolving. “We don’t know how many treatments will be needed,” Rosenfeld said. “In this study patients were treated twice or three times over a twelve week period.  As most patients commonly get wet AMD in both eyes, an added advantage of this therapy is that both eyes can be treated with a single infusion into the arm.

A large multi-center trial is needed to determine the true safety and efficacy of this drug, but despite the small number of patients and the short-term follow-up in the SANA Study, these preliminary results are promising. “I hope we can organize a larger trial with retinal specialists around the world who appreciate the importance of these findings,” said Rosenfeld.

Other treatments and experimental therapies currently in development for AMD require an injection into the eye while Avastin™ is given systemically.  As a result, there are no apparent intraocular complications that arise from treatment with Avastin™ therapy.  However, Rosenfeld added “the potential disadvantage of Avastin™ is that it is a systemic therapy with the risk of systemic side-effects.  The most significant risk we observed in the SANA Study was the risk of elevated blood pressure, but this was easily controlled with medication.”  However, the FDA has issued an updated warning for Avastin™ in cancer patients receiving chemotherapy plus Avastin™ (http://www.fda.gov/medwatch/SAFETY/2005/Avastin_dearhcp.pdf).  In these patients, there was an increased risk of thromboembolic diseases such as stroke and heart attack.  The risk of thromboembolic events in cancer patients was approximately two-fold higher in patients receiving infusions of 5-fluorouracil based chemotherapy plus Avastin™ compared with patients receiving chemotherapy alone, with an estimated overall rate of up to 4.4%.  “We don’t know the true risk of Avastin™ in elderly AMD patients, and further study is necessary to determine these risks,” Rosenfeld said.  “Also, cancer patients receive Avastin™ every 2 weeks for many months while our patients initially received only 2 or 3 doses of Avastin™ given 2 weeks apart.  Only 2 treatments were sufficient to dry up the leakage in the eyes of wet AMD patients and the treatment benefit lasted for at least 3 months. However, we are very concerned that physicians will attempt this therapy without taking necessary precautions, and for this reason, we must conduct a larger clinical trial to determine if the benefits of Avastin™ therapy outweigh the risks.”

For those patients who have experienced vision loss and are stable, there is a new low vision device that is undergoing clinical investigation at Bascom Palmer Eye Institute. This device is known as an intraocular miniature telescope (IMT) and is inserted into the eye at the time of cataract surgery. While this device may not help all patients with AMD, there is a very good chance that the IMT could improve the ability to read and watch television. To determine if you are a candidate, you should contact your ophthalmologist.

All of our treatments, so far, are designed to treat the vision loss associated with wet AMD and slow the progression of the disease. None of the therapies, really treat the underlying cause of AMD. While we do not yet know the cause, we do know this is a disease with a strong genetic basis. For this reason, Bascom Palmer Eye Institute is trying to find the genes responsible for AMD in the hope of someday developing a cure. To achieve this goal, we need the help of any family where one or more family member is affected with AMD. We are years away from developing a successful therapy based on genetic information, but the basis for this therapy begins with the genetic research currently underway and the help of families with AMD

What is a macular hole?

As people age, the vitreous gel in the eye shrinks and pulls away from the retina. Usually this occurs without consequence, however, in some cases where the vitreous is attached to the macula, it can result in the formation of a macular hole. Fluid may leak under the edges of the hole, causing a microscopic retinal detachment, which results in blurring and distortion of vision.

What are the symptoms of a macular hole?

A macular hole can cause blurred or distorted vision. A hole that goes all the way through the macula can result in significant loss of central vision.

How is a macular hole diagnosed?

An ophthalmologists who suspects a macular hole may:

  • perform a visual acuity test to measure vision at a distance
  • perform a dilated pupil examination to see the inside of the eye with an ophthalmoscope
  • perform a fluorescein angiography. During this test, a dye is injected into the arm and quickly travels throughout the blood system. Once the dye reaches the blood vessels under the retina, a color photograph is taken of the eye. The dye allows the ophthalmologist to detect blood vessels that are leaking dye.

What are the treatment options for a patient with a macular hole?

Current treatment options for macular holes are limited to vitrectomy with an internal tamponade. The most commonly used procedure involves using a long-acting gas. During the surgery, the ophthalmologist will remove the vitreous gel from the eye so that it is no longer pulling on and distorting the macula. The vitreous gel is replaced with a bubble containing a mixture of air and gas or even silicone oil can be used. The long-acting gas acts as an internal, temporary bandage that holds the edge of the macular hole in place as it heals, though it prohibits the patient from traveling by air for at least six weeks. Under extenuating circumstances a shorter acting gas or the silicone can be used to possibly reduce or eliminate the prohibition of air travel. They physicians at Bascom Palmer believe the shorter acting gas and silicone oil do not offer quite as high success rates, but they are substantially successful. In order to maximize the effect of the repair, the patient is usually required to remain in a face down position for one week postoperatively to allow the bubble to press against the macula and seal the hole. While Bascom Palmer physicians believe that strict, continuous positioning enhances success rates, substantially high rates are obtained even in patients who are unable to maintain this position. The bubble will gradually be reabsorbed by the eye within a few weeks following surgery. As the bubble is reabsorbed, the vitreous cavity refills with a naturally produced fluid.

Currently, it is customary to peel the internal limiting membrane during surgery, as this may remove an impediment to healing the hole, and possibly even stimulate healing. This issue is controversial and studies of its efficacy are ongoing.

What advantage does Bascom Palmer offer for patients with a macular hole?

Bascom Palmer Eye Institute surgeons were among the first to perform macular hole surgery, dating back to 1991. Much of the framework of knowledge of pathogenesis, diagnostic methodology, and classification was laid at this institute. Because of this early experience, we continue to perform treatment on a high volume of patients. This allows us to make observations and conclusions regarding the most effective treatment modifications relatively rapidly.

What research in being conducted in the United States and at Bascom Palmer Eye Institute on macular holes?

Research is currently aimed at efforts to improve the 90+% success rate even more, and in a more convenient way to the patient. This is through ongoing surveillance of success in clinical series. Bascom Palmer Eye Institute conducts such series similarly to many other study centers in the country.

Who are the Macular Specialists at Bascom Palmer Eye Institute?

Thomas Albini, M.D.
John G. Clarkson, M.D.
Janet L. Davis, M.D.
Sander Dubovy, M.D.
Harry W. Flynn, Jr., M.D.
Jaclyn L. Kovach, M.D.
Geeta Lalwani, M.D.
Wen-Hsiang Lee, M.D.
Andrew A. Moshfeghi, M.D.
Timothy G. Murray, M.D., M.B.A., F.A.C.S.
Philip J. Rosenfeld, M.D., Ph.D.
Stephen Schwartz, M.D.
William E. Smiddy, M.D.

Other Macular Disease Resources

AMD Alliance International
American Academy of Ophthalmology
Eye Resources on the Internet
Foundation Fighting Blindness
Macular Degeneration Partnership
National Eye Institute
Prevent Blindness America
Research to Prevent Blindness

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