Advances in Wet AMD


The need to keep abreast of current therapies, particularly those used to treat the neovascular or wet form of Age-Related Macular Degeneration (AMD), is crucial because the incidence of AMD related visual loss is reaching epidemic proportions. Thankfully, the fruits of years of research into new treatments for the advanced stages of AMD have now ripened.

California Retina Consultant physicians and researchers have been privileged to play a role in this emerging research that provides unprecedented success in treating patients with neovascular (Wet or Bleeding) AMD. Although neovascular AMD occurs in only 10% of all AMD cases , it accounts for 90% of cases in which there is severe vision loss. In the United States, there are an estimated 150,000 – 200,000 new cases of neovascular AMD each year, with numbers increasing as the population ages. In addition, there are currently millions of patients with earlier stages of AMD that are at risk for developing neovascular AMD.

The treatment for neovascular AMD has advanced considerably since the 1980s, when laser photocoagulation was first used, and remained the only treatment option for over a decade. Numerous other therapies were tried since the mid- 1990s, yielding unsatisfactory results. These included submacular surgery, radiation therapy, and drug therapies such as Interferon.

In 1994 Robert Avery, founder of California Retina Consultants and co-founder of California Retina Research Foundation, implemented clinical trials in Santa Barbara and in collaboration with Lloyd Aiello of The Joslin Diabetes Center, published their results in the New England Journal of Medicine. Their research demonstrated the role of vascular endothelial growth factor (VEGF) in contributing to a variety of eye diseases. VEGF is one growth factor that likely stimulates the development and progression of neovascular AMD. Once the link was identified, doctors began developing and testing various treatments using anti-VEGF therapies and these showed considerable improvement over previously used modalities.

In June 2005 the doctors of California Retina Consultants commenced the off-label use of Bevacizumab (Avastin, Genentech,Inc.). They were encouraged by results of intravitreal Ranibizumab (Lucentis) in patients enrolled in ongoing clinical trials, thereby inspiring the consideration of Avastin, a molecule similar in design and function to Lucentis, but one that was more readily available since it had been previously approved by the FDA for use in cancer patients. The use of Avastin had first been reported by Dr. Philip Rosenfeld at The Bascom Palmer Eye Institute in Miami. Dr. Rosenfeld’s group suggested that Avastin yielded promising results when used systemically and intravitreally in patients with Neovascular AMD. California Retina Consultant doctors were the first ophthalmic group in the nation, following Bascom Palmer, to use the drug in this fashion. Over 500 patients participated in local trials, providing our doctors with some
of the most comprehensive research on the subject. We thank these patiets for their willingness and courage to participate in this work at a time when the outcomes were uncertain. As a result of their efforts, the vision of tens of thousands of patients worldwide may have been saved.

The success with Avastin for treating AMD inspired the California Retina Research doctors to implement trials of Avastin in patients experiencing visual complications resulting from a variety of eye diseases in which VEGF was thought to play a role, such as diabetic retinopathy and retinal vein occlusions.

The physicians at the California Retina Research Foundation have collaborated on this work with physicians around the world and locally with researchers at the University of California Santa Barbara Neuroscience Research Institute. In the last two years, the California Retina Consultants have shared their knowledge of anti-VEGF therapy at scientific meetings in six different continents including meetings in Cannes, Capetown, San Juan, Bahamas, Rome, Miami, Boston, Portugal, Israel, Las Vegas, Ft. Lauderdale, Aspen, Vail, Salt Lake City, Vancouver and Hawaii. Meetings in Sydney, Tokyo and London are scheduled for later this year. In addition to presenting their findings, CRC was the first to publish a comprehensive series of articles demonstrating the efficacy of Avastin in patients with AMD and Diabetic Retinopathy. In fact, Medicare required these articles and a toxicology study, of which we were also a part, before it would cover the use of Avastin.

National media, including Forbes, the Wall Street Journal and the Miami Herald have cited California Retina’s contributions and presented some of our very own local cases.

Both Lucentis and Avastin were designed and manufactured by Genentech, a San Francisco Bay Area Company. Lucentis was designed for intraocular use while Avastin was originally designed for systemic use in the treatment of cancer. Lucentis is FDA approved for intraocular use in AMD and the safety and efficacy of this drug has been demonstrated in phase III multi-center clinical trials (the gold standard in clinical research). Avastin, on the other hand, has not undergone such testing, but it has been the clinical impression of many retinal specialists and researchers that the two drugs work similarly in AMD patients. These drugs are not a one-time-use miracle drug and are not a cure for the disease. In fact, some patients may require monthly injections for years.

The use of Avastin and Lucentis in Neovascular AMD is revolutionary, ushering in a paradigm shift in the treatment of patients afflicted with severe proliferative retinal diseases. Whereas just two years ago we were happy to slow down the vision loss in patients with neovascular AMD, we now expect to halt the progression, and in about half of the cases we anticipate visual improvement. Neovascular AMD is estimated to develop in almost 1 million Americans older than the age of 55 years by 2009, and as the population of older persons in the United States continues to increase, the potential of these therapies to prevent vision loss is extremely significant.

The most obvious difference in these medications is the cost. Lucentis costs over $2000 per injection, whereas Avastin costs between $50 to $100 per injection. While Medicare covers 80% of the cost of these treatments, some patients must pay the rest themselves. Those with less health coverage may find it unaffordable, although Genentech does provide free or reduced cost drugs for certain eligible patients.

The Lucentis vs. Avastin showdown has stood the pharmaceutical world on end, but now the federal government hopes to settle the dispute by funding a head-to-head comparison of the two biotechnology drugs, the first such trial by the National Institutes of Health. California Retina Consultants are currently planning to participate in the CATT trial comparing Avastin and Lucentis.

Research does not stop here. Current investigations focus on improvements in the drug’s efficacy and enhancement in dosing and delivery. We have certainly cleared one major hurdle, but the race is far from over.