Clement Chan, MD, of Southern California Desert Retina, discusses the intraocular pharmacokinetic profile of aflibercept in patients undergoing treatment for neovascular age-related macular degeneration.
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This is a multicenter, prospectively randomized, masked and controlled, interventional investigator sponsored phase I/II study of subjects with high-risk nonexudative age-related macular degeneration (AMD) treated with intravitreal ranibizumab quarterly for prophylaxis of conversion to exudative age-related macular degeneration.

The objective of this study is to investigate the safety and efficacy of prophylactic anti-vascular endothelial growth factor (VEGF) therapy with ranibizumab to prevent the development of exudative AMD in eyes with high-risk nonexudative AMD. In addition, baseline characteristics of high-risk eyes (fundus features, optical coherence tomography (OCT) parameters and genetic profile) will be evaluated to determine their predictive value in conversion to exudative AMD. The effect of ranibizumab on the atrophic component of AMD will also be monitored.

In 2001, the Age-Related Eye Disease Study (AREDS) led by the National Eye Institute (NEI) established that daily high doses of vitamins (beta-carotene, C, E) and the mineral (zinc and copper) can slow the progression to advanced AMD. While many patients have benefited from the AREDS formulation, beta-carotene use has been linked to a heightened risk of lung cancer in smokers. Also, there are concerns that high doses of zinc may cause minor side effects such as upset stomach.

In 2006 the NEI launched AREDS 2, a five-year study designed to test whether the original formulation could be improved by adding omega-3 fatty acids; adding lutein and zeaxanthin; continuing or removing beta-carotene; or reducing zinc. The study also examined how different combinations of the supplements performed. Omega-3 fatty acids are produced by plants, including algae, and are present in oily fish such as salmon. Lutein and zeaxanthin are carotenoids, a class of plant derived vitamins that includes beta-carotene; both are present in leafy green vegetables and, when consumed, they accumulate in the retina. Prior studies had suggested that diets high in lutein, zeaxanthin, and omega-3 fatty acids protect vision. Before the AREDS2 study finished, manufacturers began marketing supplements based on the study design.

In the original AREDS, participants with AMD taking supplements were 25% less likely to progress to advanced AMD over five years as compared to those who took a placebo. In AREDS2, there was no overall additional benefit from adding omega-3 fatty acids or a 5-to-1 mixture of lutein and zeaxanthin to the formulation. However, the investigators did find some benefit when they analyzed two subgroups of participants; those not given beta-carotene, and those who had very little lutein and zeaxanthin in their diets. These participants had an 18% reduction in developing advanced AMD in 5 years when compared to those who took a formulation with beta-carotene but no lutein or zeaxanthin. The new recommended formula consists of 400 IU Vitamin E, 500 mg Vitamin C, 10 mg Lutein and 2 mg Zeaxanthin, 80 mg Zinc and 2 mg Copper.

Furthermore, similar to the original AREDS findings, the AREDS2 reaffirmed that none of the modified formulations reduced the risk of progression to cataract surgery.

Multiple SCDRC patients participated in the AREDS2. The physicians thank the efforts of our study department and patients who contributed to this landmark clinical trial.

People who take aspirin for health reasons and are also concerned about age-related macular degeneration (AMD) may be worried about news reports on three recent studies. All three found that people who take aspirin regularly may be at higher risk for “wet” AMD, the form of this eye disease that’s most often linked with sudden vision loss. The latest study from Australia reported that those who took aspirin at least once a week were twice as likely as nonusers to develop wet AMD within the study’s 15 year period. A U.S.-based study reported similar results in December 2012. But these scary-sounding statistics don’t tell the whole story.

First, the actual increase in risk is small, up only about one percent for aspirin users compared to nonusers in these studies.

Second, all three studies were based on people’s self-report of aspirin use; this type of research cannot prove direct cause-and-effect. Third, expert physicians who specialize in AMD say that it’s important for people who’ve been advised by their doctors to take aspirin to keep doing so. The benefits in reducing their risks for heart disease or stroke outweigh their potential risk for AMD. But these experts also say it’s best if doctors weigh each patient’s risks and benefits individually. If aspirin is used for pain control only, other options can be considered, especially for someone who has a family history of AMD or other risk factors.

A new, US-based national study is underway to help clear up these questions.

The U.S. Food and Drug Administration today approved the Argus II Retinal Prosthesis System, the first implanted device to treat adult patients with advanced retinitis pigmentosa (RP). The device, which includes a small video camera, transmitter mounted on a pair of eyeglasses, video processing unit (VPU) and an implanted retinal prosthesis (artificial retina), replaces the function of degenerated cells in the retina (a membrane inside the eye) and may improve a patient’s ability to perceive images and movement. The VPU transforms images from the video camera into electronic data that is wirelessly transmitted to the retinal prosthesis.

RP is a rare genetic eye condition that damages the light-sensitive cells that line the retina. In a healthy eye, these cells change light rays into electrical impulses and send them through the optic nerve to the area of the brain that assembles the impulses into an image. In people with RP, the light-sensitive cells slowly degenerate resulting in gradual loss of side vision and night vision, and later of central vision. The condition can lead to blindness.

“This new surgically implanted assistive device provides an option for patients who have lost their sight to RP – for whom there have been no FDA-approved treatments,” said Jeffrey Shuren, M.D., director of the FDA’s Center for Devices and Radiological Health. “The device may help adults with RP who have lost the ability to perceive shapes and movement to be more mobile and to perform day-to-day activities.”

The Argus II system is intended for use in adults, age 25 years or older, with severe to profound RP who have bare light perception (can perceive light, but not the direction from which it is coming) or no light perception in both eyes, evidence of intact inner layer retina function, and a previous history of the ability to see forms. Patients must also be willing and able to receive the recommended post-implant clinical follow-up, device fitting, and visual rehabilitation.

In addition to a small video camera and transmitter mounted on the glasses, the Argus II Retinal Prosthesis System has a portable video processing unit (VPU) and an array of electrodes that are implanted onto the patient’s retina. The VPU transforms images from the video camera into electronic data that is wirelessly transmitted to the electrodes. The electrodes transform the data into electrical impulses that stimulate the retina to produce images. While the Argus II Retinal Prosthesis System will not restore vision to patients, it may allow them to detect light and dark in the environment, aiding them in identifying the location or movement of objects or people.

The FDA approved the Argus II Retinal Prosthesis System as a humanitarian use device, an approval pathway limited to those devices that treat or diagnose fewer than 4,000 people in the United States each year. To obtain approval for humanitarian use, a company must demonstrate a reasonable assurance that the device is safe and that its probable benefit outweighs the risk of illness or injury. The company also must show that there is no comparable device available to treat or diagnose the disease or condition.

The FDA reviewed data that included a clinical study of 30 study participants with RP who received the Argus II Retinal Prosthesis System. Investigators monitored participants for adverse events related to the device or to the implant surgery and regularly assessed their vision for at least two years after receiving the implant.

Results from the clinical study show that most participants were able to perform basic activities better with the Argus II Retinal Prosthesis System than without it. Some of the activities tested included locating and touching a square on a white field; detecting the direction of a motion; recognizing large letters, words, or sentences; detecting street curbs; walking on a sidewalk without stepping off; and matching black, grey and white socks.

Following the implant surgery, 19 of the 30 study patients experienced no adverse events related to the device or the surgery. Eleven study subjects experienced a total of 23 serious adverse events, which included erosion of the conjunctiva (the clear covering of the eyeball), dehiscence (splitting open of a wound along the surgical suture), retinal detachment, inflammation, and hypotony (low intraocular pressure).

Three government organizations provided support for the development of the Argus II. The Department of Energy, National Eye Institute at the National Institutes of Health and the National Science Foundation collaborated to provide grant funding totaling more than $100 million, support for material design and other basic research for the project.

Second Sight Medical Products, Inc. is based in Sylmar, Calif.

Image Credit: Second Sight
For more information please visit FDA Medical Devices

This February we are helping to raise awareness about Age Related Macular Degeneration (AMD). Please take a moment to visit www.savingvision.org for more information and resources on treatments that can help prevent blindness.

SCDRC was proud to sponsor the 6th Annual Heroes Brunch Awards, Honoring Betty White. Betty was honored with a Hero of a Lifetime Award for her dedication to the welfare of animals. Guide Dogs of the Desert continue to improve the lives of the blind in the Coachella Valley. Dr. Steven Lin was able to attend the brunch and said it was an amazing event to be part of. To learn more about Guide Dogs of the Desert please visit their website at www.gddca.org

Dr. Chan was invited to present his research at the annual ASRS meeting (American Society of Retina Specialists) in Las Vegas on August 29, 2012. Please visit www.asrs.org to read further on the American Society of Retina Specialists.