AMD - Age-Related Macular Degeneration

For those who already know the basics, please refer to an article on

Macular Degeneration on emedicine.com  that has been authored by me and is

updated on a yearly basis.  Emedicine is the premier on-line text book of medicine

that has a review board and is verified by experts prior to being published.

The Eye

        The eye is like a camera. The lens of the eye focuses light against the back wall of the eye. This back wall is called the retina. The retina is like film in a camera. When the focused light falls upon the retina, you see a picture.

The retina is a highly complex structure containing millions of cells. The macula is the central part of the retina and is responsible for central (straight ahead) vision. Macular Degeneration is a disease of the retina affecting sharp vision required to read or see fine detail. Peripheral vision (side vision) is usually not affected.

Macular Degeneration occurs due to a genetic predisposition, poor nutrition or certain medical disorders. For example, persons with high blood pressure are more likely to develop Macular Degeneration.  Usually, Macular Degeneration is associated with aging. Most patients with Macular Degeneration are 50 years of age or older. Thus, macular degeneration is generally called Age-related Macular Degeneration or AMD.

AMD is one of the leading causes of severe, irreversible vision loss.  However, early detection and treatment can prevent severe loss of eyesight. It is very important to have regular retinal examinations, particularly after the age of 50.

Symptoms of AMD

1.          The most common symptoms of AMD are distortion, waviness or smudge-like areas in the central vision. Persons often notice these changes when looking at objects with straight edges, like tiles on the floor. A door frame or building may seem crooked or irregular.  These vision changes are important indicators of possible retinal disease.  If you have such symptoms, you should consult an eye doctor promptly. Your eye doctor will refer you to a retina specialist if necessary.
   
   Sometimes, patients don't notice vision changes until an eye doctor checks each eye separately.  The eye doctor does this by covering one eye while testing vision in the other.  In unusual cases patients have no symptoms at all, and only an eye doctor can discover the disease.
   
   An Amsler grid can be obtained from an eye doctor to check the sensitive central area of the eye.  The grid has vertical and horizontal black lines and can show a patient that his or her vision has become distorted. If you would like to see an Amsler grid, please click here.
   

2. Examination for AMD
   

3.         The retina specialist will examine the eyes with lenses and instruments to find abnormalities. If the doctor sees bleeding, fluid or scarring, he or she will obtain a fluorescein angiogram.
   

4.         During fluorescein angiography, a fluorescent dye (vegetable dye) is injected into a vein in the arm.  This dye does not contain any iodine. When the dye reaches the back of the eye, a special camera takes a rapid series of pictures.  The pictures allow areas of abnormalities to be better seen.
   

5.         Additionally, OCT scanning, a rapid accurate method of measuring the thickness of the retina will also be used to determine the presence of fluid or other abnormalities.  This test will generally be used frequently to measure changes in retinal thickness.
   

6. Types of AMD
   

Dry AMD

      In dry AMD, the retina slowly thins in the center of vision. Usually, yellow deposits called drusen are present in the macular area. In most dry AMD cases visual acuity is not drastically affected, and loss of vision is slow and progressive.  This is the most common type of AMD.

At this time there is no treatment that can reverse dry AMD.  Dry AMD progression can be slowed by the use of AREDS recommended vitamins and changes in lifestyle.  However, eyesight may be helped with special low vision lenses and low vision counseling.  Persons with dry AMD should remember that dry AMD may change to wet AMD, so central vision must be regularly monitored.  If you would like to read a detailed chapter on dry AMD (authored by yours truly), click here.  Please note that the chapter is geared towards physicians, not the general population.

Wet AMD

      Wet AMD is less common than dry AMD. However, it is much more likely to cause irreversible vision loss.  In wet AMD, abnormal blood vessels grow in the layer beneath the retina called the choroid. This growth is called choroidal neovascularization or CNV. 

When the abnormal blood vessels grow, they can leak fluid, bleed, and lift up the retina.  Over time, this results in the development of scar tissue underneath the retina. If the scarring occurs under the macula, central vision may be distorted or lost.

There are several available treatments for wet AMD.  Though none of them can restore vision that has been lost, they may stabilize vision and prevent further vision loss.  These treatments are discussed below.

Family Members of patients with AMD

        Many patients with early macular degeneration as well as family members of these patients ask us about their specific risk for the disease.  The best suggestion for family members and patients until  recently was to suggest to each person that they reduce the modifiable risk factors for the disease.  These included 1) stopping smoking, 2) eating a low-fat diet 3) consuming omega-3 rich foods weekly 4) other specific to each person.  Recently, we are excited to announce that a new genetic test for AMD is available for those family members who wish to know their specific risk for the disease.  A simple cheek sample (or spit sample) is all that is necessary to determine each individual’s specific risk for AMD that is associated with vision loss.  Detailed information on this testing is available as a PDF here.

      

Treatment of Wet AMD

        Treatment with Anti-VEGF agents

        These new treatments, first introduced in July 2005, have literally revolutionized the treatment of wet AMD.  The treatment with Avastin or Lucentis, both manufactured by Genentech, Inc., stops the ability of new blood vessels to form or grow under the retina.  In addition, they help the body absorb fluid that leaks from the newly formed vessels.  These drugs, however, require injections into the eye on a monthly or every two month basis.  Avastin, generally costs the patients between $50 - 100 per shot, while Lucentis costs about $2,000 per shot.  Avastin was developed for the treatment of colon cancer (and more recently lung cancer, with breast cancer being treated in an “off-label” manner.  The Avastin molecule is very similar to the Lucentis molecule, both targeting the VEGF molecule in the eye.  However, the Avastin molecule is larger and thus stays in the eye longer.  This, in my opinion, is what results in fewer doses of drug being used.  As Avastin is now being used in an ‘off-label” manner, certain issues need to be understood by patients.

         LINKS:

         Consent form that we use for Avastin

         New York Times article from 2006 that describes the Lucentis vs Avastin debate

        Genetech’s decision to limit Avastin was reported (Oct 2007 New York Times).  

Steroid, triamcinolone injection

        Steroids injections into the eye was the main injection treatment of wet AMD prior to the development of Avastin or Lucentis.  Steroids have many effects on the eye, including a tendency to decrease blood vessel production.  Recent studies have indicated that the genetic defect in AMD may be due to an abnormal immune system (complement system) function of the retina-choroid layer.  Steroids, in theory, can locally suppress the complement activation system, and possibly help.  However, we don’t exactly know how they help.  We continue to use steroid treatment as a “second line”  treatment after Avastin.  Often, we will combine Avastin with steroid (into one injection) so that fewer overall injections needs to be given.  Some recent studies (2007) have shown that combining steroids with Avastin can decrease the overall number of treatments and still result in the same overall amount of visual improvement.   At this time, steroids are “off-label”.  The steroid that is used in our practice (as of 2007) is made by a special compounding pharmacy that provides this medicine without preservatives or additives.  However, a company Allergan, is developing a steroid that is going to be “labelled” for injection into the eye by the FDA in the near future.

         Steroids can have some significant side effects when injected directly into the eye.  The two major ones include:  Cataracts and glaucoma (increased eye pressure).  Cataracts are only caused if you have not already had cataract surgery.  If you already have cataracts, they can be made worse by the steroid.  The steroid however will not affect cataract surgery that will replace the lens in your eye.  Glaucoma is a complex disease with increased eye pressure found in many patients.  About 20% of patients with injection will have an increase in eye pressure in the first six months after treatment.  If the pressure is increased, drops may be necessary to bring it back to normal.  About 1-2% (1 or 2 in 100 patients) of people who get streroid injection will have a pressure increase that is not able to be treated with drops alone - they may need laser surgery or operating room surgery to decrease pressure.   Once patients have had surgery in the operating room for glaucoma, they can usually continue to receive steroid injections afterwards.

         I have enclosed the consent form that we typically use prior to steroid injection.  It is more comprehensive than the short discussion above. 

        Photodynamic Therapy (PDT)

       This laser-dye technique was approved by the FDA in 2001. PDT allows abnormal blood vessels to be sealed without damaging the retina itself. In other words, PDT treats AMD without creating a permanent blind spot in the patient's vision.   Generally, the only blind spot is the area of poor vision due to the presence of abnormal blood vessels - not due to thermal damage from laser.

In PDT, a dye called Visudyne is injected into the patient's arm.  Fifteen minutes later, the retina specialist directs a laser light into the eye, using measurements from previously taken fluorescein angiograms of the eye. The laser treatment is painless and takes less than two minutes.

Patients must take certain precautions after PDT.  For 5 days after treatment, the patient should avoid direct sunlight. They should avoid very bright indoor lights like halogen lamps for the fist 24 hours.  Patients who do go outdoors must wear long-sleeved shirts, full-length pants, sunglasses and hats - however going outside is NOT recommended.  Patients may watch TV anytime.

Follow-up examinations are necessary at three-month intervals after treatment. Usually, treatment must be repeated for successful sealing of abnormal blood vessels. 

PDT has distinct advantages over standard laser treatment. It stabilizes vision and effectively controls abnormal blood vessels without producing a permanent blind spot in the patient's vision. Furthermore, PDT can be administered even if blood vessels are growing directly under the fovea.  While standard laser treatment is useful for only 5% of patients with wet AMD, PDT may be useful in about 10-20% of patients with wet AMD.

        Standard Laser Treatment

      If abnormal blood vessels are discovered early enough, standard laser treatment may be able prevent severe vision loss.  Standard laser treatment is a proven method of treatment and, until recently, had been the usual therapy for wet AMD.  This method has largely been replaced by Avastin (or Lucentis) use.

Standard laser treatment is painless, non-invasive and done on an outpatient basis.  First, anesthetic drops are administered to the eye. Then, a laser light is used to destroy abnormal vessels. The treatment usually stabilizes a patient's vision. If left untreated, the abnormal blood vessels continue to grow and eventually destroy vision. 

Unfortunately, only 5% of patients with wet AMD are even eligible for standard laser treatment.  The decision to use laser treatment depends on the appearance and location of the abnormal blood vessels and the general health of the macula.  In some cases, standard laser treatment may not be helpful and could even be harmful.

There are distinct disadvantages to standard laser treatment.  Standard laser treatment always produces scar tissue in a patient's retina; this scar tissue creates a permanent blind spot in the patient's vision.  Furthermore, over 50% of patients who receive standard laser treatment later develop regrowth of blood vessels and eventually do lose central vision.

An additional problem is that standard laser treatment is generally not used if abnormal blood vessels are growing under the fovea, the central part of the macula.