AMD

Age-related macular degeneration (AMD) is the number one cause of legal blindness (vision less than 20/200) in persons over the age of 50 in the United States. This disease has two specific presentations: non-exudative or "dry" macular degeneration and exudative or "wet" macular degeneration. AMD almost never causes complete loss of vision and usually involves only the central vision, leaving the peripheral vision intact. Although two specific presentations, wet and dry, are described, they are actually a spectrum of disease. The wet form usually occurs after the dry form has been present for a long period of time and both forms can be present in one patient. Eye care specialists ask patients to evaluate themselves with an Amsler Grid each day and return immediately if any changes occur.

The dry form occurs when there are pigmentary changes and loss of pigmented cells in the center part of vision along with the hallmark of macular degeneration, drusen. These are small, white spots under the retina at the level of Bruch’s membrane (see Anatomy), and are thought to indicate problems with the normal function of the retinal pigment epithelium (RPE), the pigmented cells. 80 to 90% of patients with macular degeneration have the dry form, but only 10 to 20% of severe visual loss is in the dry form. The wet form, therefore, accounts for the majority of severe visual loss in this disease.

Drusen large soft in AMD

Drusen

Drusen are the hallmark of macular degeneration, particularly the large, soft drusen shown here. These usually precede the formation of wet changes.

The wet form of age-related macular degeneration consists of the changes of dry macular degeneration plus the development of either subretinal choroidal neovascular membranes (subretinal scar tissue), subretinal hemorrhage (bleeding), or an RPE detachment (blister of the retina). The subretinal neovascular membrane that is responsible for the majority of marked visual loss in AMD also occurs in many other conditions, most notably in the presumed ocular histoplasmosis syndrome (OHS), myopia, in various conditions with angioid streaks (breaks in Bruch's membrane) including pseudoxanthoma elasticum (PXE), and as an idiopathic entity (occurs without apparent cause). This "membrane" is actually scar tissue thought to be growing in the macula to try to heal the area due to sick RPE cells in AMD or damage from previous scarring, breaks in Bruch's membrane, or other causes in the other diseases mentioned above. The "membrane" grows and leaks serum and fibrin, causing a small retinal detachment in the center of vision (exudative retinal detachment) which in addition to the damage caused by the scarring of the membrane itself also causes a decrease in vision.

Wet AMD

RPE Detachment (left) (blister of retina) and Subretinal Neovascular Membrane (new scar tissue under retina) (right)

The current thought is that AMD may have many causes with genetic, toxic, nutritional, and unknown components. Some researchers feel that AMD occurs in susceptible patients in part due to light "toxicity." Over a period of many years photochemical damage from light occurs at the photoreceptor/RPE level, and peroxidation of the photoreceptors and RPE result from the formation of activated forms of oxygen at these levels. The retina (photoreceptors and RPE) basically "rusts." Some authors felt that deficiencies in various vitamins and minerals may be in part the cause of age-related macular degeneration and this thought stimulated a national clinical trial, the Age-related Eye Disease Study, to evaluate the use of vitamins and minerals in this disease. The study showed a significant difference in patients with dry AMD taking the vitamins and those not taking them. Physicians are now recommending these "eye vitamins" to help protect their patients’ vision. One study of neovascular AMD (choroidal neovascular membranes) suggests that the carotenoids leutein and zeaxanthin (the "spinach" vitamins)--actually pigments in the retina--might play a protective role in this disease and these are being added to the "eye vitamins" (they were not studied in the AREDS since they weren't available when that study began). The AREDS2 Study is now underway to determine the efficacy of lutein and zeaxanthine. Baylor College of Medicine (Dr. Richard Lewis) is the Houston Center for the AREDS2.

Medical treatment of AMD includes the use of the vitamins and minerals mentioned above. Multiple vitamin companies have formulations particularly designed for the eye and can include lutein and zeaxanthin in their vitamins. Some vitamins specifically designed for senior citizens and for smokers have been added these as well.

Interferon, a substance used in cancer treatment to stimulate a person's immune system, was evaluated as a possibility in the treatment of macular degeneration, but did not prove to be beneficial.

Radioactive plaques and external beam radiation (x-ray therapy) have been tried, but no study to date has shown any benefit of the treatment of subretinal membranes with radiation. Other treatments being touted by some include passing an electrical current across the eye and "Rheo" therapy--an technique that washes the blood of patients to decrease AMD--neither of which, in our opinion, are scientifically sound (you might be better off spending your money on a trip to "Rio").

One of the first major studies in the last 15 years related to the subretinal neovascular membrane formation was the Macular Photocoagulation Study (MPS). This study addressed the treatment of subretinal neovascular membranes in age-related macular degeneration with long-term, multi-centered clinical trials using a laser to cauterize the membrane. The Macular Photocoagulation Study showed the benefit of the laser treatment of extrafoveal and juxtafoveal membranes (subretinal new vessel membranes--scar tissue--outside of the center and just adjacent to the center of vision) and that their progression to the center of vision could be stopped in approximately 50% of patients. For membranes directly under the center part of vision laser cauterization limited the size of the blind spot but there was little chance of visual recovery for either the group observed (no treatment) or those undergoing laser. Patients with treatment of a subfoveal membrane (accounting for 90-95% of membranes when first seen) had slightly better vision and a better reading speed than patients not treated when evaluated two years later. Unfortunately, treated patients did have an average of three lines of loss of vision immediately after the laser treatment. The laser cauterizes not only the membrane, but also the photoreceptors and RPE above and below the membrane. The MPS has divided subfoveal membrane patients into subgroups that better define the best membranes to treat with laser.

Another set of studies completed are the Laser for Drusen trials. These studies were started when it was observed that drusen disappear in some instances when patients undergo laser photocoagulation for other conditions. The thought is that lasering around or on drusen may, in fact, decrease the amount of drusen, and therefore decrease the progression of macular degeneration. Several trials have not shown this to be a viable treatment.

A more recent addition to our treatment armamentarium is Photodynamic Therapy (PDT). PDT is a laser technique using a "cold" laser, and has been shown to halt the progression of the growth of new vessel membranes under the center of vision in AMD. In PDT, a special dye is injected in the blood stream (Visudyne) that is specifically absorbed by the new membranes. The laser activates the dye to kill the membrane without killing the surrounding seeing cells and stabilizes vision in many patients. This therapy can improve vision in some patients (14% in the study) but stops the leakage from the membranes and stabilizes vision, limiting the vision loss in most. The goal of this treatment in the study was, in fact, to limit the loss of vision, not to return vision. Re-treatment is commonly necessary with an average of 3.4 treatments necessary the first year and 2.1 the second year, i.e. patients require 5-6 treatments in a two-year period on average. The FDA released the dye and laser for use in AMD in April 2000. Another type of laser therapy recently studied is called Transpupillary Thermotherapy (TTT) in which a low powered laser is used to treat lesions. This did not prove to be a beneficial therapy.

Since laser photocoagulation of membranes directly under the center of vision in the MPS (cauterization type laser, not PDT laser) did not afford the possibility of improvement in vision, many surgeons began to look at the surgical treatment of subretinal neovascular membranes via vitrectomy, retinotomy, subretinal membrane removal, and retinal reattachment. When a subretinal membrane develops, fluid leaks from the membrane causing a detachment of the retina overlying the membrane (exudative retinal detachment), causing further loss of vision. A major trial at multiple centers evaluating the surgical treatment of subretinal membranes did not show improvement in vision (although did show stabilization) on average. In our studies at RVT published in 1999, we found that 30% of people having subretinal membrane removal had a significant improvement in vision, 40% of patients stabilized with surgical therapy, and the remaining 30% continued to decrease vision (the observation and laser photocoagulation studies all had patients with decrease in vision) in AMD. Surgical removal in other diseases, particularly the OHS and idiopathic membranes, appear to have a much better result (some to 20/20!). See the section on Subretinal Membrane Removal for further explanation of these techniques.

Macular translocation has been studied to determine if the retina can be moved to a slightly different location, allowing "fresh" RPE to help improve vision in patients with subretinal neovascular membrane formation. Please see the section on Macular Translocation for further discussion of this therapy. This was less successful than originally hoped.

Anecortave acetate, Macugen, Lucentis, Avastin and Anecortave Acetate are similar new treatments under or have just completed investigation in the treatment of AMD. These medications have been developed to halt the growth of subretinal neovascular membranes. and is a constructed molecule aimed at blocking vascular endothelial growth factor (VEGF) and similar growth factors which stimulate CNV growth. Macugen was released by the FDA to halt the growth of membranes and requires injections into the eye every six weeks. Macugen is an aptamer (a molecule that attaches to another) that attaches and deactivates VEGF. Results is Macugen were similar to PDT. Lucentis, a similar medication (an antibody to VEGF) was approved on 30 June 2006 and stabilizes vision in approximately 90% of patients with improvement in approximately 1/3. Avastin, a medication already approved for the treatment of cancer and the parent molecule of Lucentis, is also an anti-VEGF drug and has been used as an off label medication and now in many small studies has been suggested to be effective. Macugen, Lucentis and Avastin all require periodic injections. The CATT (Comparison of Age-related macular degeneration Treatments Trial) began in February 2008 and is comparing Avastin and Lucentis directly. RVT is a center for the CATT. See Studies. All of these current medications are treatments and not cures for AMD. Multiple injections are necessary and even after stabilized, the disease can recur Injections are performed every month to six weeks depending upon the medication and treatment is based on tests including fluoroscein angiography and ocular coherence tomography (OCT).

The future of the treatment of macular degeneration, we at RVT feel, lies in the possibility of transplantation of the RPE and photoreceptors or the use of stem cells, possibility the use of growth factors to stimulate the re-growth of a person’s own retinal pigment epithelium and, hopefully, techniques to stop the progression of AMD (vitamins, minerals, factors not yet know) and stop the membranes when they occur and the further development of medications like Avastin to block the complications of this disease. We at RVT are working on various innovative techniques for the treatment of age-related macular degeneration and are hoping to be able to begin treatments in the not-too-distant future (The Texas Foundation for Eye Research).

Disclaimer Stuff: The opinions expressed in this website are those of RVT. Diagnosis and therapy should be based on a thorough examination by and recommendations of a qualified eye provider.

Age-related Macular Degeneration