Safe And Effective Inhibition Of Ophthalmic Blood Vessel Growth Shown By Gene Signal GS-101 Data

Gene Signal, a company focused on developing innovative drugs to manage angiogenesis based conditions, today announced the publication of interim results from a phase II study suggesting that the antisense oligonucleotide GS-101 (eye drops) is safe and effective at inhibiting and regressing corneal neovascularisation (abnormal new blood vessel growth). Neovascularisation in this part of the eye is a major risk factor in corneal graft rejection, the most common transplantation procedure that saves the sight of approximately 46,000 people worldwide each year.

The data were published in the September 2009 issue of Ophthalmology by researchers led by Claus Cursiefen, MD, from the Department of Ophthalmology at the Friedrich-Alexander University Erlangen-N??rnberg, in Erlangen, Germany. Gene Signal is now conducting an international phase III trial with GS-101 for the prevention of pathologic corneal neovascularisation and thereby corneal graft rejection. GS-101 has been granted Orphan Drug status for this indication in Europe.

“Compared to the placebo group in which 100% of patients suffered from progression of corneal neovascularisation, the optimal GS-101 treatment group showed regression in 86% of patients. We are very encouraged by these results as they represent real progress in the development of GS-101 as a new treatment to combat corneal graft rejection,” explained Dr. Claus Cursiefen of the Department of Ophthalmology, Friedrich-Alexander University Erlangen-N??rnberg. “We urgently need new options for the thousands of graft recipients, whose current treatment options for threatened rejection such as immunosuppressants are not ideal due to side effects. GS-101 is the first specific angiogenesis inhibitor that has demonstrated activity at the anterior part of the eye, where numerous diseases associated with pathologic angiogenesis endanger vision.”

“The publication of these positive phase II results for GS-101 is a major milestone for Gene Signal. As a novel approach to the management of ophthalmic angiogenesis, we are keen to provide rigorous scientific backup to support our ongoing clinical development program. We also recently published data in the Journal of Pharmacology and Experimental Therapeutics confirming that GS-101 prevents in vivo expression of IRS-1, a protein associated with new blood vessel formation (angiogenesis), and we intend to present additional data on GS-101 at various scientific forums in the near future,” noted Eric Viaud, CEO of Gene Signal.

Study Data

The aim of this randomised, double-blind, multicenter phase II clinical study was to test the efficacy and tolerability of GS-101 (eye drops), an antisense oligonucleotide against insulin receptor substrate-1 (IRS-1), versus placebo, against progressive corneal neovascularisation (excessive or harmful angiogenesis). Forty patients non-responsive to conventional therapy participated in the study. Four groups of 10 patients were treated for three months comparing three doses of GS-101 (eye drops: 2x/day; 43, 86 and 172 g/day total) to placebo (10 patients per group). The primary endpoint was measured by the reduction in area covered by pathologic corneal blood vessels measured morphometrically on digitised slit-lamp pictures using image analysis techniques.

Treatment with GS-101 was generally well tolerated, with no associated serious side effects. At 86 micro g/day GS-101 eye drops produced a significant inhibition and regression of corneal neovascularisation (-2.04 ?�1.57% of total corneal area; p=0.0047). The low dose tended to stabilise growth (0.07?�2.94; p=0.2088) compared to placebo (0.89?�2.15), where corneal neovascularisation progressed in all patients in the 3 month period. The high dose of GS-101 was found to have no additional benefit.

About Corneal Grafts and GS101

Every year, approximately 46,000 corneal grafts are performed worldwide to cure or prevent blindness making this procedure the most frequently performed transplant surgery. However, the 5 year failure rate for corneal grafts is currently around 35%. As with many other graft procedures, donor grafts are always in limited supply, with waiting times for the procedure ranging from6 months to 2 years. One of the main reasons for graft failure is the natural immune response of the body.

Normally, the cornea is avascular, or deprived of blood and lymphatic vessels, protecting the donor cornea from being rejected. However, under certain circumstances, abnormal new blood vessel creation or neovascularisation occurs, inducing an immune response against the donor graft that can lead to immunological corneal graft rejection.

As currently there is no therapy available, Gene Signal is working on new ways to prevent this syndrome. With GS-101, its antisense oligonucleotide approach, which benefits from orphan designation in Europe, the company aims to block the pathways leading to the formation of blood vessels in the cornea. This approach uses short DNA fragments that specifically target and block the production of IRS-1, a protein required for the formation and growth of new blood vessels.

Source:
Mike Sinclair

Halsin Partners

People With Limitations In Function Benefit From Computer Custom Interfaces

Insert your key in the ignition of a luxury car and the seat and steering wheel will automatically adjust to preprogrammed body proportions. Stroll through the rooms of Bill Gates’ mansion and each room will adjust its lighting, temperature and music to accommodate your personal preference. But open any computer program and you’re largely subject to a design team’s ideas about button sizes, fonts and layouts.

Off-the-shelf designs are especially frustrating for the disabled, the elderly and anybody who has trouble controlling a mouse. A new approach to design, developed at the University of Washington, would put each person through a brief skills test and then generate a mathematically-based version of the user interface optimized for his or her vision and motor abilities. A paper describing the system, which for the first time offers an instantly customizable approach to user interfaces, was presented in Chicago at a meeting of the Association for the Advancement of Artificial Intelligence.

“Assistive technologies are built on the assumption that it’s the people who have to adapt to the technology. We tried to reverse this assumption, and make the software adapt to people,” said lead author Krzysztof Gajos, a UW doctoral student in computer science and engineering. Co-authors are Dan Weld, a UW professor of computer science and engineering, and Jacob Wobbrock, an assistant professor in the UW’s Information School.

Tests showed the system closed the performance gap between disabled and able-bodied users by 62 percent, and disabled users strongly preferred the automatically generated interfaces.

“This shows that automatically generating personalized interfaces really does work, and the technology is ready for prime time,” Weld said.

The system, called Supple, begins with a one-time assessment of a person’s mouse pointing, dragging and clicking skills. A ring of dots appears on the screen and as each dot lights up, the user must quickly click on it. The task is repeated with different-sized dots. Other prompts ask the participant to click and drag, select from a list, and click repeatedly on one spot. Participants can move the cursor using any type of device. The test takes about 20 minutes for an able-bodied person or up to 90 minutes for a person with motor disabilities.

An optimization program then calculates how long it would take the person to complete various computer tasks, and in a couple of seconds it creates the interface that maximizes that person’s accuracy and speed when using a particular program.

Researchers tested the system last summer on six able-bodied people and 11 people with motor impairments. The resulting interfaces showed one size definitely did not fit all.

A man with severe cerebral palsy used his chin to control a trackball and could move the pointer quickly but spastically. Based on his skills test, Supple generated a user interface where all the targets were bigger than normal, and lists were expanded to minimize scrolling.

By contrast, a woman with muscular dystrophy who participated in the study used both hands to move a mouse. She could make very precise movements but moved the cursor very slowly and with great effort because of weak muscles. Based on her results, Supple automatically generated an interface with small buttons and a compressed layout.

“There is a temptation to think that we can come up with a universal design. But if we look at the results, the design that helps one person will actually be hurtful to a person with a different set of abilities,” Gajos said.

“From an accessibility standpoint, it’s always better to change the environment, rather than use specialized assistive technologies,” said Kurt Johnson, a UW professor of rehabilitation medicine who coordinated the tests. “Supple could be useful for many people with limitations in function, ranging from the elderly, to people with low vision, to people with hand tremors.”

The program could also be used to create interfaces that can adapt to different sizes of screen, for example on handheld devices.

But deploying this system would require a radically different approach to designing computer interfaces, Gajos said. He predicts the first applications are likely to be for Web-based applications. The researchers also plan to look at adapting interfaces that were designed in the traditional way into ones that Supple can use.

Source: Hannah Hickey

University of Washington

Glaucoma Patients Are Prone To Other Serious Illnesses

A nationwide study in Taiwan compared glaucoma patients with people who did not have this eye disease and found that the glaucoma patients were significantly more likely to have other serious health problems, including high blood pressure, diabetes, ulcers and/or liver disease. The study is published in November’s Ophthalmology, the journal of the American Academy of Ophthalmology.

“Doctors who treat glaucoma or these other medical conditions should be aware that their patients may have multiple illnesses; medical specialists should test and treat such patients accordingly and work collaboratively to provide the best, safest care,” said lead researcher Jai-Der Ho, MD, PhD, of Taipei Medical University, Taiwan.

Dr. Ho and his colleagues reviewed year 2005 medical records of 76,673 people with open-angle glaucoma (OAG), the most common form of this sight-threatening illness, and compared them with 230,019 people without OAG, matched for age, gender and other factors. More than half of the OAG patients had hypertension (high blood pressure), and more than 30 percent had either diabetes or hyperlipidemia (high levels of unhealthy fats in the blood). The prevalence of these diseases as well as stroke, liver disease or ulcer was at least 3 percent higher in OAG patients than in controls.

Glaucoma can be considered a systemic disease, rather than a disorder of the eyes only. One theory says that glaucoma may result from abnormalities in the blood vessels and circulation that nourish the optic nerve, eye and brain. For example, when a person has hypertension, blood vessels in the retina-the light-sensitive area at the back of the eye that conveys images to the optic nerve-may also become narrow and constricted, a condition associated with OAG. Other studies have found significant associations between glaucoma, stroke, and migraine. And glaucoma itself can lead to other health problems: when OAG damages vision so that a person is less able to read, drive, or enjoy other aspects of daily life, he or she is at higher risk for depression or other psychological illnesses.

Ophthalmologists (Eye M.D.s) estimate that glaucoma is undiagnosed in as many as 50 percent of people who have it. Dr. Ho’s study took precautions to ensure that people in the control group were unlikely to have missed diagnoses.

The researchers caution, though, that since nearly all subjects in this study were ethnically Chinese, the study results may not be applicable to other populations.

Source:

American Academy of Ophthalmology

News From The American Journal Of Pathology, December 2009

New Molecule Implicated in Diabetes-Associated Blindness

A group led by Dr. Jian-xing Ma at The University of Oklahoma Health Sciences Center, Oklahoma City, OK has demonstrated that the Wnt signaling pathway plays a role in diabetic retinopathy. Their report can be found in the December 2009 issue of The American Journal of Pathology.

Diabetic retinopathy, damage to the retina in the eye as a result of inflammatory complications of diabetes mellitus, affects up to 80% of all patients who have had diabetes for 10 years or more. Diabetic retinopathy is the leading cause of blindness in the working age population; however, the mechanisms by which diabetes induces this inflammation remain unclear.

To determine if the Wnt signaling pathway, which is activated under numerous pathological conditions, plays a role in diabetic retinopathy, Chen et al examined retinal expression and activation of a Wnt signaling molecule in human patients with diabetic retinopathy as well as in mouse models. They found high retinal expression and activation of Wnt signaling molecules in patients with diabetic retinopathy. Moreover, blocking Wnt signaling decreased the severity of diabetic retinopathy in mouse models. Wnt therefore provides a new target for diabetic retinopathy therapy.

Taken together, the data by Dr. Ma and colleagues suggest that “Wnt pathway activation is a novel pathogenic mechanism for [diabetic retinopathy] in both human patients and in animal models. Thus, the Wnt pathway represents a new target for pharmaceutical intervention of [diabetic retinopathy].”

Chen Y, Hu Y, Zhou T, Zhou KK, Mott R, Wu M, Boulton M, Lyons TJ, Gao G, Ma J: Activation of the Wnt Pathway Plays a Pathogenic Role in Diabetic Retinopathy in Humans and Animal Models. The American Journal of Pathology2009, 175: 2676-2685

New Cause for Alzheimer Disease

Dr. Carme Espinet and colleagues at the University of Lleida, Lleida, Spain have discovered that a precursor to nerve growth factor (pro-NGF) may play a pathogenic role in Alzheimer disease. They present these findings in the December 2009 issue of The American Journal of Pathology.

Alzheimer disease is a degenerative, terminal form of dementia that affects over 35 million people world-wide. Oxidative stress, which occurs in the early stages of Alzheimer disease, may modify molecules, resulting in loss or alteration of their function.

A precursor to nerve growth factor (pro-NGF) is expressed at high levels in Alzheimer disease-affected individuals, and accumulation of pro-NGF may lead to neural cell death. Kichev et al showed that pro-NGF is modified in an Alzheimer disease stage-dependent manner by oxidative stress and that modified pro-NGF blocked processing to mature NGF and led to neuronal cell death. Furthermore, injection of modified pro-NGF or pro-NGF derived from human Alzheimer disease patients into mice resulted in cognitive and learning impairment, suggesting that modified pro-NGF may provide a novel pathogenic pathway for Alzheimer disease.

Dr. Espinet’s group suggests “that intra-cerebroventricular administration of AGE/ALEs modified pro-NGF to mice impairs learning tasks, thus reinforcing the idea that pro-NGF could have a relevant role in the ethiopathogenesis of the disease.”

Kichev A, Ilieva EV, Pi?�ol-Ripoll G, Podlesniy P, Ferrer I, Portero-Ot?�n M, Pamplona R, Espinet C: Cell death and learning impairment in mice caused by in vitro modified pro-NGF can be related to its increased oxidative modifications in Alzheimer disease. The American Journal of Pathology 2009, 175: 2574-2585

Genetic Abnormality in Tumor-Associated Endothelial Cells

Dr. Kyoko Hida and colleagues at Hokkaido University Graduate School of Dental Medicine, Sapporo, Japan and Harvard Medical School in Boston, MA have found that endothelial cells associated with tumors have cytogenetic abnormalities. They report their data in the December 2009 issue of The American Journal of Pathology.

Angiogenesis, or the growth of new blood vessels, plays a key role in tumor spread and metastasis. The endothelial cells that comprise tumor-associated blood vessels have previously been thought to be genetically stable, but recent evidence has been provided for abnormal copies of chromosomes in vascular endothelial cells in some tumor types.

Akin et al hypothesized that endothelial cells associated with human renal cell carcinoma would have cytogenetic abnormalities. They found that a portion of tumor-associated endothelial cells had aneuploidy, an abnormal number of chromosomes, and that many of these cells had stem cell-like characteristics. Abnormal endothelial cells may therefore contribute to the pathogenesis of metastatic carcinoma.

Dr. Akin and colleagues conclude that “aneuploid [tumor-assoicated endothelial cells] that organize tumor tissue surrounding the stroma might affect tumor progression and metastasis. It will be important to target abnormal tumor stroma in order to develop more effective cancer therapies.”

Akino T, Hida K, Hida Y, Tsuchiya K, Freedman D, Muraki C, Ohga N, Matsuda N, Akiyama K, Harabayashi T, Shinohara N, Nonomura K, Klagsbrun M, Shindoh M: Cytogenetic Abnormalities of Tumor-Associated Endothelial Cells in Human Malignant Tumors. The American Journal of Pathology 2009, 175: 2657-2667

EMT Contributes to Vision Loss Due to Bone Marrow Transplantation

Researchers from the Keio University, School of Medicine, Tokyo, Japan have discovered that epithelial-mesenchymal transition (EMT) plays a role in damage in the eye after bone marrow transplantation. These results are presented in the December 2009 issue of The American Journal of Pathology.

After bone marrow transplantation, transplanted immune cells can recognize the graft recipient as foreign (similar to how the immune system recognizes bacteria as foreign), resulting in an attack on host tissues. When this attack occurs in the eye, it may lead to vision loss and excessive fibrosis.

EMT, which is characterized by a change in cells from adherent to mobile, has been implicated in fibrotic diseases. Ogawa et al therefore explored the potential role of EMT in eye disease following bone marrow transplantation. They observed several features of EMT in eyes after bone marrow transplantation including down-regulation of adhesion molecules and up-regulation of EMT markers in epithelial cells. These results indicate that EMT may be at least partially responsible for fibrotic eye damage in patients following bone marrow transplantation.

Ogawa et al suggest that “a full understanding of the contribution of different extracellular triggers in ??� fibrosis [in the eye] will elucidate the mechanism of the dynamic process of EMT [in transplanted cell attack on the new host] and improve the quality of life of patients [after bone marrow transplantation].”

Ogawa Y, Shimmura S, Kawakita T, Yoshida S, Kawakami Y, Tsubota K: Epithelial Mesenchymal Transition in Human Ocular Chronic Graft-Versus-Host Disease. The American Journal of Pathology, 175: 2372-2381

Source: Angela Colmone, Ph.D.

American Journal of Pathology

Macular Degeneration Could Be Affected By Genetic Variant

Genetic variations that affect the production of various chemicals in
the inflammation pathways could provide more information about age
related macular degeneration (AMD), according to research released in
the British Journal
of Ophthalmology on February 28, 2008.

AMD is a
progressive eye diseases which affects the center of the retina, known
as the macula, at the back of the eye. This portion of the eye is most
specialized for fine, central vision tasks, including reading or
driving. It is most common among the elderly, and in developed
countries it is a major cause of untreatable blindness.

Researchers from the University of Southampton in the UK investigated
genes controlling the production and suppression of cytokines, which
play an important role in the inflammatory response. They focused on
four specific genetic variations, each related to control of expression
of certain cytokines.

To this end, they examined DNA samples from people aged 55 or older.
478 were people presenting with AMD and 555 people showed no signs of
the disease. One of the genetic variants examined (251A/T) is
associated with the gene boosting production of interleukin 8 (IL-8).
In previous studies, this genetic variation has been linked to several
inflammatory diseases and cancer, and this genetic variant was
significantly more prevalent in patients with AMD. The results remained
conclusive after normalization for age, sex, weight, and smoking, all
of which can specify a higher risk of AMD.

The authors indicate that, in a larger study, their findings could help
create a test to screen for AMD genetically, as well as potential
directions for development of drugs to control it.

In an editorial accompanying the article, opthamology specialists from
the National Institutes of Heath and the University of Michigan
cautiously commend the results. They note that many further studies are
necessary before any direct causal relationship can be confirmed.
However, they claim that the explanation is plausible, because the
development of AMD has been linked to cooperative effects from genetic
and environmental factors. That is, natural changes that come with
aging, such as the accumulation of oxidative stress, seem to initially
give rise to the disease, which becomes worse with additional immune
system activity.

Interleukin 8 promoter polymorphism -251A/T is a risk factor
for age related macular degeneration
Srini V Goverdhan, Sarah Ennis, S R Hannan, K C Madhusudhana, A J Cree,
A J Luff and Andrew J Lotery
Online First Br J Ophthalmol 2008
doi: 10.1136/bjo.2007.123190
Click
Here For Abstract

Anna Sophia McKenney

First Pepose Award From Brandeis Goes To Vision Researchers Jay And Maureen Neitz

Brandeis University selected Jay and Maureen Neitz, the husband-and-wife team whose pioneering research may lead to the use of gene therapy to treat vision disorders, as the inaugural recipients of the Jay Pepose ’75 Award in Vision Sciences.

The award is funded by a $1 million endowment established this year through a gift from Brandeis graduates Jay Pepose ’75 and Susan K. Feigenbaum ’74, his wife. The endowment primarily supports graduate research fellowships in vision science.

The Neitzes, both of whom are faculty members in the Department of Ophthalmology at the University of Washington in Seattle, will visit Brandeis to receive the Pepose Award. They will each deliver a public lecture in Gerstenzang 121: Jay will discuss “Gene Therapy for Red-Green Color Blindness in Adult Primates” at 3:30 p.m. on Feb. 8, and Maureen will talk about “Retinal Activity Patterns and the Cause and Prevention of Nearsightedness” at noon on Feb. 9.

Pepose is a professor of clinical ophthalmology at Washington University and the owner and medical director of the Pepose Vision Institute in St. Louis. During his time as an undergraduate, Pepose worked closely with John Lisman, the Zalman Abraham Kekst Chair in Neuroscience and Professor of Biology at Brandeis. He was part of the inaugural class of Fellows inducted into the Association for Research in Vision and Ophthalmology (ARVO) in 2009.

“We look forward to the Neitzes’ visit to campus to discuss their groundbreaking research,” said Brandeis President Jehuda Reinharz, PhD ’72. “We thank Jay and Susan, whose gift to establish the Pepose Award in Vision Sciences has made it possible for Brandeis faculty and students to learn more about the Neitzes’ work.”

In a recent issue of the journal Nature, the Neitzes and their colleagues detailed a study in which they used gene therapy to cure two squirrel monkeys of color blindness. The research offers hope for the use of gene therapy to treat adult vision disorders involving cone cells – the most important cells for vision in humans.

“The Neitzes’ recent paper in Nature will revolutionize the way we understand color perception,” Pepose said. “I am delighted that Brandeis has chosen such outstanding contributors to vision research for this award.”

Source: Laura Gardner

Brandeis University

Allergan Receives FDA Approval For OZURDEX(R) As Treatment Option For Non-Infectious Uveitis Affecting The Posterior Segment Of The Eye

Allergan, Inc. (NYSE: AGN) announced that the United States Food and Drug Administration (FDA) has approved OZURDEX(R) (dexamethasone intravitreal implant) 0.7 mg for the treatment of non-infectious ocular inflammation, or uveitis, affecting the posterior segment of the eye. Uveitis is characterized by inflammation of the eye’s uvea, which is the middle vascular layer consisting of the iris (anterior), ciliary body (intermediate) and choroid (posterior). Uveitis of the anterior (front) of the uvea is more common and typically does not lead to vision impairment;1 while posterior uveitis (back of the eye) is associated with more severe outcomes that can include blindness, cataracts, secondary glaucoma and macular abnormalities.2 Posterior uveitis is the cause of 10 to 15 percent of cases of blindness in the United States.3 OZURDEX(R) is a biodegradable implant that delivers an extended release of the corticosteroid dexamethasone via intravitreal injection with Allergan’s proprietary and innovative NOVADUR(R) solid polymer delivery system.

The efficacy of OZURDEX(R) for the treatment of non-infectious uveitis affecting the posterior segment of the eye was assessed in a 26-week, multi-center, double-masked, randomized clinical study in which 77 patients received OZURDEX(R) 0.7 mg and 76 patients received sham injections. Eligible patients had non-infectious ocular inflammation of the posterior segment with intermediate or posterior uveitis, a vitreous haze grade of >+1 on the 0-4 classification scale and best corrected visual acuity (BCVA) of 10 to 75 letters on the Snellen eye chart. In terms of vitreous haze, a score of +1 on the scale indicates slightly blurred optic nerve and vessels. Severity increases with each grade of the scale, with grade 4 indicating that the optic nerve head is obscured. Key exclusion criteria included history of glaucoma or use of intraocular pressure (IOP) lowering medications within the last month.

After a single injection of OZURDEX(R), the percent of patients reaching a vitreous haze score of zero (where a score of zero represents no inflammation) was statistically significantly greater for patients in the OZURDEX(R) treated group versus sham (47 versus 12 percent, respectively) at the week eight primary endpoint. In addition, the percent of patients achieving a 3-line improvement in BCVA was 43 percent in the OZURDEX(R) treated group, versus seven percent for the sham group at week eight.

“The approval of OZURDEX(R) offers physicians another option to treat ocular inflammation resulting from uveitis affecting the posterior segment of the eye,” said Scott Whitcup, M.D., Allergan’s Executive Vice President, Research and Development and Chief Scientific Officer. “It is also a milestone for Allergan’s Retina franchise, which exemplifies our continued commitment to developing and bringing to market advanced therapies that meet the unmet medical needs of patients with difficult-to-treat retinal diseases.”

OZURDEX(R) is administered as an in-office procedure. The treatment is currently available to physicians and patients in the United States and the European Union. OZURDEX(R) implants were initially approved in June 2009 as the first drug therapy indicated for the treatment of macular edema following retinal vein occlusion (RVO).

About Non-Infectious Uveitis Affecting the Posterior Segment of the Eye

Symptoms of uveitis affecting the posterior segment of the eye may include photopsia (perceived flashes of light), floaters (appearing as spots or threads), scotomata (area of diminished vision), and metamorphopsia (vision distortion),4 which lead to vitreous haze and loss of BCVA. Uveitis causes an estimated 10 to 15 percent or more of cases of blindness in the United States; the large majority of these cases occur in people between the ages of 20 to 60 years old, usually in their 30s and 40s.5

More severe cases of non-infectious intermediate, and most cases of non-infectious posterior uveitis, are typically treated with local and systemic steroids, along with immunosuppressives in certain cases.6 Tablets or injections are needed to deliver the drug effectively to the middle and back of the eye. However, steroids that are administered systemically for a prolonged period may have potential serious systemic side effects that can limit use of the drugs.7

INDICATIONS AND USAGE

OZURDEX(R) (dexamethasone intravitreal implant) 0.7 mg

Retinal Vein Occlusion

Ozurdex(R) (dexamethasone intravitreal implant) is indicated for the treatment of macular edema following branch retinal vein occlusion (BRVO) or central retinal vein occlusion (CRVO).

Posterior Segment Uveitis

Ozurdex(R) is indicated for the treatment of non-infectious uveitis affecting the posterior segment of the eye.

DOSAGE AND ADMINISTRATION

FOR OPHTHALMIC INTRAVITREAL INJECTION ONLY.

The intravitreal injection procedure should be carried out under controlled aseptic conditions. Following the intravitreal injection, patients should be monitored for elevation in intraocular pressure and for endophthalmitis. Patients should be instructed to report any symptoms suggestive of endophthalmitis without delay.

IMPORTANT SAFETY INFORMATION

CONTRAINDICATIONS

Ocular or Periocular Infections

Ozurdex(R) (dexamethasone intravitreal implant) is contraindicated in patients with active or suspected ocular or periocular infections including most viral diseases of the cornea and conjunctiva, including active epithelial herpes simplex keratitis (dendritic keratitis), vaccinia, varicella, mycobacterial infections, and fungal diseases.

Advanced Glaucoma

Ozurdex(R) is contraindicated in patients with advanced glaucoma.

Hypersensitivity

Ozurdex(R) is contraindicated in patients with known hypersensitivity to any components of this product

WARNINGS AND PRECAUTIONS

Intravitreal Injection-related Effects

Intravitreal injections have been associated with endophthalmitis, eye inflammation, increased intraocular pressure, and retinal detachments. Patients should be monitored following the injection.

Potential Steroid-related Effects

Use of corticosteroids may produce posterior subcapsular cataracts, increased intraocular pressure, glaucoma, and may enhance the establishment of secondary ocular infections due to bacteria, fungi, or viruses.

Corticosteroids should be used cautiously in patients with a history of ocular herpes simplex.

ADVERSE REACTIONS

The most common ocular adverse reactions reported by greater than 2% of patients in the first 6 months following injection of Ozurdex(R) for retinal vein occlusion and posterior segment uveitis include: intraocular pressure increased (25%), conjunctival hemorrhage (22%), eye pain (8%), conjunctival hyperemia (7%), ocular hypertension (5%), cataract (5%), vitreous detachment (2%), and headache (4%).

Increased IOP with Ozurdex(R) peaked at approximately week 8. During the initial treatment period, 1% (3/421) of the patients who received Ozurdex(R) required surgical procedures for management of elevated IOP.

Forward-Looking Statements

This press release contains “forward-looking statements,” including the statements by Dr. Whitcup and other statements regarding research and development outcomes, efficacy, adverse reactions, market and product potential, product availability and other statements regarding OZURDEX(R) for the treatment of noninfectious ocular inflammation due to intermediate or posterior uveitis implant. These statements are based on current expectations of future events. If underlying assumptions prove inaccurate or unknown risks or uncertainties materialize, actual results could vary materially from Allergan’s expectations and projections. Risks and uncertainties include, among other things, general industry and pharmaceutical market conditions; technological advances and patents attained by competitors; challenges inherent in the research and development and regulatory processes; challenges related to product marketing, such as the unpredictability of market acceptance for new pharmaceutical products and/or the acceptance of new indications for such products; inconsistency of treatment results among patients; potential difficulties in manufacturing a new product; general economic conditions; and governmental laws and regulations affecting domestic and foreign operations. Additional information concerning these and other risk factors can be found in press releases issued by Allergan, as well as Allergan’s public periodic filings with the Securities and Exchange Commission, including the discussion under the heading “Risk Factors” in Allergan’s 2009 Form 10-K and Allergan’s quarterly reports on Form 10-Q for the quarters ended March 31, 2010 and June 30, 2010.

© 2010 Allergan, Inc. Irvine, CA 92612. (R) marks owned by Allergan, Inc.

References

(1) M S A Suttorp-Schulten, A Rothova, The possible impact of uveitis in blindness: a literature survey. British Journal of Ophthalmology 1996;80:844-848.

(2) M S A Suttorp-Schulten, A Rothova, The possible impact of uveitis in blindness: a literature survey. British Journal of Ophthalmology 1996;80:844-848.

(3) M S A Suttorp-Schulten, A Rothova, The possible impact of uveitis in blindness: a literature survey. British Journal of Ophthalmology 1996;80:844-848.

(4) AT Gerstenblith et al. Punctate inner choroidopathy: a survey analysis of 77 persons. Ophthalmology. 2007 Jun;114(6):1201-4. Epub 2007 Apr 16.

(5) M S A Suttorp-Schulten, A Rothova, The possible impact of uveitis in blindness: a literature survey. British Journal of Ophthalmology 1996;80:844-848.

(6) S Sudharshan et al. Current approach in the diagnosis and management of posterior uveitis. Indian J Ophthalmol. 2010 Jan-Feb; 58(1): 29-43.

(7) FR Zakka et al. Current trends in the management of ocular symptoms in Adamantiades-Beh?�et’s disease. Clinical Ophthalmology. Oct 15 2009

Source: Allergan, Inc

OptumHealth Donates More Than $2 Million In Eyeglass Frames To Prevent Blindness America

OptumHealth Inc. announced that it is partnering with Prevent Blindness America, the nation’s oldest volunteer eye health and safety organization, to donate 50,000 eyeglass frames worth more than $2 million to residents in Ohio who participate in the Prevent Blindness Ohio Vision Care Outreach program. The program provides access to eye exams and eyeglasses for children and adults without medical coverage.

“By providing these frames to those who may not otherwise be able to afford them, OptumHealth is contributing greatly to the well-being of individuals in Ohio with the most common eye problems,” said Prevent Blindness America President and CEO Hugh R. Parry.

According to research from Prevent Blindness America, in Ohio alone there are nearly 2 million people older than age 40 who have some form of near- or farsightedness. Most vision impairments from refractive errors can be corrected through prescription eyeglasses.

“Our goal in making this donation to Prevent Blindness America is to further the message that routine eye exams should be part of the overall goal to live a healthy lifestyle,” said Don Yee, president of OptumHealth Vision. “Eye exams are an important part of health and wellness because an exam can often signal to an eye care professional that an individual is facing a larger medical issue.”

OptumHealth Vision is a business unit of OptumHealth Specialty Benefits, which offers a broad array of ancillary products, including vision, dental, group and voluntary insurance, worksite individual insurance and non-insurance programs.

About OptumHealth

OptumHealth Inc. helps individuals navigate the health care system, finance their health care needs and achieve their health and well-being goals. The company’s personalized health advocacy and engagement programs tap a unique combination of capabilities that encompass public sector solutions, care solutions, behavioral solutions, specialty benefits and financial services. Serving nearly 60 million people, OptumHealth is one of the nation’s largest health and wellness businesses, and is a UnitedHealth Group (NYSE: UNH) company. More information about OptumHealth can be found at optumhealth.

Source
Prevent Blindness America

The Alcon Research Institute Recognizes Seven Top Researchers In Ophthalmology With Unrestricted Grants

Now in its 28th year, the Alcon Research Institute (ARI) recognized seven outstanding researchers who have dedicated their lives to enhancing the understanding of vision and eye health. These seven doctors, who were nominated by previous winners and selected by ARI’s independent Scientific Selection Committee, will receive $100,000 in unrestricted grant money from the ARI to continue pursuing their research into the underlying causes of eye disease. They also will be recognized at the ARI’s biennial symposium in 2009, where they will present their research to all of the members of the ARI.

“The Alcon Research Institute is proud to recognize the career achievements of the world’s leading researchers in ophthalmology,” said Dr. Stanley Chang, chairman of the Alcon Research Institute, and Edward Harkness professor and chair of Ophthalmology, Columbia University. “The impressive accomplishments and contributions of these current winners to the preservation, restoration and enhancement of vision carry on the long-standing tradition of excellence in scientific and medical investigation of the many previous award winners.”

The 2008 ARI Award winners are:

– Vadim Y. Arshavsky, Ph.D. for his paradigm-shifting work into the behavior of G-Proteins and photoreceptors in an effort to understand humans’ response to light. Dr. Arshavsky is a graduate of Moscow State University and is currently professor of Ophthalmology and Pharmacology and scientific director, Department of Ophthalmology, Duke University, Durham, NC.

– Emily Y. Chew, M.D. and Frederick L. Ferris, M.D. who were jointly instrumental in designing, developing and executing the Age-Related Eye Disease Study, with results that could prevent the development of age-related macular degeneration in more than 300,000 people in the next five years. Dr. Chew is a graduate of the University of Toronto and serves as deputy director, Division of Epidemiology and Clinical Research at the National Eye Institute/National Institute of Health. Dr. Ferris is a graduate of the Johns Hopkins Medical School and currently is the director of Epidemiology and Clinical Research at the National Eye Institute/National Institute of Health.

– David R. Copenhagen, Ph.D. for his extensive body of work studying visual system development. Dr. Copenhagen is a graduate of and has continued his career at the University of California where he is now a professor and vice chair in the Department of Ophthalmology.

– Reza Dana, M.D. for his significant contributions in the area of corneal transplants. Dr. Dana completed his education at Johns Hopkins and Harvard Universities and is now a professor in the Harvard Department of Ophthalmology, director, Cornea Service at Massachusetts Eye & Ear Infirmary and senior scientist at Schepens Eye Research Institute.

– Elizabeth C. Engle, M.D. for her extensive research into the genetics of ocular defects. Dr. Engle is a graduate of Johns Hopkins University and is currently associate professor in Neurology at Harvard Medical School, investigator at Howard Hughes Medical Institute and Senior Research Associate in Ophthalmology at Children’s Hospital Boston.

– Simon W. John, Ph.D. for his distinguished career and groundbreaking research directed to understanding the underlying causes and potential treatments of glaucoma. Dr. John is a graduate of McGill University, is a Professor at The Jackson Laboratory, Research Assistant Professor at Tufts University School of Medicine, Investigator at Howard Hughes Medical Institute and a member of the Graduate Faculty at the University of Maine.

In addition to the unrestricted grants, the awardees will join an impressive list of previous ARI winners to participate in a biennial symposium next year that will review, evaluate and discuss cutting edge research into the causes and treatments of eye disease.

About the Alcon Research Institute

The Alcon Research Institute (ARI) supports global advancements in eye health by honoring those who make outstanding research contributions to the vision sciences. The goal of the ARI is to further the study of eye health by fostering ongoing dialogue and partnerships within the vision research community around the world. As it has for 28 years, the ARI annually identifies exemplary leaders in ophthalmic research and honors them with this prestigious award and unrestricted grants to fund their ongoing research. Since its inception in 1981, the ARI has granted almost $21 million to 235 researchers in support of their research into eye disease and ophthalmology. The nominees are put forth independently by former winners and voted on by an independent committee, made up solely of ARI members.

Alcon Research Institute

Research Study Of Near Vision

The Cornea and Laser Eye Institute is participating in a research study to determine if an investigational corneal inlay can safely and effectively reduce the need for reading glasses. Dr. Peter Hersh, the study doctor, will perform the procedures.

The investigational AcuFocus Corneal Inlay (ACI) is intended to improve near vision in patients with presbyopia, which is the loss of near vision, and reduce dependency on reading glasses. Qualified participants will receive the procedure at no charge.

Presbyopia, the loss of near vision happens when the eye’s natural lens loses the ability to focus light from both far and near objects. As a result, near tasks like reading or computer work are blurry. However, it is possible for far objects to still be clear. Presbyopia is a natural occurrence that happens to most of us by age 45. Patients 45 to 60 years are eligible to participate.

Smaller than a contact lens, the ACI Corneal Inlay looks like a small brown ring. It is 5 microns thick and 3.8 mm across with a small hole in the center. Over 8,000 tiny holes throughout the ACI help maintain the health of the cornea. It is placed within the body of the cornea, directly in front of the pupil. The ACI lets the central rays of light continue on to the retina while blocking out some of the more out-of-focus rays. This is similar to the effect seen when one looks through a small pinhole. This increased focus may improve near vision. With the ACI placed in one eye, the depth of focus is anticipated to provide improved near and in-between vision while having little effect on far away vision.

“We are excited about this technology,” said Dr. Hersh who has performed more than 15,000 laser and surgical vision correction procedures. “This procedure is very different from anything we’ve done with vision correction procedures before.”

“We are very pleased to have Dr. Hersh and his research team involved in the leadership of this research study,” said AcuFocus Chief Executive Officer, Ed Peterson. “They have established a great reputation for excellent patient care and for running very efficient studies while following protocols to the letter.”

Anyone may benefit who is dependent upon reading glasses to see near objects. However, because this is a research study, benefits cannot be guaranteed.

Before beginning research procedures, participants must go through an informed consent process. Implanting the inlay is a surgical procedure that takes less than 15 minutes. After the procedure, participants will be required to return for scheduled follow-up examinations. Return visits will occur over a three-year period and participants will receive the procedure and all examinations at no charge.

Source: Stacey Lazar

The Cornea and Laser Eye Institute, P.A.