CRC contributes to Ground-Breaking Research


GAwebBWFollowing major advances in the treatment of wet AMD, researchers at CRRF and around the world are now focusing their attention on treating AMD at earlier stages of the disease process. Genentech, maker of Avastin and Lucentis, is developing a novel inhibitor of Factor D (a protein involved in complement activation and inflammation) for treatment of geographic atrophy, a major cause of vision loss in dry AMD. Dr. Pieramici, the principal investigator, led The California Retina Research Foundation’s efforts in a Phase 1 FDA trial of this drug. Working in conjunction with other top eye institutions, including Johns Hopkins Wilmer Eye Institute, Harvard and Duke Universities, investigators hypothesize that inhibiting the complement system as discussed above might retard the progression of cellular and visual loss, and prevent the progression to more advanced stages of AMD. Dr. Avery presented the initial results at the Retina Society’s annual meeting this past fall in San Francisco. He comments,

“The purpose of the Phase 1 study was to test and identify any safety issues associated with the new treatment, and we are pleased to report that the drug passed this first phase successfully, leaving us very hopeful.”

Enrollment for Phase 2 of this study is underway.

Anti-VEGF Research
The doctors of the California Retina Consultants and Research Foundation have had the privilege of playing a role in the advancement of the use of anti-VEGF agents in the treatment of retinal diseases. According to Dr. Pieramici,

“The advent of these agents in the treatment of our patients is probably the single most significant advancement in ophthalmology in the last 25 years. Today, because of these agents millions of patients around the world will avoid blindness.”

California Retina Consultants’ involvement dates back to 1993 when Dr. Robert Avery began collecting intraocular samples on patients with diabetic retinopathy and retinal vein occlusions. These samples were analyzed with collaborators at the Joslin Diabetes Center, Harvard University and Johns Hopkins University to identify the growth factor, VEGF (vascular endothelial growth factor). Napoleone Ferrara, a collaborator from Genentech on this project, has recently been awarded the Lasker Award – an award which often precedes the Nobel prize. Genentech was the first pharmaceutical company to produce inhibitors of VEGF, and the doctors at CRC were among the first medical groups to adapt these agents to treat patients, first with neovascular (wet) AMD and then with other diseases. The data from California Retina’s first large series of patients was collected and published in Ophthalmology and has become the single most cited retina paper in the last decade. Dr Avery comments:

“It has been an extremely exciting time to be a researcher in retinal diseases. Conditions that were at one time considered irreversible and destined to lead to permanent, significant visual impairment are now treatable with remarkable results. It’s been very rewarding to be involve in both discovering VEGF’s role in retinal disease, and years later, pioneering the treatment of these disease with VEGF inhibitors.”

California Retina Consultants’ dedication to the investigation and clinical application of new treatments continues unabated despite these advances. Much of the emphasis is now directed to extending the treatment duration and efficacy of current therapies while focusing on treating retinaldiseases at earlier stages in the pathologic process.

Comparison of Age Related Macular Degeneration
Treatments Trial (CATT)

There are currently two widely used drugs approved by Medicare for the treatment of wet AMD: Avastin and Lucentis. Both drugs are manufactured by Genentech, however, Avastin is not FDA approved for retinal diseases, but is commonly used “off-label.” It is significantly more affordable than Lucentis which is FDA approved and is accepted by most insurance carriers. The Comparison of Age-Related Macular Degeneration Treatments Trial (CATT) is the first major clinical trial to compare these two drugs. Dr. Avery has been involved in this trial’s design as a member of its executive committee. Data analysis is now beginning for the first year of this two-year trial, with results expected to be reported in the first half of 2011. Genetic analyses of blood samples collected from patients enrolled in the study were recently added to explore potential relationships between an individual’s genetic composition and the degree to which an individual responds to treatment.

Complement Pathway Trials and Other
Novel Treatments

Two multi-centered clinical trials at CRC are testing new combination therapies for wet AMD. Each study evaluates the efficacy of using Lucentis in combination with another treatment. By adding an additional mechanism of action, the hope is to improve the efficacy and durability over Lucentis monotherapy. The first study tests a compound designed to strip the abnormal vessels of pericytes, which act to facilitate blood vessel development, growth and stability. This compound seems to preferentially eliminate the abnormal vessels that result in retinal bleeding and scar formation. The second study tests a complement pathway inhibitor. The complement pathway is an important inflammatory pathway. Overactivation of this pathway may lead to inflammatory damage within the outer retina, and could be an inciting and propagating factor in the development of both wet and dry AMD. Patients with genetic abnormalities predisposing to complement over action have heightened risk of developing advanced macular degeneration. Histo-chemical evaluation of drusen (deposits under the retina associated with AMD) conducted at The University of California Santa Barbara have confirmed that inflammatory proteins of the complement system are present in these deposits. This is additional evidence supporting the hypothesis that inhibiting this inflammatory system may be a rational approach to treating AMD patients.


CRVOwebBWAn occlusion, or blockage, of a retinal vein is a common cause for vision loss. When the central vein becomes blocked, blood flow out of the eye is reduced. This leads to bleeding and swelling of the retina, a condition known as macular edema. Given the success of both Lucentis and Avastin in treating retinal fluid accumulation in wet macular degeneration, California Retina researchers set out to determine if these two drugs could be effective treatments for patients suffering from central retinal vein occlusions. California Retina Research Foundation began the studies in 2005 and results were presented at the Association for Research in Vision and Ophthalmology’s annual meeting. Using the data from this small clinical trial, Genentech and investigators around the country initiated large scale national clinical trials to further evaluate the treatment of retinal swelling or macular edema associated with branch and central retinal vein occlusions using Lucentis. These trials were conducted at multiple centers across the United States, including California Retina Consultants. The majority of participants in the trials demonstrated an improvement in visual acuity and a reduction in macular edema. In June 2010, Lucentis was approved by the FDA for treating this condition. The CRRF is conducting additional trials to find longer lasting treatments for retinal vein occlusions, testing the effectiveness of higher doses of Lucentis as well as combination therapies using Lucentis with laser.


EDEMAwebBWSwelling of the retina, or macular edema, is a major cause of vision loss in patients with diabetic retinopathy. Until recently, laser therapy was the only effective treatment for patients with diabetic macular edema. Despite this therapy, many experienced incomplete resolution of the swelling and persistent visual loss. Newer therapies were needed. CRRF researchers have been members of the NIH (National Institutes of Health) sponsored Diabetic Retinopathy Clinical Research Network investigating various treatments for diabetic eye diseases over the last eight years. Recently the DRCR reported favorable results using anti-VEGF agents in the treatment of diabetic macular edema. Drs. Pieramici and Nasir recently presented the findings of this trial at the Retina Society and California Retina Consultants’ annual meetings. Dr. Nasir stated,

“This new treatment option will forever change the management of diabetic eye disease and potentially save the vision in thousands of our patients. We are grateful to be part of this groundbreaking study and proud to have offered patients in our various offices a chance to receive treatment before it was commercially available. We thank all of our patients who participated in these clinical research trials.”