Sydney Eye Doctors

Eylea (VEGF Trap-Eye) Receives Unanimous Recommendation for Approval for Treatment of Wet AMD from FDA Advisory Committee
From Regeneron Pharmaceuticals, Inc.
Retina

Regeneron Pharmaceuticals, Inc. (Tarrytown, NY) announced that the Dermatologic and Ophthalmic Drugs Advisory Committee of the FDA voted unanimously to recommend that the approval of Eylea, also known as VEGF Trap-Eye, for the treatment of the neovascular form of age-related macular degeneration (wet AMD) at a dose of 2 milligrams (mg) every eight weeks, following three initial doses given every four weeks.

The committee's recommendation will be considered by the FDA in its review of the Biologics License Application (BLA) for Eylea, but the committee's recommendation is not binding on the FDA. Regeneron submitted a BLA for marketing approval in wet AMD in the U.S. in February 2011 and received a Priority Review designation. Under Priority Review, the target date for an FDA decision on the Eylea BLA is August 20, 2011.

"The positive recommendation by the advisory committee is an important step toward providing wet AMD patients with a new treatment option that could potentially reduce the burden that exists with current therapies," said George D. Yancopoulos, MD, PhD, President of Regeneron Research Laboratories. "We look forward to continuing to work with the FDA as it completes its evaluation of the Eylea BLA."

About Eylea

Vascular Endothelial Growth Factor (VEGF) is a naturally occurring protein in the body. Its normal role in a healthy organism is to trigger formation of new blood vessels (angiogenesis) supporting the growth of the body's tissues and organs. However, in certain diseases, such as age-related macular degeneration, it is also associated with the growth of abnormal new blood vessels in the eye, which exhibit vascular permeability and lead to edema.

Eylea (aflibercept ophthalmic solution), also known as VEGF Trap-Eye, is a fully human fusion protein, consisting of portions of VEGF receptors 1 and 2, that binds all forms of VEGF-A along with the related Placental Growth Factor (PlGF). Eylea is a specific and highly potent blocker of these growth factors. Eylea is specially purified and contains iso-osmotic buffer concentrations, allowing for injection into the eye.

Regeneron and Bayer HealthCare are collaborating on the global development of Eylea for the treatment of the neovascular form of age-related macular degeneration (wet AMD), central retinal vein occlusion (CRVO), diabetic macular edema (DME), and other eye diseases and disorders. Bayer submitted an application for marketing authorization in Europe in wet AMD in June 2011.

The Eylea wet AMD regulatory submissions are based on the positive results from two Phase 3 trials, the VIEW 1 study and the VIEW 2 study. In these trials, all regimens of Eylea, including 2 milligrams (mg) of Eylea dosed every two months (following three loading doses), successfully met the primary endpoint of non-inferiority compared to the current standard of care, ranibizumab 0.5 mg dosed every month. The primary endpoint analysis was statistical non-inferiority in the proportion of patients who maintained (or improved) vision over 52 weeks compared to ranibizumab. A generally favorable safety profile was observed for both Eylea and ranibizumab. The most frequent ocular adverse events were conjunctival hemorrhage, macular degeneration, eye pain, retinal hemorrhage, and vitreous floaters.

Bayer HealthCare will market Eylea outside the United States, where the companies will share equally the profits from any future sales of Eylea. Regeneron maintains exclusive rights to Eylea in the United States.

ACT Announces First Patients Enrolled In Two Clinical Trials Using Embryonic Stem Cells To Treat Stargardt's Disease
From Advanced Cell Technology, Inc
Retina

Advanced Cell Technology, Inc. (Santa Monica, CA), a leader in the field of regenerative medicine, announced the enrollment of the first patients in its two Phase 1/2 clinical trials for Stargardt's Macular Dystrophy (SMD) and Dry Age-Related Macular Degeneration (Dry AMD) using retinal pigment epithelial (RPE) cells derived from human embryonic stem cells (hESCs). The patients were enrolled at the Jules Stein Eye Institute at the University of California, Los Angeles (UCLA).

The Phase 1/2 trials are prospective, open-label studies primarily designed to determine the safety and tolerability of the RPE cells following sub-retinal transplantation into patients with SMD and Dry AMD. Each study will enroll 12 patients with cohorts of three patients in an ascending dosage format. The primary endpoint of both studies is to determine the safety and tolerability of hESC-derived RPE cells at 12 months.

"The enrollment of the first patients in our two clinical trials marks an important step forward for the field of regenerative medicine," said Gary Rabin, interim chairman and CEO of ACT. "We are very pleased with the progress that has been made toward bringing this ground-breaking technology to the patients who need it most. If these therapies work as we hope they will, particularly with small volumes of cells, then we should be in an excellent position to take advantage of our patented techniques for manufacturing large numbers of doses of RPE cells that can be conveniently stored and shipped to clinicians following the basic manufacturing and distribution systems already familiar to pharmaceutical and biotech companies."

Principal investigator Steven Schwartz, M.D., Ahmanson Professor of Ophthalmology at the David Geffen School of Medicine at UCLA and retina division chief at the Jules Stein Eye Institute at UCLA, said, "These trials mark a significant step toward addressing what is one of the largest unmet medical needs of our time -- treatments for otherwise untreatable and common forms of legal blindness, Dry AMD, SMD and other forms of atrophic macular degeneration. Dry AMD is the most common form of macular degeneration. It is the leading cause of blindness in the developed world, and is the leading cause of blindness in people over the age of 55. The incidence of Dry AMD is expected to double over the next 20 years as the population ages. This trial will begin the process of understanding whether stem cell-derived RPE cells have the potential to be a safe and effective treatment for these debilitating diseases. We are looking forward to evaluating the safety and tolerability data of these Phase 1/2 trials, and hope that these early trials will also produce key information relating to engraftment and function of the transplanted RPE cells."

The progress of disease in both SMD and Dry AMD includes atrophy or thinning of the layer of RPE cells in the patient's macula at the center of the retina, the region specialized for high acuity vision. With the loss of RPE cells in the macula comes the eventual loss of photoreceptors. Over time, the progressive loss of RPE cells and concomitant loss of photoreceptors can cause severe central visual deterioration and even blindness as the macula becomes less functional and central vision is gradually lost. ACT's SMD and Dry AMD therapeutic programs utilize transplanted RPE cells to treat these conditions by replacing RPE cells in the patient's eyes before all RPE function is lost.

"Initiating these two clinical trials represents an important milestone for embryonic stem cell research," said Robert Lanza, M.D., chief scientific officer of ACT. "After a decade of extensive research and preclinical studies, it is very satisfying to finally be moving into the clinic. We hope that these cells will, in the future, provide a treatment not only for these two untreatable diseases Stargardt's disease and macular degeneration but for patients suffering from a range other debilitating eye diseases."

About hESC-RPE Cells

The retinal pigment epithelium (RPE) is a highly specialized tissue that is located between the choroids and the neural retina. RPE cells support, protect and provide nutrition for the light sensitive photoreceptors. Human embryonic stem cells (hESCs) can differentiate into any cell type, including RPE cells. hESC-RPE cells have a similar expression of RPE-specific genes compared to human RPE cells and demonstrate the full transition from the hESC state.

Vision Loss in Eye Disease Slowed Using Novel Encapsulated Cell Therapy

From UC San Diego Health System
Medical Studies

A phase 2 clinical trial for the treatment of a severe form of age-related macular degeneration (AMD) called geographic atrophy (GA) has become the first study to show the benefit of a therapy to slow the progression of vision loss for this disease.  The results highlight the benefit of the use of a neurotrophic factor to treat GA and provide hope to nearly one million Americans suffering from GA.

The multi-center research team, including Kang Zhang, MD, PhD, of the University of California, San Diego, Shiley Eye Center, the lead author of the paper and one of the leading investigators in the study, found that long-term delivery of ciliary neurotrophic factor (CNTF) served to re-nourish the retina and stop or slow the loss of visual acuity caused by the disorder.  The results were recently published online in the Proceedings of the National Academy of Science (PNAS).

According to Zhang -- professor of ophthalmology and human genetics at the UCSD School of Medicine and director of UCSD’s Institute of Genomic Medicine – there is currently no effective treatment for dry AMD or GA, though there is a very big need.  “This could open the door to long-term treatment of dry AMD, using a simple surgical procedure.”

In the trial, high-dose CNTF was delivered to 27 GA patients using encapsulated cell therapy (ECT).  Another 24 patients received either a sham surgery (12) or a low-dose of CNTF (12).  CNTF affects survival and differentiation of cells in the nervous system, including retinal cells. CNTF has been shown to retard the loss of photoreceptor cells in many animal models of retinal degeneration.

The ECT utilized a capsule that contains genetically engineered cells to continuously produce CNTF over a 12-month period.  The CNTF-secreting capsule was implanted in the back of the study subject’s eye.  The implant allows the CNTF molecules to diffuse into the eye tissue, while keeping out antibodies and immune cells that would attack and destroy the CNTF-producing cells.

There was a statistically significant difference in the change of the total macular volume in the eyes of study participants at the 12-month point, versus baseline in the high-dose group, according to Zhang.  “In addition, all but one of the patients in the high dose group, or 96.3 percent, maintained stabilized vision, compared to only 75% of the patients in the sham-treatment group.”
The patients treated with a high dose of CNTF also showed an increase in retinal thickness as early as four months after implant, an increase that correlated to the stabilization of vision.

Omega-3 Fatty Acid Linked to Reduced Risk of AMD in Women

Women whose diets were rich in omega-3 fatty acids found in fish had a significantly reduced risk of developing AMD, according to a study in the Archives of Ophthalmology.1

William G. Christen, ScD, of Harvard Medical School and Brigham and Women’s Hospital in Boston, MA, conducted a study of 38,022 women who did not have AMD at baseline. A detailed food-frequency questionnaire was administered to all participants. The main outcome measure was incident AMD responsible for a reduction in BCVA to 20/30 or worse.

During a mean 10 years of follow-up, 235 cases of AMD were identified. Women in the highest tertile of intake for docosahexaenoic acid had a 38% lower risk of AMD than women in the lowest tertile (95% CI, 0.44–0.87). For eicosapentaenoic acid, women in the highest tertile of intake had a 34% lower risk of AMD than women in the lowest tertile (95% CI, 0.48–0.92). Furthermore, women who consumed one or more servings of fish per week had a 42% lower risk of AMD than women who consumed less than one serving per month (95% CI, 0.38–0.87).

“These prospective data from a large cohort of female health professionals without a diagnosis of AMD at baseline indicate that regular consumption of docosahexaenoic acid and eicosapentaenoic acid and fish was associated with a significantly decreased risk of incident AMD and may be of benefit in primary prevention of AMD,” the study authors concluded.

Second Phase 3 Trial of Ranibizumab for DME Meets Primary Endpoint

Genentech announced that the second of two phase 3 trials evaluating ranibizumab (Lucentis) for the treatment of diabetic macular edema (DME) has met its primary endpoint. Patients who received monthly injections of ranibizumab in the RIDE trial were significantly more likely to gain at least 15 letters of best corrected visual acuity (BCVA) than those who received sham injections at 24 months, according to a company news release.

The multicenter, randomized, double-masked study included 382 patients with DME. Patients were randomly assigned to receive monthly injections of 0.3 mg ranibizumab (n=125), 0.5 mg ranibizumab (n=127), or sham (n=130). Like the earlier, parallel RISE study, the purpose of RIDE was not to compare the two doses of ranibizumab, but to compare the effects of each dose with those of the control group. Beginning at 3 months, rescue laser treatment was made available to all patients on an as-needed basis based on prespecified criteria.

At 24 months, 33.6% of patients (n=42) who received 0.3 mg ranibizumab and 45.7% of patients (n=58) who received 0.5 mg ranibizumab gained at least 15 additional letters compared with 12.3% (n=16) of patients who received sham injections. A preliminary analysis showed an ocular and systemic safety profile consistent with previous ranibizumab phase 3 trials, the news release said. After month 24, patients in the sham injection group will be eligible to receive monthly injections of 0.5 mg ranibizumab, and all patients will continue to be followed and dosed monthly for a total of 36 months.

The 24-month results of the RIDE study are consistent with those from RISE, which showed that patients who received ranibizumab experienced rapid improvements in vision that began at day 7 and were sustained at 24 months. RIDE and RISE are identical studies designed to support a marketing application to the US Food and Drug Administration (FDA) for a potential new indication for ranibizumab in DME, according to the news release. The topline results of RIDE will be presented at the Euretina Congress in London on May 29, 2011.

FDA clears trials on embryonic stem cells to treat Stargardt’s macular dystrophy, dry AMD.

The U.S. Food and Drug Administration has approved initiation of the first clinical trials using retinal cells derived from human embryonic stem cells to treat Stargardt’s macular dystrophy and dry age-related macular degeneration.

Advanced Cell Technology submitted investigational new drug applications to undertake the open-label studies of retinal pigment epithelial (RPE) cells derived from stem cells, according to company news releases. The Stargardt’s trial was cleared in late November, and the AMD trial was approved in early January.

The prospective, multicenter phase 1/2 clinical trial is designed to assess the safety and tolerability of RPE cells after subretinal implantation in patients with advanced Stargardt’s macular dystrophy. It will include 12 patients older than 18 years of age. Advanced Cell Technology is in the process of finalizing contracts with three trial sites, which will be identified on clinicaltrials.gov.

Inclusion criteria include visual acuity of 20/320 or worse, pathology consistent with Stargardt’s macular dystrophy, and tolerance to vitrectomy and subretinal injection under general anesthesia or waking sedation. Patients with HIV, cancer, hepatitis B or C, or a history of illicit drug use will not be included.

Investigators will perform optical coherence tomography, fluorescein angiography, slit lamp examination, fundus photography and electroretinography to confirm implantation of RPE cells in the intended location.

“We will be looking at patients with advanced disease,” Mr. Mickunas said. “We are looking at the safety of this particular product. So, the agency’s perspective is that you do not want to go into an eye that has good vision to begin with. There is always that risk that with a new therapy you do not know what is going to occur. You would not want to introduce this into a patient who has good vision with the risk of possibly losing that.”

Treatment involves subretinal injection of RPE cells generated from human embryonic stem cells. Patients will first undergo a partial pars plana vitrectomy.

“Then, a very small needle is introduced to puncture the retina at a certain point,” Mr. Mickunas said. “A small hole is created. Then, a cannula is introduced and a bleb is created subretinally. Once that is done, then the cells are injected into that bleb.”

Dry AMD

Advanced Cell Technology will also conduct a phase 1/2 clinical trial using RPE cells derived from human embryonic stem cells to treat dry AMD.

The prospective, multicenter, open-label study is designed to gauge the safety and tolerability of RPE cells transplanted by subretinal injection. It will also include 12 patients.

“It will be a much older population for the most part,” Mr. Mickunas said. “Age-related macular degeneration does not fall directly into that hereditary retinal disease category. This is a more typical retinal and macular degeneration that occurs in people who are 55 to 60 years old and older.”

Like the Stargardt’s macular dystrophy trial, the AMD study will focus on the ability of RPE cells to preserve photoreceptors and slow or halt the progression of macular degeneration.

“The RPE cells can, in fact, help support the health of the retinal cells,” Mr. Mickunas said. “We are hoping ultimately that we can at least retard that progression of the disease or perhaps stop it altogether.”

The same RPE cells derived from human embryonic stem cells will be used in both clinical trials, according to a news release from Advanced Cell Technology.

A huge international meeting of eye doctors is about to commence in Sydney. I will be giving an instructional course during the meeting. The link will take you to the news section of the academy website for breaking news. http://www.apaosydney2011.com/News.htm

Prior to the surgery, the eye is marked with small purple spots to facilitate later alignment of the intraocular lens. In this instance the lens is used to correct astigmatism and thus has to be placed in a certain axis. 87 degrees in this case. Watch the short video here   Toric IOL

Here is a video of cataract surgery using phacoemulsification and with insertion of an IOL. The blue liquid is a dye called VisionBlue. This is used to facilitate a stage in the operation known as capsulorrhexis and increases safety of the procedure. Cataract & IOL

Many people take Plaquenil for various arthritic and inflammatory conditions. There is a small risk of retinal toxicity from this drug, although the mechanism for retinal damage is not understood. New recommendations for screening, just released, are:
1. initial baseline eye examination within first year of use
This exam to include a 10-2 white threshold visual field test and one or more of the following - multifocal ERG, spectral domain OCT, fundus autofluorescence.
2. Annual screening after 5 years of continuous use of Plaquenil using same strategies.