Treatments for Macular Degeneration
Age-related macular degeneration (AMD) is the leading cause of irreversible vision loss and blindness in people age 65 and older. It is a degeneration of the macula, which is a very small portion of the retina responsible for central vision. There is no total cure for AMD and it can lead to central vision loss affecting a person’s ability to drive, read and perform daily tasks. There are several factors that put a person more at risk of developing AMD and there are preventative measures that can be taken to protect the eyes.
Macular Degeneration comes in the dry form (non-exudative) and the wet form (exudative or neovascular). The dry form is the early stage of the disease and is usually diagnosed by the presence of drusen, which is the deposit of debris from degenerating tissue and appears as yellow spots in the macula.
Macular Degeneration Treatment with Nutrition Supplements
A major study by the National Eye Institute has produced evidence that certain vitamins and nutrition supplements can reduce the progression of dry macular degeneration by up to 25%. Learn exactly what supplements and amounts are needed for optimum eye health.
Treatment can delay and possibly prevent intermediate AMD from progressing to the advanced stage, in which vision loss occurs. The National Eye Institute's Age-Related Eye Disease Study (AREDS) found that taking a specific high-dose formulation of antioxidants significantly reduces the risk of advanced AMD and its associated vision loss. Slowing AMD's progression from the intermediate stage to the advanced stage will save the vision of many people.
Wet Macular Degeneration Treatment with Anti-VEGF
Dry AMD may cause gradual vision loss but it usually is not as severe as the wet form. No FDA approved treatments are available for dry AMD but there are numerous current clinical trials investigating treatments for dry AMD.
Wet AMD makes up about 10% of all AMD cases but it is much more visually devastating. Approximately 200,000 new cases of wet AMD occur each year in the United States. It is estimated that about 1.6 million people in the United States currently have wet AMD. Angiogenesis is the physiological process whereby new blood vessels grow from existing vessels. Angiogenesis is desired and normal in healing of wounds and normal growth of tissue but it is also involved in the progression of dormant tumors into malignant cells. Angiogenesis is the same process that tumors use to create their own blood supply and metastasize.
Due to damage from dry AMD the dying cells make an attempt to increase oxygen supply to the retina by growing new blood vessels. This process is called angiogenesis and is triggered by a chemical called vascular endothelial growth factor (VEGF) that is released from the damaged retinal cells.
In macular degeneration the problem is that these new vessels are very weak and commonly break and bleed below the retina destroying the rod and cone cells responsible for vision. The bleeding causes scarring. This process is called choroidal neovascularization and is the hallmark of wet AMD. The vessel growth is usually classified as occult or classic. Occult is characterized by vessel growth that is not as pronounced and blood leakage, which is less obvious. This form usually creates less severe vision loss. Classic refers to vessel growth that has a clear outline beneath the retina and usually results in more severe vision loss.
There is no cure for macular degeneration but there are treatments aimed at preventing progression of wet AMD and even improving vision in some cases of wet AMD. The most recent advances in wet AMD treatments are the anti-VEGF (anti-Vascular Endothelial Growth Factors) drugs which stop angiogenesis.
VEGF is a protein created naturally by the body. Body tissues release this protein to signal the need for additional oxygen. Nearby blood vessels sense this protein and grow new blood vessels into the area needing additional oxygen. VEGF's normal function is to create new blood vessels during embryonic development and after injury.
Lucentis and Avastin Treatments for Macular Degeneration
Anti-VEGF drugs are also used to treat various forms of cancer due to the similar pathological process. There are two FDA-approved anti-VEGF drugs and one that is used off-label. The first to be approved was Macugen (pegaptanib; OSI/Eyetech Pharmaceuticals) in 2004 which blocks one VEGF. Lucentis (ranibizumab; Genentech Inc) was approved in 2006 and has become much more popular than Macugen due to its effectiveness and tolerability and its ability to block multiple VEGF proteins. Avastin (bevacizumab; Genentech Inc) has not been FDA-approved for AMD but is used to treat various forms of cancer (especially colon cancer) and performs as well as Lucentis according to many physicians. Another advantage of Avastin is that it is much cheaper than Lucentis.
The cost of Lucentis is extremely high reaching $2,500 or more for each monthly treatment. This cost is for both the doctor's injection procedure and the medicine.
Anti-VEGF drugs are administered by ocular injection into the vitreous of the eye and according to studies for Lucentis are most effective if given once a month for two years according to the MARINA and ANCHOR clinical trials.
Other Treatments for Wet Macular Degeneration
- Laser surgery - This procedure uses a laser to destroy the fragile, leaky blood vessels. A high energy beam of light is aimed directly onto the new blood vessels and destroys them, preventing further loss of vision. However, laser treatment also may destroy some surrounding healthy tissue and some vision. Only a small percentage of people with wet AMD can be treated with laser surgery. Laser surgery is more effective if the leaky blood vessels have developed away from the fovea, the central part of the macula. (See illustration at the beginning of this document.) Laser surgery is performed in a doctor's office or eye clinic.
The risk of new blood vessels developing after laser treatment is high. Repeated treatments may be necessary. In some cases, vision loss may progress despite repeated treatments.
- Photodynamic therapy - A drug called verteporfin is injected into your arm. It travels throughout the body, including the new blood vessels caused by wet macular degeneration in the eye. The drug tends to "stick" to the surface of new blood vessels. Next, a light is shined into the eye for about 90 seconds. The light activates the drug. The activated drug destroys the new blood vessels and leads to a slower rate of vision decline. Unlike laser surgery, this drug does not destroy surrounding healthy tissue. Because the drug is activated by light, you must avoid exposing your skin or eyes to direct sunlight or bright indoor light for five days after treatment. Photodynamic therapy is relatively painless. It takes about 20 minutes and can be performed in a doctor's office.
Photodynamic therapy slows the rate of vision loss. It does not stop vision loss or restore vision in eyes already damaged by advanced AMD. Treatment results often are temporary. The treatment often must be repeated.
Monthly Anti-VEGF Treatments are More Effective
In summary, monthly dosing of Anti-VEGF treatment appears to be more effective than quarterly dosing. PRN dosing may be as effective as monthly if criteria for retreatment are standardized. The studies soon to come out should help to answer many of these questions.
EYELEA (aflibercept; Regeneron Pharmaceuticals Inc) is a new anti-VEGF drug that received FDA approval in December 2011. In two late stage trials Eyelea was as effective and safe as Lucentis with half the number of injections (bimonthly). Regeneron conducted a study of 1217 patients in North America and Bayer (Regeneron’s European partner) conducted a study of 1240 patients in Europe, Asia and Latin America. Vision was maintained or improved in 96% of patients receiving 0.5mg monthly injections and 95% receiving 2mg monthly or every two months with VEGF Trap-Eye compared to 94% receiving 0.5mg monthly Lucentis. The study conducted by Bayer had similar results with 96% maintaining or improving with 0.5mg monthly and 2mg monthly or bimonthly VEGF Trap-Eye and 94% with 0.5mg monthly Lucentis.
Due to the severity of vision loss and the incurable nature of Age-Related Macular Degeneration we are sure to see much more research as well as updates in treatment methods in the near future.
RECENT RESEARCH on Treatments for Macular Degeneration Show Positive Outcomes
MARINA and ANCHOR were phase III clinical trials using Lucentis. They consisted of 716 patients with wet AMD in MARINA and 423 patients in ANCHOR. The MARINA results over two years were that the patients who received Lucentis had a mean increase in visual acuity of 5.4 and 6.6 letters for the 0.3mg and 0.5mg dose respectively. The patients who received placebo injections had a mean decrease of 14.9 letters. ANCHOR results after two years consisted of a mean increase in visual acuity of 8.1 and 10.7 letters for the 0.3mg and 0.5mg doses of Lucentis. It also showed a mean decrease of 9.8 letters in the group receiving a different method of treatment called Photodynamic Therapy or PDT.
Studies are now being conducted to maximize treatment efficiency by determining if less frequent dosing is as effective as monthly dosing. This variable dosing method is being researched in order to decrease cost as well as avoid unnecessary treatment. The studies consist of the following…
· PIER: This was a phase IIIb multicenter, double-masked, sham injection-controlled trial using a fixed variable injection in which 184 patients received Lucentis (0.3 or 0.5mg) every month for 3 months then went to a quarterly injection schedule. This study was based on the phase I and II studies which indicated that Lucentis may be clinically effective for up to 90 days. The results showed a mean visual improvement over the first 3 months then the vision declined to less than baseline at 12 months. The mean change in visual acuity was a decrease of 1.6 and 0.2 letters for the 0.3 and 0.5mg groups. There was a decrease of 16.3 letters for the sham group. This study demonstrated that the results of monthly injections are superior to quarterly.
· PrONTO: This is a phase I/II prospective, open-label 2-year trial of 40 patients. It consisted of 3 monthly 0.5mg injections of Lucentis followed by selective injections at monthly follow-ups. Criteria for follow-up injections were very strict and included several factors which would indicate the disease progression. The results were a mean increase in visual acuity of 9.3 letters and an average of 5.6 injections in the first year. The second year the vision improved by 11.1 letters from baseline with a mean number of 9.9 injections. These results are favorable and have been adopted in practice by many doctors.
· SAILOR: This is the largest trial to date consisting of 4,307 patients and was a phase IIIb multicenter, 1-year evaluating a variable-dosing regimen of 3 monthly injections of 0.3 and 0.5mg of Lucentis followed by PRN (as needed) dosing in two patient cohorts. Three month follow ups were required and the retreatment criteria were not as strict as PrONTO. The first cohort consisting of 2,378 patients showed vision increase of 0.5 and 2.3 respectively for patients who had never been treated before and an increase of 1.7 and 2.3 letters for previously treated patients. The results compare adversely to MARINA, ANCHOR and PrONTO. Though the variable regimen and retreatment criteria were different for PrONTO.
· HORIZON: This study was designed as an extension study. It was phase III open label for patients who had completed the two years in MARINA and ANCHOR either as controls or receiving Lucentis injections and for patients who had been part of the FOCUS trial evaluating results of another treatment called PDT. These 853 patients were switched to a PRN regimen with injections to be given at the physician’s discretion and required follow ups every 3 months. There were 600 previously treated patients, 168 who were in the control group and 85 who did not require further treatment in the previous studies. The results showed a mean vision decrease of 5.3 letters in the first group and a decrease of 2.4 and 3.1 in the next two groups.
· EXCITE: This trial is starting with 3 monthly doses of either 0.3 or 0.5mg followed by quarterly injections through 12 months. Data have not been published yet.
· SUSTAIN: This trial starts with 3 monthly injections followed by PRN dosing but data have not been published yet.
· CATT: This is an upcoming trial currently consisting of 1200 patients which will compare Lucentis to Avastin treatment in both monthly and variable dosing regimen.
· There are several trials of Avastin currently underway in addition to CATT including IVAN, MANTA and VIBERA.
There are also many studies investigating combination therapies. This would be a combination of an anti-VEGF drug with other methods of treatment such as verteporfin PDT (photo dynamic therapy) in order to determine if there may be a synergistic effect. One such trial was FOCUS which was a phase I/II multicenter, 2-year, randomized, single-masked, controlled study in which 162 patients received PDT 7 days before first injection then quarterly as needed with monthly Lucentis in 0.5mg concentration or sham injections. At the 2-year follow up patients treated showed mean vision increase of 4.6 letters compared with the sham group who had a mean decrease of 7.8 letters. Upcoming studies investigating combination therapy are DENALI, MONT BLANC, CARBON, CABERNET, LuceDex, RADICAL and PDEX.
Future Developments in the Treatment of Macular Degeneration
Genentech, the maker of Lucentis, is currently investigating an implantable ocular device that would automatically administer Lucentis anti VEGF treatments without subjecting patients to monthly administration of intravitreal injections. Using a refillable drug port delivery system for sustained delivery of the system would be beneficial to many macular degeneration patients. This system is not yet available and is still in a research phase.
A Possible Treatment for Dry Non-Exudative Macular Degeneration
Another encouraging possible treatment in the quest to help patients with macular degeneration is using stem cells injected into the macular area. This is a potential treatment for DRY macular degeneration.