Macular Degeneration
AGE-RELATED MACULAR DEGENERATION, ARMD
Age-related Macular Degeneration, ARMD, the leading cause of blindness in patients over the age of 50, mainly effects the macula. The macula is responsible for our ability to read, see fine detail, see people\'s faces, and appreciate color. ARMD destroys the macula.
Lifestyle and ARMD
Smoking, sun exposure, high blood pressure, heart disease, genetics, and diet have been found to be risk factors for ARMD. Several of these risk factors may cause degeneration of the retina and the retinal pigment epithelium (RPE). Blue light exposure and UV radiation are thought to directly damage the retina. Factors such as UV filters in glasses and contact lenses, yellow tinted lenses and antioxidants may help prevent this light damage.
Vitamins and herbs
Vitamins and nutritional supplements fight oxidation. Oxidation is a process where energy, such as sunlight or chemicals from sources like cigarette smoking, produces free radicals. These free radicals injure cells and damage the DNA. Antioxidants prevent or ameliorate this damage. Enzymes in our bodies can also help to neutralize these dangerous elements. Some nutrients, such as zinc, also work by helping these enzymes perform their work.
The silent start of ARMD
ARMD has many forms and presentations. Most patients are not symptomatic at the start. Drusen, yellowish spots within the RPE in the macula, mark the start. Drusen can vary in size and appearance. The majority of patients with ARMD will develop withering of the retina. Withering of the retina without fluid or blood leakage is termed non-exudative or the “dry” form of ARMD. ARMD with fluid or blood leakage is called the “wet” form.
Stopping “dry” ARMD
The dry form cannot be cured or slowed by medicine, laser or surgery. Recent research has studied low intensity laser treatment on the retina and specifically targeted at drusen. This and other studies have failed to show this treatment slows or stops the disease. New drugs targeting growth factors, such as Anecortave Acetate (Reetane, Alcon Labs) are being studied to treat dry ARMD.
The “wet” form of ARMD
The exudative or “wet” form effect about 10 percent of patients with ARMD, however, is responsible for greater than 80 percent of the patients who are legally blind from the disease. This wet form can present in many different ways. The RPE can separate, becoming incompetent and allow fluid to leak beneath the retina. Multiple blood vessels can start to grow within the RPE. Blood vessels may break through the RPE and invade the subretinal space. This last process is called a choroidal neovascular membrane or CNVM. All forms of leakage distort the retina and the blood and fluid destroy the retina.
Angiography, the study of blood vessels and ARMD
In order to treat to the CNVM, doctors must find these abnormal blood vessels growing beneath the retina. A fluorescein angiogram is performed to detect the CNVM. In this test the patient receives a special dye injected into a vein in the arm. The retina is photographed with a special light which causes the dye to “light up” the normal and abnormal blood vessels. The problem with the exudative form is that 50 percent of CNVM are ill-defined, and cannot be detected by conventional fluorescein testing. Another retinal imaging study, ICG angiography, using Indocyanine green dye, can help to find the CNVM in an additional 30 to 50 percent of patients with the wet form of ARMD.
Ocular Coherence Tomography, OCT
Ocular Coherence Tomography, OCT, is also employed to measure the retinal thickness and obtain microscopic images of the area of concern. OCT helps the doctor “track” the course of the disease and give actual measurements of the retinal swelling.
TREATMENT OPTIONS FOR THE “WET” FORM OF ARMD
INHIBITING ANGIOGENESIS=BAD BLOOD VESSEL FORMATION = ANTIANGIOGENESIS
Angiogenesis research dates to the late 1960s, when cancer researchers started searching for new drugs to stop unwanted blood vessel growth in an attempt to starve tumors of their blood supply. Today, more than 80 diseases are thought occur from “bad” blood vessels growing in a destructive manner. Research is pursuing therapies for a host of conditions, from cancer and atherosclerosis to diabetic retinopathy, macular edema and ARMD. VEGF (vascular endothelial growth factor), a protein “signal” produced in our body, has a significant role in the process of new blood vessel growth; however, VEGF is vital to limiting damage in stroke and heart attacks. Controlling VEGF, and in the future other chemical signals in the body, will be the key to controlling these diseases.
LUCENTIS and AVASTIN
Lucentis: Researchers originally thought that Avastin, a VEGF antibody FDA approved for use in cancer patients, was too large to penetrate the retina and stop blood vessel leakage and growth in wet ARMD. They designed a smaller version of Avastin called Lucentis. Early Lucentis testing with monthly injections into the eye found that 92% of patients stabilized, with 32% improving 3 or more lines of vision and 44% gaining at least 2 lines. One year studies with Lucentis showed that it stabilized 95% of patients. Lucentis patients gained over three lines of visual acuity improvement chart compared to control group. Lucentis is the first ARMD treatment to improve vision with over 40% having 20/40 or better vision. Lucentis trials are focusing on different doses and treatment intervals. Patients who receive Lucentis receive monthly injections into the eye until the leakage is controlled. Most will receive between 5 to 7 injections in the first year, and less thereafter. Less than 1% of patients will have side effects from these injections, which can include bleeding, infection, and retinal tear and detachment. Lucentis has potential severe side effects, such as stroke, particularly in patients with a history of prior stroke.
Avastin: Retinal specialists began using Avastin in patients who were not responding well to other treatments prior to the availability of Lucentis. High dosages of intravenous Avastin worked very well for treating the wet form of ARMD, but has some potential severe side-effects such as hypertension, stoke, bleeding ulcers and heart attack. Retinal specialists inject much smaller amounts (1/80th of a single “cancer dose”) of Avastin directly into the eye to decrease the risk of systemic side effects, but the true risk of causing the problems listed above are not known. Intraocular Avastin appears to work very well at stopping the growth and leakage of the new blood vessels in wet ARMD. We have used Avastin at Chester County Eye Care for several years with a remarkably impressive safety record and benefit to our patients. Patients who receive Lucentis receive an injection into the eye about every 6 weeks until the leakage is controlled. Most will receive between 2-3 injections in the first year, and less thereafter. Less than 1% of patients will have side effects from these injections, which can include bleeding, infection, and retinal tear and detachment. Avastin has the same potential as Lucentis of stroke in patients with a history of prior stroke. Avastin is not FDA approved for use in ARMD. This does not prevent its use, or its “coverage” by insurance companies. Avastin is being used to treat a disease it was not originally intended. Medical research has shown that Avastin is safe and effective in treating wet ARMD; however, the studies are not as extensive as those conducted for Lucentis. The National Eye Institute is conducting a trial that will directly compare Lucentis vs. Avastin to help determine which may be more effective and safe, which is not known today.
LASER The Macular Photocoagulation Study, or MPS, demonstrated that targeted laser destruction of a CNVM could reduce the risk of severe visual loss, if the bad blood vessels were not directly in the center of the vision. This is rarely the case and that is why other treatments are preferred. Also, 40% percent of patients receiving laser lost 2 or more lines of vision, and the blood vessels grow back in well over half of the patients, and this was increased with cigarette smoking. The study also found that the presence of certain types of drusen and pigmentation in the fellow eye was predictive of the development of a CNVM in the other eye.
Photodynamic Therapy, PDT
PDT involves injecting Visudyne into a patient’s arm vein that is selectively activated by “cool” laser light. Chester County Eye Care was part of a multi-center national trial examining the effect of PDT with Miravant another PDT dye to treat ARMD. The activated dye selectively destroys the abnormal, leaky blood vessels while leaving the overlying retina and nearby RPE unharmed. Chester County Eye Care employs Verteporfin (Visudyne), an FDA approved PDT drug for ARMD. This treatment may need to be repeated 3-4 times in the first year and less often thereafter. An in-office injection of a steroid, Kenalog (triamcinolone), into the eye around the time of PDT is reported to diminish the need for re-treatment and improve the chances of visual recovery. Kenalog increases the risk of glaucoma (high pressure in the eye that is treated with drops and rarely surgery) and cataract formation.
Treatments/Drugs Under Study
Reetane
Reetane, anecortave acetate, is a synthetic steroid that inhibits abnormal blood vessel growth. Reetane is delivered through a sub-Tenon\'s injection, an injection under the conjunctiva, the outside surface surrounding the eyeball. This drug is thought to inhibit the enzymes that blood vessels use to invade tissue. A 15mg single (sub-Tenon) injection has been shown to inhibit CNVM when given every 6 months with 18% of patients having a 2 line improvement in vision. Problems with drug leakage from the injection track have delayed development. A combination trial with PDT showed that this drug stabilized vision in 78% of patients vs. 65% of patients treated with PDT alone. Phase 3 trials are under way.
Acuity: siRNA
Acuity Pharmaceuticals has a novel drug called Cand5. It is a VEGF siRNA. The molecule works by stopping VEGF before it is produced and is broken down by enzymes in the body. Cand5 is given as a single injection into the eye. Chester County Eye Care was chosen as 1 of only 4 sites in the world for the Phase I trial of this drug.
Regeneron
Regeneron has created a novel drug called VEGF Trap that has been shown to prevent the development of abnormal blood vessels in the eyes of animals with conditions resembling diabetic retinopathy and ARMD.
Agouron Pharmaceuticals
Matrix Metalloproteinase Inhibitor, MMPs, stops enzymes that allow new blood vessels to break through the foundation layer in normal blood vessels. AG3340 is an MMP that stops “bad” new blood vessels from being allowed to break into subretinal space. Research involves systemic and intravitreal trials.
Retinal Chips
There are several implanted retinal chips that are being studied and are not presently commercially available. These chips have restored some vision in a few significantly blind ARMD patients. All of these chips are investigational. “The Chicago chip” from Optobionics is 2 mm in diameter and 25 µm thick and consists of 5,000 microscopic solar cells that convert light into electrical impulses. These impulses “activate” the nerves on the retinal surface, which in turn send these signals to the brain. It is implanted under the retina in an out-patient surgery. “The Los Angeles artificial retina” is a 2 chip design with a miniature video camera spectacle mounted in spectacles that transmit signals to a 4-mm-by-5-mm retinal implant via a wireless receiver embedded behind the ear. Surgeons implant an array of 16 platinum electrodes on the surface of the retina. The system receives images from external camera and external power from a battery pack/image-processing unit that clips to the patient’s belt. Australian researchers from the University of New South Wales are working on an implant with 100 electrodes. German researchers have a device that is similar to its southern California counterpart.
Implantable Miniature Telescope
The Implantable Miniature Telescope (IMT) was invented by Israeli Dr. Isaac Lipshitz in 1996. The IMT is a micro-sized precision telescopic device with a magnification of 3.0X or 2.2X. It is implanted into the eye by removing the natural lens, a surgical technique performed in cataract surgery. Phase III U.S. trials involved 300 individuals with no previous surgery. The first year results found that 91% of patients reported improvement in viewing television and 66% reported improvement in reading vision. It is not FDA approved.
Radiation Treatment of ARMD: Published studies found mixed results for radiation treatment. The most recent international studies found no benefit from this treatment.
Retinal transplantation
Surgeons cannot transplant the whole retina for many reasons, including the difficulty with “rewiring” all 1.2 million nerve fibers connecting it to the brain and reconnecting the delicate blood supply. Researchers are developing methods of RPE transplantation before applying it in wide-scale human studies. Researchers are examining the feasibility of transplanting RPE within an eye, like a skin graft, from a healthy area to the damaged central portion in the macula, and from other donors such as relatives and from fetal tissue.
ARMD is a complicated disease, which has many forms. Many factors including genetics, lifestyle and health status predisposes people to ARMD. Today, treatment for ARMD only exists for the wet form. Researchers are working on many levels to determine who is at risk for ARMD, to prevent ARMD in those patients, and to cure or meliorate its effects on afflicted patients. The doctors at Chester County Eye Care are dedicated to helping our patients and families with ARMD.