Treatments for Wet Macular Degeneration
Wet age-related macular degeneration (AMD) can be treated with injections of angiogenesis inhibitors into the eye, with photodynamic therapy, or with laser surgery. None of these treatments will cure wet AMD, but each may slow the rate of vision decline or stop further vision loss. However, the disease and loss of vision may also progress despite treatment. Options should be discussed with a doctor
Angiogenesis inhibitors work by blocking the activity of vascular endothelial growth factor (VEGF), a protein that promotes blood vessel growth.
Four treatments for wet AMD using angiogenesis inhibitors—brolucizumab (Beovu®), aflibercept (Eylea®), ranibizumab (Lucentis®), and pegaptanib sodium (Macugen®)—were approved by the U.S. Food and Drug Administration (FDA) in 2019, 2011, 2006, and 2004 respectively. There is also a fifth drug, called bevacizumab (Avastin®), approved by the FDA as a blood vessel growth inhibitor to treat colorectal and other cancers, that has been used off-label (i.e., for purposes other than the approved uses) by some doctors to treat AMD.
Beovu is also prescribed as an injection to be given in the vitreous of the eye after it has been numbed. It is the only anti-VEGF agent recommended up to three-month dosing intervals in eligible patients. The treatment with other anti-VEGF agents is typically given at every 4-6 weeks frequency.
The most common side effects reported with Beovu include blurred vision, cataract, broken blood vessels in the eye, vitreous floaters, and eye pain. Rare but serious side events include eye infection, eye inflammation, retinal detachment, increased eye pressure, and blood clots in blood vessels.
After numbing the eye, the doctor injects Eylea into the clear, jelly-like substance (the vitreous) that fills the eye from the lens back to the retina and then monitors the patient’s progress. After an initial three-month period of injections every four weeks, Eylea can be administered every eight weeks. In comparison, treatments with the other angiogenesis inhibitors are normally given every four weeks (Lucentis and Avastin) or every six weeks (Macugen). The actual number of injections needed is determined by the physician, taking the individual patient’s disease status and response to treatment into consideration.
The most commonly reported side effects of Eylea (affecting no more than five percent of patients) include hemorrhage of the conjunctiva (the membrane that covers the white of the eye), eye pain, risk of cataract, vitreous detachment, vitreous floaters (specks or clouds moving in the field of vision), and increased eye pressure. There is a greater risk for endophthalmitis (severe inflammation of the eye interior) and retinal detachments, as can follow any injection into the vitreous.
Lucentis is also injected into the vitreous portion of the eye after it has been numbed. Injections are given regularly over a period of time. The frequency and actual number of injections needed are determined by the physician and the individual patient’s disease status and response to treatment.
Findings from international studies announced in 2012 indicate that an injection every four weeks may be optimal. The most commonly reported side effects of Lucentis include hemorrhage of the conjunctiva, floaters, eye pain, increased eye pressure, and inflammation of the eye. Rare but serious adverse events include endophthalmitis, retinal detachment, retinal tear, increased eye pressure, and traumatic cataract.
In October 2021 the U.S. Food and Drug Administration approved Susvimo as a new treatment for wet AMD. For some patients, Susvimo will be an alternative to frequent eye injections of anti-vascular endothelial growth factor (anti-VEGF). Susvimo will use a port delivery system, a grain of rice-sized device implanted in the eye, which will require refills of anti-VEGF far less frequently than many currently receive injections.
Macugen is also injected into the vitreous portion of the eye that has been numbed. It is usually administered every six weeks. The actual number of injections needed is determined by the physician, taking the individual patient’s disease status and response to treatment into consideration. Macugen is still available for treatment of wet AMD, but is not used as often as other injectable angiogenesis inhibitors. Common side effects of Macugen include inflammation of the eye, blurred vision, other changes in vision, cataracts, bleeding in the eye, swelling of the eye, eye discharge, irritation or discomfort of the eye, and “spots” in vision. Injection can also make the eye susceptible to infection for a period of time.
Avastin is an FDA-approved cancer therapy drug manufactured by the same company that makes Lucentis. Avastin has been used by doctors as an off-label treatment for AMD. Both drugs are similarly administered. However, Avastin is much less expensive, and many doctors believe these drugs are equally effective against macular degeneration. The National Eye Institute of the National Institutes of Health conducted clinical trials (Comparison of Treatments Trials, or CATT) to study the relative efficacy and safety of Avastin and Lucentis.
Photodynamic therapy (PDT) is most effective in a subtype of wet AMD called predominantly classic subfoveal AMD, in which blood vessel growth and leakage in the fovea—the small region in the center of the macula—are well defined. It should be noted that PDT is rarely used now that there are drugs (EYLEA, Lucentis, Macugen, and Avastin) that specifically block the vessel-promoting VEGF protein. During the PDT procedure, a drug called Visudyne® is injected into the arm. The drug courses through the body and is absorbed by the fragile, leaking blood vessels in the eye.
Because Visudyne is activated by light, the doctor directs a low-intensity laser at the retina for a little over a minute. This activates the Visudyne, allowing it to destroy the abnormal vessels. One treatment normally takes about twenty minutes and is relatively painless. The most common side effects of PDT include headache, injection site reaction, and blurred or reduced vision. Because the drug is activated by light, it is important to avoid exposing eyes or any part of the skin to sunlight or bright indoor light for up to five days after treatment. PDT may help to stabilize vision, but it will not restore lost vision.
Laser photocoagulation surgery was the first treatment used for wet AMD, but it is only an option for a small number of patients. During the outpatient procedure, the eye is numbed, and a high-energy laser heats, seals, and destroys abnormal leaky blood vessels. This can potentially prevent further vision loss, but it results in a permanent blind spot due to scarring. Some patients experience mild pain during and/or shortly after the procedure. When successful, laser surgery is done once. However, if new blood vessels grow, surgery may have to be repeated.
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