Eye Care Medical Blog

Soft contact lens wear does not result in clinically significant acceleration in the development of nearsightedness in children and does not cause relevant increases in axial length or corneal curvature, a new study shows. Findings from the three-year study, the largest randomized trial of its kind, appear in the November issue of Investigative Ophthalmology & Visual Science, the official journal of The Association for Research in Vision and Ophthalmology.

According to the multi-site wearing trial study, which tracked the myopic progression of 484 children ages 8-11 randomly assigned to wear glasses or contact lenses, there is no clinically meaningful difference between the two forms of vision correction for the treatment of nearsightedness, a vision problem experienced by approximately one-third of the population.

The new research further dispels a long held myth that soft contact lenses increase myopia progression (a/k/a “Myopic Creep”) in children more than other vision correction options.

“Children as young as eight years old who require vision correction are capable of contact lens wear and this study confirms that they can safely be fit in soft contact lenses to correct their myopia,” says Jeffrey J. Walline, O.D., Ph.D., Ohio State University College of Optometry and leader of the Adolescent and Child Health Initiative to Encourage Vision Empowerment (ACHIEVE) Study, of which this research was a part.

“Recent clinical studies have demonstrated that contact lenses provide a number of quality of life benefits to children beyond simply correcting their myopia,” he adds. “The combined body of research should give both doctors and parents greater confidence in presenting children with the option of contact lens wear when vision correction is required.”

Myopia affects approximately 15 percent of children in the United States, but is much higher in some other countries such as Singapore and China. It typically develops around 8 years of age and worsens until age 15 or 16. A nearsighted child has difficulty seeing objects clearly at a distance, like a blackboard, but can see clearly up-close, such as when reading a book. Myopia can be corrected with glasses, contact lenses and refractive eye surgery.

Doctors will typically evaluate a child’s maturity and level of parental support in deciding whether the child is ready for contact lenses.

About the Study

The purpose of this part of the ACHIEVE study was to measure the refractive error, corneal curvature, and axial length of eight to 11 year old children randomly assigned to wear single vision glasses or soft contact lenses (1???DAY ACUVUE® Brand Contact Lenses or ACUVUE® 2 Brand Contact Lenses, VISTAKON®, Division of Johnson & Johnson Vision Care, Inc.) for three years to compare the rate of myopic progression with each mode of correction over three years.

A total of 484 eight- to 11-year old myopic children participated in the randomized, single-masked, trial conducted from September 2003 to October 2007 at five clinical centers in the United States. Children were randomly assigned to wear spectacles (n = 237) or contact lenses (n = 247) for three years.

Among those who were assigned to wear contact lenses, 93.3 percent elected to wear

1???DAY ACUVUE® Brand Contact Lenses, a single use lens, rather than the other two-week modality. At the conclusion of the study, nine in ten children (90.7 percent) originally assigned to wear contact lenses at the first visit were still wearing contact lenses.

Measurements were conducted prior to randomization and annually. Nearly all (467 – 96.5%) of the subjects were examined at the final visit. The spectacle wearers progressed – 1.08 ?� 0.71 D, and the contact lens wearers progressed – 1.27 ?� 0.72 D (analysis of covariance, p = 0.005); although this difference is statistically significant, the difference is less than can be clinically measured. The axial growth of the spectacle wearers was 0.59 ?� 0.37 mm and 0.63 ?� 0.34 mm for the contact lens wearers (analysis of covariance, p = 0.27). The change in the steep corneal meridian was 0.05 ?� 0.69 D for the spectacle wearers and 0.10 ?� 0.70 D for the contact lens wearers (analysis of covariance, p = 0.43). These differences were not statistically significant.

The study was supported by funding from VISTAKON®, Division of Johnson & Johnson Vision Care. Inc.

ACUVUE®, Brand Contact Lenses are indicated for vision correction. As with any contact lenses, eye problems, including corneal ulcers, can develop. Some wearers may experience mild irritation, itching or discomfort. Lenses should not be prescribed if patients have any eye discomfort, excessive tearing, vision changes, redness or other eye problems. Consult the package insert for complete information. Complete information is also available from VISTAKON®, Division of Johnson & Johnson Vision Care, Inc., by calling 1-800-843-2020 or by visiting jnjvisioncare (for eye care professionals) or acuvue (for consumers).

Johnson & Johnson

Details on the progress of research into unravelling the mystery of glaucoma were provided today as part of the Glaucoma Research Foundation’s 31st Anniversary Benefit and Celebration held here at the legendary Palace Hotel. The annual report by the four principal investigators of the GRF-funded Catalyst For a Cure (CFC) research consortium was among the highlights of this year’s event.

Catalyst For a Cure

Now in its 7th year of funding by the Glaucoma Research Foundation (GRF), the project involves scientists from the world of neuroscience and genetics who work in a real-time, collaborative approach. This process has led to a better understanding of glaucoma as a neurodegenerative disease and could open the door to treatments that actually treat the disease rather than current treatments that lower intraocular pressure as a means of reducing disease progression.

The latest results that were presented focused on two fronts – prevention of vision loss in glaucoma and the potential for therapeutic treatment to stop glaucoma progression.

– Catalyst For a Cure researchers conducted two interventional studies that firmly establish that oxidative stress is a factor in the rate of loss of cellular function from glaucoma – effectively preventing vision loss in a relevant model of glaucoma. Results of these studies were published in 2008 in the scientific journal Investigative Ophthalmology and Visual Science and reported at the annual meeting of the Association for Research in Vision and Ophthalmology.

– In another important pair of studies, the CFC discovered that the cell death that causes vision loss in glaucoma has two distinct phases, and that axonal degeneration precedes neuronal loss. These facts point to a therapeutic window for interventions. Importantly, the studies have determined that vision loss from glaucoma can be predicted by observing changes specific to genes and proteins. The CFC published both of these findings in the highly regarded Journal of Neuroscience.

“As the conventional understanding of glaucoma evolves from being described as an eye disease to a neurodegenerative disease,” said Thomas M. Brunner, CEO and President of the Foundation. “There is an emerging sense that glaucoma could actually be the first neurodegenerative disease we can cure. And that extraordinary possibility was the dominant theme of the presentations tonight.”

Catalyst For a Cure Principal investigators include: David Calkins PhD, Vanderbilt University; Philip Horner PhD, University of Washington; Nicholas Marsh-Armstrong PhD, Johns Hopkins University; and Monica Vetter PhD, University of Utah. Now in its third and final three-year cycle, major funding for Catalyst For a Cure is provided by a grant from the Melza M. and Frank Theodore Barr Foundation through the Glaucoma Research Foundation.

Honorees

In addition to the research update presented, the Foundation’s anniversary benefit was also an opportunity to honor those who have made a significant contribution to glaucoma research.

– The President’s Award was presented to Dr. Rohit Varma, MD, from the Doheny Eye Institute at the University of Southern California. Dr. Varma has undertaken groundbreaking research that shows the Latino community to be among those at highest risk for development of glaucoma.

– The Catalyst Award, the Glaucoma Research Foundation’s highest honor, was presented to Dr. H. Dunbar Hoskins, Jr., MD, Executive Vice President of the American Academy of Ophthalmology. Dr. Hoskins was recognized for his lifetime commitment and service to the field of ophthalmology. “Dr. Hoskins has earned The Catalyst Award several times over,” said Mr. Brunner. “While in private practice, there was his visionary leadership as co-founder of GRF and the thoughtful guidance he provided during those all-important formative early years, along with co-founders Robert Shaffer, MD (1912-2007), and John Hetherington, MD. Certainly he is the personification of ‘catalyst’.”

About the Glaucoma Research Foundation

Located in San Francisco, the Glaucoma Research Foundation is the nation’s most experienced foundation dedicated solely to glaucoma research and education. In addition to funding innovative research like the Catalyst For a Cure research consortium and its Shaffer Grants for Innovative Glaucoma Research, GRF also is the “go to” agency for education materials, including the definitive reference for newly diagnosed, Understanding and Living with Glaucoma (available in both English and Spanish editions); a special brochure serving those at highest risk, including African-Americans, Latinos, and children; and a toll free phone line, 800-826-6693, staffed during office hours with an information specialist to handle a variety of inquiries.

Glaucoma Research Foundation

Alimera Sciences, Inc., a privately
held biopharmaceutical company that specializes in the research,
development and commercialization of prescription ophthalmic
pharmaceuticals, reported that after completing its review of safety
and efficacy data currently available, an independent Data Safety
Monitoring Board (DSMB) has again recommended that the two pivotal Phase 3
clinical trials for the use of Iluvien(TM) in the treatment of diabetic
macular edema (DME) continue under the current protocol, without change. A
DSMB provides an independent evaluation of all trial data to identify
potential safety issues that might warrant modification or early
termination of ongoing clinical studies.

These clinical trials, known collectively as the FAME(TM) Study
(Fluocinolone Acetonide in Diabetic Macular Edema), consist of two double
masked, randomized, multi-center trials that are following 956 patients in
the U.S., Canada, Europe and India for 36 months in support of a planned
global registration filing, with safety and efficacy assessed after 24
months of follow-up. Enrollment for the FAME study was completed in October
2007.

“Alimera is excited about the potential of Iluvien to help the growing
number of people suffering from DME,” said Alimera CEO Dan Myers. “The
DSMB’s recommendation to continue the FAME Study without change keeps the
development for Iluvien on track for regulatory submissions in early 2010.”

Iluvien is an intravitreal insert being developed for the treatment of
DME. DME is a disease of the retina, which affects individuals with
diabetes and can lead to severe vision loss and blindness. Each Iluvien
insert is designed to provide a sustained therapeutic effect, up to 36
months for the low dose and up to 24 months for the high dose. Iluvien is
inserted into the patient’s eye with a 25-gauge needle, which allows for a
self-sealing wound. This insertion is very similar to an intravitreal
injection, a procedure commonly employed by retinal specialists.

Currently, nearly 24 million people, or 8 percent of the population, in
the U.S. have diabetes. Over time, all diabetics are at risk of developing
some form of diabetic retinopathy, an ophthalmic condition of diabetes. In
the U.S., diabetic retinopathy causes approximately 12,000 to 24,000 new
cases of blindness each year, making diabetes the leading cause of new
cases of blindness in adults aged 20 to 74. Based on published data,
Alimera estimates that there are as many as 300,000 new cases of DME each
year and 1 million people have DME. There are no ophthalmic drug therapies
currently approved by the U.S. Food and Drug Administration for the
treatments of DME.

About Alimera Sciences, Inc.

Alimera Sciences is a biopharmaceutical company that specializes in the
research, development and commercialization of prescription ophthalmic
pharmaceuticals. Presently the company is focused on diseases affecting the
back of the eye, or retina. Its most advanced product candidate is
Iluvien(TM), which is being developed for the treatment of diabetic macular
edema, or DME. DME is a disease of the retina, which affects individuals
with diabetes and can lead to severe vision loss and blindness. Under one
protocol, enrollment was completed in October 2007 in two Phase 3 pivotal
trials for the use of Iluvien in the treatment of DME conducted across the
U.S., Canada, Europe and India, with a combined total enrollment of 956
patients.

Alimera also has entered into an exclusive worldwide agreement with
Emory University to explore oxidative stress management — specifically the
reduction of reactive oxygen species (ROS) — as a treatment strategy for
ophthalmic diseases. Under this agreement, Alimera has acquired options to
exclusive, worldwide licenses for two classes of nicotinamide adenine
dinucleotide phosphate reduced form (NADPH) oxidase inhibitors, which
Alimera is studying as potential treatments for conditions such as the dry
form of age-related macular degeneration (AMD), particularly the late stage
of this condition known as geographic atrophy. Alimera has exercised its
option to acquire a license with respect to one of these classes of NADPH
oxidase inhibitors.

Alimera Sciences
www.alimerasciences

The nerve cell-damaging plaque that builds up in the brain with Alzheimer’s disease also builds up in the retinas of the eyes – and it shows up there earlier, leading to the prospect that noninvasive optical imaging of the eyes could lead to earlier diagnosis, intervention and monitoring of the disease, according to new research.

Scientists discovered characteristic amyloid plaques in retinas from deceased Alzheimer’s disease patients and used a noninvasive optical imaging technique to detect retinal plaques in live laboratory mice genetically modified to model the human disease. The combined results suggest the possibility that noninvasive retinal imaging may be helpful in early diagnosis of the disease.

The research was conducted by a team of scientists at Cedars-Sinai Medical Center in collaboration with colleagues from the Weizmann Institute of Science in Israel and the University of Southern California. Results were published online in the journal NeuroImage, and related findings will be presented July 13 at the Alzheimer’s Association International Conference on Alzheimer’s Disease.

Alzheimer’s disease is a devastating condition that is becoming more prevalent worldwide as the baby-boom generation advances into its senior years, but there is no conclusive, noninvasive way to diagnose it. Previous studies have suggested that changes in the brain may begin years or even decades before symptoms occur – emphasizing the need for earlier, reliable detection for early therapeutic intervention to achieve effective remedy. The new study suggests the possibility of monitoring Alzheimer’s disease through a simple retinal imaging approach.

Abnormal deposits in the brain called beta-amyloid plaques, which damage cells and interrupt cell-to-cell communications, are recognized as a hallmark sign of the disease. However, because existing noninvasive brain-imaging technologies cannot provide sufficient detail about these changes, the most definitive diagnosis of Alzheimer’s disease comes after an autopsy.

The research team considered the retina a better target for noninvasive imaging of Alzheimer’s disease because it is readily accessible and, unlike other components of the eye, it is part of the central nervous system, having a direct connection and thus many similarities with the brain. Previous studies have documented non-specific visual disturbances, eye disorders and certain types of retinal abnormalities occurring with Alzheimer’s disease and other neurodegenerative conditions, but this is the first to identify human retinal plaque deposits that could provide a specific diagnostic marker of Alzheimer’s disease.

Among the new findings:
In lab tests, plaques in the retinas of mice genetically modified to model Alzheimer’s disease could be detected at a very early, pre-symptomatic stage – before the plaque appeared in the brain.
A high-resolution, noninvasive optical imaging approach was developed to monitor individual beta-amyloid plaques in the retinas of live mice. The system is based on a harmless specific marker and the adaptation of an existing optical system used to examine rodent eyes.
The research team used a fluorescent compound called curcumin to label and detect retinal plaques. This is believed to be the first use of curcumin as an imaging agent to detect Alzheimer’s disease-related plaques in the retinas of live animals. Curcumin, a natural component of the spice turmeric, binds to beta-amyloid plaques and makes them visible when viewed microscopically. In the Cedars-Sinai research, curcumin injected into the bloodstream of live mice crossed the blood-retinal barrier and specifically bound to the retinal plaques, allowing them to be viewed in high resolution with a noninvasive procedure.
Observations from multiple genetically engineered mouse models of Alzheimer’s disease demonstrated a correlation between retinal plaques and brain plaques as disease progressed.
In the laboratory mice, a unique immune system-based therapy that reduces the amount of plaques in the brain also reduced plaque load in the retina to the same extent, suggesting that the retina could faithfully represent the brain in assessing response to therapy.
Beta-amyloid plaques were identified in retinal samples from human patients who had died from Alzheimer’s disease, and their features correlated with the diagnosed stage of the disease. Importantly, plaques were clearly detected not only in patients who definitely had the disease, but also in the retinas of some people who were suspected of having early-stage Alzheimer’s disease based on clinical diagnosis and microscopic examination of brain tissue after death.

Together, the results offer the first evidence for the existence of Alzheimer’s-specific plaques in the retina of human patients and the ability to detect individual plaques in live mouse models, creating a strong basis for future research building on these findings. According to the authors, these studies establish the potential of direct retinal beta-amyloid plaque imaging in live subjects as a tool for early Alzheimer’s disease diagnosis and prognosis, as well as assessment of therapies.

Notes:

Specialists in neurosurgery, ophthalmology, imaging systems, neuroimmunology, pathology, neurology and biomedical engineering collaborated on these studies, which were conducted at Cedars-Sinai Medical Center by scientists from Cedars-Sinai, the Weizmann Institute of Science in Israel, and the University of Southern California.

The journal article’s first authors are Maya Koronyo-Hamaoui, Ph.D., a research scientist and assistant professor of neurosurgery at Cedars-Sinai’s Maxine Dunitz Neurosurgical Institute and a principal investigator in the Neuroimmunology Laboratory at Cedars-Sinai; and Yosef Koronyo, M.Sc., LL.B., a research associate in the departments of Surgery and Neurosurgery at Cedars-Sinai. Michal Schwartz, Ph.D., visiting professor in the Department of Neurosurgery at Cedars-Sinai, and the Ilze and Maurice Professorial Chair of Neuroimmunology at the Weizmann Institute of Science in Rehovot, Israel, is a senior author.

The work was supported by the Marciano Family Foundation, the Maxine Dunitz Neurosurgical Institute, the U.S. Navy Bureau of Medicine and Surgery, the National Eye Institute, the Winnick Family Foundation, and a National Institute on Aging grant to the University of Southern California Alzheimer’s Disease Research Center.

Source: Cedars-Sinai Medical Center

Scientists have known for more than 200 years that vision begins with a series of chemical reactions when light strikes the retina, but the specific chemical processes have largely been a mystery. A team of researchers from the United States and Switzerland, have she new light on this process by “capturing” this chemical communication for future study. This research, published in the February 2009 issue of The FASEB Journal (fasebj), may lead to the development of new treatments for some forms of blindness and vision disorders.

At the center of the discovery is the signaling of rhodopsin to transducin. Rhodopsin is a pigment in the eye that helps detect light. Transducin is a protein (sometimes called “GPCR”) which ultimately signals the brain that light is present. The researchers were able to “freeze frame” the chemical communication between rhodopsin and transducin to study how this takes place and what goes wrong at the molecular level in certain disorders.

According to Krzysztof Palczewski, a senior scientist involved in the research, “The results may have important implications for discovery and development of more specific medicines to treat GPCR-linked dysfunction and disease.” Examples of health problems involving GPCR dysfunction include blindness, diabetes, allergies, depression, cardiovascular defects and some forms of cancer.

To make their discovery, scientists isolated rhodopsin/transducin directly from bovine retinas. These membranes were suspended in solution and exposed to light to start the chemical signaling process. After light exposure, any contaminating proteins were removed, and the remaining rhodopsin and transducin “locked” in their chemical communication were removed using a centrifuge. In addition to helping scientists understand how vision begins, this research may also impact disorders affecting heart beat, blood pressure, memory, pain sensation, and infection response because it is believed that they are regulated by similar chemical communications involving similar proteins.

“Until now, scientists have been in the dark when it comes to exactly how vision begins. This exciting new work shows how light becomes a chemical signal to the brain,” said Gerald Weissmann, Editor-in-Chief of The FASEB Journal. “Now that we see the light, so to speak, entirely new types of custom-fit become possible for a wide range of diseases.”

A recent and related article in The FASEB Journal on milestones in photochemistry is available at fasebj/cgi/content/full/22/12/4038. The FASEB Journal is published by the Federation of the American Societies for Experimental Biology (FASEB) and is the most cited journal worldwide according to the Institute for Scientific Information. FASEB comprises 22 nonprofit societies with more than 80,000 members, making it the largest coalition of biomedical research associations in the United States. FASEB advances biological science through collaborative advocacy for research policies that promote scientific progress and education and lead to improvements in human health.

Source: Cody Mooneyhan

Federation of American Societies for Experimental Biology

Gift commitments totaling $13.7 million, including $10 million from the family of the late Roy J. Carver Sr., will fund three new endowed chairs at the University of Iowa, create a new genetics testing laboratory and rename the UI’s world-renowned Center for Macular Degeneration.

The Carver Family Center for Macular Degeneration (CMD) at the UI Roy J. and Lucille A. Carver College of Medicine is being named in recognition of the overall gift commitment by the Carver family: Lucille A. Carver of Muscatine, Iowa, who is the widow of Roy J. Carver Sr., who died in 1981; John and Marcia Carver of Rapids City, Ill.; Martin G. and Ruth A. Carver of Muscatine, Iowa; and Roy J. Carver Jr. of Bettendorf, Iowa.

The renaming of the Center for Macular Degeneration for the Carver family is pending approval by the Board of Regents, State of Iowa, at its next meeting March 20 to 21 in Ottumwa.

The $5 million portion of the Carver family gift that created and named the John and Marcia Carver Nonprofit Genetic Testing Laboratory (NGTL), and $1.2 million for the Carver NGTL from the Foundation Fighting Blindness, were previously announced by the UI on Feb. 3.

“The Carver family has long understood this university’s strengths, capabilities and needs in many areas, but nowhere more so than in the health sciences,” said UI President David Skorton. “This creative act of generosity on the part of the Carver family will enable one of the UI’s premier centers of excellence to continue pursuing innovative research that holds great promise for all who have, or some day may be affected by, blinding eye diseases. This gift from the Carvers, along with those from Gary and Cammy Seamans, Leo Hauser and the Foundation Fighting Blindness, constitute a landmark for UI biomedical research.”

The three endowed chairs and the faculty recipients are:

* The Roy J. Carver, Jr. Chair in Bioinformatics and Computational Biology, established with a $2.5 million endowment from the Carver family. This chair is a joint appointment in the UI Carver College of Medicine and the UI College of Engineering, the first time a UI-named, endowed chair has been shared by two colleges. It has been awarded to Thomas Casavant, Ph.D., professor of electrical and computer engineering and biomedical engineering in the College of Engineering. Casavant directs the UI Center for Bioinformatics and Computational Biology. The center develops computer-based approaches for accessing, interpreting and understanding genetic information as it applies to basic biological science and applied medical research. Among his research projects, Casavant and his colleagues are involved in studies of the molecular genetics of macular degeneration and glaucoma.

* The Martin and Ruth Carver Chair in Genetics, established with a $2.5 million endowment from the Carver family. This chair has been awarded to Val C. Sheffield, M.D., Ph.D., professor of pediatrics in the UI Carver College of Medicine and a Howard Hughes Medical Institute investigator. Sheffield directs the Laboratory for Disease Gene Discovery. Its goal is to identify and characterize genes involved in hereditary human disease with special emphasis placed on the study of hereditary retinopathies including age related macular degeneration. The main strategies used by the laboratory are genetic mapping methods and genomic resources to identify disease genes based on their function and/or position within the genome.

* The Seamans-Hauser Chair in Molecular Ophthalmology, established to support the directorship of the Carver Family Center for Macular Degeneration with a $2.5 million endowment from Gary and Camille Seamans of Galena, Ill., and Tucson, Ariz., and Leo Hauser of Incline Village, Nev. This chair has been awarded to Edwin M. Stone, M.D., Ph.D., professor of ophthalmology and visual sciences in the UI Carver College of Medicine, a Howard Hughes Medical Institute investigator, and director of the Center for Macular Degeneration.

“This gift from the Carver family will be very important to the work of the UI Center for Macular Degeneration in many ways,” Stone said. “First, it will help us build upon our already strong group of interdisciplinary vision scientists and allow these scientists to accelerate their work toward a cure for a number of blinding eye diseases. Second, it will help us expand our model for nonprofit genetic testing laboratory to an international level. The combination of these things will bring hope, and some very real help, to countless patients affected by heritable blinding eye diseases.”

Stone also expressed appreciation to Gary and Camille Seamans and Leo Hauser for their generosity in creating a third endowed chair for the Carver Family CMD. “These three people have played such an important role in the Center from its inception that it is a particularly wonderful honor for me to be chosen for the chair that bears their names,” he said.

“Understanding a disease as devastating as macular degeneration truly requires the efforts of world-class physicians and scientists from many disciplines. Indeed, our work with colleagues in the UI College of Engineering and other colleges and units on campus has led to important discoveries in this area,” said Jean Robillard, M.D., dean of the UI Carver College of Medicine. “With these generous gifts, the Carver Family Center for Macular Degeneration will continue to lead the way in developing interdisciplinary approaches to study and treat degenerative diseases of the eye.”

The Carver NGTL plans to develop a clinically useful test, to be offered nationally on a not for profit basis, for every gene known to cause an inherited eye disease. The work done at the laboratory will strengthen the UI’s interdisciplinary research efforts in the area of degenerative eye diseases.

The Carver NGTL will serve as an international resource for large scale genetic testing for more than 100 forms of inherited eye diseases. It will continue and expand on the research done at the UI Carver Laboratory for Molecular Diagnosis, created in 1997 with an endowment from the Roy J. Carver Charitable Trust.

The UI Center for Macular Degeneration was established in 1997 by the Board of Regents, State of Iowa. It mission is threefold: to identify the primary causes of age-related macular degeneration, glaucoma and other heritable eye diseases; to apply improved understanding of disease mechanisms to the prevention of vision loss in the majority of people at risk, as well as to the development of effective treatments for those already affected; and to deliver the most advanced medical, surgical, rehabilitative and educational services available in a timely, caring and cost-effective manner.

The Carver Family CMD has grown to include more than 100 individuals in eight departments and in four colleges of the university. With expertise in a wide range of areas, including internal medicine, genetics, molecular biology, computer engineering, biomedical engineering and statistics, the center’s faculty and staff focus on genetic research and testing, which requires multidisciplinary and large-scale teamwork.

STORY SOURCE: University of Iowa Health Science Relations, 5139 Westlawn, Iowa City, Iowa 52242-1178

CONTACTS: Steve Maravetz, UI Health Science Relations, 319-335-8033, steven-maravetzuiowa.edu. Edwin Stone, Carver Family Center for Macular Degeneration, 319-335-8270, edwin-stoneuiowa.edu.

Contact: Steve Maravetz
steven-maravetzuiowa.edu
University of Iowa

Lpath, Inc. (OTCBB: LPTN) today announced that the laboratory of Peter Campochiaro, MD at Johns Hopkins University School of Medicine(1) recently published peer-reviewed findings of a research study of iSONEP™, Lpath’s Phase 1 anti-S1P antibody, demonstrating promising results in various animal models of ocular disorders.

The findings of the study appeared online ahead of print in the Journal of Cellular Physiology (www3.interscience.wiley/journal/121402497/abstract).

The paper, titled “Blockade of Sphingosine-1-Phosphate Reduces Macrophage Influx and Retinal and Choroidal Neovascularization,” presents preclinical proof-of-concept data that Lpath’s iSONEP (1) mitigates blood vessel growth in the choroidal layer of the eye; (2) reduces formation of new blood vessels in the retina following retinal ischemia; and (3) suppresses the infiltration of macrophages, an important inflammatory response that is thought to contribute to the pathology of diabetic retinopathy and, possibly, the onset or exacerbation of dry AMD (age-related macular degeneration).

The authors suggest iSONEP could be promising in the treatment of diabetic retinopathy, the most significant cause of vision loss in working-age adults in developed countries.

The paper adds to the body of evidence that S1P, which iSONEP binds to and neutralizes, may have both independent and overlapping effects with VEGF and is therefore a particularly appealing ocular target. Because of this, the authors argue, iSONEP may provide a more optimal therapy for wet AMD when administered in combination with Lucentis® or Avastin®.

Among other findings, the paper reveals that intra-vitreal injections of iSONEP in 22 Cynomolgus monkeys did not cause identifiable toxicities at dose levels of 0.25mg (n=6), 0.70mg (n=6), and 1.80mg (n=10) per eye.

“This is the first published paper demonstrating that S1P is a mediator of key inflammatory processes in the eye,” said Glenn Stoller, MD, head of Lpath’s ocular division. “This anti-inflammatory mechanism of iSONEP appears to hold great promise for the treatment of diabetic retinopathy and possibly for dry AMD, representing two of the largest unmet medical needs in ophthalmology today.”

Scott Pancoast, Lpath’s president and CEO, added, “These study results, in combination with those recently published in Experimental Eye Research, demonstrate iSONEP’s broad-ranging mechanisms of action in the eye. We believe that iSONEP may provide a comparative advantage in the treatment of various ocular diseases and that it represents a significant market opportunity for Lpath.”

(1) Dr. Campochiaro, who holds the Eccles Professorship of Ophthalmology at Johns Hopkins University, is a member of Lpath’s Ocular Advisory Board. He does not hold shares of Lpath stock, nor does he have any stock options. The studies described above were funded by Lpath. Participation by Dr. Campochiaro’s laboratory in these studies does not constitute or imply endorsement by the Johns Hopkins University or any affiliation thereof.

Lucentis® and Avastin® are registered trademarks of Genentech, Inc.

About Lpath

Lpath, Inc., headquartered in San Diego, California, is the category leader in bioactive-lipid-targeted therapeutics, an emerging field of medical science whereby bioactive signaling lipids are targeted for treating important human diseases. ASONEP™, an antibody against S1P, is currently in Phase 1 clinical trials for the treatment of cancer and also holds promise against multiple sclerosis and various other disorders. ASONEP is being developed with the support of our partner, Merck-Serono. A second product candidate, iSONEP™ (the ocular formulation of the S1P antibody), has demonstrated superior results in various preclinical AMD and retinopathy models and has received FDA authorization to begin Phase 1 clinical trials. Lpath’s third product candidate, Lpathomab™, is an antibody against LPA, a key bioactive lipid that has been long recognized as a valid disease target (fibrosis, cancer, neuropathic pain). The company’s unique ability to generate novel antibodies against bioactive lipids is based on its ImmuneY2™ drug-discovery engine, which the company is leveraging as a means to expand its pipeline. For more information, visit Lpath.

About Forward-Looking Statements

Except for statements of historical fact, the matters discussed in this press release are forward looking and reflect numerous assumptions and involve a variety of risks and uncertainties, many of which are beyond our control and may cause actual results to differ materially from stated expectations. For example, there can be no assurance that results will be timely, necessary regulatory approvals will be obtained, the proposed treatments will prove to be safe or effective, or required clinical trials will be ultimately successful. Actual results may also differ substantially from those described in or contemplated by this press release due to risks and uncertainties that exist in our operations and business environment, including, without limitation, our limited experience in the development of therapeutic drugs, our dependence upon proprietary technology, our history of operating losses and accumulated deficits, our reliance on research grants, current and future competition, and other risks described from time to time in our filings with the Securities and Exchange Commission. We undertake no obligation to release publicly the results of any revisions to these forward-looking statements to reflect events or circumstances arising after the date hereof.

Lpath, Inc.

View drug information on Avastin; Lucentis.

Researchers at Tufts University School of Medicine and the Sackler School of Graduate Biomedical Sciences at Tufts have developed a new tool for gene therapy that significantly increases gene delivery to cells in the retina compared to other carriers and DNA alone, according to a study published in the January issue of The Journal of Gene Medicine. The tool, a peptide called PEG-POD, provides a vehicle for therapeutic genes and may help researchers develop therapies for degenerative eye disorders such as retinitis pigmentosa and age-related macular degeneration.

“For the first time, we have demonstrated an efficient way to transfer DNA into cells without using a virus, currently the most common means of DNA delivery. Many non-viral vectors for gene therapy have been developed but few, if any, work in post-mitotic tissues such as the retina and brain. Identifying effective carriers like PEG-POD brings us closer to gene therapy to protect the retinal cells from degeneration,” said senior author Rajendra Kumar-Singh, PhD, associate professor of ophthalmology and adjunct associate professor of neuroscience at Tufts University School of Medicine (TUSM) and member of the genetics; neuroscience; and cell, molecular, and developmental biology program faculties at the Sackler School of Graduate Biomedical Sciences at Tufts.

Safe and effective delivery of therapeutic genes has been a major obstacle in gene therapy research. Deactivated viruses have frequently been used, but concerns about the safety of this method have left scientists seeking new ways to get therapeutic genes into cells.

“We think the level of gene expression seen with PEG-POD may be enough to protect the retina from degeneration, slowing the progression of eye disorders and we have preliminary evidence that this is indeed the case,” said co-author Siobhan Cashman, PhD, research assistant professor in the department of ophthalmology at TUSM and member of Kumar-Singh’s lab.

“What makes PEG-POD especially promising is that it will likely have applications beyond the retina. Because PEG-POD protects DNA from damage in the bloodstream, it may pave the way for gene therapy treatments that can be administered through an IV and directed to many other parts of the body,” said Kumar-Singh.

Kumar-Singh and colleagues used an in vivo model to compare the effectiveness of PEG-POD with two other carriers (PEG-TAT and PEG-CK30) and a control (injections of DNA alone).

“Gene expression in specimens injected with PEG-POD was 215 times greater than the control. While all three carriers delivered DNA to the retinal cells, PEG-POD was by far the most effective,” said first author Sarah Parker Read, an MD/PhD candidate at TUSM and Sackler and member of Kumar-Singh’s lab.

Age-related macular degeneration, which results in a loss of sharp, central vision, is the number one cause of vision loss in Americans age 60 and older. Retinitis pigmentosa, an inherited condition resulting in retinal damage, affects approximately 1 in 4,000 individuals in the United States.

This study was supported by grants from the National Eye Institute of the National Institutes of Health, the Foundation for Fighting Blindness, The Ellison Foundation, The Virginia B. Smith Trust, the Lions Eye Foundation, and Research to Prevent Blindness. Sarah Parker Read is part of the Sackler/TUSM Medical Scientist Training Program, which is funded by the National Institute of General Medical Sciences, part of the National Institutes of Health.

Read SP, Cashman SM, Kumar-Singh R. The Journal of Gene Medicine. 2010 (January). 12(1): 86-96. “A poly(ethylene) glycolylated peptide for ocular delivery compacts DNA into nanoparticles for gene delivery to post-mitotic tissues in vivo.” Doi: 10.1002/jgm.1415

Source:
Siobhan Gallagher
Tufts University, Health Sciences

Based on the top-level analysis of a Phase II study, EyeGate Pharma announces that EGP-437, a corticosteroid solution administered by a non-invasive ocular drug delivery system, improved signs and symptoms in patients with dry eye syndrome (DES).

For the dry eye clinical trial, EyeGate worked with Ora, Inc., a leading global clinical research and development organization located in Andover, MA. Over the past 30 years, Ora has been a pioneering force in the development of advanced research models across the field of ophthalmology.

This Phase II single-center, randomized (105 patients), double-masked, placebo-controlled patient study evaluated the safety and efficacy of a corticosteroid solution (EGP-437) administered by the EyeGate® II Delivery System (at two dose levels) twice over a three-week period. Ora’s Controlled Adverse Environment (CAE) clinical research system, which simulates the acute environmental challenges regularly faced by DES patients, was used for this study.

In the top-level analysis, investigators observed that EGP-437 significantly (p < 0.05) improved signs and symptoms of DES during the three-week environmental component, which included three CAE exposures and two doses. EGP-437 also improved signs and symptoms when studied as a treatment and preventative in conjunction with the CAE. “This exploratory Phase II study demonstrated significant improvements in signs and symptoms of dry eye during and after CAE exposure following EGP-437 dosing. These effects were observed within hours of dosing, suggesting a rapid onset of action. In addition, EGP-437 significantly improved the post-CAE recovery for patients in the active treatment groups. The impact on signs and symptoms was also observed during the study’s three-week environmental component, further supporting the potential benefits of EGP-437 for these patients,” commented George Ousler, Director of Dry Eye Department at Ora. According to Stephen From, President and CEO of EyeGate Pharma, “Ora’s CAE clinical research system, which provides a unique ability to screen and qualify patients, played an integral role in minimizing the study’s patient numbers while still delivering highly relevant biostatistics. We are excited about the prospect that EGP-437 may prove to be a useful therapy for the moderate to severe dry eye patients that are currently underserved by available treatments. This non-invasive drug delivery technology has the potential to help patients with a broad range of eye diseases, and we are encouraged by these results.” An abstract describing the study and results was submitted to an upcoming scientific conference, for which more details will follow. About Dry Eye Syndrome Dry Eye Syndrome (DES) is the most prevalent form of ocular discomfort and irritation, accounting for one in four patient visits to a general ophthalmologist. It is estimated that as many as 20 to 40 million Americans suffer from DES, including a significant number of patients who suffer from DES after Lasik surgery. Symptoms such as pain, light sensitivity, blurred vision, and irritation decrease the quality of life for patients and can ultimately lead to loss of function and blindness. The incidence of DES is increasing due to environmental factors, the aging population and the increasing prevalence of co-morbid diseases such as diabetes. There is no cure for DES, and the few treatment options currently available primarily provide temporary symptomatic relief. About Ora, Inc. Ora is the world’s leading independent ophthalmic drug and device development firm. Ora provides technology-based concept-to-market services and solutions that accelerate development timelines and improve the scientific quality of clinical research. Over the past 30 years, Ora has played a central role in the development and FDA approval of more than 30 ophthalmic products. For more information, please visit oraclinical. Source
EyeGate Pharma

This month’s Ophthalmology, the journal of the American Academy of Ophthalmology, reports on eye disorders that may occur in people taking statins, on a new system that predicts soldiers’ visual recovery after combat eye trauma, and on use of glaucoma patients’ opinions to improve testing and treatment.

Eye Disorders Linked to Statin Drug Use in Some Patients

Statin medications are used to lower patients’ cholesterol levels, thus helping prevent coronary heart disease, stroke and other deaths related to high cholesterol levels. Statin use has grown rapidly since 1992, and seems likely to increase in light of the recent, widely-reported Jupiter Study on statin benefits in patients with low cholesterol but elevated C-reactive protein. Eye disorders related to statins are rare, occurring in about 0.1 percent of patients (0.5 to 2.5 percent when gemfibrozil, another type of cholesterol-lowering drug, is taken simultaneously). The study led by F.W. Fraunfelder, MD, of the Casey Eye Institute, Oregon Health & Science University, is the first to systematically report on the association of eye disorders with statin use.

Dr. Fraunfelder’s group analyzed statin-associated reports of double vision (diplopia), drooping of the upper eyelid (ptosis), and loss of full range of motion of the eyes (ophthalmoplegia) in the databases of the National Registry of Drug-Induced Ocular Side Effects, the World Health Organization, and the Food and Drug Administration. Since statins were known to cause skeletal muscle disorders in some patients, a similar affect was plausible in the eye muscles. The average patient age was 64.5 years, and the case reports included 143 males, 91 females, and 22 persons with gender unspecified. The average statin dose of patients who exhibited one or more eye disorder was within ranges recommended by drug manufacturers, and the average time from beginning of therapy to developing an adverse drug reaction (ADR) was 8.3 months. There were 23 cases of loss of eye range of motion, 8 cases of ptosis, and 18 cases of ptosis in conjunction with double vision; disorders in all patients apparently resolved completely when statins were discontinued. From the ADR reports, the researchers could not determine precisely which eye muscles were involved, or time needed to full recovery after statin discontinuation, for individual cases.

“We advise physicians prescribing statins to be aware that these eye disorders may result, and that medications should be discontinued if so. When a patient has one of these eye disorders, he should be rigorously evaluated to determine the cause, and statin use should be taken into account,” Dr. Fraunfelder concludes.

Predicting Visual Recovery: a New System Helps Soldiers, Families Cope

When soldiers sustain eye injuries on the battlefields of Iraq or Afghanistan, one of the first questions families ask military doctors is whether their loved ones will recover good vision. But until Eric D. Weichel, MD, and his colleagues at Walter Reed Army Medical Center (WRAMC) tackled the issue, there was no standard for predicting visual recovery. Dr. Weichel’s team studied patient records for 523 consecutive eye injuries sustained by 387 US soldiers treated at WRAMC between March 2003 and October 2006. The researchers wanted to know whether a system called the ocular trauma score (OTS), developed for use with non-combat eye trauma by Ferenc Kuhn, MD, was applicable to soldiers’ eye injuries. The OTS enables the care provider to calculate the probability that a particular eye trauma patient will obtain a visual range by six months after the injury. This study concluded that the OTS is a valid system for predicting visual acuity outcomes following combat ocular trauma (COT).

“We can now answer many questions about visual prognosis for service members and their families,” said Dr. Weichel. “The assessment, treatment, and counseling protocols we developed based on this and related COT studies have been integrated into all phases of eye injury care, from military surgical intensive care units through follow-up and rehabilitation in Veterans’ Administration centers.”

Dr. Weichel’s team collected 201 eye injury-related variables for each soldier studied, as well as measurements of the soldier’s best-corrected visual acuity (BCVA) taken as soon as possible after the injury and at six months post-injury. Initial BCVA measurements were not available for all subjects since severely injured soldiers (unconscious or intubated) were unable to communicate with doctors about their visual status. The data was then categorized using the OTS. A higher OTS score indicated a higher likelihood that good visual acuity would be recovered. The visual recovery prognosis was worst for soldiers who sustained injuries to the globe of the eye combined with lacerations to the eyelids or fractures to the bones around the eye, and/or with injuries to the cranial nerves, visual nerves or brain structures. Thirty-three percent of the soldiers had worse than 20/200 vision in one eye, and globe injuries occurred in both of the patient’s eyes in 36 percent of the 523 eyes studied. Many soldiers sustained other devastating injuries such as traumatic brain injury (66%) and severe arm/ leg injuries (44%).

Patient Opinions Help Eye MDs Improve Glaucoma Testing

The first quantitative study of how glaucoma patients perceive glaucoma assessment tests and how these perceptions may impact test results and follow-up care was completed by Stuart K Gardiner, PhD, and his colleagues at the Discoveries in Sight Laboratory, Devers Eye Institute of the Legacy Health System, Portland OR. Patients who have or are at risk for glaucoma, a disorder of the optic nerve that can lead to severe vision loss, are evaluated by their Eye MDs (ophthalmologists) in a series of tests, often at yearly follow-up visits. Though the quality of assessment data gleaned from each test is the key use criteria, patients’ experiences are also important, since dislike of or discomfort with testing may affect whether patients are willing to keep future appointments and follow treatment plans. Most glaucoma visual field tests require patients to concentrate and respond accurately; if a patient is unmotivated, test result validity could be reduced.

The 101 patients in the study had either high risk ocular hypertension (OH), a precursor of glaucoma, or early glaucoma. Most had been followed in the clinic for about 10 years. The patients rated each of seven commonly used glaucoma tests from 0 (absolute dislike) to 10 (perfect satisfaction). The researchers then ranked the resulting scores for each subject from 1 (favorite test) to 7 (least favorite). Patients were also asked to describe why they liked or disliked the tests. Their remarks were considered anecdotal evidence, but when responses were similar for many subjects the evidence was accepted as a useful conclusion. The intraocular pressure (IOP) test was most favorably ranked, and many patients also liked the Heidelberg retinal tomography (HRT) test, in part because they could view images of the heads of their optic nerves during the exam. The short wavelength automated perimetry (SWAP) test was the “least favorite” of 48 patients; most said they disliked having to concentrate and respond for a sustained time period. Optic nerve photography was also disliked because of discomfort caused by dilation drops and exposure to bright light, and the inconvenience of lingering blurry vision.

Dr. Gardiner said, “Our study shows the importance of carefully explaining to patients the purpose of each test and of obtaining valid results. We also learned that modifying testing patterns, for example offering rest breaks or changing the test order, may improve the patient’s experience and results. The findings will be useful in developing improved test formats and allowing clinicians to choose tests that patients tolerate well from the available alternatives.”

Eds: Full texts of the studies are available from the Academy’s media relations department.

About the American Academy of Ophthalmology

AAO is the world’s largest association of eye physicians and surgeons-Eye M.D.s-with more than 27,000 members worldwide. Eye health care is provided by the three “O’s” – opticians, optometrists and ophthalmologists. It is the ophthalmologist, or Eye M.D., who can treat it all: eye diseases and injuries, and perform eye surgery. To find an Eye M.D. in your area, visit the Academy’s Web site at aao.

American Academy of Ophthalmology