Sustained-release implants on track for retinal vascular disease treatment

by:Elias Reichel

KAANAPALI, Hawaii — Sustained-release corticosteroids will play a significant role in retinal vascular disease, but the current implants still need improvements, one presenter here said.

"It is important to realize [steroids] will have a continued role in our treatment of diseases. They may also serve for adjunctive [therapies] like stem cell treatments and [instances] where transplantation or immunoreactions may occur," Elias Reichel, MD, who discussed outcomes using Ozurdex (dexamethasone intravitreal implant, Allergan) and Iluvien (fluocinolone acetonide intravitreal implant, Alimera), said at Retina 2011. "So, having a better delivery system for corticosteroids is very useful for many of the diseases we are seeing in our offices."

Challenges include needing to achieve and maintain clinically effective concentrations in the vitreous over time while maximizing efficacy and minimizing adverse effects, Dr. Reichel said.

As part of a 6-month study, the dexamethasone implant demonstrated 2- to 3-month peak efficacy, had a low incidence of IOP issues and conferred a cataract progression of approximately 5%. Additionally, 45% of the patients gained three lines of visual acuity, Dr. Reichel said.

The U.S. Food and Drug Administration has approved the device for all retinal venous obstructive disease.

The fluocinolone implant is now part of a 36-month study and has demonstrated efficacy to at least 30 months. Between 30% and 40% of patients gained at least three lines of visual acuity. However, the device has a moderately higher risk of IOP issues and a cataract progression rate of 50%, according to Dr. Reichel.

The device has received a complete response letter from the FDA.

"Current formulations that we have are good but can be better," Dr. Reichel said. "We really have to look at longer duration and this reduced risk trade-off."

* Disclosure: Dr. Reichel is a consultant to Alimera and Allergan.

Genetic Testing for AMD is here Today

By; Diana Shechtman OD FAAO & Steven Ferrucci OD FAAO
Age-Related macular degeneration (AMD) is a progressive disease and the leading cause of vision loss among the elderly, affecting central vision required for daily activities such as driving and reading. There are a number of factors affecting AMD, such as advanced age, smoking, UV exposure, overall health (that contribute to high blood pressure, obesity, diet) and family history. Many factors may be modified and yet others like genetics cannot. Although AMD may seem to be hereditary in some families and not others, genetics have been shown to contribute significantly to the disease. Multiple twin and sibling studies have collaborated to the familial nature of the disease. First-degree relatives of patients with AMD are at a significantly increased risk for the disease. Furthermore, large epidemiological studies have suggested a strong genetic risk factor for AMD. In fact, the risk of developing AMD increases 4 fold among patients with a positive family history. In 2005 a breakthrough occurred in the area of genetic research and AMD; Klein and associates discovered a strong link between AMD and certain genetic variants. Similarly, numerous other genes have been implicated in AMD, which may increase the risk of AMD up to 70%.
Until recently there was no test to help determined patient’s inherited risk for AMD. Today, Macula Risk (ArcticDX, Toronto, Ontario) is a genetic test specifically designed to determine genetic predisposition to AMD and vision loss attributed to the more advanced stage of the disease.
Macula Risk  genetic test separates individuals into one of 5 macula risk (MR) categories, with MR 3 through 5 representing an increased risk for the more advance stage of the disease. This accounts for approximately 20% of the general population. MR1 has less than a 5% risk of the advanced stage of the disease, while MR 5 carries greater than 55% risk. These results can aid the doctor in devising a specific management plan and follow-up protocol in order to reassure early intervention to prevent vision loss.
The test only requires a simple in-office cheek swab, which is sent directly to the genetic lab. The report includes test results and written genetic support information (including access to genetic counseling). Macula Risk genetic testing is covered by most insurance providers, including Medicare, as long as the specific diagnosis (ICD-9) are identified by the doctor. The prognostic genetic test is intended for patients who have a diagnosis of early or intermediate AMD. Thus, the “at risk patient,” would have to pay a fee for the test.
Despite our best efforts and new treatment options available today, many people are still losing vision from AMD. New advancements in the area of AMD are becoming an integral part in preventing future visual deterioration. AMD is affected by both environmental and genetic factors that interact with one another to determine prevalence and progression of the disease. Furthermore, at this time we do not know all of the genes linked to AMD. Hence, genetic testing in the area of AMD is only a risk indicator and cannot predict “without a shadow of a doubt,” which patients will and which will not develop the disease. However, this test provides a genetic profile screening to help identify those at risk as well as aids in tailoring a distinct management approach for those with the disease. With various researches devoted to treatment options for AMD, genetic testing in the area of AMD is at the frontier of providing crucial information.
REFERENCES
1. Swaroop, Branham KE, Chen W, Abecasis G. Genetic susceptibility to age-related macular degeneration: a paradigm for dissecting complex disease traits. Hum Mol Genet 2007; 16: 174-82.
2. Klein ML, Mauldin WM, Stoumbos VD. Heredity and age-related macular degeneration. Observations in monozygotic twins. Arch Ophthalmol. 1994; 112: 932-7.
3. Meyers SM, Greene T, Gutman FA. A twin study of age-related macular degeneration. Am J Ophthalmol. 1995; 120: 757-66.
4. Heiba IM, Elston RC, Klein BE, et al. Sibling correlations and segregation analysis of age-related maculopathy: The Beaver Dam Eye Study. Genet Epidemiol. 1994; 11: 51-67.
5. Klaver CC, Wolfs RC, Assink JJ, et al. Genetic risk of age-related maculopathy. Population-based familial aggregation study. Arch Ophthalmol. 1998; 116: 1646-51.
6. Seddon JM, Ajani UA, Mitchell BD. Familial aggregation of age-related maculopathy. Am J Ophthalmol. 1997; 123: 199-206.
7. Klein RJ, Zeiss C, Chew EY, et al. Complement Factor H Polymorphism in Age-Related Macular Degeneration. Science 2005; 308: 385-389.
8. Seddon JM, Reynolds R, Maller J, Fagerness JA, Daly MJ, Rosner B. Prediction model for prevalence and incidence of advanced age-related macular degeneration based on genetic, demographic, and environmental variables. Invest Ophthalmol Vis Sci 2009; 50 (65): 2044-53.
9. www.macularisk.com/en/physicians/order.html (accessed Dec. 14th , 2010)

Zinc and Macular Degeneration

By: Admin
Are you someone who has realized that they are suffering from age related macular degeneration?
Our sense of sight is something that is incredibly important to us, and the idea of having it threatened can be terrifying. The issue is that age related macular degeneration, often abbreviated to AMD is relatively common and after the age sixty, there is a thirty percent chance that this disorder can be developed and it is highly recommended that you use a antioxidant supplement as treatment/ therapy for macular degeneration.
The more research that you do into this condition and into the things that might have a hand in causing it, the more likely it is that you are going to see zinc listed as being something that can help this condition.

Acceleron's ACE-041 Demonstrates Clinical Efficacy

By Acceleron
CAMBRIDGE, Mass – November 19, 2010 – Acceleron Pharma, Inc., a biopharmaceutical company developing novel protein therapeutics that regulate the growth and development of tissues and cells, including muscle, bone, red blood cells, and vasculature, today announced the presentation of interim results from the first-in-human clinical study of ACE-041 in patients with advanced cancer at the 22nd EORTC-NCI-AACR Symposium on Molecular Targets and Cancer Therapeutics in Berlin, Germany. The presentation was given by Professor Sunil Sharma, the Jon and Karen Huntsman Presidential Professor of Cancer Research at the Huntsman Cancer Institute, University of Utah, Salt Lake City, Utah.

“It has been very encouraging to see so many signals of efficacy in this trial, in particular because these are end-stage cancer patients,” said Dr. Sunil Sharma. “It is also important to note that while we have demonstrated significant activity with ACE-041 monotherapy in this study, we might expect to see even more efficacy in future studies with ACE-041 used in combination with other therapies.”

“The clinical activity and safety profile of ACE-041 confirms our understanding that the ALK1 pathway plays a fundamental and distinct role compared to the VEGF-axis in tumor angiogenesis,” said Dr. Matthew Sherman, M.D., Chief Medical Officer at Acceleron Pharma. “This has significant implications because nearly all patients treated with VEGF inhibitors eventually either fail therapy or develop resistance to these drugs. There is a tremendous need for novel therapies that go beyond VEGF to target the tumor blood supply.”

In a phase 1, first-in-human clinical study, patients with advanced-stage tumors were treated with multiple ascending doses of ACE-041, to evaluate the safety and pharmacokinetics of ACE-041. This study also explored antitumor activity of ACE-041.

Summary of interim findings presented:

· ACE-041 subcutaneously (SC) injected once every three weeks (q3w) is generally well-tolerated · Common side effects include mild or moderate peripheral edema, fatigue, nausea, headache, anorexia, and anemia. A single case of Grade 3 congestive heart failure was reported · Toxicities commonly associated with VEGF inhibition (hypertension, proteinuria, or bleeding) have not been observed · ACE-041 pharmacokinetics support dosing every 3 weeks · One patient with refractory head and neck cancer achieved a partial response and three patients had prolonged disease stabilization · Rapid reduction in tumor metabolic activity observed in several patients, measured by FDG-PET imaging · An expanded cohort study is ongoing at the dose level intended for Phase 2 studies,

ACE-041 is being developed for the treatment of advanced cancer and age-related macular degeneration (AMD).

About ACE-041

ACE-041 is a recombinant receptor fusion protein that inhibits angiogenesis by preventing BMP9 and BMP10, members of the TGFβ protein superfamily, from interacting with activin receptor-like kinase 1 (ALK1), a receptor that is found on proliferating endothelial cells. ACE-041 inhibits ALK1 signaling, which is required for the development of mature, functional capillary networks. In animal studies, treatment with ACE-041 inhibits tumor angiogenesis and growth and ocular neoangiogenesis. In a clinical study of patients with advanced, refractory solid tumors, treatment with ACE-041 was generally well-tolerated and antitumor activity was observed, resulting in tumor shrinkage and stabilization of disease. ACE-041 is being developed for the treatment of advanced-stage cancer and age-related macular degeneration (AMD).

About Acceleron Pharma

Acceleron is a privately-held biopharmaceutical company committed to discover, develop, manufacture and commercialize novel biotherapeutics that modulate the growth of red blood cells, bone, muscle, fat and the vasculature to treat musculoskeletal, metabolic and cancer-related diseases. Acceleron’s scientific approach takes advantage of its unique insight into the regenerative powers of the TGF-β superfamily of proteins. Acceleron utilizes proven biotherapeutic technologies and capitalizes on the company’s internal GMP manufacturing capability to rapidly and efficiently advance its therapeutic programs. The investors in Acceleron include Advanced Technology Ventures, Alkermes, Bessemer Ventures, Celgene, Flagship Ventures, MPM BioEquities, OrbiMed Advisors, Polaris Ventures, QVT Financial, Sutter Hill Ventures and Venrock. For further information on Acceleron Pharma.

Macular Degeneration Treatments/Therapies Breakthroughs

by Isobel Washington

Macular degeneration is an eye condition characterized by the deterioration of the macula, which is the central "lens-like" part of the eye's retina responsible for sharp central vision. Affecting central vision and often leading to vision loss, macular degeneration has had limited treatment options. Recently, there have been some breakthroughs to help patients retain vision.

Significance
Macular degeneration is the leading cause of vision loss and blindness among Americans age 65 and older. Vision loss from this condition is a growing problem, since this age demographic represents an increasingly larger percentage of the U. S. population.

Function
Treatments for macular degeneration work to preserve vision ability at the time of treatment, and slow the progression of the disease (it's a progressive disease that affects vision over time). Treatment cannot restore vision that is already lost through the disease. There is no cure or treatment to stop the progression of macular degeneration, there are ways to preserve and prolong current vision.

Eye Injections
Lucentis and Macugen are FDA-approved ocular injection treatments, and are highly effective for preserving vision and inhibiting macular degeneration symptoms, according to AllAboutVision.com. A 2005 study on Lucentis demonstrated success rate of 95 percent for improving and sustaining vision in macular degeneration patients.

Laser Treatment
Laser technology is now used to destroy the abnormal, leaky blood vessels that cause vision loss in macular degeneration patients. The National Eye Institute points out, however, that while this treatment may be effective for preventing vision loss, it is also comes with the risk of destroying healthy tissue that surrounds the treatment area.

Photodynamic Therapy
This method uses special light treatment to activate an injected drug, verteporfin, in the blood vessels, so that it destroys the new, abnormal blood vessels being hyper-produced in the eye (those that cause vision impairment or loss). The National Eye Institute reports that this light-activation method slows vision loss, but doesn't stop it.

Investigational Treatments
Investigational treatments for macular degeneration, in various stages of research and FDA clinical studies, include Avastin, a cancer treatment drug. As of 2009, the National Eye Institute reports that no available treatment provides a cure for macular degeneration, and that vision loss may result, despite treatment.

About the Author
Isobel Washington has been a freelance journalist since 2007. Washington's work first surfaced in Europe, where she served as a restaurant critic and journalist for "LifeStyles" magazine. Her love of travel and culture inspired her first novel, which is currently underway. Washington has a 10-year career in marketing communication and holds a Bachelor of Science degree.

Food For The Eyes

Food for the Eyes

Last Update: 3/20 1:19 pm
Source: WXYZ Detroit

Many of us plan our meals around certain foods hoping to keep our bodies healthy, but not many of us think specifically about our eyes. We have a heads up on culinary choices that can help you see better, longer. In fact, these can be called 'food for the eyes!'

Blair Carper, (worried about his vision)
"I used to be able to see things really sharp and now I don't see things as well."

He's heard carrots are good for the eyes and he's right, but they're not the only way to protect your view of the world. A recent study shows several nutrients in supplemental form help slow the progression of serious eye diseases. Ophthalmologist Sunil Srivastava says incorporating even small amounts into your regular diet can only help. One food with benefits-eggs.

Sunil Srivastava, MD, Ophthalmologist, Emory University
"Eggs do have a lot of good vitamins, such as vitamin A. Vitamin A is important in the function of the eye, specifically the retina, so vitamin A deficiencies can actually lead to night blindness."

Then there are raspberries. The vitamin C in them helps reduce the risk of cataract formation. Almonds are up next because they contain vitamin E.

Sunil Srivastava, MD, Ophthalmologist, Emory University
"Vitamin C and vitamin E have been shown to, at elevated levels, reduce the risk of things like macular degeneration in high risk patients."

Salmon or more specifically fish oil, along with green leafy vegetables, also help prevent macular degeneration, an illness that causes blindness. Ten million Americans are already coping with the disease.

Sunil Srivastava, MD, Ophthalmologist, Emory University
"Lutein and zeaxanthin are certain types of pigments that actually are concentrated in the macula of our retina, which is the center part of our vision, and foods like broccoli and spinach have high levels of lutein and zeaxanthin."

Aslo, try yogurt because the zinc in it helps the body absorb antioxidants, which also help the eyes.

Other good sources of vitamin A are cantaloupe, sweet potatoes, and mango.