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Anti-VEGF Treats Wet Macular Degeneration

By Jennifer Anderson

Anti-VEGF therapy has been shown to be an effective macular degeneration treatment that improves functional capabilities and reduces the need for nursing home placement.

Age-related macular degeneration (AMD) leads to progressive eyesight deterioration and often to blindness. But a treatment introduced within the last decade has significantly reduced the number of Americans who lose their vision and subsequently require nursing home placement due to compromised independence.

Although early diagnosis and treatment initiation are the best ways to preserve vision, physicians now have effective ways to reduce patients’ vision loss along with the resulting need for long term care due to blindness.

In a study published in January in JAMA Ophthalmology, Frank A. Sloan, PhD, the J. Alexander McMahon Professor of Health Policy and Management and a professor of economics at Duke University, and colleagues found that technologies under development since the 1980s have saved significant numbers of people diagnosed with the most severe form of AMD from losing their vision and having to move into assisted-care facilities.

“Age-related macular degeneration is a horrible disease that can lead to blindness, the inability to take care of oneself, dependence on others, and admittance into nursing homes,” Sloan says. “At last we have found a way of managing this horrible and very common disease among the oldest of the old.”

For the JAMA Ophthalmologystudy, researchers reviewed Medicare claims data from 1994 to 2011. Beneficiaries were included if they were at least 68 years old and had received their first diagnosis of wet AMD within the past three years.

Beneficiaries were separated into three groups based on the time of diagnosis, with those in the last group (2005 to 2008) in the anti–vascular endothelial growth factor (VEGF) group. Of the 35,726 beneficiaries included in the final sample, approximately two-thirds were women, 3% belonged to minority groups, and most were around the age of 80.

In the two-year follow-up, beneficiaries treated with anti-VEGF experienced not only a 41% reduction in vision loss but also were 19% less likely to be admitted to a nursing home, Sloan says, noting that the results controlled for general health and other eye conditions.

As the study explains, “The reductions in long term care facility use attributable to the use of anti-VEGF therapy are important not only because of their implications for health care spending but also for the improvement in functional status that underlies the reductions.”

“We’re documenting that these therapies really do affect the general Medicare population,” Sloan says. Looking at a population of more than 35,000 people newly diagnosed with wet AMD (exudative), researchers found the therapies reduced vision loss by 41% and the onset of severe vision loss or blindness by 46%. The researchers explain that their study is the third to demonstrate gains in vision from a population standpoint for patients diagnosed with wet AMD and the first using patients in a high-income country such as the United States.

The medications do not cure wet AMD but slow its progression enough to prevent blindness in a patient’s lifetime, he says. “That has a tremendous impact on keeping people out of nursing homes,” Sloan says, describing assisted living as “the true bankrupter of the elderly.”

Landmark Treatment
Michael W. Stewart, MD, chair of ophthalmology at the Florida Mayo Clinic, describes the medications as revolutionary. Before the first anti-VEGF drug, bevacizumab (Avastin), became available in 2005, “we saw people go blind,” he says. “It was a very frustrating disease. There were only a small percentage of patients we could treat with a laser.”

With the use of Avastin and then ranibizumab (Lucentis) a year later, and more recently aflibercept (Eylea), Stewart estimates that 95% of treated patients avoid significant vision loss, which he describes as moving from 20/50 vision to, perhaps, 20/100. More than 70% of patients experience some gain in vision, he says, noting that a person is considered legally blind at 20/200.

Stewart explains that wet AMD is characterized by a growth of abnormal blood vessels under the retina caused by VEGF, which is part of a system that leads to compensatory cellular mechanisms when there is a lack of tissue oxygen. VEGF exists throughout the body and is essential for creating new cells, such as following an injury. But when it is overexpressed, it can contribute to disease.

In the eye, VEGF can lead to fluid leaking from the vessels into the macula, causing central vision loss. Wet AMD develops rapidly and insidiously and can lead to scarring if left untreated. Once there is scarring, Stewart says, vision cannot be restored. By comparison, the more common dry form is characterized by deterioration of the macula and can lead to blurry vision. Wet AMD almost always begins as dry AMD.

It’s unknown what triggers the abnormal blood vessel growth, but the discovery of VEGF in the 1980s launched a series of research projects, Stewart says.

The three anti-VEGF medications currently available attach to and essentially deactivate the free-floating VEGF, removing the stimulus causing the blood vessel growth and leakage, according to Stewart. All three anti-VEGF medications are given monthly or bimonthly as injections using topical anesthesia. Each injection takes less than a second, and most people tolerate the treatment well, he says.

Although AMD rarely is seen in people under the age of 50, the medications can be used on people of all ages who have the disease. And depending on their overall vision, most patients can drive themselves home following treatment.

Stewart estimates the cost of Avastin, a cancer treatment that has not been approved for treatment of the eyes, at approximately $50 per dose. Eylea and Lucentis, both approved for eye treatment, are closer to $2,000 per dose, he says, based partly on the way they are prepared.

Most patients require anti-VEGF treatment for the rest of their lives, Stewart says, and physicians work with patients to determine the appropriate interval between treatments. It is important not to overtreat, he says, noting concerns that long-term, regular use of the medications could accelerate the progression of dry AMD. “We don’t want too much or too little [of the medications]; we want just the right amount,” he says.

New drugs are on the horizon, some of which could be taken orally, Stewart says, possibly sparing patients from having to visit a clinic for regular injections. One is an extended release version of the existing drugs and the other has new mechanisms of action focused on suppressing other growth factors of blood vessels.

Promising Retinal Treatments
Anti-VEGF medications also are biologics, with favorable side effects, says John W. Kitchens, MD, a vitreo-retinal surgeon with Retina Associates of Kentucky in Lexington. “These same medicines also are very effective in treating diabetic retinopathy and other retinal vascular diseases,” he says.

In addition to the medications, other technologies are revolutionizing the entire field of retinal conditions. New optical coherence tomography scanners have advanced to the point that physicians can compare one exact scan of the eye with a scan from a previous visit. “We can do a laser scan of the retina,” Kitchens says. “It gives us a cross-section of the retina, showing exactly how much leaking is going on and how the patient is doing with treatment. It is intuitive, and patients and their families can understand and follow it.”

But even with all of the advances, Kitchens says early detection yields the best outcome for patients. And since wet AMD can progress quickly, sometimes in as little as a few weeks, vigilance and awareness among patients, family members, and primary care physicians is the key to receiving proper and timely treatment, he says.

Typically, if a patient is diagnosed with dry AMD, the opthamologist will evaluate the risk for a progression to the wet form, Kitchens says. If a dry AMD patient has characteristic findings on the dilated eye exam, he or she may be prescribed a combination of antioxidant vitamins and minerals, including zinc, copper, and carotenoids (lutein and zeaxanthin), which have been shown to reduce by about 25% the risk of progression to wet AMD.

While the next steps include longer follow-up periods and ultimately finding an outright cure for AMD, Sloan says, the technologies are effective enough to prevent blindness in a patient’s lifetime, and this benefit likely will impact greater numbers of people as advances in health care continue to increase life expectancy.

— Jennifer Anderson is a freelance health and science writer based in Falls Church, Virginia.