For More Information on Age-Related Macular Degeneration see the following documents below:
This section is intended to educate patients and their families about macular degeneration, its treatment and low vision rehabilitation. Macular degeneration is the most common cause of severe visual loss in people over the age of 50. Over 8 million people in the United States alone have some form of this disease.
The term “macular degeneration” includes many different eye diseases, all of which affect central, or detail vision. Age-related macular degeneration is the most common of these disorders, mainly affecting people over the age of 60. Although age-related macular degeneration is the primary focus of this article, much of the information also applies to the other types of macular degeneration.
We hope that this article increases your understanding of macular degeneration and enhances your communication with your ophthalmologist and other health-care providers.
Age-related macular degeneration is an eye disease that primarily affects the central portion of the retina known as the macula. The risk for developing macular degeneration increases with age and is in excess of 30% by age 75. Other risk factors include: a family history of the disease, cigarette smoking, diet, excessive sunlight exposure, hypertension and cardiovascular disease.
This photograph shows a normal, healthy retina as viewed by an eye doctor during an examination. The ophthalmologist will pay careful attention to the appearance of the macula and fovea when examining the retina.
The majority of people with macular degeneration have an early form of the condition and experience minimal visual loss. For many of these people, macular degeneration will not progress to a more serious condition.
In the early stages of macular degeneration, the transport of nutrients and wastes by the RPE slows down. As waste products accumulate under the retina, they form yellowish deposits called drusen.
In the healthy retina, a layer of cells called the retinal pigment epithelium (RPE) supplies the photoreceptors with nutrients and pumps out the waste products created as the photoreceptors convert light into nerve signals.
An eye doctor examining a patient at this stage may note the presence of these drusen, even though most people have no symptoms. When drusen have been noted on examination, monitoring will be needed over time, although most patients will not progress to develop visual loss. Many people over the age of 60 will have some drusen.
A portion of people with drusen may begin to experience mild visual loss. At this point, macular degeneration may progress in one of two ways. These two types of degeneration are known as the dry (atrophic) and the wet (exudative) forms of the disease.
This retinal photograph shows numerous yellow drusen in and around the macular region of the retina.
Dry (atrophic) macular degeneration is a slowly progressive condition characterized by the accumulation of drusen in the retina with some visual loss. Dry macular degeneration alone rarely causes severe visual impairment or blindness.
As portions of the RPE continue to slow down the transport of nutrients and wastes, the overlying photoreceptors become damaged. The size and number of drusen in the macula increase. Vision may be affected as RPE and photoreceptor cells are lost due to atrophy.
This retinal photograph shows many drusen in the macula. These drusen are typical of dry macular degeneration.
In dry macular degeneration, waste products from the photoreceptors accumulate underneath the retinal pigment epithelium (RPE). The wastes appear as yellowish spots called drusen.
The visual changes in dry macular degeneration correlate with the loss of function of corresponding areas of the retina. Occasionally, a large region of cells will be lost. This is called “geographic atrophy” and produces a blind spot in the central portion of vision. This blind spot is called a scotoma.
If you have macular degeneration, it is essential that you report any changes in your vision to your eye doctor immediately. Careful self–monitoring with the Amsler grid and regular examinations by an eye doctor are critical to preserving your vision. This is because some people with dry macular degeneration will develop the more severe “wet” form of the disease.
This retinal photograph shows geographic atrophy in the macular region resulting from advanced dry macular degeneration.
Aside from vitamin therapy and controlling your risk factors, there is no proven prevention or treatment for the dry form of macular degeneration. Fortunately, the majority of people who have reached this stage of macular degeneration will not progress to the more serious “wet” form.
Wet (Exudative) Macular Degeneration
For reasons that are not fully understood, a minority of people with macular degeneration develop a more serious form of the disease. People with large “soft” drusen (drusen with indistinct borders), many drusen that run together, or focal pigmentation are at greater risk for developing the wet (exudative) form of the disease.
In the wet form of macular degeneration, new blood vessels begin to grow underneath the retina. The proliferation of these new blood vessels is called choroidal neovascularization, or CNV.
In a variant form of the disease, the new blood vessels may begin within the retina and grow toward the choroid layer. This form is called retinal angiomatous proliferation, or RAP. Another variant is called polypoidal choroidal vasculopathy, or “polypoidal.” The polypoidal vessels in this condition tend to cause extensive bleeding under the retina.
In wet macular degeneration, new blood vessels grow underneath the retina in a process called choroidal neovascularization, or CNV.
It is believed that the diseased retina stimulates the production of these new blood vessels in response to a decreased supply of nutrients and slow transport of wastes. Unfortunately, new blood vessels do not improve the health of the retina. Instead, they often leak blood or fluid into the retina.
This retinal photograph shows fluid and blood beneath the retina, which suggests the presence of choroidal neovascularization (CNV).
As CNV continues, the new vessels may leak blood or fluid under the retina, causing the retinal surface to become uneven. As a result, objects in that portion of your visual field may appear wavy or distorted. The neovascularization may even break through some of the retinal layers. Blind spots may appear in your vision if portions of the retina become damaged by the CNV.
Often, the first sign of fluid under the retina is distortion of straight lines. Just as in a camera, if the film is not lying flat, images will be distorted. Since these changes can be subtle, regular testing with the Amsler grid can be helpful in the early detection of problems.
As the surface of the retina becomes uneven, objects in your vision may appear blurred, wavy, or distorted. As the condition progresses, blind spots may appear.
Any change in the appearance of the grid may be a sign of choroidal neovascularization and should prompt a visit to the eye doctor. If caught early enough, the CNV might be treatable before it causes too much damage.
The first indication of fluid under the retina may be a distortion of straight lines. The Amsler grid test is an important tool for the early detection of any changes in your vision.
Eventually, areas of neovascularization and leakage can lead to the death of the overlying photoreceptors and scarring of the macula. Scarring is the final stage of macular degeneration, and it frequently results in significant visual loss.
It is important to realize that this entire process occurs only in the macula, and affects only central, or detail vision. Peripheral, or side vision is rarely affected by macular degeneration. While macular degeneration is the leading cause of legal blindness, it rarely leads to total blindness.
Legal blindness means the vision is 20/200 or worse in the better eye even with corrective lenses or that the peripheral visual field is restricted sufficiently to cause tunnel vision.
This retinal photograph shows a large yellow scar in the macular region resulting from advanced CNV. A person with this type of scarring would experience a significant loss of vision in that eye.
Examination & Diagnosis
A thorough examination by an eye doctor is the best way to determine if you have macular degeneration or if you are at risk for developing the condition.
The exam begins by testing your visual acuity or the sharpness of your vision. There are several different tests for visual acuity. The most familiar one has lines of black letters on a white chart.
Next, your eyes may be tested with an Amsler grid. This test helps your doctor determine if you are experiencing areas of distorted or reduced vision, both common symptoms of macular degeneration. If you do have macular degeneration, your doctor will use the Amsler grid to determine if your vision has changed. Your ophthalmologist may provide you with a small version of the Amsler grid such as the Yannuzzi card to carry with you in your purse or wallet.
After these visual tests, the front part of your eyes will be examined to determine if everything is healthy. Your doctor may put anesthetic drops in your eyes before measuring the pressure in each eye.
After, drops are administered, which cause your pupils to dilate. This will allow your doctor to examine the retina through the enlarged pupil. The drops typically take between 20 and 45 minutes to work, and will wear off in about 4 hours. While the pupils are dilated, it is usually difficult to read, and bright lights may be uncomfortable. Some patients use sunglasses after dilation to reduce light sensitivity.
After the dilating drops are administered and allowed time to work, the eye doctor will seat the patient at a device called a slit lamp. The slit lamp is a special microscope that enables the doctor to examine the different parts of the eye under magnification. When used with handheld lenses or special contact lenses, the slit lamp gives the examiner a highly magnified view of the retina.
The slit lamp is a microscope that gives the examiner a magnified view of the retina. Your doctor will look for drusen and other areas of the retina that appear suspicious or abnormal. Since choroidal neovascularization (the new blood vessel growth found in the “wet” form of macular degeneration) occurs beneath the retina, the blood vessels themselves are not usually visible. But the examination can reveal clues such as: bleeding, elevation of the retina, or fluid behind the retina, which suggest the presence of choroidal neovascularization (CNV). In these cases, further testing may be necessary.
This retinal photograph shows many drusen and fluid under the retina, suggestive of choroidal neovascularization. Additional testing will be required for complete diagnosis and treatment.
A technique called angiography is the most useful test for determining the presence of choroidal neovascularization (CNV). The procedure is painless and very safe. The patient will be seated at a fundus camera, which takes pictures of the retina. A small IV catheter is inserted into a large vein, usually in the arm. Several pictures are taken at this time.
The fundus camera takes pictures of the fundus, or retina. The camera may use film, or it may display the images on a computer screen.
A small IV catheter is inserted into a vein for the injection of fluorescein or ICG dye.
Then, a dye is injected into the vein. The dye circulates throughout the blood vessels of the body. As the dye enters the blood vessels of the eye, a series of photographs is taken of the retina. Special filters make the dye stand out against the background of the retina.
By looking at the pattern of the blood vessels and observing whether dye leaks from any of the vessels as time passes, your ophthalmologist can locate sites of choroidal neovascularization if they are present.
Two dyes are commonly used in ophthalmology: an orange dye called fluorescein and a green dye called indocyanine green. These dyes are different than those used for angiograms of the heart or brain. Unlike an angiography used in other parts of the body, X-rays are not used in this procedure since the examiner can look through the pupil and see the blood vessels directly.
This fluorescein angiogram shows choroidal neovascularization (CNV) in the macula. The bright area indicates dye leaking from the neovascular vessels.
The majority of treatable CNV can be seen with fluorescein dye. Fluorescein angiography is an extremely safe procedure, and it has been performed in millions of patients for over 25 years. The overwhelming majority of patients experience no symptoms when the dye is injected. A small minority may feel flushed or briefly nauseated. Rarely, someone has an allergy to fluorescein and may experience itching or other symptoms that require treatment.
Sometimes, an area of CNV is not clearly defined, or it may be obscured by overlying fluid or blood. In these cases, it is sometimes helpful to perform the angiography using a different dye called indocyanine green. As its name implies, this dye is bright green in color, and is useful for visualizing deeper blood vessels. Side effects from indocyanine green dye are rare, and are similar to those from fluorescein. Indocyanine dye does contain a form of iodine, so patients allergic to iodine should tell their doctors.
This ICG angiogram shows a bright area of CNV in the macula. The CNV was not visible with fluorescein dye because of abnormal fluid beneath the retina.
Optical Coherence Tomography
An OCT device is used to map the anatomy of the retina.
Optical Coherence Tomography (OCT) is a new technique for imaging the retina. It is a non–invasive test which records the features of the retina and displays this information as cross-sectional views, or optical “slices.” For this procedure, the patient is seated at the OCT device.
Laser light is used to map the anatomy of the retina, and the resulting computer images are saved for analysis. OCT evaluations are not a replacement for angiography, rather they are complementary techniques.
This is an OCT image of the macula of a normal, healthy eye. The depression in the center is the fovea. The colors in the OCT image represent the different layers of the retina. Note how smooth and even the layers are.
This is an OCT image of the macula in an eye with wet macular degeneration. The affected tissue layers beneath the retina are no longer smooth and flat.
Autofluorescence imaging of the retina is a new technique which involves capturing a response from molecules in the retinal pigment epithelium (RPE). There are two ways to capture these images. One uses a specialized scanning laser, and the other uses special filters attached to the fundus camera. Both types are noninvasive. The images show areas of stress and damage to the retina and can be used to monitor these changes over time.
This is an autofluorescence image of the retina in a normal, healthy eye. The macula is at the center.
This is an autofluorescence image of the retina in an eye with dry macular degeneration. The dark spot in the center shows a large area of atrophy in the macular region.
This is an autofluorescence image of the retina in an eye with wet macular degeneration. The image shows neovascularization underneath the macula.
Since the year 2000, photodynamic therapy has been used to treat some forms of wet macular degeneration. This treatment couples a laser with a light-sensitive drug to destroy leaking blood vessels in the retina.
To begin the treatment, a special light-sensitive drug is infused into a vein in the arm and allowed to circulate throughout the body. In the bloodstream, the drug attaches itself to molecules of low–density lipoprotein, or LDL.
Photodynamic therapy is an experimental treatment that combines low-level laser treatment with a light-sensitive drug. The drug is infused into the arm much like the dyes used in angiography.
Inside the retina, the abnormal blood vessels attract and absorb LDL. Since the drug is attached to the LDLs, it also accumulates inside the abnormal vessels. With time, the drug is cleared from the normal nearby blood vessels.
The injected drug accumulates in the abnormal blood vessels.
Next, eye drops will be used to numb the eye, and a special contact lens is placed on the eye to focus the laser. At this point, low intensity laser energy is directed through the contact lens, onto the area of choroidal neovascularization (CNV).
Low intensity laser energy is applied to the area of CNV. The laser destroys the abnormal vessels where the light-sensitive dye is concentrated, sparing the overlying retina.
The laser energy activates the drug concentrated in the abnormal blood vessels, causing them to close and stop growing. Using this low-intensity laser spares the overlying retina from damage. In some cases, your ophthalmologist may also inject a steroid into the treated eye. The steroid reduces inflammation and swelling.
Usually, the whole procedure takes less than 30 minutes. When you go home afterwards, and for the next 5 days, you do have to be careful to not expose yourself to direct sunlight or other bright lights before the drug is cleared from your system.
Several sessions of photodynamic therapy are typically required to control the neovascular growth. It is common for patients to have three or four treatments in the first year and two treatments during the second year. Your ophthalmologist will use angiograms and/or OCT imaging of your retina to determine if additional treatments might be beneficial. The goal of treatment is to stabilize your vision. Your ophthalmologist will discuss the risks, benefits, limitations and alternatives for your particular case.
After preparation, the eyelids are pulled back and Macugen is injected into the vitreous body of the eye.
Macugen is the first drug therapy for wet macular degeneration, approved late in 2004. Treatment with Macugen aims to block the stimulus of blood vessel growth in order to stabilize vision.
In wet macular degeneration, new blood vessels grow in the choroid layer underneath the retina. Growth of these new, leaky vessels is stimulated by proteins known as Vascular Endothelial Growth Factor, or VEGF.
To control the growth of the leaky blood vessels, a drug called Macugen is injected directly into the vitreous body of the eye. The drug then diffuses throughout the retina and choroid. Your ophthalmologist will take precautions to minimize the risks of injection.
Inside the eye, Macugen binds strongly to the abnormal VEGF proteins it comes in contact with. This prevents the VEGF molecules from stimulating further blood vessel growth and leakage.
Over a period of weeks, Macugen is slowly absorbed into the circulatory system, and excreted from the body. In order to keep an adequate amount of medicine in the eye, injections are repeated every 6 weeks. Initial studies show that a course of therapy of one or two years may be necessary to stabilize vision in most patients.
Macugen attaches to VEGF molecules in the retina and choroid, preventing them from stimulating more abnormal vascularization.
Lucentis is another drug that blocks VEGF. Like Macugen, treatment with Lucentis involves injecting the drug into the vitreous body of the eye. As it diffuses throughout the back of the eye, the drug comes in contact with VEGF proteins in the damaged area of the retina and choroid. Lucentis binds to the VEGF proteins, preventing them from stimulating further blood vessel growth and leakage.
In the early stages of treatment, injections are repeated every 4 weeks. Lucentis is the first drug to offer hope of improvement in vision for some patients while stabilizing vision in the majority of patients.
Other drugs which target the production of VEGF, the circulation of VEGF, or the receptor for VEGF are currently under investigation in preliminary clinical trials. Research is also underway to develop better methods of delivering drugs to the eye to reduce the need for frequent injections.
Before the approval of Lucentis, retinal specialists had started using a related drug called Avastin (bevacizumab), hich was not approved for ocular use but was available for cancer treatment and was chemically related to Lucentis (both drugs are made by the same company Genentech). The results that retinal specialists have seen with Avastin (which is now in use worldwide for AMD) appear to be similar to the results seen with Lucentis. There has been a great deal of media attention to both of these drugs because although they may both help in AMD, they have very different costs. Lucentis is expensive and Avastin is very inexpensive. Both drugs are now covered by insurance plans for the treatment of wet AMD. However, only Lucentis has been approved for use in this indication (so far). The National Eye Institute has initiated a study which will compare these two drugs to each other which should help retinal specialists advise patients in an informed way.
There are potential risks and benefits of these varied drug options which a retinal specialist would discuss with an AMD patient before helping him or her to decide which treatment is best for his condition.
This is an exciting and hopeful time for patients and their doctors. Macular degeneration is now receiving the attention it has long–deserved. With a vast amount of ongoing research, we expect to see continued progress in treating this disease in coming years.
The thermal laser used for this surgery emits a series of precisely controlled beams of light energy. Only minimal discomfort is felt as several pulses of laser light are directed at the CNV.
One treatment for wet macular degeneration uses a thermal laser to coagulate the CNV and stop it from spreading. In some cases, the area of involvement may be too extensive to treat. Your doctor will discuss with you the risks, benefits, limitations and alternatives in your particular case.
Laser treatment for wet macular degeneration is done on an outpatient basis with local anesthesia (eye drops). To begin the procedure, the patient is seated at a special slit lamp. A lens is placed on the eye to give your ophthalmologist a magnified view of the retina. Next, your ophthalmologist will aim the laser directly at the CNV beneath your retina. Only minimal discomfort is felt as several small pulses of laser light are directed at the CNV.
The laser light passes through the tissues of the retina where the light is absorbed by the CNV and pigmented tissues beneath the retina (RPE and choroid). The absorption of laser energy produces heat, which burns the CNV and some of the surrounding retinal tissues, causing a small scar to form. After treatment, the scarred area will appear as a permanent blind spot in your vision.
The laser light (shown in green) passes through the tissues of the retina. In the area of CNV, the laser energy is converted into heat (white spot). This heat burns the CNV and some of the surrounding retinal tissues.
It is important to realize that laser treatment generally doesn’t improve your vision. Laser treatment is a compromise: a small portion of retina is sacrificed in order to prevent damage to a much larger area which would occur if the CNV were allowed to continue growing. When laser treatment is successful, the scar produced by the laser is smaller than the scar that would have resulted if the CNV had been left untreated.
Before treatment: This fluorescein angiogram shows a well-defined area of choroidal neovascularization (CNV) underneath the macula.
Even if successful, laser treatment treats the CNV but not the underlying disease process of macular degeneration. It is not uncommon for CNV to come back in the future. Following laser treatment is often necessary to use angiography to detect any recurrences of CNV. If new CNV is found, your eye doctor may recommend additional treatment to preserve your remaining vision.
After treatment: This fluorescein angiogram shows the same eye after laser treatment. The CNV beneath the macula has been successfully treated.
Although there are now effective treatments for macular degeneration, there is no cure for the chronic disease process. For this reason and for the hope of better visual results for the patient, many new methods of treatment are being developed and tested. A wide variety of therapies are being considered, including:
We will briefly discuss each of these experimental treatments.
If you look under the retina in an eye that has wet macular degeneration, you will see new, leaky blood vessels growing in the choroid layer.
To control the growth of these new blood vessels, a drug called Retaane is deposited behind the eye. In this procedure, a curved cannula is slid alongside the eye until the end is resting directly underneath the macula.
A curved cannula is slid alongside the eye until the end is resting directly underneath the macula.
The drug is deposited behind the eye, where it is slowly absorbed into the tissues of the retina.
Retaane (shown in green) is deposited just behind the eye, and diffuses into the retina and choroid.
Inside the choroid and retina, Retaane slows the growth of abnormal vessels seen in wet macular degeneration. It helps to keep the tiniest blood vessels of the retina--the capillaries, from breaking down. When these capillaries remain intact and healthy, neovascularization does not occur.
Treatment with Retaane is typically repeated after six months to maintain therapeutic levels of the drug in the retina. In 2006, this drug was in the late stages of testing.
The term “off-label” means using drugs for a purpose for which they were not originally approved. For example, aspirin is used to prevent heart attacks and for blood thinning even though the FDA label did not initially list these specific reasons. Now these reasons have been added to the list of indications.
Physicians may use any available drug to treat macular degeneration, including drugs approved for other reasons. Steroids injected into the eye and Avastin injected into the eye are examples of off-label uses of medications. Your doctor may discuss these drugs as part of treatment.
The initial results of steroids used in combination with photodynamic therapy showed better visual results than would be expected from PDT alone. Several larger trials are underway to confirm these findings.
Avastin is a drug which is related to Lucentis and acts in the same fashion. Avastin was developed to block new blood vessel growth to tumors in patients with cancer. Several reports with a limited number of patients have been published. Your doctor may consider if Avastin might be right for you.
Rheopheresis attempts to remove abnormal circulating proteins from the bloodstream. In this procedure, blood is removed from the veins in the arm and filtered with a machine to remove heavy proteins. The rest of the blood is returned to the bloodstream. This treatment is under investigation in a number of research centers. A small study has indicated there may be some beneficial effects. Larger, controlled trials are ongoing.
Radiation therapy for wet macular degeneration is under investigation in a number of research centers. Because growing blood vessels are sensitive to radiation, it has been suggested that radiation may stop or slow choroidal neovascularization.
It is not yet known if low dose radiation can stop or slow choroidal neovascularization. Several small studies have demonstrated some beneficial effects of radiation while other trials have shown no benefit.
The implantable miniature telescope is a surgical device that magnifies the central visual images on a larger retinal area than normal to improve vision and the quality of life for patients who have lost significant vision. After surgical implantation, patients undergo a visual rehabilitation program.
With the IMT, central vision is projected on the central and peripheral retina.
Submacular surgery attempts to remove abnormal blood vessels (CNV) and/or blood from under the retina.
To begin the surgery, a technique called a vitrectomy is performed. In a vitrectomy, microsurgical instruments are used to remove the vitreous gel from the eye and replace the gel with a saline solution.
For many surgeries involving the retina, the vitreous gel must first be removed from the eye in a procedure called vitrectomy.
Next, a small incision is made in the retina to gain access to the sub-retinal space. Using fine microsurgical instruments, the surgeon will pull the neovascular vessels out from under the retina and remove them from the eye.
Early results using this technique have been somewhat disappointing. Vision is rarely significantly improved and the blood vessels may grow back.
Fine microsurgical instruments are used to remove neovascular vessels from underneath the retina.
In many cases of macular degeneration, it appears that the retinal pigment epithelium, or RPE layer, is the first component of the retina to fail. RPE transplantation attempts to replace diseased RPE tissues with healthy RPE cells.
First, a vitrectomy is performed to remove the vitreous gel from the eye. Then, a small incision is made in the retina to gain access to the sub-retinal space. At this point, RPE cells are injected under the retina.
New RPE cells are injected under the retina to replace atrophied or diseased RPE tissue.
As time passes and the retina heals, it is hoped that these transplanted RPE cells will arrange themselves properly to replace lost or diseased RPE.
This technique is still highly experimental. Although RPE cells can be implanted successfully, the cells may not form the necessary connections with their neighboring cells and tissues. Additionally, rejection of these cells by the body is possible.
Macular translocation is an experimental surgical technique. This technique aims to move the macula when it overlies diseased sub-retinal tissues.
First, a vitrectomy is performed to remove the vitreous gel from the eye. Then, a flap of retina is detached from the underlying tissues, cut and rotated into a new position. The rotated retina is reattached to an area of healthier sub-retinal tissue.
At this time, this experimental technique is associated with a high percentage of serious complications.
Most people with macular degeneration have some drusen, yellow deposits underneath the retina. Some studies have found that low intensity laser treatment causes drusen to shrink and even disappear in some people.
Although this low intensity laser treatment can make the drusen disappear, there is no scientific proof so far that this treatment is beneficial.
These experimental treatments are being studied by numerous researchers around the world. It is hoped that some of these procedures will lead to more effective treatment of macular degeneration in the near future.
Low level laser energy has been found to shrink spots of drusen in some people. Studies are being conducted to determine if this procedure might stabilize or improve vision.
Because macular degeneration results in impaired functioning of the retina, researchers are attempting to bypass the retina using electronics or silicon chips to send signals to the brain to improve vision. Typically, surgery is required to implant the device into position. This type of technology is many years away from helping people with macular degeneration, but it may offer hope for improved visual function in the future.