If you are getting injections for wet age-related macular degeneration (AMD), you are not alone.  The treatment has now surpassed cataract surgery as the most frequently reimbursed procedure in Medicare.  

This remarkable statistic is due to a number of factors:  The prevalence of wet AMD in our aging population, the availability of effective medications and the need to give these treatments about every month indefinitely to stabilize the condition. 

Although the wet form is less common than dry AMD, it can be more severe and is considered an advanced stage of AMD.  It happens when abnormal blood vessels grow under the macula and leak blood and fluid, called choroidal neovascularization. Damage to the macula can occur quickly and cause irreversible loss of central vision.

After decades of research and testing, three medications are now available that target vascular endothelial growth factor (VEGF), a chemical signal in eye cells that triggers uncontrolled growth of these fragile blood vessels. Injected into the vitreous of the eye, these drugs slow the disease and help avoid more vision loss.  Some patients even experience better vision.

However, researchers at Casey Eye Institute and elsewhere continue to compare and refine these therapies and to develop more long-lasting alternatives that are less invasive and more cost effective.

Lucentis and Avastin – Is there a difference?

At this time, most patients being treated for wet AMD are receiving injections of either Lucentis (ranibizumab) or Avastin (bevacizumab), both developed by Genentech and similar in makeup.  Lucentis was specifically formulated for wet AMD and approved for that purpose by the Food and Drug Administration.  Avastin, on the other hand, is a cancer drug used off-label for wet AMD and much less expensive than Lucentis. Some ophthalmologists began using small amounts of Avastin in their patients before Lucentis became available and found it to be beneficial.  A single dose of Lucentis costs approximately $2,000 while a single dose of Avastin is approximately $50.

Studies are being conducted throughout the world to compare the safety and effectiveness of these two popular drugs.

Casey Eye Institute was one of several research centers involved in the Comparison of Age-Related Macular degeneration Treatments (CATT) Trial, sponsored by the U.S. National Eye Institute.

In the study more than 1,000 participants received one or the other drug. Study patients underwent injections as frequently as monthly and less often in other cases. Their vision was tracked throughout the study and was nearly identical for both groups of patients at the end of two years.

The findings, published in the May 2012 issue of the medical journal Ophthalmology, also showed that Lucentis and Avastin had similar effects on vision when the dosing schedules were the same; vision effects changed little after one year; patients who received monthly injections with either drug had slightly better vision and there was no difference in side effects normally expected with these drugs, such as stroke, heart attack or death.

“While effectiveness and cost are always important factors, patients and physicians need to consider all the information on hand to decide the best medication for treating AMD,” explains retina specialist Christina Flaxel, M.D., principal investigator of the study at Casey’s Macular Degeneration Center. “Although this study provides important information about effectiveness, it should not be considered the only data to guide treatment decisions,” she says.

One-year results from a comparison study in the United Kingdom, also announced in May, found that Lucentis and Avastin were equally effective in treating wet AMD.  In this clinical trial, known as IVAN, researchers also learned that patients given the drug as needed instead of monthly experienced almost identical levels of vision.  The study is continuing to follow participants to two years, when a more detailed analysis will be presented.

Eylea: The Newest Option

Approved by the Food and Drug Administration in late 2011, Eylea (aflibercept) is the newest treatment option for patients with wet AMD.  “Although it acts in the same way as Avastin and Lucentis, it is made up of a different molecule,” says Casey retina specialist Steven Bailey, M.D. Not only does Eylea block VEGF, but it also traps a second growth factor called placental growth factor (PIGF) that while less studied, may also play a role in blood vessel growth, according to Regeneron, the company that developed the drug.

One possible advantage of Eylea is that its dosing schedule calls for fewer injections than its counterparts and costs slightly less than Lucentis, though significantly more expensive than Avastin.  Patients receive injections monthly for the first three months and then every eight weeks after that.  

Based on that dosing schedule, clinical trials of Eylea after one year yielded results similar to those in Lucentis studies, notes Dr. Bailey.  “There are now three drugs available with equal effectiveness and safety,” he says. Dr. Bailey recommends that patients talk to their ophthalmologist to determine the most beneficial treatment and dosing schedule.

An Eye to the Future

While anti-VEGF drugs have helped preserve the vision of millions of patients, researchers at the Macular Degeneration Center and elsewhere are exploring ways to extend their benefit.

Some experimental approaches involve supplementing Lucentis with other treatments, such as anti-inflammatory agents, nutritional supplements, low-level laser or infrared radiation. These additional therapies may tackle other factors that contribute to the disease -- such as inflammation -- and consequently lengthen the time between injections.  

Also on the drawing board are less invasive methods of delivering the medication over the long term.  Several companies are developing devices implanted beneath the sclera (white part of the eye) that continually release an anti-angiogenic drug.   

Helpful Genes to Treat Wet AMD

Gene therapy is also earning attention as a promising weapon against wet AMD, with Casey joining the RetinoStat Phase I clinical trial  sponsored by Oxford Biomedica.  In this ongoing study, a single injection of two anti-angiogenic genes is delivered directly to the retina via a non-active virus, where they express anti-angiogenic proteins.  “The aim is to preserve vision by blocking in a sustained fashion the growth of harmful and sight-threatening abnormal new blood vessels,” says Casey retina specialist Andy Lauer, M.D., principal investigator of the study.  The treatment was found to be safe in an earlier group of study patients.  Casey is testing a final group in the clinical trial, with the first patient expected to undergo the procedure at Casey in late 2012.  “We are excited to be part of this innovative effort,” says Dr. Lauer.

Casey scientists are also focusing their efforts to better understand what causes angiogenesis in the eye and to learn more about the genes involved.  “There are dozens of genes that control blood vessel growth in the space beneath the retina, “says Timothy Stout, M.D., Ph.D., M.B.A., a retina specialist and genetics expert at Casey.  His research team is working to develop therapeutic genes that target AMD and other eye disorders.