RxPG News : Ophthalmology

First sign of injury in glaucoma occurs in the neuronal connections in the brain

Mon, 01 Mar 2010 13:08:32 PST

( from http://www.rxpgnews.com ) In a recent study, David Calkins, Ph.D., director of Research at the VEI, discovered that the first sign of injury in glaucoma actually occurs in the brain.

Glaucoma is generally considered a disease of the eye in which sensitivity to ocular pressure causes damage to the retina and optic nerve, which are components of the central nervous system and do not regenerate. The damage begins in the peripheral visual field and progresses toward the center resulting in complete blindness unless detected early. For this reason, degeneration in glaucoma is often hard to detect.

The report this week in the Proceedings of the National Academy of Sciences describes recent experiments in which Calkins' laboratory shows that glaucoma is very much like other central nervous system diseases.

"This is a paradigm shift on how we think about this disease," said Calkins, associate professor of Ophthalmology at VEI and a member of the neuroscience program. "This will have global implications. This information opens up an entirely new domain of nerve-derived therapeutics."

Combining this new understanding of where the first neuronal injury for glaucoma occurs, with the fact that the incidence of injury increases with age, researchers now have insight into how the loss of sensory function occurs in normal aging.

Traditionally, glaucoma therapies have focused on lowering ocular pressure within the eye. But the recent PNAS study gives credence to taking a new direction of study focusing on neuronal activity in the middle of the brain where the optic nerve forms its first connections.

"This is very exciting work that demonstrates that we must consider not just the eye, but also the brain, in our efforts to understand blinding diseases such as glaucoma," said Paul Sternberg, M.D., chair of Ophthalmology and Visual Sciences and director of VEI. "We are optimistic that Dr. Calkins' neurobiological approach will lead to new targets for potential treatment of this devastating condition."

Calkins explained that in other age-related diseases, like Alzheimer's and Parkinson's, the most significant contributor to neuronal susceptibility to injury is age.

"In these diseases, the injury to neurons occurs very early in the distal projections in a process called dying back. In dying back, the neuronal axon loses its ability to communicate with the target.

"In the case of glaucoma, we have shown that the axons in the optic nerve lose their ability to communicate with their projection site in the mid-brain."

Calkins' team expected to find a loss of communication in the optic nerve of the eye, but what they also discovered was that the connectivity between the optic nerve and the brain was dying first.

Using animal models with high pressure glaucoma, the team was able to see that a very early mechanism of vision loss involves the loss of communication between the optic nerve and the mid-brain, where sensory information about sound, heat, cold, pain and pressure originate.

"If you followed the disease long enough, eventually the optic nerve, then the retina, show signs of degeneration," said Calkins. "So the degeneration works in reverse order. It starts in the brain and works its way back to the retina so that in the very latest stages of the disease, the earliest structures, the ones nearest the eye, are the last to go."

Now the team is working on finding drugs that can improve or restore the connectivity between the optic nerve and the mid-brain. Using both synthetic compounds and natural nerve growth factors such as Brain-Derived Neurotrophic Factor (BDNF), the team is examining how to restore communication in the pathway.

According to National Eye Institute projections, by the year 2020, 80 million people worldwide will have glaucoma. The risk of vision loss in glaucoma cases increases sevenfold after the age of 55.

Since 1915 there have been fewer than a dozen articles about glaucoma published in PNAS, said Calkins.

"People really thought we were crazy when we first suggested that the first signs of injury for glaucoma were in the brain," he said. "What this discovery does is to allow us to view this disease through the same lens that we view other age-related neurodegenerative disorders."

Quit smoking to save your eyes

Fri, 01 Jan 2010 11:08:44 PST

( from http://www.rxpgnews.com ) A UCLA study finds that even after age 80, smoking continues to increase one's risk for age-related macular degeneration (AMD), the leading cause of blindness in Americans over 65.

The American Journal of Ophthalmology publishes the findings in its January edition.

"The take-home message is that it's never too late to quit smoking," said lead author Dr. Anne Coleman, professor of ophthalmology at the Jules Stein Eye Institute at UCLA. "We found that even older people's eyes will benefit from kicking the habit."

AMD causes progressive damage to the macula, the center of the retina that allows us to see fine details. When the macula degenerates, people experience darkness or blurring in their central vision, preventing them from being able to read, drive and recognize faces.

After age, smoking is the second most common risk factor for AMD. This study sought to determine whether age influences the effects of smoking on AMD risk.

Coleman and her colleagues followed a group of 1,958 women who underwent retinal photographs at five-year intervals, starting with a baseline exam at age 78. Four percent, or 75 of the women, smoked.

The researchers compared the retinal images at ages 78 and 83 to check for the appearance of AMD, and evaluate whether smoking affected the women's likelihood of developing the disease.

"Age is the strongest predictor for AMD, yet most of the research in this field has been conducted in people younger than 75," explained Coleman. "Our population was considerably older than those previously studied. This research provides the first accurate snapshot of how smoking affects AMD risk later in life."

Overall, women who smoked had 11 percent higher rates of AMD than other women their same age. In women over 80, however, those who smoked were 5.5 times more likely to develop AMD than women their age who did not smoke.

"We saw a slightly higher rate of AMD in women after age 80, but the rate was dramatically higher in older women who smoked," said Coleman. "The bottom line is that AMD risk increases with age. And if you smoke, your risk of developing the disease rises even more."

Cigarette smoking has been hypothesized to increase AMD risk by reducing serum antioxidant levels, altering blood flow to the eyes and decreasing retinal pigments.

"This study provides yet another compelling reason to stop smoking and suggests that it is never too late to quit," said Dr. Paul Sieving, director of the National Eye Institute.

New effort to battle antibiotic resistance rallies researchers throughout Harvard University

Tue, 13 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Boston. MA--The National Institute of Allergy and Infectious Diseases of the National Institutes of Health (NIH) have awarded $5 million to an interdisciplinary group of Harvard researchers to launch the Harvard-wide Program on Antibiotic Resistance. Headed by Michael S. Gilmore, Ph.D., (Senior Scientist, Schepens Eye Research Institute and Schepens Professor of Ophthalmology [Department of Microbiology and Molecular Genetics], HMS), the group is uniting Harvard institutions in the fight against methicillin-resistant Staphylococcus aureus (MRSA) and other antibiotic resistant infection. The goal of the project is for the research team with a range of expertise to tackle the problem from different directions, and then to translate those findings into better treatments.

It shocked many a year and a half ago when CDC researchers noted that methicillin-resistant S. aureus (MRSA) were killing more in the US than HIV/AIDS (over 18,000 deaths per year). According to Gilmore, other penicillin resistant strains of S. aureus cause almost half again as many deaths. Worse, since 2002, MRSA have been acquiring resistance to one of the last line drugs used to treat those infections, vancomycin, a problem he has been studying with scientists at CDC.

MRSA are a major concern for hospitalized patients. More recently they have begun causing infections in healthy individuals in the community as well -- approximately 15% of invasive MRSA infections occur in patients with no known underlying cause. Most of these infections begin as skin infections, some acquired in sports locker rooms and other shared facilities. The infections become life-threatening when the microbe enters the bloodstream. New strains of MRSA have emerged that are causing many of the community infections.

Gilmore credits the Harvard-wide Microbial Sciences Initiative (an initiative launched in 2004 to bring together microbiology researchers from all Harvard campuses), the Harvard Catalyst Clinical and Translational Science Center, and a Schepens program to launch interdisciplinary research projects, for bringing this team together.

We have been friends and collaborators on this important problem and also the new interdisciplinary and translational efforts on campus. Formalizing these relationships was a small and logical step that each of us embraced. We were lucky that all of the pieces fell into place so well, said Gilmore.

Working with molecular microbiologist Gilmore are: David Hooper, MD (Associate Chief of Infectious Diseases and Head of Infection Control, MGH and Professor of Medicine, HMS); Suzanne Walker, Ph.D. (Professor of Microbiology and Molecular Genetics, HMS); Eleftherios Mylonakis, MD, PhD (Assistant Professor of Medicine, HMS and Member, Infectious Diseases, MGH); and Frederick M. Ausubel, Ph.D., Professor of Genetics HMS, and Member, Molecular Biology, MGH).

Walker, Mylonakis and Ausubel will be taking different high-throughput approaches to screen libraries of compounds for possible new drugs. Gilmore, Hooper and Mylonakis will then test these compounds for their ability to clear an infection, and will also examine possible pathways for the development of resistance. These projects will additionally benefit from input from, Richard Losick, Ph.D. (Harvard College Professor and Maria Moors Cabot Professor of Biology), who will assist Gilmore on his subproject, as well as head an advisory panel.

Researchers discover mechanism that helps humans see in bright and low light

Tue, 13 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Oct. 13, 2009 -- Ever wonder how your eyes adjust during a blackout? When we go from light to near total darkness, cells in the retina must quickly adjust. Vision scientists at Washington University School of Medicine in St. Louis have identified an intricate process that allows the human eye to adapt to darkness very quickly. The same process also allows the eye to function in bright light.

The discovery could contribute to better understanding of human diseases that affect the retina, including age-related macular degeneration, the leading cause of blindness in Americans over 50. That's because the disease and the pathway the researchers have identified both involve cells called cone cells.

Age-related macular degeneration may be modulated, perhaps, through this pathway we've identified in the retina, says principal investigator Vladimir J. Kefalov, Ph.D. Deficiencies in this pathway affect cone cells, and so does macular degeneration, so it's possible that if we could enhance activity in this pathway, we could prevent or reverse some of that damage to cone cells.

The retina's main light-sensing cells are called rods and cones. Both use similar mechanisms to convert light into vision, but they function differently. Rods are highly sensitive and work well in dim light, but they can quickly become saturated with light and stop responding. They don't sense color either, which is why we rarely see colors in dim light. Cones, on the other hand, allow us to see colors and can adapt quickly to stark changes in light intensity.

The researchers began with studies of salamanders because their cone cells are abundant and easy to identify. Cones rely on light-sensing molecules that bind together to make up visual pigments. The pigments get destroyed when they absorb light and must be rebuilt, or recycled, for the cone cells to continue sensing light. After exposure to light, key components of pigments called chromophores can leave the cells and travel to the nearby pigment epithelium near the retina. There the chromophore is restored and returned to the photoreceptor cells.

Earlier this year, the research team removed the pigment epithelium layer in salamander retinas, so that pigment molecules could not be recycled that way. Then they exposed retinal cells both to bright light and to darkness. The rods no longer worked, but the cones continued to function properly, even without the eye's pigment epithelium.

Exposure to bright light destroyed visual pigments in rods, and those cells could not recycle chromophores, says principal investigator Vladimir J. Kefalov, Ph.D., assistant professor of ophthalmology and visual sciences. Pigments in cones, by contrast, quickly regenerated and continued to detect light even without the pigment epithelium, so it was clear a second pathway was involved.

In the new study, Kefalov did the same experiments in cells from mice, primates and humans with the same result.

Major health care challenges persist for D.C. children despite high rates of health insurance coverage, RAND study finds

Thu, 08 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Despite high rates of health insurance coverage among children in the District of Columbia, children's access to health care is inadequate and poses a significant health problem for the city's young residents, particularly those who are publicly insured, according to a RAND Corporation study issued today.

The study, conducted by RAND Health and funded by Children's National Medical Center, assesses health and health care among the more than 100,000 youth residing in Washington, D.C. Researchers suggest that health promotion efforts must focus on a partnership involving numerous private and public sector organizations that serve children, including schools, community-based organizations and child care centers.

The District of Columbia leads the nation in children with health coverage, with only 3.5 percent estimated to be uninsured in 2007. Nationally, an estimated 9.1 percent of children lack health insurance.

But having health insurance in the District of Columbia does not automatically translate into access to health care, said Anita Chandra, the report's lead author and a behavioral scientist at RAND.

Access problems appear especially profound for children who have publicly funded insurance. The study finds that rates of well-child care among publicly insured children are substantially below national norms and more than one in four publicly insured children in the District receives care at a hospital emergency department at least once a year.

The study is the first to comprehensively focus on children's health issues and examine not only the health service delivery system, but the communities in which children live in the District of Columbia. Researchers aim to provide a foundation for District policymakers to examine children's health issues, as well as assist the Children's National Medical Center in allocating its community benefit resources.

The study finds that numerous barriers prevent residents from getting primary and specialty health care in non-hospital settings. One major factor is the uneven distribution of primary and specialty care providers across the District. Other barriers cited by District residents in the study include a perceived lack of provider understanding of cultural and neighborhood issues, as well as a limited availability of health care providers who speak languages other than English. The study also finds that particular health conditions and health behaviors require special attention because of their prevalence and potential severity. Although children are generally healthier than adults, researchers identified several chronic health conditions that are prevalent among District youth, including asthma, sickle cell anemia, HIV/AIDS and obesity.

Children with asthma, in particular, are substantial users of hospital-based care, said Carole Roan Gresenz, a study co-author and senior economist at RAND. District of Columbia leaders will want to focus on services that will help children manage their asthma and other chronic conditions before they end up in the emergency department or hospital.

Researchers find that socioeconomic, environment and safety conditions also are crucial issues facing District youth.

Though the rate of children in poverty in the District has declined in recent years, the percentage of children who live in poverty in the District remains higher than the national percentage (23 percent versus 18 percent).

Safety and violence are particularly important issues. The rate of dating violence in the District increased from 11 percent to 17 percent from 2005 to 2007, and rates of child abuse and neglect are twice the national average. As a result, far more children are in the District's foster care system than the national average.

The study includes a unique synthesis of information from previous research, including vital statistic reports and studies of school nursing and school mental health programs, along with original data analysis of existing survey and administrative information. The research also included information obtained from focus groups with parents, adolescents and health care providers.

The report's key recommendations include:

Case Western Reserve awarded $1.57M for corneal infection research

Wed, 07 Oct 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Researchers at Case Western Reserve University School of Medicine have been awarded a $1.57 million renewal grant from the National Eye Institute (NEI) of the National Institutes of Health to continue their study of corneal infections, specifically, bacterial keratitis, associated with contact lens wear. The grant will extend the work initiated last year with the receipt of a $2.4 million, five-year grant from the NEI.

The funding will support for four years the work of Eric Pearlman, Ph.D., professor and research director in the Department of Ophthalmology and Visual Sciences, as well as two postdoctoral investigators and one student working toward a Ph.D. The researchers hope to discover specific toll-like receptor (TLR) antagonists to regulate corneal inflammation, which could lead to the development of novel anti-inflammatory medications that could serve as alternatives to steroids to treat the infections.

Bacterial keratitis is a serious cause of visual impairment not only in the United States but also worldwide, and contact lens wear is a major risk factor for the infection in the cornea, the clear covering over the front part of the eye.

Organisms can infiltrate an intact cornea of a lens-wearer, and a biofilm can form on the contact lens, Dr. Pearlman says. Although correctly performed cleaning of contact lenses can remove the biofilm, or aggregation of micro-organisms, he adds, When one considers that 34 million people in the United States and about 140 million people worldwide wear contact lenses, even a low percentage of side effects translates into a large number of affected individuals.

The TLR family of pathogen recognition molecules plays a critical role in recognizing and responding to pathogens in the body, initiating anti-microbial inflammatory responses to them that often result in damage to tissue. In the absence of live bacteria, TLRs also respond to microbial products and can induce an inflammatory response in the cornea.

With the latest grant, the researchers will study the activation of TLR4, which is the major stimulatory component of Gram-negative bacteria, by large molecules called lipopolysaccharides, which elicit strong immune responses. They also will examine responses inside epithelial cells in the human cornea and in a murine model of corneal inflammation. The investigators' goal will be to identify potential areas on the cell surface and inside the cells that would be good targets for anti-inflammatory intervention.

Dr. Pearlman is the principal investigator leading a multidisciplinary team investigating fungal and bacterial keratitis that also includes Mahmoud A. Ghannoum, Ph.D., E.M.B.A., professor and director of the Center for Medical Mycology in the Department of Dermatology; Loretta B. Szczotka-Flynn, O.D., M.S., associate professor of ophthalmology and visual sciences; and Arne Rietsch, Ph.D., assistant professor of molecular biology and microbiology.

The Department of Ophthalmology and Visual Sciences is part of the Visual Sciences Research Center, which encompasses more than 40 vision researchers in 18 departments at Case Western Reserve University and University Hospitals Case Medical Center campus, including pharmacology, pathology, molecular biology, epidemiology and biostatistics, chemistry and biomedical engineering.

K-State scientist receives grant from National Institutes of Health to research cataracts

Tue, 14 Jul 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Research at Kansas State University is investigating the molecular composition of cataracts in hopes of developing a nonsurgical method to prevent or reverse the eye disease.

Cataracts, a clouding of the eye lens, are the leading cause of blindness in the world, according to the National Institutes of Health. Currently, surgery to remove and replace the cloudy eye lens is the only recommended method for restoring sight.

Larry Takemoto, a university distinguished professor of biology at K-State, has received nearly $500,000 from the National Institutes of Health to study the changes of protein interactions in the lens of the eye, which are believed to trigger cataracts.

Presently, there is no known drug that can reverse or stop cataracts, Takemoto said. By understanding the nature of the protein interactions on a biochemical level, we hope it will be possible in future studies to screen various drugs for their ability to inhibit or reverse the abnormal processes that cause cataracts.

In a healthy eye, a delicate and balanced interaction of proteins is normal and allows the lens to retain its transparency and ability to focus light. However, Takemoto's prior research suggests that changes in these interactions result in fluctuations of protein concentration. A change in concentration cause proteins to clump together, forming the cataract, and thus decreasing lens transparency. He has been collaborating with Chris Sorensen, university distinguished professor of physics at K-State, regarding theoretical aspects of this interaction.

We think that the proteins have very specific interactions amongst themselves, and that cataracts result from changes in these interactions, leading to lens opacity, Takemoto said. My laboratory has developed a methodology to study these interactions and their possible changes during the cataractous formation.

Takemoto is using a technique known as microequilibrium dialysis to measure protein interactions in a normal eye versus a cataractous eye. This process is normally used to study the interaction of smaller organic compounds; however Takemoto's lab will be the first to use it to study the interactions of proteins.

In microequilibrium dialysis, a mixture of two different types of proteins is put into one chamber, separated from another chamber by a filter that will only allow the passage of one type of protein. Over time, the protein concentrations in the chambers equalize, and if an interaction occurred, then the proteins should bind to one another.

This technique allows us to both detect and quantitate possible changes in these interactions for the first time, under true equilibrium conditions, Takemoto said. This study will establish the presence of interactions and will determine whether these interactions are altered during cataractogenesis.

K-State scientist receives grant from National Institutes of Health to research cataracts

Tue, 14 Jul 2009 03:59:36 PST

Queen's University study aims at early diagnosis for ADHD and Parkinson's disease

Mon, 13 Jul 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Eye movement tests developed by Queen's University researchers to aid in understanding childhood brain development and healthy aging may also help in the diagnosis of Attention Deficit Hyperactivity Disorder and detecting the early onset of Parkinson's disease. The project has received close to $1 million in recent funding from the Canadian Institutes of Health Research (CIHR).

An important aspect of what makes us human is the ability to control our behaviour, says Physiology professor Douglas Munoz, who leads the study. Our project investigates how the brain provides this control by observing eye movements. Our experiments have been designed to combine high speed eye movement recording with modern brain imaging techniques to identify brain regions that control our behaviour.

To test this, the team designed a simple yet ingenious experiment. Participants from a wide range of age groups were placed in a magnetic resonance imaging unit that measured their brain activity. While in the unit, they were shown a series of lights and asked to move their eyes toward or away from the lights. The speed and accuracy of their eye movements were recorded and correlated to the activity being documented in specific areas of their brains.

The study showed that at early ages, children scored low. Although they understood the task, sometimes they couldn't help but look at the light, even when asked to look away from it. As the age of the subjects increased, response times decreased and accuracy improved, peaking at age 20-25. As the subjects continued to age, the response times started to increase.

The researchers could also see which sections of the participant's brains were active, and which were less active, with age. With these baselines in place, the same experiments can now be conducted with patients who have ADHD and Parkinson's disease.

In preliminary experiments, kids with ADHD could not help but look at the light no matter if they were asked to look away or not. Normal brain activity was also decreased, says Professor Munoz. When they took their ADHD medication the success rates, and the activity in certain areas of the brain, increased. This test could therefore be used to examine the effectiveness of new ADHD medication.

The same holds true for Parkinson's disease. In preliminary experiments, patients with the disease had a consistent pattern of eye movement time and brain activity. Introducing the tests in clinics as part of regular health exams could result in earlier diagnosis of Parkinson's, allowing the disease progression to be controlled with diet and medication, Dr. Munoz adds.

Other members of the research team include, from Queen's, Drs. Giovanna Pari (Neurology), Angela Garcia (Geriatrics) and Patrick Stroman (Diagnostic Radiology); and Thomas Trappenberg, a computer scientist at Dalhousie University. The investigation into ADHD and Parkinson's disease will take place over the next five years, thanks to the $953,000 funding grant from CIHR.

Queen's University study aims at early diagnosis for ADHD and Parkinson's disease

Mon, 13 Jul 2009 03:59:36 PST

IU School of Optometry named national vision research center

Mon, 29 Jun 2009 03:59:36 PST

( from http://www.rxpgnews.com ) BLOOMINGTON, Ind. -- A group of scientists working in Indiana University's School of Optometry and the Department of Biology will share more than $2.2 million from the National Institutes of Health to support their ongoing vision research.

The grant from the National Eye Institute, an arm of NIH, places the Indiana University Bloomington campus among an elite group of vision research centers in the nation. By providing core services to investigators who have already independently received funding from NEI, the grants will accelerate the progress of vision research through support for widely used research services.

Because the grant can ultimately assist individuals with National Eye Institute support across the entire campus, it will be a resource for all vision scientists. Currently, the core grant supports the research efforts of 10 NEI-funded IU researchers, including optometry Professor Stephen Burns, principal investigator on the grant. Burns has been continuously funded by NEI since 1982.

Joining Burns as co-investigators are:

School of Optometry Professors Joseph Bonanno, Ann Elsner, William Swanson and Larry Thibos

IU School of Optometry Interim Dean Sarita Soni said award of the grant confirms recognition by the National Eye Institute and NIH that the expansion of vision research under way at the school warranted additional support. Faculty at the school have received four additional independent research grants from NEI in just the past two years, and the number of research laboratories at the school has grown from eight to 15 in the past eight years.

The school has also added nine new faculty members in the past eight years, including Burns, Elsner, Swanson and assistant professor Shirin Hassan in the past four years, and plans to hire three more investigators over the next five years to meet the needs of its growing vision science and optometry programs.

This award fulfills one of the key strategic goals that the School of Optometry faculty set for its research program 10 years ago. The research funding and publications have increased exponentially in the last few years, and we anticipate this growth to continue, Soni said. With this new support the National Eye Institute has recognized the strength of the program that we have built and our commitment to be one of the very best vision science research programs in the country. This new award will help insure that our vision scientists remain focused and that IU continues to attract and support the very best investigators with the greatest potential to establish vigorous program in vision research.

The grant aims to support infrastructure improvements in three areas where researchers share resources -- electronics, machine shop and scientific computing -- and will play an integral role in allowing for the seamless integration of mechanical, electronic and software components in the design and use of custom research equipment and new clinical technology.

The new funding will have broad applications to vision research projects related to microscopic and ocular fluorimetry, cell physiology and molecular biology, advanced measurement and modeling of the optics of the eye, novel imaging of the structures of the normal and pathological living human eye, studies of the normal and abnormal developing human visual system, and the development of new quantitative strategies to assess visual function in a clinical setting.

This award will also allow for a new level of coordinated activity among laboratories and groups and support sustained interaction with sophisticated supercomputing and 3D visualization resources, including collaboration with University Information Technology Services. The school already has active collaborations under way with the cognitive science, computer science, mathematics and neuroscience departments at IU.

We are thrilled the National Eye Institute saw the numerous concrete examples of the significant support the school and the IU Bloomington campus has provided for vision research in its quest to become a major center for vision research and for training future vision researchers, Burns said. By funding improvements in electronics, mechanical design and computing assets, the research group will be able to improve and speed up the design and implementation of new and customizable instrumentation, a process that currently demands some of the work to be contracted out, which can be costly, relatively slow and inflexible during the testing process. Furthermore, our current machine shop structure has many non-research tasks that compete for time with research jobs, and additional core support will make this system much more responsive to our research needs.

K-State professor awarded $1.48 million to study LASIK complictions

Fri, 01 May 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Gary Conrad, a university distinguished professor at Kansas State University's Division of Biology, has received a four-year grant renewal of $1.48 million from The National Eye Institute of the National Institutes of Health to study the cornea.

The NIH renewal will make Conrad's grant the longest continuously funded R01 grant in the state of Kansas at 41 years, said Jim Guikema, K-State associate vice president for research.

From the beginning, Conrad has been fascinated by the unique structure of the cornea.

Among all body tissues, the cornea is unique in being transparent, very highly innervated, free of blood vessels and yet composed of three layers of living cells, he said.

Conrad's research on embryonic development of the eye has led to knowledge that could possibly improve LASIK surgery. He and his research associates have identified a difference in the connective tissue of normal corneas compared to those that have been cut during LASIK.

LASIK, which stands for laser-assisted in situ keratomileusis, is a surgery using a laser to reshape the cornea as an alternative to wearing glasses or contact lens. During the procedure a thin-hinged flap is cut in the front of the cornea and peeled back out of the way to allow the laser to reshape the corneal connective tissue underneath the flap. When the laser is finished the flap is pulled back to its original position.

It was once believed that the flap would re-adhere permanently. However, the unique connective tissue of the cornea and a lack of blood vessels limit its ability to fully heal even years after the procedure, Conrad said. A trauma to the face, such as impact from an automobile air bag provides enough force to dislodge the flap, reopening the cornea, infecting it with dirt and debris, and causing instant loss of visual acuity.

After LASIK, differences in the structure of sugar molecules made the cornea prevent cut nerve ends from regenerating, as well as preventing the flap from re-adhering. However, the National Institutes of Health grant renewal will enable the lab group to test a possible solution that would strengthen the stromal flap and allow it to permanently bind back to the cornea after LASIK, Conrad said. It uses a combination of riboflavin and UVA light to permanently cross-link the connective tissue of the flap to the underlying corneal connective tissue. The treatment is currently in clinical trials in the U.S. for another eye dysfunction known as keratoconus.

The density of sensory nerve fibers that normally develop in our cornea is higher than anywhere else on the surface of our entire body, Conrad said. However, they regenerate extremely slowly if they are cut, so if we could get those nerves to regenerate, it would be a major medical advance.

Since the grant began in 1971, Conrad's lab group has discovered many properties of embryonic and adult corneas. He credits these accomplishments to the research professors, postdoctoral research associates, graduate students, research assistants and undergraduates in his lab who co-author many research publications that have made continuing grant funding possible.

His closest colleagues include his wife, Abigail Conrad, a K-State molecular, cellular, and developmental biologist; Yuntao Zhang, a K-State structural carbohydrate chemist; Peter Lwigale, a 2001 K-State doctoral graduate in biology and now an assistant professor at Rice University; Scott McCall, a K-State senior in biology and biochemistry and a 2008 Goldwater Scholar from Parker, Colo.; and Conrad's first doctoral student Gerald Hart, director of the department of biological chemistry at the Johns Hopkins University School of Medicine, Baltimore, Md.

Conrad is known for mentoring and encouraging undergraduates in his lab. As a result, Conrad has recommended McCall for a summer position in Hart's lab, researching structural chemistry.

Our molecular biology research is only as good as our K-State freshmen dishwashers and autoclavers, so we try to train them carefully, listen to their questions, and counsel them as our closest research colleagues, Conrad said. They teach us many things.

Study reports success in treating a rare retinal disorder

Tue, 14 Apr 2009 03:59:36 PST

( from http://www.rxpgnews.com ) Ann Arbor, MI--Patients with a rare, blinding eye disease saw their vision improve after treatment with drugs to suppress their immune systems, according to researchers at the University of Michigan Kellogg Eye Center. Because autoimmune retinopathy (AIR) is difficult to diagnose, the biggest challenge now is to find biologic markers that identify patients who can benefit from treatment.

In a review of 30 patients with autoimmune retinopathy, 21 individuals showed improvement after receiving treatment with immunosuppression therapy. The study, reported in the April issue of Archives of Ophthalmology, is the largest review of AIR cases to date. Improvement was defined by several measures, including the ability to read a minimum of two additional lines on the standard eye chart or expansion of at least 25% in visual field size.

The results challenge the commonly held belief that autoimmune retinopathy is untreatable, says John R. Heckenlively, M.D., author of the report and an international expert on retinal dystrophies. In this disease, antibodies attack the retina, resulting in progressive vision loss and eventual blindness.

AIR is like other autoimmune diseases in which the immune system goes awry and begins to attack healthy tissue. The patients in the current study were treated with various combinations of immunosuppression medications to counteract the unwanted autoantibodies from the immune system.

It is not easy to identify patients with AIR because the clinical symptoms are very similar to other diseases involving retinal degeneration, says Heckenlively. Typically these patients are diagnosed as having retinitis pigmentosa, a blinding eye disease for which there is no treatment. When someone asks how to distinguish one group from the other, says Heckenlively, the answer often is with difficulty.

We do not yet have a single test to confirm a diagnosis of AIR, explains Heckenlively. However most patients have characteristic symptoms and findings, as well as subtle abnormalities on electrophysiologic testing. All patients have anti-retinal antibodies on blood testing, but that finding alone is not diagnostic. The majority of cases have other family members with autoimmune disorders. A clear diagnosis of AIR relies on carefully weighing all these factors, he concludes.

Heckenlively observes that few reports on AIR treatment are available in scientific publications, due largely to the difficulty in establishing the diagnosis. It is also possible that many patients are undertreated because we do not have good markers to evaluate treatment effects, observes Heckenlively. Now that we have evidence that immunosuppressant therapies work, we need further studies to evaluate which medications will be effective in treating autoimmune retinopathy.

ORNL, UT project could save vision of millions

Tue, 17 Feb 2009 04:59:36 PST

( from http://www.rxpgnews.com ) OAK RIDGE, Tenn., Feb. 17, 2009 -- In the blink of an eye, people at risk of becoming blind can now be screened for eye diseases such as diabetic retinopathy and age-related macular degeneration.

Using a technology originally developed at the Department of Energy's Oak Ridge National Laboratory to understand semiconductor defects, three locations in Memphis have been equipped with digital cameras that take pictures of the retina. Those images are relayed to a center where they are analyzed and the patient knows in minutes whether he or she needs additional medical attention.

Once we've taken pictures of the eyes, we transmit that information to our database, where it is compared to thousands of images of known retinal disease states, said Ken Tobin, who led the ORNL team that developed the technology. From there, the computer system is able to determine whether the patient passes the screening or it provides a follow-up plan that includes seeing an ophthalmologist.

Already, this technology is making a difference as two patients at the Church Health Center in Memphis have been identified as needing laser treatment for moderate and severe diabetic retinopathy and macular edema, both conditions that can lead to blindness.

While some cameras have been installed, others will be installed at several rural and urban health care centers serving the Mississippi Delta. Another camera is planned for a federally funded health center in Chattanooga. Eventually, the goal is to have hundreds of cameras throughout the United States and beyond. If disease can be detected early, treatments can preserve vision and significantly reduce the occurrence of debilitating blindness.

This project takes advantage of ORNL's proprietary content-based image retrieval technology, which quickly sorts through large databases and finds visually similar images. For more than a decade manufacturers of semiconductors have used this technology to rapidly scan hundreds of thousands of tiny semiconductors to learn quickly about problems in the manufacturing process.

Our approach allows us to adapt a proven technology to describe key regions of the retina, and this information can then be used to index images in a content-based image retrieval library, Tobin said. What separates this from other methods is that we have automated the process of diagnosing retinal disease by capturing the expert knowledge of an ophthalmologist in a patient archive.

Leading the medical portion of the project is Edward Chaum, an ophthalmologist and Plough Foundation professor of retinal diseases at the University of Tennessee Health Science Center (

Vigorous exercise may help prevent vision loss

Mon, 09 Feb 2009 04:59:36 PST

( from http://www.rxpgnews.com ) Berkeley, CA -- There's another reason to dust off those running shoes. Vigorous exercise may help prevent vision loss, according to a pair of studies from the U.S. Department of Energy's Lawrence Berkeley National Laboratory. The studies tracked approximately 31,000 runners for more than seven years, and found that running reduced the risk of both cataracts and age-related macular degeneration.

The research, which is among the first to suggest that vigorous exercise may help prevent vision loss, offers hope for people seeking to fend off the onset of eye disease.

In addition to obtaining regular eye exams, people can take a more active role in preserving their vision, says Paul Williams, an epidemiologist in Berkeley Lab's Life Sciences Division who conducted the research. The studies suggest that people can perhaps lessen their risk for these diseases by taking part in a fitness regimen that includes vigorous exercise.

A cataract, which is a cloudy opacity of the eye lens, is the leading cause of blindness. More than one-half of people in the U.S. over the age of 65 suffer from some form of cataracts. Age-related macular degeneration, which is damage to the retina, is the leading cause of irreversible vision loss in older white Americans, affecting 28 percent of people aged 75 and older.

The diseases have several known risk factors, such as sunlight exposure and diabetes in the case of cataracts, but few interventions. Now, it appears that vigorous cardiovascular exercise may be one way to derail the diseases.

To conduct the research, Williams analyzed data collected in the National Runners' Health Study, which he established in 1991 to determine the health benefits of running.

In this case, he followed approximately 29,000 male runners and 12,000 female runners for more than seven years. Of these people, 733 men reported being diagnosed with cataracts on a questionnaire filled out at the end of the study. Too few women reported cataracts to track.

Men who ran more than 5.7 miles per day had a 35 percent lower risk of developing cataracts than men who ran less than 1.4 miles per day. The study also analyzed men's 10-kilometer race performances, which is a good indicator of overall fitness. The fittest men boasted one-half the risk of developing cataracts compared to the least-fit men.

A second study found that running appeared to reduce the risk of age-related macular degeneration. In the study, 152 men and women reported being diagnosed with the disease. Compared to people who ran less than 1.2 miles per day, people who averaged between 1.2 and 2.4 miles per day had a 19 percent lower risk for the disease, and people who ran more than 2.4 miles per day had between 42 percent and 54 percent lower risk of the disease.

These findings are compelling because of the large size of the study, and the fact that we are looking at something that is fairly well defined: vigorous exercise, as opposed to more moderate exercise, says Williams.

Most of the runners in the study exceeded the current public health recommendations for physical activity, which is at least 30 minutes of moderate-intensity activities such as brisk walking five days a week, or smaller doses of more vigorous exercise such as running. It is unclear whether people might also lower their risk for cataracts and age-related macular degeneration by walking.

We know there are important health benefits to walking, including lowering heart disease risk, says Williams. It is quite likely that the studies' results might apply to a lesser extent to smaller doses of more moderate exercise.

Williams also adds that further research is needed to explore why there is a link between vigorous exercise and a decreased risk for eye disease.

We know some of the physiological benefits of exercise, and we know about the physiological background of these diseases, so we need to better understand where there's an overlap, says Williams.

From outer space to the eye clinic: New cataract early detection technique

Mon, 12 Jan 2009 04:59:36 PST

( from http://www.rxpgnews.com ) A compact fiber-optic probe developed for the space program has now proven valuable for patients in the clinic as the first non-invasive early detection device for cataracts, the leading cause of vision loss worldwide.

Researchers from the National Eye Institute (NEI), part of the National Institutes of Health, and the National Aeronautics and Space Administration (NASA) collaborated to develop a simple, safe eye test for measuring a protein related to cataract formation. If subtle protein changes can be detected before a cataract develops, people may be able to reduce their cataract risk by making simple lifestyle changes, such as decreasing sun exposure, quitting smoking, stopping certain medications and controlling diabetes.

By the time the eye's lens appears cloudy from a cataract, it is too late to reverse or medically treat this process, said Manuel B. Datiles III, M.D., NEI medical officer and lead author of the clinical study. This technology can detect the earliest damage to lens proteins, triggering an early warning for cataract formation and blindness.

The new device is based on a laser light technique called dynamic light scattering (DLS). It was initially developed to analyze the growth of protein crystals in a zero-gravity space environment. NASA's Rafat R. Ansari, Ph.D., senior scientist at the John H. Glenn Research Center and co-author of the study, brought the technology's possible clinical applications to the attention of NEI vision researchers when he learned that his father's cataracts were caused by changes in lens proteins.

Several proteins are involved in cataract formation, but one known as alpha-crystallin serves as the eye's own anti-cataract molecule. Alpha-crystallin binds to other proteins when they become damaged, thus preventing them from bunching together to form a cataract. However, humans are born with a fixed amount of alpha-crystallin, so if the supply becomes depleted due to radiation exposure, smoking, diabetes or other causes, a cataract can result.

We have shown that this non-invasive technology that was developed for the space program can now be used to look at the early signs of protein damage due to oxidative stress, a key process involved in many medical conditions, including age-related cataract and diabetes, as well as neurodegenerative diseases such as Alzheimer's and Parkinson's, said NASA's Dr. Ansari. By understanding the role of protein changes in cataract formation, we can use the lens not just to look at eye disease, but also as a window into the whole body.

The recent NEI-NASA clinical trial, reported in the December 2008

Research 'A' team to fast track Bionic Eye, Australian consortium announced

Wed, 12 Nov 2008 04:59:37 PST

( from http://www.rxpgnews.com ) Tens of thousands of people with severe vision loss are set to benefit after the announcement today of a landmark partnership of world-leading Australian research institutes.

Bionic Vision Australia will pursue the development of the most technologically advanced bionic eye to improve the sight of people with degenerative or inherited retinal disease.

Bionic Vision Australia's members include the University of Melbourne, the University of New South Wales, the Bionic Ear Institute, Centre for Eye Research Australia and the Victoria Research Laboratory of NICTA.

Bionic Vision Australia Chairman, Professor Emeritus David Penington A.C, said the partnership brings together Australia's international experts in medical bionics, covering the many disciplines required to develop a safe and technologically advanced device able to restore functional vision.

Our team is well placed to undertake the critical research required to deliver an advanced Bionic Eye, which would deliver improved quality of life for patients suffering from common causes of severe loss of vision and blindness, he said.

Over 50,000 Australians have severe to profound vision loss. The major cause of severe vision impairment is degeneration or death of the cells in the eye that receive light signals.

It has been estimated that the cost of severe and profound vision loss in Australia is approximately $3B per year, and rising.

A bionic eye will assist in restoring patient mobility, independence and quality of life by effectively replacing the function of damaged light-sensing cells in the eye.

While the clarity and definition of vision will not be equal to normal sight, the device will allow patients to move around, detect large objects and, in time, read text and recognise faces and emotions.

Bionic Vision Australia has submitted a detailed plan and funding request to the Australian Government to enable it to undertake the required research and early clinical testing.

The New South Wales and Victoria governments have both provided support to the partnership to enable the development of the detailed plan.

The proposal follows an 18-month feasibility study undertaken by members of the consortium and heightened public interest in the bionic eye, most notably at the recent Australia 2020 Summit where it was flagged as a big idea worthy of consideration for Australia to pursue.

Bionic Vision Australia proposes to have its first advanced prototype ready for the first human implant by early 2012 that delivers significant benefits to patients with severe mobility and light perception difficulties.

This device is the result of research undertaken over a 10-year period by the Australian Vision Prosthesis Group at the University of New South Wales.

An enhanced second prototype developed at the Victoria Research Laboratory of NICTA could be available for the first human implant by late 2013 and would provide further improved quality of life for patients where image perception is the primary consideration.

This is an exciting opportunity for Australia to reinforce its leadership in medical bionics, first demonstrated with the development in Melbourne of the bionic ear in the 1970's, said Professor Anthony Burkitt, Research Director of Bionic Vision Australia and Chair of the Department of Electrical and Electronic Engineering at the University of Melbourne.

BVA is inspired by the bionic ear experience to build a world-class multi-disciplinary team capable of restoring functional vision to sufferers of inherited and degenerative retinal diseases and thereby make a contribution to addressing the significant cost this disease imposes on the Australian and other economies.

The implications for improved health are significant, he said.

Sunlight, low anti-oxidant levels likely to damage vision

Mon, 03 Nov 2008 13:27:30 PST

( from http://www.rxpgnews.com ) London- The combination of low antioxidant levels and exposure to sunlight may damage certain kinds of vision. It is also linked with age-related macular degeneration -.

Animal and lab studies suggest that blue light or short-wavelength light may damage the retina and contribute to the development of AMD, which occurs when the area of the retina - responsible for sharp vision deteriorates.

'The retina is vulnerable to the damaging effects of light,' the authors of the study wrote. 'While wavelengths in the UV - radiation range are largely absorbed by the cornea and lens, the retina is exposed to visible light, including blue light'.

Antioxidant enzymes - including vitamins C and E, the carotenoids - and zinc - may protect against the harmful effects of blue light on the retina, according to a release of American Medical Assocation.

Astrid E. Fletcher of the London School of Hygiene and Tropical Medicine and colleagues measured levels of these nutrients in the blood of 4,753 older adults - who were part of the European Eye Study.

Participants also were interviewed about their lifetime sunlight exposure and had photographs taken of their retinas to detect AMD.

Of the 4,400 participants with complete information available, 2,117 did not have AMD, 101 had neovascular - AMD and 2,182 had early-stage AMD.

Overall, there was no association between blue light exposure and early AMD. However, blue light exposure was associated with neovascular AMD in the one-fourth of individuals with lowest antioxidant levels.

The study was published in the October issue of Archives of Ophthalmology.

Kuwaiti surgeon develops new method to treat cataract

Sat, 18 Oct 2008 17:04:19 PST

( from http://www.rxpgnews.com ) Dubai, Oct 18 - A Kuwaiti eye specialist has invented a process by which cataracts can be treated with a rentiscope without going for the complex option of retina transplant.

Khaled Al-Sabti, head of the retina ward in the Al-Bahar Eye Centre in Kuwait, told the official Kuwait News Agency - that his invention would spare eye cataract patients the time and money consuming process of retina transplant.

He claimed that his process improved the eyesight of his patients by 40 to 60 percent.

Al Sabti's invention has been recorded in the British Journal of Opthalmology.

Elaborating on the process, he said that in conventional surgeries of the retina, the eyesight starts to improve six months after the operation, but in many cases, bodies of the patients reject the transplanted retina.

The surgeon said he applied his innovative medical technique on nine patients, aged between 50 and 74, which helped improve their condition noticeably.

He said he would present his breakthrough method in scientific conferences and events in Canada and the US over the next month.

Kuwait's Health Minister Ali Al-Barrak Saturday praised Al-Sabti for the innovation.

Al-Barrak, in his statement, also urged other Kuwaiti doctors to follow the new method for overall promotion of national medical services.

Post Menopausal Hormones - reduces risk of macular degeneration

Mon, 14 Apr 2008 13:52:04 PST

( from http://www.rxpgnews.com ) Women who take postmenopausal hormones appear to have a lower risk of developing advanced stages of the eye disease age-related macular degeneration, especially if they had also taken oral contraceptives in the past, according to a report in the April issue of Archives of Ophthalmology, one of the JAMA/Archives journals.

Age-related macular degeneration (AMD) is the leading cause of vision loss and blindness among older adults, affecting 1.75 million Americans, according to background information in the article. “Although genetics plays a key role in susceptibility to AMD, environmental factors, such as smoking, are also important,” the authors write. “Evidence of higher rates of AMD in women than in men and links between AMD and cardiovascular disease suggested a role for estrogen in the etiology” or development of the condition.

Diane Feskanich, Sc.D., of Brigham and Women’s Hospital and Harvard Medical School, Boston, and colleagues assessed estrogen-related factors such as postmenopausal hormone use, past use of oral contraceptives, ages at first period and menopause and childbirth history in 74,996 post-menopausal women in the Nurses’ Health Study. Between 1980 and 2002, 554 of the women developed early (beginning-stage) AMD and 334 women developed neovascular (more advanced, involving the formation of new blood vessels) AMD.

“Current postmenopausal hormone users had a notable 48 percent lower risk of neovascular AMD compared with those who had never used postmenopausal hormones, although risk did not decline linearly with longer durations of use,” the authors write. “Risk was lowest for postmenopausal hormone users who had used oral contraceptives in the past.”

In contrast, risk of early AMD was 34 percent higher among current postmenopausal hormone users and oral contraceptive use was not associated with early AMD risk. “The higher risk of early AMD among postmenopausal hormone users was unexpected and in apparent conflict with the observed inverse association for neovascular AMD,” the authors write. Women who had given birth had a 26 percent lower risk of early AMD.

“Taken together, these findings suggest a role for estrogen in the pathogenesis of AMD that requires further research in specific early and late signs of disease,” they conclude.

New Findings Indicate That Eyes Can Regenerate Damaged Retinas

Thu, 20 Mar 2008 11:32:27 PST

( from http://www.rxpgnews.com ) Washington, March 20 - It might be possible to turn on the eye's own resources to regenerate damaged retinas, without the need for transplanting outside retinal tissue or stem cells, according to a new study.

Researchers have discovered a chemical in the eye that triggers the dormant capacity of certain non-neuronal cells to transform into progenitor cells, a stem-like cell that can generate new retinal cells.

If the next step works in animal disease models, then clinical testing would be a possibility soon, offering hopes for millions of victims of degenerative eye diseases.

Scientists have long been aware of Muller cells -, presuming that they were responsible for keeping retinal tissue protected and clear of debris.

In recent years, however, researchers have reported that these cells sometimes exhibit progenitor cell behaviour and re-enter the cell cycle.

Progenitor cells are similar to stem cells but are more mature and are more limited in the number of cells types they can become.

But until this study, scientists have not understood what triggers the transformation.

In their study, Dong Feng Chen of Harvard Medical School and her team observed that when the naturally occurring chemicals known as glutamate and aminoadipate - were injected into the eye, Muller cells began to divide and proliferate.

Not certain if these chemicals directly signalled the transformation, they tested them in the lab and in mice. They added each chemical separately to cultures of pure Muller cells and injected each into the space below the retina in healthy mice.

In both cases, the cells became progenitor cells and then changed into retinal cells. And with aminoadipate, the newly minted retinal cells migrated to where they might be needed in the retina and turned into desirable cell types.

Specifically, they showed that by injecting the chemical below the retina, the cells give rise to new photoreceptors - the type of cells that are lost in retinitis pigmentosa or macular degeneration leading to blindness.

The discovery has been published in the March issue of Investigative Ophthalmology and Visual Science.

Coffee drinking protects against an eyelid spasm

Thu, 21 Jun 2007 03:59:37 PST

( from http://www.rxpgnews.com ) People who drink coffee are less likely to develop an involuntary eye spasm called primary late onset blepharospasm, which makes them blink uncontrollably and can leave them effectively "blind", according to a study published online ahead of print in the Journal of Neurology Neurosurgery and Psychiatry.

The effect was proportional to the amount of coffee drank and one to two cups per day were needed for the protective effect to be seen. The age of onset of the spasm was also found to be later in patient who drank more coffee - 1.7 years for each additional cup per day.

Previous studies have suggested that smoking protects against development of blepharospasm, but this Italian study did not show a significant protective effect.

Late onset blepharospasm is a dystonia in which the eyelid muscles contract uncontrollably; this starts as involuntary blinking but in extreme cases sufferers are rendered functionally blind despite normal vision because they are unable to prevent their eyes from clamping shut.

The study involved 166 patients with primary late onset blepharospasm, 228 patients with hemifacial spasm (a similar muscle spasm that usually begins in the eyelid muscles but then spreads to involve other muscles of the face) and 187 people who were relatives of patients. The second two groups acted as controls.

The participants were recruited through five hospitals in Italy and asked whether they had ever drank coffee or smoked and for how many years. They were also asked to estimate how many cups of coffee they drank and/or packs of cigarettes they smoked per day. The age of onset of muscle spasms was recorded for patients who experienced them and a reference age was calculated for each of the patients' relatives based on the duration of the spasms in the other group.

Regression analysis was used to observe the relationship between coffee drinking and smoking on the development of blepharospasm.

The authors say: "Our findings raise doubt about the association of smoking and blepharospasm but strongly suggest coffee as a protective factor."

"The most obvious candidate for the protective effect is caffeine, but the low frequency of decaffeinated coffee intake in Italy prevented us from examining the effects of caffeine on blepharospasm.

They suggest that caffeine blocks adenosine receptors as has been proposed for its mechanism in protecting against Parkinson's disease.

The authors estimate that people need to drink one to two cups of coffee per day for the protective effect to be seen.

"Considering that the caffeine content of a cup of Italian coffee (60-120 mg) is similar to the average content of a cup of American coffee (95-125 mg), the protective effect on the development of blepharospasm might be exerted at caffeine doses greater than 120-240 mg, comparable with the caffeine doses suggested to be protective in Parkinson's disease," they say.

Higher fish consumption have a reduced risk of advanced age-related macular degeneration

Mon, 14 May 2007 20:33:35 PST

( from http://www.rxpgnews.com ) Individuals who have higher dietary intake of foods with omega-3 fatty acids and higher fish consumption have a reduced risk of advanced age-related macular degeneration, while those with higher serum levels of vitamin D may have a reduced risk of the early stages of the disease, according to two reports in the May issue of Archives of Ophthalmology, one of the JAMA/Archives journals.

Age-related macular degeneration (AMD) occurs when the macula, the area at the back of the retina that produces the sharpest vision, deteriorates over time. It is the most common cause of blindness among older adults in the United States, affecting more than 7 million individuals older than 40 years, according to background information in the articles. The prevalence of AMD is likely to increase as the population ages. There is currently no known way to prevent the condition, but research has begun to identify potentially modifiable risk factors and nutrient-based treatments.

The Age-Related Eye Disease Study Research Group assessed 4,519 individuals who were age 60 to 80 when they enrolled in 1992 through 1998. At that time, photographs were taken of their retinas to determine if they had AMD, and if so, to which of four stages the condition had progressed. The participants also completed a food frequency questionnaire that measured how often they consumed foods rich in certain vitamins, minerals and other nutrients, such as omega-3 fatty acids commonly found in tuna, salmon and other fish.

A total of 1,115 participants did not have any symptoms of AMD at the beginning of the study, and were compared with those who did, including 658 individuals with neovascular (severe) AMD. "Dietary total omega-3 long-chain polyunsaturated fatty acid intake was inversely associated with neovascular AMD, as was docosahexaenoic acid," or DHA, a fatty acid that previous evidence suggests affects the retina, the authors write. "Higher fish consumption, both total and broiled/baked, was also inversely associated with neovascular AMD." Eating more than two medium (4-ounce) servings of fish per week or more than one medium serving of broiled or baked fish was associated with the lowest risk for advanced AMD.

Omega-3 fatty acids may influence processes involved in the development of blood vesselâ and nerve-related diseases of the retina, the authors write. For instance, DHA may protect the retina by influencing which genes turn on and off, while fatty acids overall may eventually form compounds that promote cell survival and proper blood vessel function, reduce inflammation and maintain energy balance.

"These results and those from other observational analytic investigations suggest that modifying diet to include more foods rich in omega-3 long-chain polyunsaturated fatty acids could result in a reduction in the risk of having neovascular AMD," the authors conclude. Clinical trials would provide further information about whether diet changes or supplements could prevent the development of advanced AMD.

In a related study, Niyati Parekh, Ph.D., R.D., of the University of the Medicine and Dentistry of New Jersey, New Brunswick, and the University of WisconsinâMadison, and colleagues analyzed data from 7,752 individuals (including 11 percent with AMD) who were part of the National Health and Nutrition Examination Survey, a large study designed to represent the entire U.S. population. Participants were enrolled in the study between 1988 and 1994. They had physical examinations that included blood and urine samples, photographs of the retinas, and interviews and questionnaires regarding sociodemographics, lifestyle habits and food intake.

"Levels of serum vitamin D were inversely associated with early AMD but not advanced AMD," the authors write. When participants were split into five groups based on level of vitamin D in the blood, those in the highest group had a 40 percent lower risk of early AMD than those in the lowest group. "Milk intake was inversely associated with early AMD. Fish intake was inversely associated with advanced AMD."

Vitamin D may reduce the risk of AMD by reducing inflammation or by preventing the growth of new blood vessels in the retina, which contributes to some forms of AMD, the authors speculate. "This study provides evidence that vitamin D may protect against AMD," the authors conclude. "However, at this time there is insufficient epidemiologic evidence of the relationship between vitamin D level and AMD to make recommendations regarding optimum serum vitamin D levels or milk and fish intake to protect against AMD or its progression. The results of the present research warrant further investigation for confirmation of the vitamin D-AMD association in other population studies."

Dry Eye Syndrome affects quality of life

Sat, 10 Mar 2007 00:29:53 PST

( from http://www.rxpgnews.com ) As a clinical diagnosis, Dry Eye Syndrome (DES) may not appear to be a major health issue, but in a study published in the March issue of the American Journal of Ophthalmology, researchers found that DES had a significant impact on quality of life. With an estimated prevalence of 7.8% of women and 4.7% of men over 50, it affects 4.8 million people in the United States. Although some risk factors have been identified, the cause of DES is still largely unknown.

DES is characterized by a deficiency in the quantity and/or quality of tears, an unstable tear film, ocular surface damage and bothersome symptoms such as ocular irritation, dryness, fatigue, and fluctuating visual disturbances. It is one of the most frequent reasons patients seek eye care. With few published data on the impact of DES on quality of life, the researchers assessed the effect on several common activities such as reading, driving, computer work, professional work and watching television.

Selecting subjects who were participating in two large studies, the Women's Health Study and the Physicians' Health Study, and who had answered three DES-related questions, supplementary questionnaires were filled out by almost 600 participants. One-third met the criteria for DES.

Writing in the article, Debra A. Schaumberg, ScD, OD, MPH, Schepens Eye Research Institute, Departments of Medicine and Ophthalmology, Harvard Medical School, and fellow investigators state, "DES is a common problem that may often be overlooked clinically as it tends not to be a common cause of permanent visual morbidity as traditionally measured. The interface between the tear film and the surrounding air represents the largest refractive index differential in the human optical system and is consequently of critical importance for clear vision. DES patients with an unstable tear film can usually clear a blurred image temporarily by blinking frequently to redistribute the tear film over the ocular surface. However, this may not be sustainable during activities requiring prolonged gazing, and those with more severe symptoms may experience difficulty keeping their eyes open. Our findings of nearly 3 and 5-fold increased risks of having problems with activities such as reading, computer use and professional work among both women and men with DES who did and did not use artificial tears, respectively, support and extend those of prior studies by pointing to specific areas of functioning that are problematic among people with DES".

"The present study suggests that DES can have a significant impact on visual function that can diminish a person's quality of everyday living," continues Dr. Schaumberg. "More specifically, the present study shows that crucial daily activities of modern living such as reading, computer use, professional work, driving and TV watching are all negatively impacted by DES."

Choroideremia- fault in the retinal pigment epithelium

Wed, 07 Mar 2007 18:19:02 PST

( from http://www.rxpgnews.com ) Researchers at Texas A&M University are shedding light on a rare form of early blindness, identifying the cells involved and paving the way for possible therapies to treat or even prevent what is currently an incurable disease.

The findings, funded by Fight for Sight and the National Institutes of Health, are published in the March 5-9 online Early Edition (EE) of the Proceedings of the National Academy of Sciences.

Since his post-doctoral days at Harvard University, Texas A&M biologist Dr. Brian Perkins has been studying protein transport within photoreceptorsthe rod and cone cells that allow organisms to detect their visual worldsin zebrafish, a vertebrate whose eye physiology is essentially identical to that of a human. Recently he became intrigued by a 30-year-old debate involving photoreceptor deathspecifically, whether it was a cause or an effectin choroideremia, an X chromosome-linked hereditary retinal degenerative disease that leads to blindness in an estimated one in every 100,000 people, beginning with severe loss of vision and night blindness as early as the pre-teen years and progressing to complete blindness by middle age.

Using a line of mutant zebrafish developed by Rockefeller Universitys Jim Hudspeth, Perkins and Texas A&M biology graduate student Bryan Krock zeroed in on a specific protein, the Rab escort protein-1 (REP1), which helps regulate intracellular traffic in the photoreceptors as well as a neighboring tissue called the retinal pigment epithelium (RPE). In collaboration with the University of Western Kentuckys Joseph Bilotta, they observed that mutations in REP1 disrupt cellular processes in the RPE, causing photoreceptor death as a secondary consequence. Their results suggest therapies that correcting the RPE may successfully rescue photoreceptor loss in choroideremia and even reverse the disease.

"For decades, no one knew if the photoreceptors were dying because of an internal trafficking defect or if they were dying as a secondary consequence of problems in the RPE," Perkins explains. "Previous research based on studies of human tissue said it was independent of the RPE. We wanted to see if that hypothesis was true. It turns out that it wasnt, but in making the wrong assumption, we found out something even more interestinga different way to cause photoreceptor death."

"If you disrupt protein transport, you kill the cell," Perkins notes. "In this case, the transportation process in the photoreceptors was perfectly normal, but the neighboring RPE was defective, which is why the photoreceptors were dying."

"For this particular disease, we now have the reason why people go blind. If our results translate into treating humans, it should lead to design of potential therapies. But at the very least, it helped settle the controversy of why photoreceptors are failing and why people go blind. Knowing the right cell type to target is half the battle, and were saying its the RPE, not the photoreceptor, and that the functional gene can potentially be added back to the RPE using gene therapy."

In addition to being small, relatively inexpensive and suitable for large-scale genetic experiments, zebrafish make ideal research specimens in Perkins eyes because they are model systems, both for treating human disease and for determining whats important.

"Most people think of mice, monkeys and other furry animals, rather than fish, when they think of research subjects for human diseases," Perkins says. "An advantage of zebrafish is the ability to inexpensively perform forward genetic screens. Using chemicals, we can induce random mutations throughout the genome. We then search through dozens of zebrafish families to identify mutant zebrafish with traits that resemble human diseases. We use the screen to look for specific traits we think are important, but we cant pre-select the gene that caused it."

"Rather than starting with a gene to mutate and hoping to generate a given trait, we select for the trait, then go find the mutated gene that caused it. We let nature and the organism tell us whats important and whats not."

Perkins says the next steps for his laboratory involve continuing investigation into protein transport processes and trying to find additional zebrafish models of photoreceptor-specific mutations that lead to additional causes of retinal degeneration and blindness.

Glaucoma patients at significantly higher risk for falls, motor vehicle accidents

Wed, 28 Feb 2007 10:20:00 PST

( from http://www.rxpgnews.com )

This research shows higher levels of falls and motor vehicle accidents than found in previous studies. These results have a potential useful application in patient education, licensing of drivers, and intervention programs.

Persons affected by glaucoma are over three times more likely to have been involved in falls and motor vehicle accidents than persons of the same age without the condition, say researchers from Dalhousie University in Canada. Their findings are published in the March 2007 issue of Investigative Ophthalmology & Visual Science.

The study involved 48 patients 50 years of age or older with glaucoma and 47 age-matched persons without the eye disease. Glaucoma patients were almost three times as likely to have experienced one or more falls in the previous year and over six times as likely to have been involved in one or more motor vehicle accidents in the previous five years. They were also more likely to have been at-fault for motor vehicle accidents in which they were involved. The strongest risk factor for these motor vehicle accidents was impaired useful field of view.

This research shows higher levels of falls and motor vehicle accidents than found in previous studies. These results have a potential useful application in patient education, licensing of drivers, and intervention programs.

"Based on these results, the research group has started a larger prospective study to better understand why patients with glaucoma may be more likely to have falls and motor vehicle accidents," said researcher Sharon A. Haymes, PhD, of the Department of Ophthalmology and Visual Sciences at Dalhousie University. "We need to find ways to help them minimize their risk."

Glaucoma is a group of diseases of the optic nerve involving loss of retinal ganglion cells in a characteristic pattern of optic neuropathy. If left untreated, glaucoma can lead to permanent damage of the optic nerve and resultant visual field loss, which can progress to blindness. It is the second leading cause of blindness worldwide and affects 1 in 200 people aged 50 and younger and 1 in 10 over the age of 80.

There are currently no known ways to prevent glaucoma. However, studies show that early detection and treatment of the disease, before it causes major vision loss, is the best way to control the disease. The National Eye Institute recommends that persons who are at high risk for the disease (African-Americans over 40; persons over 60; and people with a family history of glaucoma) have their eyes examined and pupils dilated every two years by an eye care professional.

Genetics key factor in retinopathy of prematurity (ROP)

Fri, 24 Nov 2006 09:23:55 PST

( from http://www.rxpgnews.com ) Genetics play a major role in predisposing infants to retinopathy of prematurity (ROP), a disease prevalent in premature infants that disrupts normal blood vessel development of the retina and can lead to blindness, researchers at Yale School of Medicine report in the November issue of Pediatrics.

“This is the first definitive study to show that genetic factors are a significant component of ROP, and to quantify the extent of that genetic contribution,” said lead author Vineet Bhandari, M.D., assistant professor of pediatrics at Yale School of Medicine.

ROP is most prevalent and severe in extremely low birth weight newborns with an overall incidence estimated to be as high as 68 percent among those born at less than 1,251 grams (2.75 pounds), and 93 percent in those born less than 750 grams (1.6 pounds). Despite early detection and intervention, ROP may lead to retinal detachment and blindness. In an attempt to treat ROP, researchers have sought significant factors, such as too much oxygen, that contribute to the disease. The Yale team hypothesized that there was a strong genetic connection involved in developing ROP.

They looked at contributing factors and outcomes for ROP within 200 twin pairs born at 32 weeks gestation or less. Study participants were from Yale, the Karolinska Institute in Sweden and the University of Connecticut. These 200 twin pairs had a mean gestational age and birth weight of 29 weeks and 1,332 grams (2.9 pounds), respectively.

“Our analyses showed that gestational age and duration of supplemental oxygen were the significant independent contributing factors for ROP,” said Bhandari. “Once significant non-genetic co-factors for ROP were identified, we calculated the genetic susceptibility and determined that 70 percent of the contribution to ROP was the result of genetic factors alone.”

“The magnitude to which genetic factors contribute to this major cause of infant morbidity accentuates the need for a shift in the paradigm utilized to identify and treat this disease process,” Bhandari added. “It is possible that a dual therapy for ROP aimed at limiting potential environmental risk factors and identifying and targeting specific genetic factors may become the model for future intervention.”

Serious eye infection linked with contact lens solution

Fri, 24 Nov 2006 00:59:37 PST

( from http://www.rxpgnews.com ) CHICAGOResearchers have additional information concerning the recent outbreak of the corneal infection Fusarium keratitis, which was associated with use of a specific contact lens solution, according to a study in the August 23/30 issue of JAMA. After preliminary findings from this investigation were released in May, the product was withdrawn from the market worldwide.

Among the estimated 34 million contact lens wearers in the United States, microbial keratitis (corneal infection) is a rare but serious complication that may lead to permanent vision loss or the need for corneal transplantation. The annual incidence of microbial keratitis is estimated to be 4 to 21 per 10,000 soft contact lens wearers depending on overnight wear, according to background information in the article. Fusarium is a filamentous fungus commonly found in soil and plants and is the major cause of fungal keratitis in certain tropical or subtropical regions. Beginning in March, 2006, the Centers for Disease Control and Prevention received multiple reports of Fusarium keratitis among contact lens wearers in the U.S.

Douglas C. Chang, M.D., of the Centers for Disease Control and Prevention, Atlanta, and colleagues conducted a study to determine the specific activities, contact lens hygiene practices, or products associated with this outbreak. Data for cases that occurred after June 1, 2005, were obtained by patient and ophthalmologist interviews for case patients and neighborhood-matched controls by trained personnel.

As of June 30, 2006, the researchers had identified 164 confirmed case patients with Fusarium keratitis in 33 states and 1 U.S. territory. Corneal transplantation was required or planned in 55 (34 percent). One hundred fifty-four (94 percent) of the confirmed case patients wore soft contact lenses. Forty-five case patients and 78 controls were included in the case-control study. In the final analysis, case patients were more than 20 times more likely than controls to report using a specific contact lens solution, ReNu with MoistureLoc. The prevalence of reported use of ReNu MultiPlus solution was similar between case patients and controls. Fusarium was not recovered from the factory, warehouse, solution filtrate, or unopened solution bottles; production of implicated lots was not clustered in time.

Other products, including ReNu MultiPlus, private label Multiplus were not associated with Fusarium keratitis compared with nonusers of those solutions, the authors write.

Our findings, together with the results of environmental testing, suggest that exposure to Fusarium was likely the result of extrinsic contamination of contact lens solution bottles or lens cases occurring outside of the manufacturing or storage processes, perhaps in patients homes. However, suboptimal contact lens hygiene practices appear unlikely as the major explanation for the outbreak, the researchers write.

On-going studies may help to determine if the infections were caused by an interaction of its ingredients with Fusarium that might have permitted growth of the organism. In the meantime, clinicians should be vigilant in diagnosing and treating fungal keratitis, and users of MoistureLoc should discontinue the use of this product. Soft contact lens users should follow the instructions of their ophthalmologist or other eye-care professional and continue to pay careful attention to optimal hygiene practices, including washing and drying hands prior to handling lenses, storing lenses in new contact lens solution after each use, and carefully following directions for use of contact lens and contact lens solution products, the authors conclude.

HTRA1 gene linked to aggressive 'wet' age-related macular degeneration

Thu, 23 Nov 2006 21:13:17 PST

( from http://www.rxpgnews.com ) A gene variant that increases the risk of developing the aggressive "wet" form of age-related macular degeneration (AMD), the most common cause of blindness in people over age 50, is reported in two recent articles in Science by researchers at Yale School of Medicine.

AMD causes light-sensitive cells in the retina to break down, resulting in progressive loss of central vision. Of the two forms of AMD, the "dry" is more common than the "wet" form. Wet macular degeneration can rapidly lead to blindness, while the dry AMD progresses more slowly.

Last year, Josephine Hoh, associate professor in the Departments of Epidemiology & Public Health and Ophthalmology at Yale and senior author on one of the two new studies, identified a gene for dry AMD and found that both wet and dry AMD are associated with a variant in the complement factor H (CFH) gene on chromosome 1.

Hoh now reports they have found a single nucleotide polymorphism (SNP)—a one-base change in the sequence—of the regulatory part of the HTRA1 gene on chromosome 10 that leads to greatly increased risk of developing the wet form of AMD.

According to Hoh, buildup of abnormal blood vessels in Caucasian patients is compounded by development of large waste deposits called drusen. Chinese patients, she said, develop little to no drusen and progress directly to wet AMD. This study demonstrates that these two major genes, CFH and HTRA1, in two different biological pathways, each affect the risk for a distinct component of the AMD phenotype: CFH influences the drusen of dry AMD, whereas HTRA1 influences blood vessel development, the hallmark of the wet disease type. When the two processes are combined, it leads to the composite characteristics that are seen in some cases of AMD.

Hoh, her collaborators in Hong Kong, and her colleagues at Yale including Michael Snyder and Colin Barnstable in the Departments of Molecular, Cellular and Developmental Biology and Molecular Biophysics and Biochemistry, and Ophthalmology, did trans-racial gene mapping by comparing genomes between precisely defined populations to find the incidence of SNP in a Chinese population—96 with AMD and 130 with normal vision.

"We found that patients with the HTRA1 SNP were 10 times more likely to have wet AMD than those without this gene variant," said Hoh. "While this is only preliminary work, it points to possible directions for future treatment of wet AMD."

Hoh also worked on a replication study led by Kang Zhang at the University of Utah School of Medicine that found a link between the same SNP and AMD. Zhang and his team studied 581 Caucasian patients with AMD and 309 with normal vision. These patients had wet AMD as well as a large amount of drusen.

To confirm the association, the Utah team also examined several donor eyes and measured the expression of the gene and the encoded protein. They found that the expressions were elevated in the eyes of patients who carry HTRA1.

"The marker we have identified is very much associated with AMD, but no one has ever pinpointed the clinical features of the gene. We need to conduct further analysis in order to understand the biological mechanisms," said Hoh.

Master Proteins Dictate Retinal Differentiation Timetable

Wed, 16 Aug 2006 08:40:37 PST

( from http://www.rxpgnews.com ) The embryonic construction of the vertebrate retina is a highly ordered affair. Following a precise timetable, six different specialized cell types emerge from a mass of identical, proliferating cells. The process of retinal cell differentiation, when so-called progenitor cells stop dividing and choose among the six fates, depends primarily on homeobox genes, major regulators of embryonic patterning. How these genes control the timing of retinal cell differentiation has remained an open questionuntil now.

In a new study, Sarah Decembrini, Federico Cremisi, and colleagues show that three homeobox genes work in conjunction with a cellular timepiece that determines the sequential emergence of distinct cell types. Surprisingly, the schedule of both homeobox gene expression and retinal cell differentiation is controlled by the translation, rather than by the transcription, of the genes.

Retinal cells transform light signals into visual information for further processing in the brain. After light stimulates the rod and cone photoreceptors, visual signals travel to horizontal and bipolar cells, which in turn interface with amacrine cells. Ganglion cells, which then relay these signals to the brain, are the first-born cellsthat is, the first to exit the cell cycle and stop dividing. Though their birthdays vary somewhat by species, the horizontal, cone, and amacrine cells come next, then the rod and bipolar cells.

Decembrini et al. suspected that cell identity may be tied to cell cycle progression because different retinal cell types are produced when cell cycle length is manipulated. To test this hypothesis, they studied a subset of homeobox genes, including otx5, which supports photoreceptor differentiation, and vsx1 and otx2, which promote bipolar differentiation. Working with Xenopus frogs, a classic developmental biology model, they found that each of the homeobox genes was expressed in sequence, in different cells. By mid-stage retinal development (stage 34), the messenger RNA (mRNA) transcripts of all three genes were expressed, but only Xotx5 proteins were detected. Xvsx1 and Xotx2 were detected at stages 37 and 38-39, respectively. By stage 42, Xotx2 and Xvsx1 proteins were observed in bipolar cells, while Xotx5b was detected only in photoreceptors. These results indicated that the genes had been regulated after transcription and were expressed as proteins after cells exited the cell cycle.

What controlled the genes translation into protein? To find out, the researchers linked a specific sequence of each homeobox genecalled the three prime untranslated region (3' UTR)with the gene encoding green fluorescent protein (GFP). These GFP sensors indicated how the 3' UTR affects expression of the gene. They delivered the DNA of sensors into embryos at an early stage of retinal development (stage 17-18), using a technique called lipofection. GFP proteins were detected only in photoreceptors (the Xotx5b sensor) and bipolar cells (Xvsx1 and Xotx2 sensors). Thus, the 3' UTRs of these genes had blocked GFP translation into protein in all but late-developing retinal cells. The 3' UTRs were able to do this because they contain sequences (called cis-regulatory sequences) that can interact with microRNAsa class of gene-repressing RNAs that bind to complementary sequences of RNA and mediate mRNA destruction. (Future experiments must confirm whether these sequences do in fact interact.) The GFP sensors were detected at the same stages as their corresponding homeobox proteins had been in the previous experiments. This timing, it turned out, coincided with the birthdates of the photoreceptors and bipolar cells.

The correlation between the timing of protein expression and the photoreceptor and bipolar cell birthdates prompted the researchers to examine the effect of cell cycle progression on protein translation. By blocking cell cycle progression with drugs that inhibit DNA replication, they found that Xotx5b, Xvsx1, and Xotr2 require progressively longer cell cycles for efficient translation. And the attenuated production of Xotx5b and Xvsx1 proteins after cell cycle inhibition, they found, reduced the number of photoreceptor and bipolar cellsan effect that was reversed when the proteins were overexpressed, supporting the connection between protein expression and cell identity.

Altogether, these results indicate that a post-transcriptional mechanism regulates when these proteins are expressed and in which cells. This mechanism operates in synch with a cellular clock that measures cell cycle length to generate the later developing photoreceptors and bipolar cells. The next step will be to determine how these findings apply to other genes controlling retinal cell fate, and then to identify the molecular mechanisms driving translational inhibition.

Yellow plant pigments lutein and zeaxanthin reduce risk of age-related macular degeneration

Tue, 15 Aug 2006 11:40:37 PST

( from http://www.rxpgnews.com ) Women younger than age 75 years who eat diets rich in the yellow plant pigments lutein and zeaxanthin may have a reduced risk of developing the eye disease age-related macular degeneration, according to a report in the August issue of Archives of Ophthalmology, one of the JAMA/Archives journals.

Age-related macular degeneration (AMD) occurs when the macula, the area at the back of the retina that produces the sharpest vision, deteriorates over time. The condition is the leading cause of blindness in aging Americans, according to background information in the article. There is no cure for AMD and limited treatment options are available to slow its progression, so research on preventive measures is essential. Previous studies have suggested a potential link between AMD and lutein and zeaxanthin, plant pigments known as carotenoids and found in leafy green vegetables, corn, egg yolks, squash, broccoli and peas. These compounds may reduce the risk of AMD by absorbing blue light that could damage the macula, by preventing free radicals from damaging eye cells and by strengthening eye cell membranes.

Suzen M. Moeller, Ph.D., University of Wisconsin, Madison, and colleagues with the Carotenoids in Age-Related Eye Disease Study (CAREDS) Research Study Group, assessed the effects of dietary lutein plus zeaxanthin in 1,787 women ages 50 to 79 years in Iowa, Wisconsin and Oregon. The women with the highest and lowest dietary intakes of lutein and zeaxanthin in the Women's Health Initiative, a large study of postmenopausal women that began between 1994 and 1998, were recruited to participate in CAREDS. At the beginning of the study, participants filled out a questionnaire to evaluate what their diets were like 15 years before the beginning of the study. Blood samples were taken to assess levels of carotenoids and color photographs of the retina were used to determine the presence and progression of AMD.

A higher intake of lutein plus zeaxanthin was associated with a lower risk of intermediate-stage AMD in women younger than age 75 years who had a stable intake of the carotenoids over the 15-year period and did not have previous AMD or a chronic disease, such as cardiovascular disease, diabetes or hypertension, that might alter their dietary habits. However, no significant difference was observed in the overall group of women or when comparing lutein and zeaxanthin levels in the blood to AMD occurrence. There was a weak association between dietary lutein plus zeaxanthin and advanced-stage AMD in all the women and in women younger than age 75 years.

The lack of a link between intake of carotenoids and AMD in the overall study group could be due to several factors, including the fact that the older women who participated in the study may have been more likely to have consumed higher levels of fruits and vegetables during their lifetimes than other older adults who have already died. Many nutrients may work together to provide protection against AMD, and the study may not have measured other dietary deficits that influence risk, the authors write.

"This exploratory observation is consistent with a broad body of evidence from observational and experimental studies that suggests that these carotenoids may protect against AMD," they conclude. "Still, given the numerous analyses performed in this study, our results could be due to chance. More conclusive evidence from long-term prospective studies and clinical trials is needed to determine whether the intake of macular carotenoids themselves, or as markers of broader dietary patterns, can protect against intermediate AMD or delay progression in individuals who have early stages of the disease.

Objective way to diagnose diseases of colour perception

Thu, 10 Aug 2006 14:58:37 PST

( from http://www.rxpgnews.com ) Pictures of brain waves that reveal our ability to see colour could provide a new objective way to diagnose and monitor diseases that affect human colour perception.

The research finding by a Universiy of New South Wales PhD student, Ms Mei Ying Boon, has earned her a nomination in this year's Fresh Science Awards.

"Eye diseases such as glaucoma can alter people's ability to accurately see colour," says Ms Boon. "Therefore, studying brain activity could be a useful way to diagnose and monitor diseases and conditions that affect colour vision pathways in the brain."

Ms Boon and her UNSW colleagues measured the brain waves of 22 adult volunteers while the volunteers viewed computer patterns composed of two different shades. The two colours ranged from very different (red and green) to very similar. If the viewer couldn't distinguish the colours, then the pattern was invisible to them.

When the volunteers could see the pattern, their brain waves included a distinctively patterned wave. The researchers measured this signal three different ways and found it could be used to reveal the finest colour discriminations that individuals can make. The result: a potential visual health test.

"People's natural ability to make fine distinctions between colours varies in the population," says Ms Boon who published her findings in Vision Science with her UNSW co-authors, Dr Catherine Suttle and Associate Professor Bruce Henry.

"For example, we've all met people who are unaware that they mix up colours, or wear colours that clash. For most of us, this isn't a big deal but for those with poor colour discrimination it can make apparently simple tasks difficult. For example, our ability to see colours affects our ability to carry out daily tasks such as food preparation (which is the ripe tomato?) and interpret signals like traffic lights," says Ms Boon.

"More seriously, poor colour vision can be a serious impediment to safety when working in some occupations, such as fire-fighting and electrical wiring. The ability to test objectively people's natural perception of fine colour discrimination could provide them with valuable information about their natural ability," says Ms Boon.

Onchocerciasis treatment reduces prevalence and intensity by 38%

Mon, 31 Jul 2006 11:44:37 PST

( from http://www.rxpgnews.com ) Onchocerciasis, river blindness or craw craw is an endemic disease in Bioko Island, Equatorial Guinea. This pathology causes a weakening in affected individuals, most of them within the labour force population, making this disease one of the limiting factors for the economic development of the island. Onchocerciasis is caused by the worm Onchocerca volvulus. It is transmitted through the bite of the black fly, Simulium. Enviromental conditions such as humidity, rapid water rivers and altitude of Bioko favour the development of this pathology, since this is the habitat of the fly acting as a vector. The parasite, in the form of larve, is inoculated to humans when the fly bites humans to obtain blood. Female parasites measure 30 to 50 cm and live 10 to 15 years, whereas male parasites measure 3 to 5 cm. Worms form tumours in infected indivuduals, and some of them are easily visible. Fecunded females emit daily 1,200 larves (microfilaria) measuring 150-360 micras, which are disseminated through the hosts skin, eyes and other organs. Affected individuals can host 50-200 million worms, especially distributed in skin and eyes, usually provoking blindness.

The work, carried out by the group of Hospital Clínic de Barcelona, was led by Dr. Jordi Mas of the Microbiology Unit of Hospital Clínic-Universitat de Barcelona, and Dr. Carlos Ascaso of the IDIBAPS Epidemiology and International Health Research Group. The objective of this study was to assess the impact of 8-year vertical distribution of Ivermectin, the only treatment available against onchocerciasis, among the rural population of 12 communities and two ethnical groups: the Bubis and the Fangs. The fact that the administered drug dose is only effective on larves, conditions the duration of this study. The study was carried out during 8 years, because this is precisely the maximum time of fertility of females, what guarantees the total elimination of the offspring.

This study, published in Tropical Medicine and Internacional Health (11(7):1082-91), has been financed by the Spanish Agency of International Cooperation, and the World Health Organisation (WHO). It continues from the achievements of previous works held in Africa in order to assess Ivermectin effects and to determine the importance of onchocerciasis. Results are highly conclusive in this case: onchocerciasis prevalence before treatment was of 74.5%, and after treatment, 38.4%. Furthermore, we want to underline that after Ivermectin administration, the incidence of onchocerciasis in children aged 0-4 decreased 2.6 times.

The follow-up of this project creeted more than a decade ago by Dr. Jordi Mas continues to be in force by the Ministry of Health of Equatorial Guinea. Nevertheless, the monitoring of the state of the disease is conducted by the Catalan group from Barcelona and Bioko.

Future strategies of the fight against river blindness go further than the administration of Ivermectin. Currently, the vector of the disease is being eliminated by the WHO African Programme for Onchocerciasis (APOC). Dr. Jordi Mas will soon travel to Bioko in order to test the effects of the new measures. The efficiency of these methods, the operation of the project, along with the results of the studies of the Hospital Clínic Group will be assessed in the near future in a joint meeting with the Ministry of Health of Equatorial Guinea, the WHO and Dr. Jordi Mas.

Antioxidants may slow retinal degeneration

Thu, 20 Jul 2006 20:21:37 PST

( from http://www.rxpgnews.com ) Scientists at Johns Hopkins have successfully blocked the advance of retinal degeneration in mice with a form of retinitis pigmentosa (RP) by treating them with vitamin E, alpha-lipoic acid and other antioxidant chemicals.

"Much more work needs to be done to determine if what we did in mice will work in humans," said Peter Campochiaro, the Eccles Professor of Ophthalmology and Neuroscience at The Johns Hopkins University School of Medicine. "But these findings have helped to solve a mystery."

In patients with RP, rod photoreceptors die from a mutation, but it has not been known why cone photoreceptors die. After rods die, the level of oxygen in the retina goes up, and this work shows that it is the high oxygen that gradually kills the cones. Oxygen damage is also called "oxidative damage" and can be reduced by antioxidants. So for the first time, scientists have a treatment target in patients with RP, added Campochiaro. His team's findings appeared in the July online edition of the Proceedings of the National Academy of Sciences.

Retinas in all mammals, from mouse to man, are made up of light-sensitive cells known as cones and rods, named for their shapes, which convert light into nerve signals that are then transmitted to the brain via the optic nerve. Cones are needed to see colors and make vision possible in bright light, whereas the far more numerous rods permit sight in low light. The human retina contains approximately 125 million rod cells and six million cone cells. In diseases like RP and age-related macular degeneration (AMD), these cells die off and eventually lead to blindness (in the case of RP) or legal blindness (in the case of AMD).

In earlier studies exposing mice to pure oxygen, the Hopkins scientists found that high levels of oxygen in the retina killed both rods and cones, said Campochiaro. "This was the clue that the high oxygen levels that occur naturally in the retina after rods die was the suspect regarding cone cell death. To test this, we used antioxidants, which protect cells from oxygen damage, and since they allowed many more cones to survive, it proves that the suspect is guilty."

In this mouse model of retinal degeneration, the rods have completely degenerated by the 18th day of age, and then the cones start to degenerate, with 85 percent of them dying off by the time the mice are 35 days old. Campochiaro and his team injected vitamin E, vitamin C, alpha-lipoic acid or an antioxidant similar to superoxide dismutase between the 18th and 35th day. In mice that received vitamin E or alpha-lipoic acid, 40 percent of the cones survived, about twice as many as in the control group or the groups treated with the other antioxidants, which had no identifiable effect.

"What's clear is the link between oxygen and photoreceptor damage, as well as the potential of antioxidant treatment," Campochiaro said. "These experiments suggest that an optimized regimen of antioxidants may help to protect patients with retinitis pigmentosa."

Campochiaro emphasized that even if found valuable, antioxidant treatment of RP, a group of inherited blinding diseases with complex genetic roots, would not cure the disease. But the salvaging of cones, which are concentrated in the retina's macula and are critical to central vision, could serve as a "maintenance therapy," he said. "That alone would be an enormous help."

RP affects only about 100,000 people in the United States. But the oxygen damage has also been implicated in other more pervasive eye diseases, like AMD and cataracts.

Antioxidants naturally occur in some fruits and vegetables, and are available as supplements, but Campochiaro said it remains unclear whether the amounts of antioxidants consumed in foods provided any benefit to people with these types of vision impairments.

Hormone Therapy Does Not Affect Age-Related Vision Loss

Wed, 12 Jul 2006 05:58:37 PST

( from http://www.rxpgnews.com ) Postmenopausal hormone therapy does not appear to increase or decrease the overall risk of AMD among women, although combination hormones may slightly reduce the chances of developing certain risk factors or types of the condition, according to a report in the July issue of the Archives of Ophthalmology, one of the JAMA/Archives journals.

Mary N. Haan, M.P.H., Dr.P.H., University of Michigan, Ann Arbor, and colleagues studied 4,262 women age 65 years and older who were part of the Women's Health Initiative Sight Exam Study, part of the larger Women's Health Initiative clinical trial of hormone therapy. Of those, 1,627 were in the estrogen-only group of the study, with 48.1 percent taking hormones and 51.9 percent taking placebo. The other 2,635 women were in the combination hormone trial; 52.3 percent of those participants were taking estrogen plus progestin pills and 47.7 percent received placebo. Participants underwent eye assessments and retinal photography at the beginning of the study, between April 2000 and June 2002.

After an average of five years of follow-up, 21 percent of the women had developed AMD. Neither combination nor estrogen-alone therapy was found to be associated with developing AMD. Among women in the combination trial only, active hormone therapy was associated with a slightly reduced risk of developing soft drusen-deposits in the eye that may precede AMD-and also lower odds of having neovascular AMD, a less common form of the condition in which blood vessels grow underneath the retina, impairing vision.

"We conclude that treatment with hormones does not influence the occurrence of early AMD," the authors conclude. "As an exception, a possible protective effect was found for soft drusen or neovascular AMD in relation to combined equine estrogens plus progestin."

Eating Fish Protects Against Macular Degeneration

Wed, 12 Jul 2006 05:52:37 PST

( from http://www.rxpgnews.com ) In a study, Brian Chua, B.Sc., M.B.B.S., M.P.H., Westmead Millennium Institute and Vision Co-operative Research Centre, Syndney, Australia, and colleagues examined the association between dietary fat intake and AMD risk in 2,895 Australians age 49 years or older, beginning in 1992-1994. At the beginning of the study and again five years later, participants had a comprehensive eye exam that included photographs of the retina. They also filled out a questionnaire with data about food types and portion sizes consumed, including specific information about margarines, butters, oils and supplements.

Of the 2,335 participants who participated in the five-year follow-up, 158 had developed early AMD and 26 late-stage AMD. After adjusting for other factors that may influence risk, including smoking, age, sex and vitamin C intake, those in the group with the highest intake of polyunsaturated fat had a 50 percent reduced chance of developing early AMD compared with those who ate the least. Those who ate fish once a week had reduced risk of early AMD by 40 percent compared with those who ate fish less than once per month, and those who ate fish three or more times per week also had reduced risk for late-stage AMD. Contrary to previous studies showing an increased risk for AMD with higher unsaturated fat intake, no link was found between AMD and consumption of butter, margarine or nuts, which all contain high levels of unsaturated fats.

"To explain our findings, we suggest that insufficient essential fatty acid intake could result in abnormal retinal metabolism and cell renewal," the authors write. "Studies have shown cardioprotective benefits of monounsaturated fatty acids in the Mediterranean diet and that diets high in n[omega]-3 fatty acids, particularly docosahexaenoic acid, derived largely from fish, may protect against retinal oxidation and degeneration. Our finding that at least weekly fish consumption was protective against incident early age-related maculopathy provides support for this hypothesis."

Research Highlights Risk Factors For Age-Related Vision Loss

Wed, 12 Jul 2006 05:49:37 PST

( from http://www.rxpgnews.com ) Eating fish frequently may be associated with decreased chances of developing age-related macular degeneration, while smoking nearly doubles the risk for this common cause of vision loss and hormone therapy appears to have no effect, according to three articles in the July issue of the Archives of Ophthalmology, one of the JAMA/Archives journals.

Age-related macular degeneration (AMD) occurs when the macula, the area at the back of the retina that produces the sharpest vision, begins to deteriorate. The condition affects approximately 30 percent of Americans age 75 years and older, with 6 to 8 percent developing advanced cases, according to background information in one of the articles. It is the most prevalent cause of vision loss and blindness in the elderly population. Researchers have hypothesized that many of the risk factors for cardiovascular disease, including atherosclerosis or blocked arteries, may also contribute to the development of AMD, possibly by affecting blood flow to the eye.

In the first study, Johanna M. Seddon, M.D., Sc.M., of the Massachusetts Eye and Ear Infirmary, Boston, and colleagues studied genetic and environmental risk factors for AMD in 681 elderly male twins. The men underwent an examination by an ophthalmologist, filled out a food questionnaire and participated in a telephone interview to assess other risk factors, including demographics, smoking, alcohol consumption and physical activity habits. AMD was diagnosed using photographs of the inner eye.

Of the 681 men, 222 (average age 75.9 years) had intermediate or late-stage AMD and 459 (average age 74.5 years) had no AMD or were in the very early stages. Those who currently smoked had a 1.9-fold increased risk of AMD and those who had smoked in the past had a 1.7-fold increased risk. Those who ate more fish and more omega-3 fatty acids (found in salmon and other fish), were less likely to have AMD. The greatest reduction in risk was seen among individuals who ate two or more servings of fish per week. The benefits of eating more omega-3 fatty acids were most apparent among those who consumed less linoleic acid, an omega-6 fatty acid, suggesting that the proper balance of fats is key, the authors write.

"About a third of the risk of AMD in this twin study cohort could be attributable to cigarette smoking, and about a fifth of the cases were estimated as preventable with higher fish and omega-3 fatty acid dietary intake," they conclude. "Age-related macular degeneration is a common eye disease in older persons, smoking is a common avoidable behavior and dietary habits are modifiable; therefore, a proportion of visual impairment and blindness due to AMD could be prevented with attention to healthy lifestyles."

How Thalamic Neurons Grab Your Attention

Wed, 12 Jul 2006 05:26:37 PST

( from http://www.rxpgnews.com ) Certain salient features in a visual scene grab our attention, such as a tiger emerging from a field of tall grass, after which we may spend more time taking in the details. Both ways of experiencing the world are automatic, and the neurons that make up the brain's visual system switch between these two modes continuously. But the exact neurons and mechanisms responsible are still a mystery to neuroscientists.

Based on their physiological properties and connectivity, neurons in the region of the brain known as the thalamus seem especially well-suited to responding dynamically to our visual world. The thalamus is considered the relay station for the brain, shuttling information between sensory neurons and the cerebral cortex. Thalamic neurons in the lateral geniculate nucleus (LGN) respond to visual scenes in two distinct modes: sustained and regular tonic responses and short, rapid bursts. Neuroscientists have long been curious about the role of these distinct firing modes in processing visual information, and whether certain features in a visual scene elicit them.

To better understand the function of bursts, Nicholas Lesica, Garrett Stanley, and colleagues investigate the interplay between external stimuli and intrinsic physiological membrane properties in modulating LGN burst responses. In a new study, they record LGN neuron activity in response to sequences of movies showing natural scenes that vary in luminance, then mathematically simulate the neurons' response properties under different intrinsic physiological states, and with or without the burst mechanism.

The researchers incorporated several well-established properties of LGN neurons into their model. For example, bursting is known to depend on a fundamental physiological feature, a neuron's membrane potential. The membrane potential refers to the electrical potential, or voltage, across the membrane resulting from a balance of negatively and positively charged ions, such as calcium. When neurons are at rest, they sit at a negative, or lower, potential; but when they are activated by a stimulus or other neurons, the potential becomes more positive, or higher. Once a certain positive voltage threshold is reached, the neuron fires an action potential. Lesica et al. designed integrate-and-fire model neurons with exactly this threshold property.

Similarly, bursting is also based on a threshold mechanism. Bursts are mediated by T-type calcium channels (T channels) that pass positively charged calcium ions into the cell; they become inactive at relatively higher membrane potentials. To model burst firing due to T channels, Lesica et al. combined a low-threshold, voltage-dependent current (channels open at relatively low voltage membrane potentials). The model also mimicked the spatial properties that activate LGN neurons. The model allowed the researchers to tweak the membrane potential of their simulated LGN neurons during the movies. And to understand how the bursting affected a neuron's response, they removed the burst-firing mechanism altogether.

By systematically changing the membrane potential, the researchers observed a strong relationship between resting potential, T channel threshold potential, and burst firing. The percentage of bursts in the LGN response was greatest when the resting potential was much more negative than the threshold potential. To characterize how luminance changes in the stimulus and membrane potential interact to evoke bursts, they analyzed the luminance features that preceded bursts for several hundred milliseconds. They found that when the resting potential was lower than the T channel threshold potential, an excitatory stimulus alone could trigger a burst. In contrast, at higher resting potentials, a prolonged inhibitory stimulus was required (to de-inactivate the T channels) before an excitatory stimulus could evoke a burst. In either case, they found that bursts mediated an enhanced detection of the stimulus, similar to a wake-up call to pay attention to the stimulus. When the researchers removed the bursting mechanism in their model neurons, they found that the tonic mode of firing was not able to induce the same level of enhanced responses. They suggest instead that tonic firing may be important for conveying the details of a stimulus.

The analysis supports a role for the thalamus in directing attention, and as the researchers explain, reveals that bursting could be used as a reliable signal to direct attention-related resources toward a behaviorally relevant area of the visual field. The mathematical simulations allowed Lesica et al. to test the role of bursting in a way that is not currently feasible with real neurons. And their findings pave the way for future experimental studies showing how LGN burst and tonic responses faithfully represent the dynamic visual world in behaving animals.

FDA approves ranibizumab for the treatment of wet age-related macular degeneration

Thu, 06 Jul 2006 02:22:37 PST

( from http://www.rxpgnews.com ) The Food and Drug Administration (FDA) today approved Lucentis (ranibizumab injection) for the treatment of patients with neovascular (wet) age-related macular degeneration (AMD). Lucentis is the first treatment which, when dosed monthly, can maintain the vision of more than 90 percent of patients with this type of AMD. Lucentis is a new molecular entity (NME), meaning it contains an active substance that has never before been approved for marketing in any form in the United States. Lucentis will be the first FDA--approved product to provide prescription information in the new format for prescription drug package inserts, to provide professionals and consumers clear and concise prescription information.

"This approval is of great importance for the 155,000 Americans who are diagnosed each year with AMD, a common cause of severe and irreversible vision loss in older adults," said Dr. Andrew von Eschenbach, Acting Commissioner of Food and Drugs. "At a time when our elderly population is rapidly increasing, this product preserves quality of life for those affected by this disease, helping them to regain the ability to participate in everyday activities such as reading and driving."

AMD, a retinal disease causing severe and irreversible vision loss, is a major cause of blindness in individuals older than 55 years. Untreated, the majority of eyes affected with wet AMD may become functionally impaired. Wet AMD, which accounts for 10 percent of all AMD, is responsible for 80 percent of the associated vision loss.

The vision loss in wet AMD is caused by the growth of abnormal leaky blood vessels that eventually damage the area of the eye responsible for central vision. Lucentis is designed to block new blood vessel growth and leakiness, which ultimately lead to disease progression and such vision loss.

Lucentis, a biologic product, administered by injection into the eye, was shown to be safe and clinically effective in three multicenter, randomized studies of patients representative of the population usually affected with AMD. In clinical trials, nearly 95 percent of the participants who received a monthly injection maintained their vision at 12 months compared to approximately 60 percent of patients who received the control treatment.

Approximately one-third of patients in these trials had improved vision at 12 months. In a single study carried out for 24 months, these findings have been maintained with continued monthly dosing. The most commonly reported adverse events included conjunctival hemorrhage, eye pain, floaters, increased eye pressure and inflammation of the eye. Serious adverse events were rare and often related to the injection procedure including endophthalmitis (severe inflammation of the interior of the eye), intraocular inflammation, retinal detachment, retinal tear, increased eye pressure and traumatic cataract.

High Body Mass Index Increase the Genetic Risk of AMD

Sat, 01 Jul 2006 17:40:37 PST

( from http://www.rxpgnews.com ) Current cigarette smoking was associated with a fivefold increased risk and high BMI (30 or higher) was associated with a twofold higher risk of AMD. The homozygous risk genotype (CC) plus smoking conferred a tenfold higher risk of AMD, compared with non-smokers with the non-risk (TT) genotype, while the risk genotype plus higher BMI increased risk of AMD almost sixfold. Gene plus environment risk scores provided an area under the receiver operating characteristic (ROC) curve of 0.70-0.75. The attributable risks for the combination of genes and environment were 69% to 73%.

Subjects in this study were Caucasians who had either advanced AMD (574 people) or no evidence of AMD (280 individuals), based on ocular examination and ocular photographs. DNA samples were obtained from the genetic repository of the Age-Related Eye Disease Study, a National Institutes of Health (NIH) clinical trial for which Johanna M. Seddon, M.D., director of the Epidemiology Unit at MEEI and an associate professor of ophthalmology at Harvard Medical School, was clinic director at MEEI. DNA samples were genotyped at the Broad Institute Center for Genotyping and Analysis, Boston, Mass. and statistical analyses were done in the Epidemiology Unit at MEEI.

These findings convey an important message. Although we cannot change our genotype, we can alter or modify our risk of getting AMD by controlling our weight and not smoking, said Dr. Seddon. There is no question that genetic factors play an important role in this disease. However, individuals with the risk genotype may be more motivated to adhere to healthy lifestyles such as not smoking, maintaining a normal weight, getting exercise, eating an antioxidant rich diet, as well as fish, and getting exercise.

AMD is the leading cause of irreversible visual impairment and blindness among persons aged 60 and older. With the elderly population steadily growing, the burden related to this loss of visual function will increase. Limited treatment options exist for the late stages of the disease and prevention remains a promising approach for addressing this public health concern.

Ranibizumab Approved for Wet Age-Related Macular Degeneration

Sat, 01 Jul 2006 16:40:37 PST

( from http://www.rxpgnews.com ) The Food and Drug Administration (FDA) approved Lucentis (ranibizumab injection) for the treatment of patients with neovascular (wet) age-related macular degeneration (AMD). Lucentis is the first treatment which, when dosed monthly, can maintain the vision of more than 90 percent of patients with this type of AMD. Lucentis is a new molecular entity (NME), meaning it contains an active substance that has never before been approved for marketing in any form in the United States. Lucentis will be the first FDA--approved product to provide prescription information in the new format for prescription drug package inserts, to provide professionals and consumers clear and concise prescription information.

"This approval is of great importance for the 155,000 Americans who are diagnosed each year with AMD, a common cause of severe and irreversible vision loss in older adults," said Dr. Andrew von Eschenbach, Acting Commissioner of Food and Drugs. "At a time when our elderly population is rapidly increasing, this product preserves quality of life for those affected by this disease, helping them to regain the ability to participate in everyday activities such as reading and driving."

AMD, a retinal disease causing severe and irreversible vision loss, is a major cause of blindness in individuals older than 55 years. Untreated, the majority of eyes affected with wet AMD may become functionally impaired. Wet AMD, which accounts for 10 percent of all AMD, is responsible for 80 percent of the associated vision loss.

The vision loss in wet AMD is caused by the growth of abnormal leaky blood vessels that eventually damage the area of the eye responsible for central vision. Lucentis is designed to block new blood vessel growth and leakiness, which ultimately lead to disease progression and such vision loss.

Lucentis, a biologic product, administered by injection into the eye, was shown to be safe and clinically effective in three multicenter, randomized studies of patients representative of the population usually affected with AMD. In clinical trials, nearly 95 percent of the participants who received a monthly injection maintained their vision at 12 months compared to approximately 60 percent of patients who received the control treatment.

Approximately one-third of patients in these trials had improved vision at 12 months. In a single study carried out for 24 months, these findings have been maintained with continued monthly dosing. The most commonly reported adverse events included conjunctival hemorrhage, eye pain, floaters, increased eye pressure and inflammation of the eye. Serious adverse events were rare and often related to the injection procedure including endophthalmitis (severe inflammation of the interior of the eye), intraocular inflammation, retinal detachment, retinal tear, increased eye pressure and traumatic cataract.

Statins reduce incidence of nuclear cataract

Wed, 21 Jun 2006 15:21:37 PST

( from http://www.rxpgnews.com ) The use of statins is linked with a lower incidence of nuclear cataract, the most common type of age-related cataract, according to a study in the June 21 issue of JAMA.

Statins are widely used to decrease serum cholesterol for cardiovascular disease prevention. Statins have also been shown to have antioxidant activity. Oxidative stress (a condition in which antioxidant levels are lower than normal) has been thought to be a risk factor for age-related cataract, particularly nuclear cataract (the most common type of age-related cataract, which occurs in the center of the lens). Some evidence has suggested an association between nutritional intake of antioxidants and age-related cataract, according to background information in the article.

Barbara E. K. Klein, M.D., M.P.H., of the University of Wisconsin School of Medicine and Public Health, Madison, and colleagues analyzed data from the Beaver Dam Eye Study to determine if statin use is associated with a reduced risk of age-related cataract. The analysis included 1,299 persons who were examined as part of the study in 1998-2000 and were deemed to be at risk of developing nuclear cataract within 5 years.

A total of 210 persons developed incident nuclear cataract in the interval from 1998-2000 to 2003-2005. The five-year incidence of nuclear cataract was 12.2 percent in statin users compared with 17.2 percent in nonusers; the odds of developing cataract were 40 percent lower for statin users after adjusting for several factors. Because smoking and diabetes increase risk of nuclear cataract, the authors analyzed results in never smokers without diabetes, and found the odds of developing nuclear cataract was 60 percent lower among statin users after adjusting for other factors. The incidence of two other types of cataracts, cortical and posterior subcapsular cataracts, did not differ significantly between statin users and nonusers.

To further explore the relationship between statin use and nuclear cataract, the authors suggest that clinical trials of statins used for lipid lowering should assess nuclear cataract. In addition, they state further study of the relationship of cataract and statin use is needed in which each type of cataract is considered individually. Further follow-up of our cohort, with anticipated increase in number of persons with cataract and wider use of statins, will permit us to evaluate whether our finding persists.

Limitations of human visual system hinders goalkeepers

Mon, 22 May 2006 03:19:37 PST

( from http://www.rxpgnews.com ) Professional goalkeepers fail to stop free kicks because of shortcomings in their visual system, according to new research by Cathy Craig and colleagues, from Queens University Belfast, Northern Ireland. The projected trajectory of a ball following a curved flight path is more difficult to judge because our visual system is not sensitive enough to gauge a change of direction at speed, mid-flight.

Free kicks are now important goal-scoring opportunities, with specialist free kick takers often choosing to make the ball spin in order to curve the ball into the goal. Because of the size of the goalmouth, goal keepers need to anticipate the direction of the ball before they take action. Cathy Craig and team looked at whether the lateral deflection of a balls trajectory, caused by sidespin2, affects professional footballers perception of where the ball is heading.

Eleven professional footballers (attackers, mid-fielders and defenders) and nine goalkeepers from AC Milan, Olympique de Marseille, Bayer Leverkusen and Schalke 04 were asked to judge whether a range of simulated free kicks would end up in the goal or not, using a virtual reality system. The viewpoint was fixed in the centre of the goal. When there was no spin, balls arriving directly opposite the goal were consistently judged to be entering the goal. When the ball was spinning clockwise, the resulting trajectories from the point of view of the goalkeeper unfolded on the right-hand side of the no-spin trajectory, resulting in a goal only if the striker shot from left of the central position in front of the goal. For conditions where the ball was spinning counter-clockwise, the balls landed in the goal only when they from the view of the striker were kicked from the right-hand side of the no-spin trajectory. There was no difference between the judgements of the field players and goalkeepers.

Players appear to be using current ball heading direction to make their judgements about whether the free kick will end up in the goal or not, rather than accurately predicting the effects of lateral acceleration on the balls trajectory. Craig and colleagues conclude that these perceptual effects find their origin in inherent limitations of the human visual system in anticipating the arrival point of an object subjected to an additional accelerative influence.The depth of experience of our participants does not seem to be able to compensate for these shortcomings in visual perception.

First look at the 'birth' of a retina cell

Sun, 07 May 2006 15:24:37 PST

( from http://www.rxpgnews.com ) Scientists at the University of Michigan Kellogg Eye Center have gained new insight into the way an embryonic retina cell develops and then commits itself to a specific role. They have observed a small window of opportunity during which a cell has been designated to play a particular role, but has not yet begun to function as such.

The discovery provides a new vantage point for understanding how a healthy visual system develops. It also raises the possibility of re-directing the production of cell types as needed to stave off eye disease.

The study reports on the role of the gene regulator NRL, which was previously shown to be essential for the development of rods, the light-sensing cells required for vision.

Anand Swaroop, Ph.D., Harold F. Falls Collegiate Professor of Ophthalmology and Visual Sciences and Professor of Human Genetics, is senior author of both studies, the latest of which appears in the March 7 issue of the Proceedings of the National Academy of Sciences (PNAS).

In PNAS, Swaroop's team reports that NRL is the earliest marker of rod precursors, or cells that are fated to become rods. They achieved this unique and early view of rod development by creating a mouse model using an NRL regulatory DNA sequence to produce a protein that appears as fluorescent green when exposed to blue light. This fluorescent protein allows scientists to identify even a few cells that are destined to be rods at very early stages of development.

"For the first time we were able to see retina cells during early development, allowing us to pinpoint the exact time at which rods are 'born,'" says Swaroop. "Because the cells have been tagged, we can watch them at each step as they develop into mature and functional rods." Kellogg scientists then purified the rods at various stages and generated the profile of genes at each stage. This, for the first time, provided a handle for investigating the precise process of rod differentiation.

Rods, along with cones, are photoreceptors, which account for 70 percent to 80 percent of all cells in the adult retina. Rods greatly outnumber cones in the mouse and in humans.

Damage to photoreceptors is at the root of eye diseases such as diabetic retinopathy, retinitis pigmentosa, and macular degeneration. In most instances, including age-related macular degeneration, rod photoreceptors die before cones.

As the mouse eye develops, rods start out as stem cells, meaning they have not yet been assigned a function and could theoretically grow to become any kind of cell. Along the way, these cells change their gene expression and acquire competence to become a specific cell type. At a certain point, cell division stops, and the cell is fated to perform a certain function.

"We can now view rod precursor cells at a crucial juncture," says Swaroop. "They are committed to becoming rod cells, but they are still adaptable and have not yet 'become' that type of cell." In mouse models, it takes five to fourteen days for rod cells to become functional, whereas in humans this time period is four to five weeks during gestation.

The Swaroop research team also confirmed that when NRL is absent, a rod precursor will change its course and acquire the identity of a cone. "This finding in particular implies the existence of pools of progenitor cells with competence to become either a rod or a cone," explains Swaroop. "We suggest that during early stages of development, these cells are not completely committed to a specific fate; there is an opportunity for regulators such as NRL to instruct these cells to produce rods or cones."

With the ability to see greater detail in events along molecular pathways, Swaroop is enthusiastic about finding new methods for disrupting the disease process. There may also be opportunities to promote the production of new rods and cones when others die off.

In future studies, the Kellogg scientist plans to use this new mouse model in conjunction with other mouse models of specific diseases, such as macular and other retinal degenerations. Gene profiling of rods and cones in disease models at various stages of pathogenesis could help scientists identify molecular targets for drug treatment.

Swaroop is hopeful that his research group can use the fluorescent protein to illuminate the chain of events that occurs when a gene mutation interferes with rod -- or even cone -- development. "This model may give us the earliest look yet at some devastating diseases we are all eager to cure," he says.

New genetic discovery explains 74 percent cases of age-related macular degeneration

Mon, 06 Mar 2006 17:30:37 PST

( from http://www.rxpgnews.com ) A new study, led by researchers at Columbia University Medical Center, pinpoints the role that two genes Factor H and Factor B play in the development of nearly three out of four cases of age-related macular degeneration (AMD), a devastating eye disease that affects more than 10 million people in the United States.

Findings indicate that 74 percent of AMD patients carry certain variants in one or both genes that significantly increase their risk of this disease.

Published in Nature Genetics, the research is a continuation of work published last year by the same team in the Proceedings of the National Academy of Sciences.

Led by Rando Allikmets, Ph.D., the Acquavella Associate Professor in Ophthalmology, Pathology and Cell Biology at Columbia University Medical Center, the research team included collaborating groups headed respectively by Gregory Hageman, Ph.D., professor of ophthalmology and visual sciences at the University of Iowa Roy J. and Lucille A. Carver College of Medicine, and by Michael Dean, Ph.D., at the National Cancer Institute of the National Institutes of Health.

The PNAS study showed that several variants in the Factor H gene significantly increase the risk of developing AMD. Factor H encodes a protein that helps shut down an immune response against bacterial or viral infection, once the infection is eliminated. People with these inherited risk-increasing variations of Factor H are less able to control inflammation caused by infectious triggers, which may spark AMD later in life.

Though the effect of Factor H on AMD is large, variation in this gene alone does not fully explain who gets AMD and who doesn't. As described in the PNAS paper, about one-third (29 percent) of people with a Factor H risk variant had not been diagnosed with AMD.

The investigators decided to look for additional culprits and focused on genes in the same immune response pathway that contains Factor H.

Their genetic analysis of 1,300 people quickly identified Factor B as the major modifier of the disease. The discovery makes good biological sense: while Factor H is an inhibitor of the immune response to infection, Factor B is an activator. Because of the complementary roles of the these two genes, a protective Factor B variation can protect against AMD, even if one carries a risk-increasing variant of Factor H, and vice versa.

As described in Nature Genetics, the two genes explained nearly three out of four AMD cases: 74 percent of the subjects with AMD had either the Factor H or Factor B risk variant (or both), but no protective variants of either gene.

"I am not aware of any other complex disorder where nearly 75 percent of genetic causality has been identified," said Dr. Rando Allikmets, who is senior author of the paper.

"These findings are significant because they absolutely confirm the roles of these two genes and, consequently, the central role of a specific immune response pathway, in the development of AMD. We confirmed this association not just statistically and genetically but, most importantly, pinpointed the biological origin of the disease," added Dr. Allikmets. "In just a few short years, we've gone from knowing very little about what causes AMD to knowing quite a lot. We now have clear targets for early therapeutic intervention."

Though the new paper explains much of the genetic risk, the specific triggers that set off the immune response and subsequent inflammation are still unknown. Researchers at Columbia University Medical Center and the University of Iowa are now searching for specific viral and bacterial culprits.

"It is my sincere pleasure to work with this talented team and to be involved in these important studies that identify the genetic basis for the role of the complement system a pathway that my colleagues and I identified a number of years ago in this truly devastating disease," said Dr. Hageman.

More than 50 million people worldwide are estimated to have irreversible blindness as a result of macular degeneration, making it the most common cause of blindness for those over 60. It's estimated that 30 percent of the population will have some form of AMD by the time they reach the age of seventy-five. The disease is marked by a progressive loss of central vision due to degeneration of the macula--a region of the retina and the area responsible for fine, central vision.

Just two genes, Factor H and Factor B, cause blindness in millions

Mon, 06 Mar 2006 16:55:37 PST

( from http://www.rxpgnews.com ) Just two genes cause blindness in millions of older people across the globe, a discovery that scientists say could aid the development of new treatments for the condition.

Nearly three-quarters of people in the world suffer from age-related macular degeneration (AMD) a most common cause of blindness. AMD is marked by a progressive loss of central vision due to degeneration of the macula - a region of the retina responsible for fine, central vision.

Researchers at New York's Columbia University studied 1,300 people and found that this common cause of blindness was linked to just two genes - Factor H and Factor B. While Factor H is an inhibitor of the immune response to infection, Factor B is an activator, the online edition of BBC News reported.

"I am not aware of any other complex disorder where nearly 75 percent of genetic causality has been identified," lead researcher Rando Allikmets said.

Factor H controls the production of a protein that helps shut down the body's immune response to infection once it has been successfully fought off.

People with these inherited variants of Factor H are less able to control inflammation caused by infectious triggers, which may spark AMD in later life, they said.

The researchers found 74 percent of the people with AMD had either the Factor H or Factor B risk factor or both - but no protective variants of either gene.

"These findings are significant because they absolutely confirm the roles of these two genes and, consequently, the central role of a specific immune response pathway, in the development of AMD," Allikmets said.

"In just a few short years, we've gone from knowing very little about what causes AMD to knowing quite a lot. We now have clear targets for early therapeutic intervention," Allikmets said.

The researchers are now searching for the specific triggers that set off the immune response, and subsequent inflammation.

Marijuana for Diabetic retinopathy ?

Tue, 28 Feb 2006 21:25:37 PST

( from http://www.rxpgnews.com ) Scientists have discovered a compound in marijuana that could protect against eye damage in diabetics.

Diabetic retinopathy is a leading cause of blindness in working-age adults and affects nearly 16 million Americans. It occurs when diabetes damages the tiny blood vessels inside the retina, the light-sensitive tissue at the back of the eye.

Gregory I. Liou and other researchers of molecular biology at the Medical College of Georgia studied the role of cannabinoid receptors and said the compound they had found could defend against diabetic retinopathy.

Liou studied the compound in diabetic animal models and found that it works to interrupt essentially all destructive points of action that cause vision loss in a diabetic patient, reported the science portal EurekAlert.

He hoped the compound in marijuana may one day be given along with insulin to stop the early changes that set the stage for damaged or destroyed vision.

Controlling SPARC levels key to controlling angiogenesis in macular degeneration

Fri, 03 Feb 2006 16:07:37 PST

( from http://www.rxpgnews.com ) For the second time in a week Dr. Jayakrishna Ambati, UK HealthCare physician and associate professor and vice chair of the Department of Ophthalmology and Visual Sciences, announced a discovery from his lab that will affect the future of macular degeneration treatment and research.

Vascular endothelial growth factor (VEGF) is a substance that promotes angiogenesis - the formation of new blood vessels from pre-existing vessels. In macular degeneration, vessels grow through angiogenesis, destroying the cells that are required for vision. Scientists have long believed that turning off the source of VEGF would lead to halting angiogenesis and disease progression.

Ambati's lab found that while withdrawing VEGF could halt angiogenesis in some areas, it actually encouraged it in others. Upon further investigation Ambati found that this previously undiscovered anti-angiogenic effect of VEGF was mediated via activating VEGFR-1 (VEGF receptor 1) and deactivating VEGFR-2 (VEGF receptor 2). Additionally, his lab found that a compound known as SPARC (secreted protein, acidic and rich in cysteine) could influence and switch the routing of VEGF away from VEGFR-1. Thus, controlling SPARC levels appears to be key to controlling angiogenesis in macular degeneration.

Dr. Jayakrishna Ambati, UK HealthCare physician and associate professor and vice chair of the Department of Ophthalmology and Visual Sciences

These surprising findings have far-reaching implications beyond ophthalmology and into all areas of medicine because angiogenesis is also the process by which other growths spread in the body, including malignant tumors. Ambati's work has opened the door into methods of controlling angiogenesis and its effects.

Microsaccades are indeed responsible for most of our visual experience

Fri, 20 Jan 2006 15:35:37 PST

( from http://www.rxpgnews.com ) For more than 40 years, a scientific controversy has raged over whether microsaccades, rapid eye movements that occur when a person's gaze is fixated, are responsible for visibility.

Research conducted at Barrow Neurological Institute in Phoenix has recently resolved the debate, establishing that microsaccades are indeed responsible for driving 80 percent of our visual experience.

Even when eyes are fixated carefully on an object, they continue to make tiny movements called fixational eye movements. These movements cause nearly constant stimulation of the retina. "If our eye was perfectly still during fixation, the world would quickly fade from view due to the fact that the neurons in our eyes and brain quickly adapt to non-changing stimulation," said lead researcher Dr. Susana Martinez-Conde.

There are three types of fixational eye movements: microsaccades, which are fast movements that travel in a straight line; drifts, which are slow curvy motions that occur between microsaccades; and tremors, which are very fast, extremely small oscillations of the eye superimposed on drifts.

"It is critical that we know which of these fixational eye movements is primarily responsible for keeping the world from fading because in normal visual conditions we fixate our gaze 80 percent of the time," said Dr. Martinez-Conde. Her lab established the vital role of microsaccades in vision by measuring fixational eye movements in subjects whose gaze was concentrated on one object.

Not only does this new discovery resolve a scientific debate, it also brings new hope to patients who are blind much of the time due to fixational eye movement problems.

Making new blood vessels: keeping the lines of sight open

Fri, 20 Jan 2006 13:55:37 PST

( from http://www.rxpgnews.com ) The creation of new blood vessels, known as angiogenesis, is a process used to supply oxygen and nutrients at sites of tissue injury. Angiogenesis is known to be stimulated during hypoxia (low oxygen conditions, when new vessels are needed). However, the mechanisms by which hypoxia leads to new vessel formation is poorly understood.

In the mouse retina specialized cells called astrocytes regulate angiogenesis by producing a structural support protein known as fibronectin during hypoxia, but until now it was unclear what triggered this pro-angiogenic event. In a new study appearing online on January 19 in advance of print publication in the February 2006 issue of the Journal of Clinical Investigation, Akiyoshi Uemura and colleagues from the RIKEN Center for Developmental Biology in Japan show that a nuclear protein called Tlx in pro-angiogenic astrocytes is regulated by oxygen levels.

Mice that were genetically engineered so that they would not express Tlx (known as "Tlx knockout" mice) show a complete absence of retinal blood vessels even though other pro-angiogenic markers are expressed. To determine whether the astrocytes were altered, the authors analyzed fibronectin levels in normal and Tlx knockout mouse retinas. The Tlx knockout astrocytes did not form fibronectin matrices, thus explaining the failure of these mice to undergo retinal angiogenesis. The authors also discovered that Tlx is induced by low oxygen levels and that Tlx gene levels are downregulated during hyperoxia (too much oxygen), revealing that Tlx is an oxygen-sensing switch in retinal astrocytes.

Together these studies demonstrate that oxygen-sensing Tlx plays an indispensable role in the development of healthy vascularized retinas via the regulation of formation of the fibronectin scaffold by pro-angiogenic astrocytes.

Sudden severe loss of vision linked with impotency drugs

Tue, 17 Jan 2006 19:08:37 PST

( from http://www.rxpgnews.com ) Viagra and Cialis, the drugs used to treat impotency, may be associated with an increased risk of optic nerve damage in men with a history of heart attack or high blood pressure, suggests a small study in the British Journal of Ophthalmology.

Healthcare professionals prescribing these drugs should warn patients of the potential risk, say the authors.

The findings are based on 76 men attending one US specialist eye clinic. Half the men had optic nerve damage, diagnosed as non-arteritic anterior ischaemic optic neuropathy (NAION).

NAION is the most common form of optic nerve damage in older US adults, with up to 6000 people developing the condition every year. One in four will go on to develop it in both eyes.

The other half, who were randomly selected and did not have the condition, were used as a comparison group.

All the patients were asked about their lifestyle, including smoking and alcohol intake, whether they had been diagnosed with heart disease, diabetes, or high blood pressure and prescribed treatment for these conditions. They were also asked if they had been prescribed Viagra and Cialis for erectile difficulties.

The two groups were similar in terms of age, race, and lifestyle, and men with optic nerve damage were no more likely to have taken the impotency drugs than men in the comparison group.

But men who had had a heart attack were 10 times more likely to have optic nerve damage if they had taken Viagra or Cialis before their diagnosis.

Men with high blood pressure were also more likely to have optic nerve damage if they had taken these drugs, although this was not statistically significant.

The authors caution that their study is small, but suggest that the drugs may reduce the blood flow to the anterior optic nerve, resulting in tissue damage. The drugs may heighten the risk of NAION in those with vascular disease, who are already more susceptible, they explain.

Any patient who has endured a sudden severe loss of vision, and is prescribed Viagra or Cialis, should inform their healthcare practitioner first, say the authors.

An accompanying editorial points out that some patients with impaired eyesight as a result of NAION have reportedly decided to sue Pfizer, the manufacturers of Viagra.

The editorial goes on to say that Pfizer have stated that there were no reports of NAION in the trials of the drug carried out before it was licensed, and that a greater number of cases related to this type of drug would have been reported by now if the association was anything other than coincidental.

But the editorial says that doctors may not be asking patients diagnosed with NAION whether they take Viagra or Cialis.

Antioxidants reduce risk of age-related macular degeneration

Wed, 28 Dec 2005 18:22:38 PST

( from http://www.rxpgnews.com ) A diet with a high intake of beta carotene, vitamins C and E, and zinc is associated with a substantially reduced risk of age-related macular degeneration in elderly persons, according to a study in the December 28 issue of JAMA.

Age-related macular degeneration (AMD) is a degenerative disorder of the macula, the central part of the retina, and is the most common cause of irreversible blindness in developed countries, according to background information in the article. Late-stage AMD results in an inability to read, recognize faces, drive, or move freely. The prevalence of late AMD steeply increases with age, affecting 11.5 percent of white persons older than 80 years. In the absence of effective treatment for AMD, the number of patients severely disabled by late-stage AMD is expected to increase in the next 20 years by more than 50 percent to 3 million in the United States alone. Epidemiological studies evaluating both dietary intake and serum levels of antioxidant vitamins and AMD have provided conflicting results. One study (called AREDS) showed that supplements containing 5 to 13 times the recommended daily allowance of beta carotene, vitamins C and E, and zinc given to participants with early or single eye late AMD resulted in a 25 percent reduction in the 5-year progression to late AMD.

Redmer van Leeuwen, M.D., Ph.D., of Erasmus Medical Centre, Rotterdam, the Netherlands, and colleagues investigated whether antioxidants, as present in normal daily foods, play a role in the primary prevention of AMD. Dietary intake was assessed at baseline in the Rotterdam Study (1990-1993) using a semiquantitative food frequency questionnaire. Follow-up continued through 2004. The Rotterdam Study included inhabitants aged 55 years or older from a middle-class suburb of Rotterdam, the Netherlands. Of 5,836 persons at risk of AMD at baseline, 4,765 had reliable dietary data and 4,170 participated in the follow-up.

Average follow-up of participants was 8.0 years. During this period, 560 persons (13.4 percent) were diagnosed as having new AMD, the majority of whom had early-stage AMD. A significant inverse association was observed for intake of vitamin E, iron, and zinc. After adjustment, a 1-standard deviation increase in intake was associated with a reduced risk of AMD of 8 percent for vitamin E and 9 percent for zinc. An above-median (midpoint) intake of beta carotene, vitamins C and E, and zinc, compared with a below-median intake of at least 1 of these nutrients, was associated with a 35 percent reduced risk of AMD, adjusted for all potential confounders. In persons with a below-median intake of all 4 nutrients, the risk of AMD was increased by 20 percent. Adding nutritional supplement users to the highest quartile of dietary intake did not change the results.

"This study suggests that the risk of AMD can be modified by diet; in particular, by dietary vitamin E and zinc. A higher intake of vitamin E can be achieved by consumption of whole grains, vegetable oil, eggs, and nuts. High concentrations of zinc can be found in meat, poultry, fish, whole grains, and dairy products. Carrots, kale, and spinach are the main suppliers of beta carotene, while vitamin C is found in citrus fruits and juices, green peppers, broccoli, and potatoes. Based on this study, foods high in these nutrients appear to be more important than nutritional supplements. Until more definitive data are available, this information may be useful to persons with signs of early AMD or to those with a strong family history of AMD. Although in need of confirmation, our observational data suggest that a high intake of specific antioxidants from a regular diet may delay the development of AMD," the authors conclude.

Successful tests of new treatments for Leber congenital amaurosis (LCA)

Wed, 02 Nov 2005 11:20:38 PST

( from http://www.rxpgnews.com ) A team led by Krzysztof Palczewski, Ph.D., chair of pharmacology at the Case Western Reserve University School of Medicine, has taken the first steps in treating an eye disease causing irreversible congenital blindness in millions of people worldwide by successfully testing two new treatments in mice.

Publishing in this month's open access journal PLoS Medicine, the researchers found that these treatments "provide highly effective and complementary means for restoring retinal function in this animal model of human hereditary blindness."

The disease studied is Leber congenital amaurosis (LCA), characterized by severe loss of vision at birth. Its causes are not fully understood. Researchers believe that the disease might be due to abnormal development of photoreceptor cells in the retina, extremely premature degeneration of these cells, or lack of essential metabolic ingredients necessary for vision in the cells. In a subset of these diseases, it is known that the retina stops functioning due to loss of the lecithin retinol acyl-transferase enzyme (LRAT). LRAT is required for regeneration of a pigment necessary for the eye to detect light.

LCA can be caused by mutations in the gene encoding RPE65, a key protein involved in the production and recycling of 11-cis-retinal in the eye. Currently, there is no treatment for LCA, although previous studies in mice have successfully tested the injection of a virus carrying the normal gene for RPE65, and, separately, oral administration of a vitamin A-like compound.

In the current paper, Palczewski (formerly of the University of Washington) examined the effect of combining the two treatments in blind mice that did not have the LRAT enzyme. They report that gene therapy carrying the LRAT gene significantly restored electroretinographic (ERG) responses and pupillary light responses. Pharmacological intervention with orally administered drugs also caused long-lasting restoration of retinal function in LRAT-deficient mice and increased ERG response.

They noted that the oral treatment was easier to administer compared with injecting the gene therapy directly into the eye, but a disadvantage of the oral treatment was a potential for long-term systemic toxicity compared with the gene therapy. However, toxicological data gathered in this and previous studies have suggested no long term ill effects in mice.

It is possible that each treatment might eventually prove to be more suitable for a specific age group of patients, and therefore, combining the therapies might offer more effective treatment for a wider age range of patients, suggest the authors.

The team hopes that if the treatments are used together, treatment with oral retinoids could begin in infancy to avoid early sight loss and the difficulties associated with surgery in very young patients. And when patients are older, long-lasting drug-free treatment could be done by surgically introducing gene therapy. This study marks the first step in finding out whether these treatments will work effectively and safely in humans.

First-ever Images of Living Human Retinas Sprung a Surprise

Thu, 27 Oct 2005 00:31:38 PST

( from http://www.rxpgnews.com ) First-ever images of living human retinas have yielded a surprise about how we perceive our world. Researchers at the University of Rochester have found that the number of color-sensitive cones in the human retina differs dramatically among peopleby up to 40 timesyet people appear to perceive colors the same way. The findings, on the cover of this week's journal Neuroscience, strongly suggest that our perception of color is controlled much more by our brains than by our eyes.

"We were able to precisely image and count the color-receptive cones in a living human eye for the first time, and we were astonished at the results," says David Williams, Allyn Professor of Medical Optics and director of the Center for Visual Science. "We've shown that color perception goes far beyond the hardware of the eye, and that leads to a lot of interesting questions about how and why we perceive color."

Williams and his research team, led by postdoctoral student Heidi Hofer, now an assistant professor at the University of Houston, used a laser-based system developed by Williams that maps out the topography of the inner eye in exquisite detail. The technology, known as adaptive optics, was originally used by astronomers in telescopes to compensate for the blurring of starlight caused by the atmosphere.

Williams turned the technique from the heavens back toward the eye to compensate for common aberrations. The technique allows researchers to study the living retina in ways that were never before possible. The pigment that allows each cone in the human eye to react to different colors is very fragile and normal microscope light bleaches it away. This means that looking at the retina from a cadaver yields almost no information on the arrangement of their cones, and there is certainly no ability to test for color perception. Likewise, the amino acids that make up two of the three different-colored cones are so similar that there are no stains that can bind to some and not others, a process often used by researchers to differentiate cell types under a microscope.

Imaging the living retina allowed Williams to shine light directly into the eye to see what wavelengths each cone reflects and absorbs, and thus to which color each is responsive. In addition, the technique allows scientists to image more than a thousand cones at once, giving an unprecedented look at the composition and distribution of color cones in the eyes of living humans with varied retinal structure.

Each subject was asked to tune the color of a disk of light to produce a pure yellow light that was neither reddish yellow nor greenish yellow. Everyone selected nearly the same wavelength of yellow, showing an obvious consensus over what color they perceived yellow to be. Once Williams looked into their eyes, however, he was surprised to see that the number of long- and middle-wavelength conesthe cones that detect red, green, and yellowwere sometimes profusely scattered throughout the retina, and sometimes barely evident. The discrepancy was more than a 40:1 ratio, yet all the volunteers were apparently seeing the same color yellow.

"Those early experiments showed that everyone we tested has the same color experience despite this really profound difference in the front-end of their visual system," says Hofer. "That points to some kind of normalization or auto-calibration mechanismsome kind of circuit in the brain that balances the colors for you no matter what the hardware is."

Images of living human retinas showing the wide diversity of number of cones sensitive to different colors. (Photo credit: University of Rochester)

In a related experiment, Williams and a postdoctoral fellow Yasuki Yamauchi, working with other collaborators from the Medical College of Wisconsin, gave several people colored contacts to wear for four hours a day. While wearing the contacts, people tended to eventually feel as if they were not wearing the contacts, just as people who wear colored sunglasses tend to see colors "correctly" after a few minutes with the sunglasses. The volunteers' normal color vision, however, began to shift after several weeks of contact use. Even when not wearing the contacts, they all began to select a pure yellow that was a different wavelength than they had before wearing the contacts.

"Over time, we were able to shift their natural perception of yellow in one direction, and then the other," says Williams. "This is direct evidence for an internal, automatic calibrator of color perception. These experiments show that color is defined by our experience in the world, and since we all share the same world, we arrive at the same definition of colors."

Dietary Fat Intake Linked to Dry Eye Syndrome in Women

Thu, 20 Oct 2005 23:10:38 PST

( from http://www.rxpgnews.com ) More than eight million people in the United States, predominantly women, suffer from dry eye syndrome, a painful and debilitating eye disease. In the first study of its kind to examine modifiable risk factors, researchers from Brigham and Womens Hospital (BWH) and Schepens Eye Research Institute (SERI) found that the amount, type and ratio of essential fatty acids in the diet may play a key role in dry eye prevention in women. The study is published in the October 2005 issue of the American Journal of Clinical Nutrition.

According to lead author Biljana Miljanovic, MD, of the Divisions of Preventive Medicine and Aging at BWH, Dry eye syndrome impacts quality of life, productivity and safety for millions of people. Unfortunately, there is little advice clinicians can offer about its prevention. Our study set out to examine how changing dietary habits in America, primarily a shift in the balance of essential fatty acids we are consuming, may be associated with onset of this eye disease. We found that a high intake of omega 3 fatty acids, often referred to as a good fat, commonly found in fish and walnuts, is associated with a protective effect. Conversely, a higher ratio of omega 6, a fat found in many cooking and salad oils and animal meats, compared to omega 3 in the diet, may increase the risk of dry eye syndrome.
Dry eye syndrome is characterized by a decline in the quality or quantity of tears that normally bathe the eye to keep it moist and functioning well. The condition causes symptoms such as pain, irritation, dryness, and/or a sandy or gritty sensation. If untreated, severe dry eye syndrome can eventually lead to scarring or ulceration of the cornea, and loss of vision. Victims can experience symptoms so constant and severe that reading, driving, working and participating in other vision-related activities of daily life are difficult or impossible.

In this study, the researchers report the following specific findings:

· Women with the highest levels of omega 3 in their diets reduced their risk of dry eye syndrome by 20 percent compared to women with the lowest levels of this fat in their diet.

· A dietary ratio of omega 6 to omega 3 greater than 15:1 was associated with a 2.5-fold increased risk of dry eye syndrome in women. Currently, the average American diet consists of a similarly high ratio of omega 6 to omega 3 fatty acids.

· Tuna consumption reduced the risk of dry eye syndrome. Women who reported eating at least five servings of tuna per week had a 68 percent reduced risk of dry eye syndrome compared to women who consumed one serving per week.

· Other fish types that have lower levels of omega 3 fatty acids did not appear to protect against dry eye syndrome.

We are accustomed to the mantra you are what you eat and our study suggests that this also applies to a persons vision, said Debra Schaumberg, ScD, OD, MPH, the senior author of the study, clinical associate scientist at SERI, and associate epidemiologist at BWH. Based on this report, preventing dry eye syndrome is another potential reason to follow a diet rich in tuna and other foods plentiful in omega 3 fatty acids.

Neural wiring in brain's visual system is not dismantled by visual deprivation

Thu, 20 Oct 2005 16:01:38 PST

( from http://www.rxpgnews.com ) New research findings led by Thomas Krahe and Ary S. Ramoa of Virginia Commonwealth University School of Medicine offer two pieces of good news for treating children with amblyopia. First, the researchers have found evidence that the neural wiring in the brain's visual system is not dismantled by visual deprivation--for example, due to a cataract--during what is known as the "critical period" of vision development. Rather, the wiring is merely deactivated, capable of being rapidly reactivated when vision is restored. And secondly, the researchers wrote in an article published in the October 20, 2005, issue of Neuron, their findings suggest that allowing children with amblyopia to use both eyes--rather than patching the stronger eye to encourage use of the weaker one--enables better recovery. Such findings are clinically important because about three percent of people suffer loss of visual acuity in one eye during early development.

In their experiments, Krahe, Ramoa, and their colleagues first deprived ferrets of vision in one eye for six days. They then uncovered the deprived eye for different periods and followed the course of recovery of the eye.

Measurement of neural signals in the ferret's visual system revealed that restoration of binocular vision began in as little as 30 minutes to two hours and was similar to normal in about four hours.

The researchers also found that blocking protein synthesis in the brain with drugs did not affect recovery. Such protein synthesis is necessary if neuronal regrowth is required for recovery, indicating that the basic visual wiring had been preserved during deprivation.

In a preview of the paper in the same issue of Neuron, Takao Hensch wrote that "The results reported here are wonderfully harmonious with the rapid improvement in the acuity of human infants upon restoring visual input during the critical period. Adapting these principles may also motivate therapeutic strategies to aid the precise recovery of function in older, well-established circuits once thought to be beyond repair."

Krahe, Ramoa, and their colleagues concluded that "The results presented here may have important implications for understanding recovery in infants that have relatively short periods of visual deprivation, as occurs in the case of congenital cataracts. These patients, who typically undergo eye operations within the first one or two months of postnatal life, were found to start recovering visual acuity as early as 1 hr after restoration of normal visual input. Our findings suggest a neurobiological basis for this rapid improvement in visual acuity. Latent deprived eye connections may rapidly reactivate upon recovery of normal vision.

"Another implication of our study is that binocular vision is likely to play an important role in recovery from amblyopia," they wrote. "Although clinical evidence suggests that patching the better eye of a child is required to improve spatial resolution in the amblyopic eye, strong support for a role of binocular recovery in the initial stages of amblyopia has been reported, and large ongoing clinical studies are re-examining the roles of patching and binocular vision in recovery."

VISION - VEGF Inhibition Study in Ocular Neovascularization Exploratory Analysis

Sat, 08 Oct 2005 05:56:38 PST

( from http://www.rxpgnews.com ) Age-related macular degeneration (AMD) is the leading cause of blindness in older patients in the developed world. Vascular endothelial growth factor is one of the key mediators stimulating the abnormal blood vessel growth and leakage characteristic of the exudative (wet) form of the condition. Pegaptanib sodium (Macugen) is a new treatment for exudative AMD, and has been shown to stabilize vision in approximately 70 percent of cases.

The researchers performed an exploratory analysis of the outcomes of patients with early exudative lesions at week 54 in clinical trials of pegaptanib sodium in the landmark VISION (VEGF Inhibition Study in Ocular Neovascularization) study. The patients were divided into two groups. The researchers found that at week 54, 76 percent of patients in group 1 receiving pegaptanib lost fewer than 15 letters or three lines of vision on the ETDRS eye chart, compared with 50 percent of patients undergoing usual care. In group 2, that proportion was 80 percent and 57 percent, respectively. A number of patients treated with pegaptanib even regained some sight. In addition, patients who underwent usual care for AMD were 10 times more likely to experience severe vision loss than those treated with pegaptanib.

The study found that early detection and treatment of age-related macular degeneration with pegaptanib sodium may enable AMD patients to maintain and, in some cases, regain vision. As a result, the Jules Stein Eye Institute is launching a prospective, open-label, multi-center trial to evaluate the efficacy and safety of pegaptanib in 40 patients with early onset of AMD.

Why do pictures look same from different angles?

Tue, 27 Sep 2005 18:27:38 PST

( from http://www.rxpgnews.com ) When you look at a picture, there is only one viewing position--the picture's center of projection--that yields a correct image at your eye. For example, there's but one place in the movie theater where the film creates the same image at your eye as the original scene. Viewing from other places causes distortion of the image at your eye. Why, then, don't moviegoers rush to the correct position? Indeed, do they even know where that position is?

Martin S. Banks, Professor of Optometry and Vision Science at the University of California at Berkeley, Dhanraj Vishwanath, Assistant Professor of Psychology at Rochester Institute of Technology, and Ahna Girshick, a Ph.D. student at UC Berkeley, have developed a new scientific model of the processes underlying the phenomena. Their results will be presented in the upcoming edition of Nature Neuroscience.

"If the brain processed pictures in the same way it did real objects, you should actually see things in the picture change and distort for every different location you view it from," Banks says. "The human visual system automatically corrects such distortions, but researchers have not been able to pinpoint how this correction occurs."

Using a series of psychophysical experiments, Vishwanath, Girshick and Banks were able to show that the human visual system flexibly adjusts to viewing position such that sitting at the right place isn't required. The brain makes small adjustments to the image the eyes receive, such that the picture appears the way it is supposed to--even when you look at it from different locations. The work has implications for designing better devices that display 3D pictures, and also for creating more realistic computer-graphic images. It will also increase our understanding of how the eyes and brain work, providing insight for both medical and psychological use.

"Visual perception of displayed images is a key factor in human decision making," Vishwanath notes, "Properly describing how humans view and perceive images will provide a better understanding of why people respond positively to some images and negatively to others."

Potential role of amyloid-beta in the pathogenesis of age-related macular degeneration

Tue, 27 Sep 2005 01:20:38 PST

( from http://www.rxpgnews.com ) Age-related macular degeneration (AMD) is the main cause of blindness in patients over the age of 60. In these AMD patients, choroidal neovascularization (CNV) is the most common cause of visual loss. The earliest clinically visible abnormality in AMD are extracellular deposits, called drusen. However, it was unclear which component of drusen contributes to AMD.

Recent data demonstrated that amyloid-beta (Abeta) deposition was found in drusen from eyes with AMD.

In a paper appearing online on September 15 in advance of print publication of the October 1 issue of the Journal of Clinical Investigation, Takeshi Yoshida and colleagues from the University of Tokyo show that Abeta contained in drusen plays an important role in the pathogenesis of AMD. These results suggest that approaches for clearing Abeta deposition might be an effective strategy against the development of AMD.

Rapid genetic testing for eye disease is becoming a reality

Mon, 19 Sep 2005 12:25:38 PST

( from http://www.rxpgnews.com ) Rapid genetic testing for eye disease is becoming a reality, thanks to a technology developed at the University of Michigan Kellogg Eye Center. Scientists have created a first-of-its-kind test on a microchip array that will help physicians hone their diagnoses for patients with the blinding disease known as retinitis pigmentosa (RP). The screening technique has proven to be reliable and cost-effective.

In the September issue of Investigative Ophthalmology & Visual Science (IOVS), scientists at the U-M Department of Ophthalmology and Visual Sciences report on the arRP-I sequencing array, the first technology to screen simultaneously for mutations in multiple genes on a single platform.

This is a novel tool for scientists and physicians alike, says lead author and Kellogg scientist Radha Ayyagari, Ph.D. "For diseases that are associated with multiple genes, like RP, we now have a new and faster method for identifying the underlying genetic basis. This is also useful in analyzing complex patterns of inheritance and for understanding how causative genes might interact with each other."

RP is a group of diseases, affecting one in every 3,500 individuals, in which retinal degeneration leads to blindness or severe vision loss.

Among the outward signs and symptoms are loss of peripheral vision, night blindness, and abnormal results from an electroretinogram (ERG), a test that measures the electrical activity and function of the retina. A patient with the autosomal recessive form of the disease (arRP) has inherited one gene from each parent, neither of whom is affected by RP.

It is nearly impossible to identify which form of the disease a patient has through a clinical examination alone, notes John R. Heckenlively, M.D., a specialist in inherited eye disease who also participated in the study.

"Identifying the precise genetic mutation responsible for an individual's disease will allow us to provide a precise diagnosis, and this knowledge will also allow us to apply genetic therapies as they are developed," he says.

Some clues to treatments are beginning to emerge in animal models, and scientists expect future therapies to be very specific to the type of RP.

"Perhaps one patient will benefit from dramatically limiting exposure to sun or artificial light, and another will use certain vitamins or supplements to stop progression of the disease," says Heckenlively. "Obtaining a molecular diagnosis is going to be very important in helping to guide gene-based treatments for patients in the coming years," he concludes.

Ayyagari's study involved 70 individuals with a clinical diagnosis of arRP. Thirty-five had not been previously screened, and 35 others with known genetic mutations were screened to validate the results.

The arRP-I chip contained sequences, or genetic codes, of 11 genes that carry approximately 180 mutations associated with early-onset retinal degenerations. To date more than 30 genes have been identified for various forms of RP. Ayyagari notes that while the size of the chip currently limits the ability to array all known RP genes, larger platforms are likely to be available soon.

The arRP-I chips designed by the Kellogg research team produced 97.6 percent of the sequence analyzed with greater than 99 percent accuracy and reproducibility. The material cost of the arRP-I chip was 23 percent less that of current sequencing methods. That figure does not take into account the substantial savings in time and labor realized by analyzing multiple genes at once. These chips can detect both previously known and novel mutations.

Kellogg scientists and physicians expect that genetic technologies will grow dramatically in the next five years, particularly as additional space becomes available in the recently approved expansion to the Eye Center.

A proposed expansion of the U-M's eye disease genetic testing and counseling center will allow Ayyagari and Heckenlively to screen large numbers of interested patients, provide counseling and education on the implications of genetic testing, and advance the pace of research toward targeted genetic therapies for RP and other inherited eye diseases.

First description of a human HOXA1 mutation syndrome

Mon, 12 Sep 2005 20:36:38 PST

( from http://www.rxpgnews.com ) Researchers at Children's Hospital Boston, who specialize in studying the genetics of rare eye-movement disorders, have found a rare genetic syndrome whose implications go far beyond the eye, raising intriguing questions about human cardiovascular and brain development.

The syndrome involves a mutation to HOXA1, a gene that has been extensively studied in mice, but about which little is known in humans. HOXA1 belongs to a large family of HOX genes that govern very early embryonic development and the making of the body plan. HOXA1 is the first HOX gene turned on in mice, and presumably in the human body, and is involved in patterning of the growth of the head, face, and brainstem.

Mice that lack both copies of HOXA1 universally die. Until this study, no human HOXA1 mutation had ever been identified, and it was assumed that complete loss of HOXA1 function would be lethal. But the Children's investigators, led by graduate student Max Tischfield and neurologist Dr. Elizabeth Engle of the Children's Hospital Boston Program in Genomics and the Harvard Medical School Program in Neuroscience, have found living people with two mutated copies of HOXA1 -- from three different parts of the world.

"This is the first description of a human syndrome resulting from any of the HOX genes involved in brain development, and the first report of a total loss of any HOX gene in humans," says Engle, senior author of the study.

Tischfield and Engle had been studying genetic disorders that interfere with peoples' ability to move their eyes horizontally (left or right). Collaborators in Saudi Arabia alerted them to patients they'd been seeing who had not only restricted horizontal eye movement, but also deafness and motor impairments. The Saudi clinicians began to carefully reexamine their patients, while Tischfield and Engle looked at the patients' DNA to try to identify a causative gene.

All 9 patients with the syndrome (dubbed Bosley-Salih-Alorainy syndrome, or BSAS, after the Saudi discoverers) had horizontal gaze abnormalities. Eight were profoundly deaf, 3 had external ear defects, 7 had delayed motor development, and 2 met criteria for autism spectrum disorder with cognitive and behavioral impairment. In addition, 7 had malformations or complete absence of one or both internal carotid arteries, one of the two carotid arteries that are the main suppliers of blood to the brain.

DNA linkage studies and follow-up analyses all implicated HOXA1 in the syndrome. But to make the case, Tischfield and Engle needed to find HOXA1 mutations in other populations. For over a decade, Engle has been collecting large pedigrees of families with eye-movement disorders. She and Tischfield tapped this database and found a child from Turkey whose symptoms were much like those of the Saudi patients. This child also had a HOXA1 mutation, but in a different location on the gene.

Fortuitously, Engle and Tischfield also recalled a paper reporting a syndrome in 10 Native American children in Arizona that had many similarities to BSAS. They obtained these children's DNA and found that they also had a HOXA1 mutation, at yet another location on the gene. Like the people with BSAS, the children had horizontal gaze restriction, deafness, and delayed motor development, and some had loss or malformation of the carotid arteries. However, all also had breathing difficulties and mental retardation, and some had facial weakness, paralysis of the vocal cords and heart defects of a type that occur very early in embryonic development. The researchers attribute the differences between the Middle Eastern and Native American patients to environmental influences and the influence of other gene variations unique to each group.

Overall, however, the findings suggest that HOXA1 is involved in early development of the cardiovascular system, a function of the gene not previously known. "The cardiovascular malformations in people with HOXA1 mutations were never reported in mice," says Tischfield, the study's first author. "We've potentially uncovered a new developmental role for HOXA1 in vascular patterning in humans, a role that may have been overlooked in mice."

Most intriguingly, the association of both mental retardation and autism with HOXA1 mutations suggests that early malformation of the brainstem, which controls "lower" functions such as eye movement and breathing, may also lead to impairment in higher cognitive and behavioral function.

"HOXA1 is expressed in the brainstem, but we do not believe it is expressed in the higher brain (the cerebrum or cerebellum)," Tischfield notes. "But there's a lot of output from the brainstem during brain development. Serotonin comes from the brainstem, and many people believe that autism and mental retardation result from an abnormal influence of serotonin. Our paper may spark ongoing interest in how serotonin systems modulate development of the higher brain."

Interestingly, in utero exposure to thalidomide very early in pregnancy, during the time when HOXA1 is turned on, causes damage in the brainstem that mimics the HOXA1 syndrome. In addition, a previous autopsy of an autistic individual showed brainstem pathology similar to that of mice whose HOXA1 genes had been deleted.

"HOXA1 is a gene that's been looking for a disorder for a long time," says Engle. "It's one of a series of interesting genes we've stumbled on by using complex eye-movement disorders as a marker for developmental defects."

FDA Approval to be filed for Ranibizumab as Treatment of Wet ARMD

Fri, 09 Sep 2005 17:24:38 PST

( from http://www.rxpgnews.com ) Genentech, Inc. (NYSE: DNA) announced today plans to file a complete Biologics License Application (BLA) for the investigational drug Lucentis (ranibizumab) in December 2005. In addition, the company announced that it is in discussion with the U.S. Food and Drug Administration (FDA) regarding plans to initiate a Phase IIIb clinical study of Lucentis for patients with wet age-related macular degeneration (AMD). The study is anticipated to begin before the end of 2005. One-year Phase III data from the MARINA study presented at the annual meeting of the American Society of Retina Specialists in July showed Lucentis improved vision in patients with wet AMD.

"We recognize the significant unmet medical needs of those with wet AMD and hope to make Lucentis available to patients by seeking FDA approval as quickly as possible," said Hal Barron, M.D., Genentech senior vice president, development and chief medical officer. "We are encouraged by the magnitude of the benefit observed in the one-year Lucentis MARINA data and are excited about this new Phase IIIb trial, which will help provide more information about the safety profile of Lucentis and the treatment regimen for this chronic disease."

The Phase IIIb SAILOR (Safety Assessment of Intravitreal Lucentis for AMD) study is being designed to evaluate the safety of two different doses (0.3 mg and 0.5 mg) of Lucentis in a broad wet AMD population. Patients will receive Lucentis once a month for three months with criteria-based re-treatment options. Genentech anticipates that patients with wet AMD who have not received prior treatment for their disease or who continue to have active disease despite treatment with FDA-approved therapies may be eligible to enroll in SAILOR. The study will be conducted at more than 100 sites in the United States and enroll approximately 5,000 patients.

Genentech has also recently been notified that the FDA did not grant the company's request for fast-track designation, which allows for a rolling BLA submission. The FDA's decision will not affect the timing for BLA submission in December or the potential to obtain priority review for Lucentis.

Phase III MARINA Results
In July, Genentech announced positive preliminary Phase III data on Lucentis from a study of 716 patients with wet AMD. In addition to meeting the studys primary efficacy endpoint of maintaining vision in patients with wet AMD, 25 percent (59/238) of patients treated with 0.3 mg of Lucentis and 34 percent (81/240) treated with 0.5 mg of Lucentis improved vision by a gain of 15 letters or more compared to approximately 5 percent (11/238) of patients in the control group as measured by the Early Treatment of Diabetic Retinopathy (ETDRS) eye chart. Nearly 40 percent (188/478) of Lucentis-treated patients achieved a visual acuity score of 20/40 or better at 12 months compared to 11 percent (26/238) in the control group. At 12 months, patients treated with Lucentis gained an average of seven letters in visual acuity compared to study entry, while those in the control group lost an average of 10.5 letters.

An analysis of the one-year data showed that adverse events were similar to those seen in earlier trials of Lucentis. Common side effects occurring more frequently in the Lucentis arms than in the control group were mild to moderate and included conjunctival hemorrhage, eye pain and vitreous floaters. Serious ocular adverse events occurring more frequently in Lucentis-treated patients were uncommon (<1 percent

Smoking and Age Related Macular Degeneration (AMD)

Wed, 07 Sep 2005 18:05:38 PST

( from http://www.rxpgnews.com ) Smoking greatly increases your chance of developing age-related macular degeneration (AMD), which leads to severe and irreversible sight-loss, according to an article published in the Royal College of Ophthalmologist's journal Eye this week (published online 7th September 2005).

AMD is the most common cause of visual impairment in the western world; over 200,000 people suffer from the disease in the UK alone. Treatments are costly and at best only slow an inevitable progression. This means that the identification of any modifiable risk factor - such as smoking - is of great importance.

Simon Kelly and colleagues reviewed 17 studies of the association between smoking and AMD and found that in 13 of these smokers were significantly more likely to develop AMD than non-smokers. They also suggest that heavier smokers are at higher risk, and that the risk is lower for ex-smokers - indicating that the negative effects can be at least partly reversed by giving up.

Kelly and colleagues also present, in a separate paper, evidence from a survey at Bolton Hospital NHS trust suggesting that the general public remain largely unaware that smoking can lead to loss of vision. Importantly, their findings also indicate that fear of blindness may provide as much of a motivation to quit as that of well-established smoking-related conditions such as lung cancer and heart disease.

The strength of evidence presented in Kelly's review, and the conclusions of the subsequent clinical study, leave little doubt that action should be taken to raise awareness of the link between smoking and sight loss.

Successful gene therapy in mice to treat retinoschisis

Mon, 05 Sep 2005 23:58:38 PST

( from http://www.rxpgnews.com ) University of Florida scientists used a healthy human gene to prevent blindness in mice with a form of an incurable eye disease that strikes boys.

Writing in the August issue of Molecular Therapy, scientists from the UF Genetics Institute describe how they successfully used gene therapy in mice to treat retinoschisis, a rare genetic disorder that is passed from mothers, who retain their sight, to their sons.

"Currently there is no treatment," said William Hauswirth, Ph.D., the Rybaczki-Bullard professor of ophthalmic molecular genetics. "These children lose their sight gradually, often with devastating results. What happens is the retina actually begins to split in the middle, causing loss of central vision - that's the vision that you need to be able to read or walk around."

Scientists say the gene transfer method eventually could be applied to many eye diseases caused by single gene defects, including a host of retinal disorders.

Retinoschisis is usually first detected in boys between 5 and 10 years of age when their vision problems cause reading difficulties. In a healthy eye, retinal cells secrete a protein called retinoschisin, or RS1, which acts like glue to connect the layers of the retina. Without it, the layers separate and tiny cysts form, devastating the vision and often leading to blindness in about 1 of every 5,000 boys.

UF researchers injected a healthy version of the human RS1 gene to the sub-retinal space of the right eyes of 15-day-old male mice, which, like boys with the disease, don't have the healthy gene to maintain the retina. In terms of disease development, the condition in the mice was roughly equivalent to retinoschisis in a 10-year-old boy.

Six months later, researchers looked at the interior of the eyes with a laser ophthalmoscope and found cyst formation was clearly evident in the untreated eyes, but the treated eyes appeared healthy. The eye's photoreceptor cells - the rods and cones that help the brain process light and color - were spared from the disease and the connections between the layers of the retinas were intact.

In addition, the protein appears capable of moving within the retina to its target sites and the beneficial changes appear to be long lasting, researchers said. Especially encouraging were signs the treatment may be able to repair retinal damage.

The treatment has promising implications for other genetic eye diseases that involve the eye's ability to process light, including retinitis pigmentosa, which affects about 200,000 people in the United States and is one of the most common inherited causes of blindness in people between the ages of 20 and 60.

"We've been very successful in curing a disease in mice that has a direct copy in humans," said Hauswirth, who, in conjunction with UF, has interest in a biotechnology company that may seek to market some of the research technology. "It may take two to five years before we try this in human patients because of the need for safety studies, but we feel based on success so far, we will be able to provide formal evidence for safety that will allow us to get treatment into the clinic."

UF researchers worked with Bernhard Weber, Ph.D., at the Institute of Human Genetics in Regensburg, Germany, and Robert Molday, Ph.D., director of the Center for Macular Research at the University of British Columbia in Vancouver.

The Foundation Fighting Blindness, the National Institutes of Health and the Macula Vision Research Foundation supported the research.

"We now have proof of principle that gene therapy can basically prevent retinoschisis," said Stephen Rose, Ph.D., chief research officer for the Maryland-based Foundation Fighting Blindness.

"Furthermore, this therapy apparently demonstrates that even if disease has begun, there is a healing that takes place. That raises hope for suffering patients that we may be able to offer something that can improve the quality of their lives."

Right Parietal Cortex Plays a Critical Role in Change Blindness

Sun, 04 Sep 2005 09:40:38 PST

( from http://www.rxpgnews.com ) A team of scientists at UCL (University College London) has discovered why we often miss major changes in our surroundings - such as a traffic light turning green when were listening to the radio. Our inability to notice large changes in a visual scene is a phenomenon often exploited by magicians - but only now can scientists put their finger on the exact part of the brain that is so often deceived.

The UCL team shows, in a research paper published in the September issue of the journal Cerebral Cortex (which goes online on 24th August) that the part of the brain called the parietal cortex, the area responsible for concentration, is also critical to our ability to detect changes. The exact critical spot lies just a few centimetres above and behind the right ear the area many people scratch when concentrating.

Using Transcranial Magnetic Stimulation (TMS), the team switched off the parietal cortex part of the brain temporarily by applying magnetic stimulation to the head via a magnetic coil which
produces small electrical currents to the brain. Without help from this region of the brain, subjects failed to notice even major visual changes in this case a change of a persons face.

In previous experiments using brain scanning (functional magnetic resonance imaging or fMRI), the team led by Professor Nilli Lavie at the UCL Department of Psychology, discovered that detection of visual changes was not only correlated with activity in conventional visual areas of the brain but also with activity in the parietal cortex.

But, until this experiment, when the team actually switched off the parietal cortex using TMS, they didnt know that noticing change critically depends on activity in the parietal cortex. When that region of the brain was effectively switched off, change blindness (a failure to notice large changes in a visual scene) occurred.

Professor Lavie said: Because the parietal lobe is not part of the visual cortex it was at first surprising to find that activity in the parietal lobe is critical for visual awareness. We have always known that the parietal cortex was responsible for concentrating. But it was a surprise to find out it is also important for detecting visual changes in a scene. The finding that this region of the brain has both these functions, concentration and visual awareness, explains why we can be so easily deceived by, say, a magicians trick. When were concentrating so hard on something that our processing capacity is at its limits, the parietal cortex is not available to pay attention to new things and even dramatic changes can go unnoticed. If youre concentrating on what the magicians left hand is doing, you wont notice what the right hand is doing.

Mycophenolate mofetil holds promise for inflammatory eye disease

Sun, 04 Sep 2005 08:34:38 PST

( from http://www.rxpgnews.com ) The immunosuppressive drug mycophenolate mofetil, used to prevent rejection of transplanted hearts, kidneys and livers, may also be effective in controlling inflammatory eye diseases, according to a study by researchers at Johns Hopkins' Wilmer Eye Institute.

"The drug seemed to be effective even in patients who had failed treatment from other immunosuppressive drugs," says lead author Jennifer E. Thorne, M.D., an assistant professor of ophthalmology.

Physicians gave the drug to 84 patients, of whom 61 percent had uveitis (intraocular inflammation), 17 percent had scleritis (inflammation of the outer wall of the eye), 11 percent had mucous membrane pemphigoid (a condition causing scarring of the eyelids) and 11 percent had inflammation behind the eye or in other areas. Patients took two pills each morning and two each evening, for a total dose of 2 grams daily. Thirty-six patients (43 percent) already had been treated with at least one other immunosuppressive drug.

Study results, published in the August issue of the journal Ophthalmology, showed that 81 patients (97 percent) had control of their ocular inflammation after one month of treatment. Eighty-two percent of patients had control of their inflammation and were able to taper their dose of the steroid prednisone to 10 or fewer milligrams daily.

Only seven patients discontinued the drug due to side effects such as stomach upset or mild diarrhea. In most cases, Thorne says, lowering the dose of medication can reduce side effects. The drug dosage often can then be increased without the side effects returning.

Cogan Award to macular degeneration scientist

Thu, 01 Sep 2005 01:22:38 PST

( from http://www.rxpgnews.com ) The Association for Research in Vision and Ophthalmology (ARVO) announced today that Joshua L. Dunaief, MD, PhD, has been selected to receive the 2006 Cogan Award during ARVO's Annual Meeting to be held in Fort Lauderdale, Fla., in May 2006.

The Cogan Award recognizes a researcher 40 years of age or younger at the time of nomination who has made important contributions to research in ophthalmology or visual science directly related to disorders of the human eye or visual system, and who also shows substantial promise for future research. Dunaief was selected to receive the award for his innovative investigations of iron metabolism and oxidative damage in the pathogenesis of age-related macular degeneration (AMD), including contributions from both human tissues and mice models of the disease.

Dunaief is an Assistant Professor of Ophthalmology at the Scheie Eye Institute's F.M. Kirby Center for Molecular Ophthalmology in Philadelphia, Pa. He received his doctorate and his medical degree from Columbia University in New York, N.Y., and served his residency in ophthalmology at the Wilmer Eye Institute at Johns Hopkins University in Baltimore, Md. He is a past recipient of the Research to Prevent Blindness Career Development Award and the Steinbach AMD Research Foundation Award. He serves as a reviewer for a number of publications including Investigative Ophthalmology & Visual Science and Journal of Neuroscience.

Age-related maculopathy (ARM) gene discovered

Wed, 17 Aug 2005 01:53:38 PST

( from http://www.rxpgnews.com ) University of Pittsburgh researchers have discovered a gene linked to age-related maculopathy (ARM), the leading cause of untreatable blindness in the elderly. Their discovery suggests a simple test might be able to identify those at risk for what is commonly known as macular degeneration (AMD) and may lead to the development of more effective preventive strategies.

Researchers report that variations of a gene called PLEKHA1 are strongly associated with a person's risk of developing ARM. The results, a culmination of 15 years of research, will be published in the September issue of the American Journal of Human Genetics and are currently available online.

The discovery of the gene came about through the team's efforts to map the genes of 612 families affected by ARM and an additional 323 individuals without a history of macular degeneration. Pooling data from a number of gene mapping studies, researchers were able to identify multiple locations on the chromosomes where there are common gene variants among people with ARM. Specifically, researchers found that a region on one of these chromosomes, chromosome 10, was the one most likely to contain a major gene that influences the risk of ARM. Further analysis of chromosome 10 found that a variation in PLEKHA1 to be strongly associated with a person's risk of developing ARM.

Earlier this year, researchers from Rockefeller University, Yale University, The National Eye Institute, Duke University, Vanderbilt University, University of Texas Southwestern, and Boston University used similar methods to identify the first gene variant thought to be a major contributor to ARM, complement factor H (CFH) on chromosome 1. The Pittsburgh study confirms involvement of this gene and, for the first time, shows that the association results also accounted for findings from previous genetic studies of AMD families. Importantly, the new study found that having both CFH and PLEKHA1 indicate a greater risk for macular degeneration.

"CFH was the first piece of the puzzle," said Michael Gorin, M.D., Ph.D., professor of ophthalmology, University of Pittsburgh School of Medicine, and professor of human genetics, University of Pittsburgh Graduate School of Public Health. "To fully understand the pathology of macular degeneration, we knew we needed to expand our investigation to find all of the genes that play a part in this condition. PLEKHA1 is an important second piece, and we'll keep searching for the rest of the pieces until we get this solved."

By identifying a number of genetic variants for ARM, researchers hope to use this information to develop a simple set of DNA tests to identify individuals who are at increased risk of this sight-robbing condition. Additionally, they hope to develop new preventive strategies and a better understanding of how ARM occurs.

An important clue to understanding the cause and mechanism of ARM was revealed through this discovery. PLEKHA1, like CFH, is involved in the cellular processes related to inflammation, which supports the hypothesis that damage caused by ARM is, in part, due to inflammation.

ARM is the leading cause of untreatable blindness in the elderly and despite recent advances in the treatment of some forms of this condition, it continues to be a serious threat to vision with no known cure. An estimated 200,000 Americans develop a severe form of AMD each year, making it the leading cause of blindness in people aged 65 and older. As many as 30 percent of individuals over the age of 75 have evidence of macular degenerative changes.

Vitamin supplementation may slow down cataract development

Wed, 10 Aug 2005 22:01:38 PST

( from http://www.rxpgnews.com ) Age-related cataract, the world's leading cause of blindness, affects more than 20 million Americans over the age of 40 years. Surgical correction is currently the only known option for intervention, but researchers at the Jean Mayer USDA Human Nutrition Research Center on Aging at Tufts University recently sought, in three different studies, to determine if prevention is possible. Their findings suggest that vitamins and polyunsaturated fatty acids--two categories of nutrients believed to have health benefits--may both affect cataract development, although not necessarily in beneficial ways.

In one study, lead scientist Paul Jacques, DSc, director of the Nutritional Epidemiology Program at the Center, and his colleagues analyzed the diets and examined the eyes of a group of Boston-area women over the course of five years. Among the study participants, who were all members of the larger Nurses' Health Study, women who reported supplementing their diets with vitamin E (a powerful antioxidant) for 10 years or more had significantly less progression of cataract development at the five-year follow-up exam. A similar relative decrease in cataract progression was seen in women who reported higher intakes of two of the B vitamins, riboflavin and thiamin, when compared to women with lower intakes.

"Our results," says Jacques, who is also a professor at the Friedman School of Nutrition Science and Policy at Tufts, "suggest that vitamin supplementation, particularly long-term use of vitamin E, may slow down cataract development." These results build upon some of Jacques' earlier work. In 2001, while examining the same group of Nurses' Health Study members, Jacques and his colleagues found support for a similar role for vitamin C in the prevention of cataracts.

"On the other hand," says Jacques, "the results were not so clear when we looked at dietary fat." In the same population of women, Jacques and his colleagues found that high dietary intake of either or both an omega-6 polyunsaturated fatty acid (PUFA) found in sunflower, safflower, corn, and soybean oils, and an omega-3 PUFA found in canola, flaxseed, and soybean oils, may increase the risk of developing cataracts in one of the three lens locations examined. The results of this study, which were published in the American Journal of Clinical Nutrition, are not consistent, however, with findings of other studies on the relationship between PUFAs and cataracts. In a study that was recently published in the American Journal of Epidemiology, Jacques and colleagues observed that higher overall fat intake increased the risk of cataract development or progression, while omega-3 fatty acids, in particular the types found in dark-fleshed fish, appeared to contribute to the prevention of cataract formation.

"The results of these studies provide added support for a relationship between nutrient intake and cataracts," says Jacques. However, since there is inconsistency among studies of fat intake and cataracts, he cautions that more research is needed. Jacques adds, "finding ways to delay age-related cataract formation through diet, or even through supplementation, would enhance the quality of life for many older people, but many questions regarding the role of diet in cataract prevention remain unanswered."

FDA approves TECNIS(R) foldable acrylic intraocular lens

Wed, 10 Aug 2005 20:32:38 PST

( from http://www.rxpgnews.com ) Advanced Medical Optics, Inc. (AMO) , today announced that the U.S. Food & Drug Administration (FDA) has approved the TECNIS(R) intraocular lens (IOL) on an acrylic platform.

The TECNIS(R) foldable acrylic IOL offers surgeons and their patients the same unique benefits as the TECNIS(R) silicone IOL. AMO is the only company to market IOLs with a claim approved by the FDA for reduced spherical aberration and improved functional vision.

"FDA approval of the TECNIS(R) acrylic IOL marks an important milestone for AMO because it represents the first approved product that combines the outstanding optical technology from our 2004 acquisition of the Pfizer ophthalmic surgical business, with our existing advanced IOL materials expertise," said AMO President and CEO Jim Mazzo. "This FDA approval broadens our portfolio of acrylic IOLs, providing more options for our customers and their patients."

Visual performance degrades with age, including a loss of functional vision, which is caused by an increase in the optical aberration of the eye that may result in difficulty seeing in low light conditions. Cataract patients with reduced functional vision may be challenged driving at dusk or at night, experience trouble reading or doing work at close range, or lack confidence navigating stairs or unfamiliar settings. The TECNIS(R) lens reduces spherical aberration and improves functional vision in varying light conditions, which is likely to provide a meaningful safety benefit for older drivers and pedestrians with whom they share the road.

In a simulated night driving study, patients viewing a rural road through the TECNIS(R) lens identified a pedestrian hazard significantly sooner than through a traditional spherical IOL. The TECNIS(R) lens also provided a 45-foot advantage in detection and identification distance. At 55 MPH, this would provide an additional 0.5 seconds to perceive and react to a pedestrian hazard.

AMO plans to release the TECNIS(R) foldable acrylic IOL commercially in the U.S. and Europe in September 2005.

About the TECNIS(R) IOL

The eyes, like other parts of the body, actually fall out of balance with age. The cornea and natural crystalline lens of a young person work together to focus light onto the retina. Over time, the natural lens loses some of its ability to balance the cornea, resulting in vision that is not quite as crisp as it used to be. Typical cataract surgery restores cornea/lens balance to a level equivalent to that of a healthy older person. The TECNIS(R) lens implant restores the cornea/lens balance to a level more like that of a healthy younger person. While most IOLs are made with a spherical (rounded) surface, the TECNIS(R) lens is an aspheric wavefront-designed optic. This design was developed by collecting actual wavefront measurements from human corneas of a representative sample of the population. Then, a modified prolate intraocular lens surface was created that reduces spherical aberration and works with the cornea in a way that more closely resembles the balance of a natural lens and cornea of a young person. The result is improved functional vision for most people after cataract surgery.

TECNIS(R) foldable intraocular lenses are indicated for primary implantation for the visual correction of aphakia in adults in whom a cataractous lens has been removed by phacoemulsification. The lenses are intended to be placed in the capsular bag. Rx Only. For a complete listing of precautions, warnings and adverse events, refer to the package insert.

Cosmic radiation associated with risk of cataract in airline pilots

Wed, 10 Aug 2005 13:07:38 PST

( from http://www.rxpgnews.com ) Airline pilots have an increased risk of nuclear cataracts [common type of cataract, associated with aging] compared with non-pilots, and that risk is associated with cumulative exposure to cosmic radiation, according to a study in the August issue of the Archives of Ophthalmology, one of the JAMA/Archives journals.

Commercial airline pilots are reported to be at an increased risk for some cancers, but studies on the biological effects of their exposure to cosmic radiation have been limited, according to background information in the article. Previous studies have shown that cataracts can be caused by exposure to radiation, including a recent study of astronauts showing an association of incidence of cataracts with space radiation at exposure levels comparable to those of commercial airline pilots.

Vilhjalmur Rafnsson, M.D., Ph.D., of the University of Iceland, Reykjavik, and colleagues conducted a case control study involved 445 men to determine whether employment as a pilot is associated with lens opacification. The cases included 71 men with nuclear cataract, and the controls (n = 374) were those men with different types of lens opacification or without lens opacification. Among the 445 men, 79 were commercial pilots and 366 had never been pilots. All participants in the study were 50 years or older and other factors that contribute to cataract risk, including smoking, age and sunbathing, were controlled for in the statistical analysis. Exposure to cosmic radiation was assessed based on employment time as pilots, annual number of hours flown on each aircraft type, time tables, flight profiles and individual cumulative radiation doses calculated by computer.

Among the 71 cases with nuclear cataract, 15 were employed as commercial pilots, whereas among the 374 controls (without nuclear cataract), 64 were employed as pilots.

"The odds ratio for nuclear cataract risk among cases and controls was 3.02 for pilots compared with nonpilots, adjusted for age, smoking status, and sunbathing habits," the researchers report. The researchers found an association between the estimated cumulative radiation dose and the risk of nuclear cataract.

"The association between the cosmic radiation exposure of pilots and the risk of nuclear cataracts, adjusted for age, smoking status, and sunbathing habits, indicates that cosmic radiation may be a causative factor in nuclear cataracts among commercial airline pilots," the authors conclude.

Ruboxistaurin to be considered for Diabetic Retinopathy

Sun, 07 Aug 2005 18:59:38 PST

( from http://www.rxpgnews.com ) Eli Lilly and Company announced today that it has completed a Phase 3 clinical trial in which its investigational drug, ruboxistaurin mesylate (proposed brand name Arxxant, pronounced ark-ZONT) reduced the occurrence of vision loss in patients with diabetic retinopathy (DR). As a result, Lilly believes it is appropriate to submit a new drug application (NDA) to the U.S. Food & Drug Administration (FDA) at the end of 2005 for the treatment of DR, the initial indication for ruboxistaurin.

In addition Lilly is announcing today that two Phase 3 clinical trials to determine the effect of ruboxistaurin on treatment of sensory symptoms associated with diabetic peripheral neuropathy (SDPN) have been completed. In these studies, statistical comparison of the change in sensory symptom scores between the placebo and ruboxistaurin-treated groups did not demonstrate significant differences and did not meet the studies' primary endpoints -- a regulatory requirement for submission. Consequently, these results do not support the NDA filing for SDPN. Importantly, however, no significant safety issues were discovered during these clinical trials that would preclude continued clinical development.

"While we are disappointed in the outcome of the trials for SDPN, we are extremely pleased to be one step closer to providing a possible solution for patients with diabetic retinopathy," said Dr. Steven Paul, Executive Vice President, Science and Technology, Eli Lilly and Company. "If ruboxistaurin is approved by the FDA, it would be the first oral medication for the treatment of this serious complication of diabetes," he added.

Results of these Phase 3 clinical trials will be presented at a future major medical meeting in late 2005 or early 2006. In addition, it is Lilly's policy to publish the results of all clinical trials; however, specific publication plans have not yet been determined.

"Since Lilly has been the industry leader in pioneering diabetes therapies for more than 80 years, we believe in the value of innovation and the need for new treatments for this epidemic disease," said Sidney Taurel, Lilly Chairman, President and Chief Executive Officer. "And ultimately, the results from these studies serve as a reminder of the high risks and high rewards associated with pharmaceutical innovation," he added.

About Diabetic Microvascular Complications

Diabetic retinopathy and diabetic peripheral neuropathy (DPN) are diabetic microvascular complications (DMCs). Nearly 75 percent of all people with diabetes have at least one DMC. And while tight blood glucose control (keeping blood sugar at near-normal levels) lowers the risk of DMCs, there are currently no treatments or medications approved in the United States to target the underlying causes of DR and DPN. Eventually, DR can lead to loss of vision or blindness, and DPN can lead to the amputation of toes, a foot or a leg.

Diabetic retinopathy (DR) is a condition that leads to progressive damage to the small blood vessels of the eye, and can lead to vision loss and possible blindness. According to the World Health Organization and the American Diabetes Association, DR is the leading cause of vision loss in adults of working age (20 to 65 years) in industrialized countries. Ruboxistaurin was studied in a Phase 3 clinical trial of 685 patients with moderately severe to severe, non-proliferative DR. The primary objective of this trial was to test the hypothesis that once-daily oral administration of ruboxistaurin over three years would reduce the occurrence of sustained moderate visual loss (equivalent to doubling of the visual angle, such as a reduction in visual acuity from 20/20 to 20/40) in these patients. This trial demonstrated a statistically significant reduction in this outcome. An ongoing trial to determine the effect of ruboxistaurin on diabetic macular edema (DME, a manifestation of DR) progression in patients with less severe DR is expected to be complete in 2010.

Diabetic peripheral neuropathy (DPN) is a progressive disorder resulting in the deterioration of nerve function, the clinical manifestations of which may include subjective sensory symptoms such as numbness, tingling and pain. Ruboxistaurin was studied in two clinical trials, involving more than 500 patients combined, for the treatment of SDPN. These studies had a duration of one year, and the change in sensory symptom scores was the primary outcome measure. Statistical comparison of the change in sensory symptom scores between the placebo- and ruboxistaurin-treated groups did not demonstrate significant differences. An ongoing, three-year, placebo-controlled trial evaluating ruboxistaurin for the treatment of nerve dysfunction of diabetic peripheral neuropathy (DPN), scheduled to complete in 2007, will continue. In contrast to the just-completed SDPN trials, change in a composite of objective nerve function measures is the primary outcome measure of the DPN trial.

About Ruboxistaurin

Ruboxistaurin is a specific protein kinase C beta (PKC beta) inhibitor, the first of a new class of compounds being investigated for the treatment of diabetic retinopathy (DR) and diabetic peripheral neuropathy (DPN). In addition, Lilly has recently presented results of a pilot study of ruboxistaurin in patients with diabetic nephropathy (kidney disease or DN) at a major medical meeting. These are the three major diabetic microvascular complications (DMCs) associated with type 1 and type 2 diabetes. Metabolic factors associated with diabetes often lead to damage to the small blood vessels in the eyes, nerves and kidneys, ultimately leading to DMCs. Pre- clinical data show that ruboxistaurin is a specific inhibitor of PKC beta. PKC beta is an enzyme that has been implicated in the underlying process of microvascular damage caused by diabetes.

Role of melanin in preventing macular degeneration

Sat, 30 Jul 2005 01:48:38 PST

( from http://www.rxpgnews.com ) Two studies from an unusual research partnership at the University of Chicago appear to have resolved a long-standing dispute about the role of melanin in the eye. The studies, one published in the Proceedings of the National Academy of Sciences (PNAS) and one early online in the Journal of the American Chemical Society (JACS), also suggest a new way to prevent a common cause of blindness.

Chemist James Norris, Ph.D., and retina surgeon Kourous Rezai, M.D., combined resources to show that melanin, a pigment found throughout the human body, acts like a neutralizing sponge inside cells in the retina to soak up and destroy reactive oxygen species. Reactive oxygen species, or free radicals, energized by light, are thought to play a major role in macular degeneration, the leading cause of blindness in people over the age of 60.

"We now have the first persuasive evidence that melanin plays an important protective role within the eye," said Norris, professor in the Department of Chemistry and the Institute for Biophysical Dynamics at the University of Chicago and one of the senior authors of both papers. "Although melanin contains its own intrinsic free radical, we found that it absorbs a far more damaging form of free radical, converting its destructive energy into harmless heat before it can hurt the retina."

An estimated 1.75 million Americans have decreased vision from age-related macular degeneration (AMD), with about 200,000 new cases each year. The incidence of AMD is expected to double within the next 25 years as the number of older persons continues to increase. The disorder is far more prevalent among whites than among black persons.

It causes gradual loss of central vision by damaging the retinal pigment epithelial (RPE) cells that lie underneath the macula, the small region of the retina responsible for fine detail at the center of the field of vision. Without RPE cells, the photoreceptors, which are the light detectors, also die. Patients lose the ability to see detail and soon they can't read.

"This is a devastating disease," said Rezai, director of the vitreoretinal service at the University of Chicago. "We do not have a cure for this disease. We can only treat the secondary complications, such as growth of abnormal blood vessels."

"Since we don't know how to replace or repair the dead or damaged retinal cells," he said, " we need to find ways to protect them."

Because people stop producing new RPE cells after birth, these cells have to last a lifetime. They live, however, in a toxic environment. Oxygen concentrations at the back of the eye are very high. At the same time the eye is constantly bombarded with light energy, which interacts with oxygen and can lead to the production of harmful free radicals which can damage cell membranes and DNA. "It's amazing," noted Norris, "that the eye lasts as long as it does."

"To prevent the damage," Rezai said, "we need to understand exactly how it happens." He grows human RPE cells in culture in his lab, but "until now, we have had no direct way to measure the production of most dangerous free radicals. They are too small and too fast."

Norris studies photosynthesis, in which energy from sunlight is converted into electrochemical energy, a process with many parallels to vision. To study the early steps, he uses a tool called electron paramagnetic resonance (EPR). EPR is similar to magnetic resonance imaging except that it measures the spin of electrons rather than of protons.

Because photochemical reactions happen extremely fast, the Norris laboratory has one of the world's few high-speed EPR spectroscopy devices, able to record actions that occur in nanoseconds, about 1,000 times faster than standard EPR.

"Free radicals are dangerous chemicals and dangerous chemistry takes place rapidly," said Norris. "This lets us see some of it."

Norris and Rezai have another valuable asset, an ambitious student, interested in chemistry and medicine, experienced with EPR and looking for a project. This was a unique opportunity for Brandon-Luke Seagle, a third-year student in the College at the time. His knowledge of chemistry and medicine enabled him to be the link between Rezai's cells and Norris's techniques. He is the first author on both papers.

Using Rezai's cells, Norris's technology and Seagle's leg work, the team was able to capture convincing and dramatic evidence that melanin protects the retinal cells. In the PNAS paper (21 June 2005), they show that increased melanin aggregation and radical migration within melanin aggregates can protect RPE cells from free-radical damage and help prevent cell death. In the JACS paper (17 August 2005, but available online) they demonstrate how melanin actually scavenges the harmful free radicals produced by high-energy blue or ultraviolet light as it flows into the eye, soaking them up and neutralizing their effects.

"We now have molecular-based evidence to support the epidemiologic data that points to the protective effects for melanin," said Rezai, who is testing ways to boost melanin levels, first in cells grown in culture and, if that appears promising, in animal models.

Melanin to the rescue

Fri, 29 Jul 2005 15:14:38 PST

( from http://www.rxpgnews.com ) Two studies from an unusual research partnership at the University of Chicago appear to have resolved a long-standing dispute about the role of melanin in the eye. The studies, one published in the Proceedings of the National Academy of Sciences (PNAS) and one early online in the Journal of the American Chemical Society (JACS), also suggest a new way to prevent a common cause of blindness.
Chemist James Norris, Ph.D., and retina surgeon Kourous Rezai, M.D., combined resources to show that melanin, a pigment found throughout the human body, acts like a neutralizing sponge inside cells in the retina to soak up and destroy reactive oxygen species. Reactive oxygen species, or free radicals, energized by light, are thought to play a major role in macular degeneration, the leading cause of blindness in people over the age of 60.

"We now have the first persuasive evidence that melanin plays an important protective role within the eye," said Norris, professor in the Department of Chemistry and the Institute for Biophysical Dynamics at the University of Chicago and one of the senior authors of both papers. "Although melanin contains its own intrinsic free radical, we found that it absorbs a far more damaging form of free radical, converting its destructive energy into harmless heat before it can hurt the retina."

An estimated 1.75 million Americans have decreased vision from age-related macular degeneration (AMD), with about 200,000 new cases each year. The incidence of AMD is expected to double within the next 25 years as the number of older persons continues to increase. The disorder is far more prevalent among whites than among black persons.

It causes gradual loss of central vision by damaging the retinal pigment epithelial (RPE) cells that lie underneath the macula, the small region of the retina responsible for fine detail at the center of the field of vision. Without RPE cells, the photoreceptors, which are the light detectors, also die. Patients lose the ability to see detail and soon they can't read.

"This is a devastating disease," said Rezai, director of the vitreoretinal service at the University of Chicago. "We do not have a cure for this disease. We can only treat the secondary complications, such as growth of abnormal blood vessels."

"Since we don't know how to replace or repair the dead or damaged retinal cells," he said, " we need to find ways to protect them."

Because people stop producing new RPE cells after birth, these cells have to last a lifetime. They live, however, in a toxic environment. Oxygen concentrations at the back of the eye are very high. At the same time the eye is constantly bombarded with light energy, which interacts with oxygen and can lead to the production of harmful free radicals which can damage cell membranes and DNA. "It's amazing," noted Norris, "that the eye lasts as long as it does."

"To prevent the damage," Rezai said, "we need to understand exactly how it happens." He grows human RPE cells in culture in his lab, but "until now, we have had no direct way to measure the production of most dangerous free radicals. They are too small and too fast."

Norris studies photosynthesis, in which energy from sunlight is converted into electrochemical energy, a process with many parallels to vision. To study the early steps, he uses a tool called electron paramagnetic resonance (EPR). EPR is similar to magnetic resonance imaging except that it measures the spin of electrons rather than of protons.

Because photochemical reactions happen extremely fast, the Norris laboratory has one of the world's few high-speed EPR spectroscopy devices, able to record actions that occur in nanoseconds, about 1,000 times faster than standard EPR.

"Free radicals are dangerous chemicals and dangerous chemistry takes place rapidly," said Norris. "This lets us see some of it."

Norris and Rezai have another valuable asset, an ambitious student, interested in chemistry and medicine, experienced with EPR and looking for a project. This was a unique opportunity for Brandon-Luke Seagle, a third-year student in the College at the time. His knowledge of chemistry and medicine enabled him to be the link between Rezai's cells and Norris's techniques. He is the first author on both papers.

Using Rezai's cells, Norris's technology and Seagle's leg work, the team was able to capture convincing and dramatic evidence that melanin protects the retinal cells. In the PNAS paper (21 June 2005), they show that increased melanin aggregation and radical migration within melanin aggregates can protect RPE cells from free-radical damage and help prevent cell death. In the JACS paper (17 August 2005, but available online) they demonstrate how melanin actually scavenges the harmful free radicals produced by high-energy blue or ultraviolet light as it flows into the eye, soaking them up and neutralizing their effects.

"We now have molecular-based evidence to support the epidemiologic data that points to the protective effects for melanin," said Rezai, who is testing ways to boost melanin levels, first in cells grown in culture and, if that appears promising, in animal models.

Chromosome region for macular degeneration pinpointed

Wed, 27 Jul 2005 01:42:38 PST

( from http://www.rxpgnews.com ) Age-related macular degeneration is the leading cause of blindness in older adults, yet researchers are still in the dark about many of the factors that cause this incurable disease.

But new insight from University of Florida and German researchers bout a genetic link between rhesus monkeys with macular degeneration and humans could unlock secrets about the earliest stages of the disease, when severe vision loss could still be stopped.

The researchers pinpointed a chromosome region and genetic markers for macular degeneration in humans and rhesus monkeys, findings recently published in the online edition of the journal Experimental Eye Research. Linking the disease in monkeys to the disease in humans allows researchers to study how it progresses in the animals, which could lead to better treatments and even a cure.

"Stopping the development of the disease is something the monkeys will help us do that we can't do with humans," said William W. Dawson, a UF professor of ophthalmology and physiology and a co-author of the study. "This is a big step forward in dealing with the disease."

The researchers studied seven genetic sites in the monkeys that correspond to human chromosomes linked to macular disease. One of those areas, the findings confirm, contains genes that predict age-related macular degeneration in humans and rhesus monkeys. Dawson and other researchers have suspected for years that the disease was very similar in humans and monkeys, but these findings finally establish that. This discovery, he said, will allow researchers to delve deeper into what causes the disease and could be the first step toward repairing the genetic defects linked to it.

According to the National Eye Institute, nearly 2 million Americans have advanced age-related macular degeneration, a disease that develops when a small, light-detecting part of the retina called the macula breaks down. Seven million more Americans have an intermediate form of the disease, and millions more are expected to develop it within the next 15 years.

The disease causes nodule-like specks to build up in the eye, chipping away central vision over time. But Dawson said most people don't even realize something is wrong until they detect changes in their vision. The disease can be controlled, but there is no known way to reverse the vision loss it causes.

Knowing more about the earliest predictors of macular degeneration could help doctors treat the disease before extensive vision loss occurs and may even prevent it in some people. The early risks associated with macular degeneration have been difficult for researchers to study in humans, and as a result, doctors know little about this aspect of the disease, Dawson said.

"It's difficult to follow closely the aging of a human over a specific period of time," he said. "People wouldn't tolerate a controlled (living) environment for weeks and years."

One of the biggest problems researchers have faced is determining how much of a role genetics plays versus lifestyle and environmental factors such as blue light, part of the spectrum of natural visible light. Frequent exposure to blue light rays has been linked to macular degeneration. If the disease is going to be treated early, Dawson said researchers must know the significance of these factors.

Aside from studying early environmental risks, the next step for researchers is to map the specific genes at work, said Dawson, who worked on the study with German geneticist Jorg Schmidtke. But because more than one gene is likely involved, this task will not be easy, Dawson said.

Dr. Johanna M. Seddon, a Harvard Medical School associate professor and director of the epidemiology unit of the Massachusetts Eye and Ear Infirmary, said studies conducted on 840 human twins have shown that genetics plays a significant role but not the only role. Even diet plays a big part, she said. Her own research with the National Eye Institute has shown that taking certain vitamins and minerals can reduce the risk of developing the disease by 25 percent over five years.

"With the increasing number of people living beyond the age of 85, it heightens the importance of this disease and the concern about (what will happen) if we don't come up with a better way to treat this," she said.

That's where Dawson thinks the monkeys can help. They age three to four times faster than humans, making it easier to track the progression of the disease. The monkeys also can remain in a controlled environment to test nongenetic factors, and their families can be studied more extensively.

Although most rhesus monkeys never show signs of macular degeneration, between 30 percent and 70 percent of the monkeys Dawson's team studied do. That's because these primates are the descendents of 50 monkeys brought to live on a Puerto Rican island just before World War II. The free-ranging monkeys on the island have multiplied to near 1,500, but because the rhesus monkeys are not native to the area, they could mate only with each other. This inbreeding has predisposed the monkeys to various genetic diseases, such as age-related macular degeneration.

Unlike most other animals, a rhesus monkey's eyes have the same complex structure as a human eye, making them a model study subject. They're so similar, he said he sometimes slips images of rhesus monkey eyes into presentations for medical residents to see if anyone notices the difference.

"I haven't been caught yet," he said. "Only the most expert would detect the differences."

Eye Saver Easy Reading Light Bulb useful in macular degeneration

Wed, 27 Jul 2005 01:38:38 PST

( from http://www.rxpgnews.com ) For years, there has been much research and development to improve poor eyesight, including the use of scratch-resistant and radiation-blocking lenses. Now, a revolutionary product for eye correction focuses specifically on the needs of those in working environments, called the Eye Saver Easy Reading Light Bulb.

Barton Pasternak, Executive Vice President of Westinghouse Lighting Corporation realized the need for more light on work surfaces. He consulted with Dr. Scott Smith of NASA's Marshall Space Flight Center, Huntsville, Ala. and Dr. Forrest Marshall, Chief Executive Officer of medical product development at Marshall Research, LLC.

Smith used his knowledge of deep space telescope optics to further enhance the Eye Saver, and Pasternak shifted his focus from developing a reflective insert on lamp shades to creating optimum lighting with a single light bulb. Pasternak also teamed with Dr. Marshall, whose research focused on developing innovative light bulbs to make seeing easier under working conditions.

The Eye Saver provides 40 percent more surface illumination on work and reading surfaces, compared to a standard incandescent light bulb, and includes a frosty finish that reduces eyestrain by lowering glare. With an average lifetime of 2000 hours, twice as long as a standard bulb, this product is suitable for people of all ages and is specifically ideal for duties requiring high light, including reading, writing, sewing, and crafting.

Such technology is particularly useful for those afflicted with macular degeneration, a common eye disease causing deterioration of the macula, the central area of the retina, and low vision, the loss of visual sharpness. Age-related macular degeneration is the number one cause of vision loss and legal blindness in American adults over the age of 60, according to the non-profit organization, Macular Degeneration Partnership.

The Eye Saver falls in line with recommendations made by Rensselaer Polytechnic Institute's Lighting Research Center, the world's largest university-based center for lighting education and research. The center believes light fixtures close to task areas and bulbs with high light output are the best ways to combat the effects of low vision. Additionally, the Discovery Fund for Eye Research recognizes the Eye Saver as a useful source for enhancement of lighting due to eye disease.

The Eye Saver can be purchased through eye care professionals and retailers around the country. Meanwhile researchers at NASA and other institutions work to develop even new and more powerful vision-enhancing products.

Susceptibility to Neurodegeneration in a Glaucoma Is Modified by Bax Gene Dosage

Mon, 25 Jul 2005 17:12:38 PST

( from http://www.rxpgnews.com ) Glaucoma is a group of diseases whose unifying characteristic is death of nerve cells (retinal ganglion cells) that connect the eye to the brain. Glaucoma is often associated with a harmfully high pressure inside the eye (intraocular pressure) contributing to nerve cell death. Various treatments are used to lower eye pressure, but currently no commonly used treatments directly protect the nerve cells.

DBA/2J mice develop elevated eye pressure with age, and this pressure kills retinal nerve cells. The authors use this mouse model to investigate how these nerve cells die in glaucoma. They show that there are distinct degeneration pathways activated in different parts of the retinal nerve cells. They found that the biochemical pathway in the nerve cell body, which resides in the retina, requires a molecule called BAX (BCL2-associated X protein).

In contrast, pathways in the part of the cell (axon) that connects the cell body to the brain do not require BAX. Because degeneration pathways in the cell body and of the axon also may be molecularly different in human glaucoma, it will be important to consider them all when designing therapies. Their data also suggest that the BAX gene is a candidate to modulate glaucoma susceptibility.

Our thirst for novelty begins in the eye itself - Study

Sun, 10 Jul 2005 15:02:38 PST

( from http://www.rxpgnews.com ) Researchers at Harvard University have found evidence that the retina actively seeks novel features in the visual environment, dynamically adjusting its processing in order to seek the unusual while ignoring the commonplace. The scientists report in this week's issue of the journal Nature on their finding that this principle of novelty-detection operates in many visual environments.

"Apparently our thirst for novelty begins in the eye itself," says Markus Meister, the Jeff C. Tarr Professor of Molecular and Cellular Biology in Harvard's Faculty of Arts and Sciences. "Our eyes report the visual world to the brain, but not very faithfully. Instead, the retina creates a cartoonist's sketch of the visual scene, highlighting key features while suppressing the less interesting regions."

These findings provide evidence that the ultimate goal of the visual system is not simply to construct internally an exact reproduction of the external world, Meister and his colleagues write in Nature. Rather, the system seeks to extract from the onslaught of raw visual information the few bits of data that are relevant to behavior. This entails the discarding of signals that are less useful, and dynamic retinal adaptation provides a means of stripping from the visual stream predictable and therefore less newsworthy signals.

For example, Meister says, in visual environments such as forests or fields of grass with many vertical elements but only rare horizontal features, the retina adjusts to suppress the routine vertical features while highlighting the singular horizontal elements.

Meister and his co-authors examined neural signals in retinal ganglion cells, which convey visual images from the eye to the brain. These cells generally record local spatial differences and changes over time rather than faithful renditions of momentary scenes. Scientists had interpreted this as a form of predictive coding, a strategy shaped by the forces of evolution in adaptation to the average image structure of natural environments.

"Yet animals encounter many environments with visual statistics different from this hypothetical 'average' scene," Meister says. "We have found that when this happens, the retina adjusts its processing dynamically: The spatio-temporal receptive fields of retinal ganglion cells change after a few seconds in a new environment. These changes are adaptive, improving predictive coding by enhancing the ability of these receptive fields to pick out unusual features."

While manipulating the visual scenes faced by salamanders and rabbits, Meister and colleagues recorded neural signals from the animals' retinal ganglion cells, testing whether adaptation to a different environment altered the encoding of retinal signals. From the neural responses to novel stimuli, the researchers computed the sensitivity of individual ganglion cells to various scenes.

For most cells, sensitivity to a novel scene was greater than sensitivity to control scenes to which the animals had already been exposed, a gap that grew gradually in the seconds after introduction to a new environment. Because this adaptation occurred in both salamanders and rabbits, Meister concluded that it typifies retinal function in both amphibians and mammals, animals that differ greatly in ecology and physiology but share the challenge of adjusting to a variable visual environment.

F4/80 protein in the eye may protect eyes from disease

Wed, 22 Jun 2005 22:48:38 PST

( from http://www.rxpgnews.com ) Scientists at The Schepens Eye Research Institute have discovered that a protein known as F4/80 found on immune cells in the eye and other parts of the body may have a function in the regulation of the body's immune response and protect delicate tissues that cannot survive the "inflammation" inherent in full-blown immunity.

"We believe that this discovery may ultimately help in the development of therapies for blinding eye diseases such as macular degeneration and autoimmune diseases that occur when the immune system goes awry," says Joan Stein-Sreilein, PhD, senior author of the study published in the May issue of the Journal of Experimental Medicine and senior scientist at The Schepens Eye Research Institute.

According to Stein-Streilein, the discovery is another piece of the "immune privilege" puzzle. Certain parts of the body, including the eyes, brain, gastrointestinal system and reproductive system have the ability to prevent the usual immune response onset when confronted with foreign invaders such as bacteria. Without this special reaction, the eye's delicate tissue would be destroyed by inflammation and the gastrointestinal tract could not tolerate the ingestion of food. The F4/80 molecule (also known as a glycoprotein) was first discovered two decades ago on immune cells in the eye, gut and other privileged sites, but its function has not been understood.

In an attempt to understand F4/80, Stein-Streilein and her team have been following the immune cells (also known as antigen presenting cells) containing the protein. In previous studies, the team found that when these F4/80 containing cells bring antigens (foreign substances) from the eye to the spleen, the spleen stimulates the production of what is known as a "regulatory" T cell which stops the immune response throughout the body as well as at the site where the invasion took place--in this case, the eye. In a full-blown immune response, other types of T Cells are stimulated that start the immune attack, inflammation, and tissue destruction.

Since the F4/80 protein was identified as a crucial player in the development of immune privilege, the Schepens' team postulated that the protein had an important role in immune regulation. In the current JEM study, the team investigated mice that did not produce F4/80. They found that the immune suppression did not occur when foreign substances were presented to the spleen by antigen presenting cells that did not have F4/80. "This led us to believe that the protein F4/80 had a direct role in stopping immune response," says Stein-Streilein.

Although the mechanism by which F4/80 stimulates the production of immune suppressing T Cells is unknown, the team believes that the protein may be involved in cell-cell communications.

The presence of F4/80 cells in other immune privileged sites, such as the brain and placenta, and its exclusion from T cell zones in the spleen suggests that F4/80 expression and immune activation may be mutually exclusive.

According to Stein-Streilein, the next steps for the group will be to tease out exactly how the protein accomplishes its goal. Ultimately knowledge of the F4/80 protein and its role in immune regulation may lead to novel therapies for autoimmune diseases of the eye and the body.

Diabetic retinopathy in pre-diabetes

Tue, 14 Jun 2005 03:19:38 PST

( from http://www.rxpgnews.com ) Diabetic retinopathy has been found in nearly 8 percent of pre-diabetic participants in the Diabetes Prevention Program (DPP), according to a report presented today at the American Diabetes Association's 65th Annual Scientific Sessions. Diabetic retinopathy, which can lead to vision loss, was also seen in 12 percent of participants with type 2 diabetes who developed diabetes during the DPP. No other long-term study has evaluated retinopathy in a population so carefully examined for the presence or development of type 2 diabetes.

"These findings reinforce the recommendation that patients with newly diagnosed type 2 diabetes should be screened for retinopathy," said Emily Chew, M.D., of the National Eye Institute, part of the National Institutes of Health (NIH) under the U.S. Department of Health and Human Services, which funded the study. "We advise good control of blood glucose, blood pressure, and cholesterol as well as regular eye exams."

"Previous studies have not accurately defined when type 2 diabetes begins, so our understanding of the onset of diabetic eye disease has been limited. Now we know that diabetic retinopathy does occur in pre-diabetes. We're also seeing it early in the course of diabetes--within an average of 3 years after diagnosis," noted Richard Hamman, M.D., DrPH, professor and chair, Department of Preventive Medicine and Biometrics, University of Colorado School of Medicine, and vice chair of the DPP. "This adds to our understanding of the development of retinopathy and suggests that changes in the eye may be starting earlier and at lower glucose levels than we previously thought."

Pre-diabetes is a condition in which blood glucose levels are higher than normal but not high enough for a diagnosis of diabetes. The condition is sometimes called "impaired fasting glucose (IFG)" or "impaired glucose tolerance (IGT)," depending on the test used to diagnose it. People with pre-diabetes have an increased risk of developing type 2 diabetes, heart disease, and stroke.

Diabetic retinopathy, which begins with changes in the small vessels in the back of the eye, often leads to loss of vision. Regular eye examinations to diagnose retinopathy are recommended for patients with diabetes because treatment with laser photocoagulation can often prevent blindness in more advanced cases. Diabetic retinopathy is still the most common cause of blindness in adults. (For more information about diabetic retinopathy, see NEI's Diabetic Retinopathy: What you should know http://www.nei.nih.gov/health/diabetic/retinopathy.asp).

"Certain retinopathy lesions are considered indicative of the presence of diabetes because they are the first retinal changes to develop in this disease," explained Dr. Hamman. "Although the retinopathy seen in the DPP participants was at a very early stage and did not affect vision, eye changes typical for diabetes were found in 8 percent of our study population before they developed diabetes. These observations may lead diabetes experts to reconsider the diagnostic thresholds used to define diabetes, which are based on levels of blood glucose associated with the development of eye, nerve and kidney complications of diabetes."

DPP study chair David Nathan, M.D., of Massachusetts General Hospital, pointed out that the retinopathy results are based on a random sample of only 12 percent of DPP participants, all of whom had impaired glucose tolerance, a form of pre-diabetes, when the study began. "These initial findings confirm what other studies have suggested. The complications of diabetes may begin before diabetes is diagnosed, at least by the current-day standards," he explained. "Ideally, an expanded study of the remaining 88 percent of DPP Outcome Study participants might enable us to define more appropriate diagnostic thresholds."

About 18.2 million Americans have diabetes, a group of serious diseases marked by high blood glucose levels that result from defects in the body's ability to produce and/or use insulin. Diabetes can lead to severely debilitating or fatal complications, such as heart disease, blindness, kidney disease, and amputations. It is the fifth leading cause of death by disease in the United States. Type 2 diabetes, which accounts for up to 95 percent of all diabetes cases, involves insulin resistance the body's inability to properly use its own insulin. It usually occurs in overweight adults, but it has increasingly been seen in obese children and teens in recent years.

About 40 percent of U.S. adults ages 40 to 74--41 million people--have abnormal blood glucose levels without having diabetes. Many will develop type 2 diabetes in the next 10 years. (In the DPP, about 10 percent of participants in the placebo group developed diabetes each year.) Once a person has type 2 diabetes, the risk of heart and blood vessel disease is 2 to 4 times that of people without diabetes.

DIABETES PREVENTION PROGRAM

The Diabetes Prevention Program was a major clinical trial in 3,234 people with impaired glucose tolerance. The study's main results were announced in 2001 and reported in the Feb. 7, 2002 issue of the New England Journal of Medicine: Losing 5 to 7 percent of body weight through diet and a modest, consistent increase in physical activity (e.g., walking 5 days a week 30 minutes a day) lowered the incidence of type 2 diabetes by 58 percent. Treatment with metformin, an oral drug commonly used to treat diabetes, reduced the chances of developing diabetes by 31 percent.

The DPP was sponsored by the National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) and co-funded by other components of the NIH, the Centers for Disease Control and Prevention, and the Indian Health Service. The American Diabetes Association provided additional funding. Sources of corporate support included Bristol-Myers Squibb, Parke-Davis, Merck and Company, Merck Medco, Hoechst Marion Roussel, Sankyo, Lifescan, Lipha Pharmaceuticals, Slimfast, Nike, and Health-O-Meter.

About 90 percent of DPP participants continue to be followed closely in the DPP Outcomes Study to examine the longer-term impact of the original treatment interventions. All participants are given access to quarterly lifestyle group sessions, while those in the original intensive lifestyle group have access to additional lifestyle activities to help them stay on track. The participants originally assigned to metformin therapy continue to have access to the drug.

RETINOPATHY FINDINGS

Three hundred two, or about 12 percent, of the DPP Outcome Study participants who had not developed diabetes during the study, and 588 of 876 participants who had developed diabetes, were selected to participate in the retinopathy study, funded by the NEI. To detect diabetic retinopathy, an evaluation of the fundus (inner lining of the eye) was performed with a special camera that provides a detailed look at the retina. Small changes in the vessels, called microaneurysms and hemorrhages, signal the development and degree of retinopathy severity.

Participants with pre-diabetes and retinopathy typically had a small number of microaneurysms in the eye characteristic of early, mild retinopathy that is not yet linked to vision loss. Those who had developed diabetes in the previous 1 to 5 years had slightly more severe retinopathy. Higher average blood glucose levels and higher blood pressure were associated with the risk of developing retinopathy in the new-onset diabetic patients, similar to previous findings in people with longstanding diabetes who develop retinopathy.

NDA Amendment Submitted for Diquafosol in the Treatment of Dry Eye Disease

Thu, 02 Jun 2005 10:37:38 PST

( from http://www.rxpgnews.com ) Inspire Pharmaceuticals, Inc. (NASDAQ: ISPH) today announced the submission of an amendment to its New Drug Application (NDA) filed in 2003 with the U.S. Food and Drug Administration (FDA) for approval to market diquafosol tetrasodium for the treatment of dry eye disease.

Diquafosol is a formulation of a dinucleotide discovered by Inspire scientists, which functions as an agonist at the P2Y2 receptor, stimulating the release of natural tear components targeting all three mechanisms of action involved in tear secretion - mucin, lipids and fluid.

Inspire previously filed an NDA with the FDA for diquafosol for the treatment of dry eye disease in June 2003 and received an approvable letter from the FDA in December 2003.

Since the initial submission of the NDA, Inspire has completed two additional diquafosol Phase 3 clinical trials, trials 108 and 109, which included a total of more than 800 patients.

The focus of the NDA amendment is on multiple analyses of ocular surface staining, including corneal staining and conjunctival staining, from Inspire's diquafosol clinical program.

Gary N. Foulks, M.D., Professor of Ophthalmology, Department of Ophthalmology and Vision Science, University of Louisville School of Medicine, and dry eye expert commented, "Dry eye disease is an extremely challenging disease to study and treat. Among the various ways to measure dry eye disease, ocular surface staining is well-recognized by clinicians as a hallmark of the disease."

"Dry eye is a painful and irritating condition that afflicts more than nine million people in North America," stated Christy L. Shaffer, Ph.D., CEO of Inspire. "Inspire remains committed to addressing this significant medical need. We believe that our NDA amendment contains a strong body of evidence demonstrating the efficacy and tolerability of diquafosol, which has now been evaluated in clinical trials involving over 2,000 patients. We expect that the FDA will act on our submission within six months."

In addition, Inspire and its partner, Allergan, Inc. (NYSE: AGN) have researched and submitted a trade name for diquafosol in the NDA amendment for FDA consideration.

About Dry Eye Disease

Dry eye disease is characterized by insufficient tears and lubrication for adequate protection of the cornea. Symptoms include pain, burning, foreign body sensation and light sensitivity. It is estimated, based on an extrapolation from U.S. data, that dry eye disease affects approximately thirty million people in the eight major international prescription pharmaceutical markets, of which nine million are in North America. Dry eye disease can be caused by various factors including eye stress, aging, environmental factors, autoimmune disorders and various medications. Since dry eye disease is more prevalent among the elderly and post-menopausal women, this market is expected to grow as populations age.

Developed and marketed by Allergan, Inc., Restasis(R) (cyclosporine ophthalmic emulsion) 0.05% is the first approved prescription product in the U.S. for dry eye disease. It is indicated to increase tear production in patients whose tear production is presumed to be suppressed due to ocular inflammation associated with keratoconjunctivitis sicca, or dry eye disease. In June 2001, Inspire entered into a joint license, development and marketing agreement with Allergan to develop and commercialize diquafosol for the treatment of dry eye disease. The agreement also allows Inspire to co-promote Restasis for the treatment of dry eye disease in the U.S.

Exploring the 'corner-of-your-eye' phenomenon

Wed, 01 Jun 2005 23:07:38 PST

( from http://www.rxpgnews.com ) Look at something red in the room, and you'll be more likely to notice something red out of the corner of your eye, elsewhere in the room. Researchers have known that this "implicit attentional selection" is outside conscious control and that we are unaware of its functioning.

Researchers, led by David Melcher of Oxford Brookes University and Zoltán Vidnyánszky of the Hungarian Academy of Sciences and Semmelweis University, have developed an experimental technique for measuring the processing of visual input outside the focus of attention as a function of what subjects are concentrating on inside their attentional focus. Their technique will enhance study of this little-understood phenomenon, they said. The research is published in the June 2 issue of Neuron.

For example, they used their technique to show that, in the process of implicit attentional selection, different features of an object are automatically "clustered." For example, subjects asked to pay attention to a particular color also attend to the motion of objects of the same color throughout the visual field.

The researchers' technique consisted basically of asking subjects to pay attention to either of two separate populations of moving colored dots on a computer display. Asking the subjects to switch their attention from one set of dots to the other, the researchers manipulated the color and motion of the dots such that they could test how well the subjects discriminated one feature, say movement, while paying attention to another.

They were even able to manipulate the experiment so that subjects would misperceive that the color and motion were "misbound." In such circumstances, the subjects still linked features, indicating that such linkage reflected perception of actual relationships between the features and could not be "fooled."

The researchers also sought to understand the difference between the "binding" of features that are within the focus of attention from those outside that focus.

"Our findings also imply that feature binding inside the focus of attention is object based and links all features belonging to the same surface or object, whereas binding outside the attentional focus is based on the physical spatiotemporal relationship between the features," they wrote.

They concluded that the perceptual system thus uses two different methods of binding features--an automatic binding that occurs throughout the visual field and another mechanism that is under attentional control.

"Our new approach for examining cross-feature attention effects may provide an effective tool in further studies to characterize the different stages and mechanism of feature binding both inside and outside the locus of attention," concluded Melcher and his colleagues.

FDA Approves Anecortave Acetate Suspension for Age-Related Macular Degeneration

Wed, 25 May 2005 11:04:38 PST

( from http://www.rxpgnews.com ) Alcon, Inc. (NYSE:ACL) announced today that the U.S. Food and Drug Administration (FDA) has issued an approvable letter for its New Drug Application (NDA) for RETAANE(R) 15 mg (anecortave acetate suspension). RETAANE(R) suspension is an investigational treatment for preserving the vision of patients with wet age-related macular degeneration (AMD).

Alcon said it will meet with the FDA to discuss the approvable letter, the clinical studies submitted with the NDA and other ongoing clinical studies for RETAANE(R) suspension to determine the steps necessary to gain final approval for the wet AMD indication.

"We believe that RETAANE(R) suspension has a positive impact on the vision of patients with AMD. As part of our mission to preserve and restore vision, we are continuing with all of our development efforts for this drug, which we believe will ultimately lead to approval," said Stella Robertson, Ph.D. and vice president, ophthalmology research and development.

About RETAANE(R) Suspension

RETAANE(R) suspension is an investigational treatment for maintaining vision in patients with wet AMD. The drug is an angiostatic cortisene that inhibits the abnormal growth of blood vessels, a process scientifically known as angiogenesis. Angiostatic cortisenes are derived from the steroid class and engineered to remove chemical groups responsible for side effects, such as the development of cataracts and elevated intraocular pressure leading to glaucoma, while preserving potency against angiogenesis.

RETAANE(R) suspension is administered with a blunt-tipped, curved cannula to deliver the drug behind the eye without puncturing the eyeball. This method of delivery avoids the risk of intraocular infection and retinal detachment, the most common side effects associated with injecting therapeutic agents directly into the eye. In addition, RETAANE(R) suspension requires less frequent dosing (once every six months) compared to some other investigational drugs, which are injected into the eye as often as 9 to 12 times a year. No clinically relevant side effects related to the medication or application procedure were reported in the study.

Alcon has conducted extensive clinical research into RETAANE(R) suspension over the last five years. The company has reported clinical study results from two pivotal studies that formed the basis of its clinical package for its NDA. The first study demonstrated that after one year 79 percent of patients treated with RETAANE(R) suspension maintained their vision, compared to 53 percent of those who received a sham application. The second study demonstrated that after one year the visual outcomes in patients who received RETAANE(R) suspension were not statistically different from those of patients who received photodynamic therapy with Visudyne(R).

Pegaptanib Injection Shows Promising Results in Diabetic Macular Edema

Fri, 06 May 2005 18:13:38 PST

( from http://www.rxpgnews.com ) Eyetech Pharmaceuticals, Inc. announced that imaging data from a Phase 2 study of Macugen(R) (pegaptanib sodium injection) in diabetic macular edema (DME) showed a reversal of capillary microaneurysms, retinal ischemia and neovascularization -- all important signs of diabetic retinopathy.

These new preliminary observations from the Macugen Phase 2 DME trial were presented at the May 5 2005 Association for Research in Vision and Ophthalmology annual meeting in Fort Lauderdale, Fla. Macugen is indicated in the United States for the treatment of neovascular age-related macular degeneration (neovascular AMD) and is not approved for the treatment of DME.

"Researchers reviewed photographs of the retina and noted evidence of regression of retinal neovascularization and other signs of diabetic retinopathy in patients treated with Macugen. We also found an improvement on the diabetic retinopathy severity scale, which suggests that Macugen may have helped slow or even reverse the progression of the disease," said Larry Singerman, M.D., Clinical Professor of Ophthalmology at Case University School of Medicine and President of Retina Associates of Cleveland. "While no final conclusions can be drawn from these preliminary and limited data as to the efficacy of Macugen in diabetic retinopathy, we are encouraged by the potential implication of these findings, which are consistent with our current understanding of the role of VEGF in diabetic retinopathy. We look forward to future research to confirm this important hypothesis."

As previously announced, Eyetech and Pfizer plan to conduct a pivotal Phase 2/3 DME clinical trial that will include the diabetic retinopathy score as a pre-specified secondary endpoint. This trial is expected to begin in the second half of 2005.

"There is a tremendous unmet medical need for the 5.3 million of people in the U.S. who suffer from diabetic retinopathy. We are hoping that future trials may demonstrate that Macugen is effective in treating or preventing the progression of diabetic retinopathy," said Anthony P. Adamis, M.D., Chief Scientific Officer of Eyetech. "Eyetech remains focused on diseases affecting the back of the eye because we believe these represent the largest unmet needs in ophthalmology. Our clinical development program for Macugen, in partnership with Pfizer, continues to progress."

Findings in Retrospective Subgroup Analysis of Macugen DME Phase 2 Data

Researchers conducted a retrospective analysis of 69 patients within the Macugen 0.3 mg and usual care arms who had recognized and gradable diabetic retinopathy at both baseline and week 36. In these two arms of the trial, patients treated with Macugen 0.3 mg therapy showed an improvement in the ETDRS diabetic retinopathy severity scale, a standard for monitoring the progression of retinopathy.

At week 36, 11 of the 39 Macugen 0.3 mg dosed patients (28.2 percent) showed improvement of greater than or equal to 1 step versus four of 30 in the sham group (13.3 percent). In addition, a higher proportion of Macugen patients (five of 39, 12.8 percent) showed an improvement of > 2 steps at week 36 compared to sham group (one of 30, 3.3 percent).

Another retrospective analysis from these two arms of the trial included 82 patients for whom assessment of retinal ischemia data was available at both baseline and week 36 (43 patients receiving 0.3 mg Macugen, 39 patients receiving usual care). In this analysis, 16 percent of Macugen patients had less capillary loss, compared to five percent of patients receiving usual care.

In another analysis of all patients treated with Macugen, (0.3 mg, 1 mg, 3 mg doses), 13 were noted to have retinal neovascularization upon their baseline examination. Of these 13 patients, regression in retinal neovascularization was noted at week 36 in eight (62 percent), while no regression of neovascularization was recognized in sham patients who had neovascularization at baseline. As well, recurrence of neovascularization followed discontinuation of Macugen in three of the eight subjects (38%) at week 52.

More About the Phase 2 DME Study

In a Phase 2, double-masked, sham-controlled study of 172 DME patients, 73 percent of patients receiving 0.3 mg Macugen experienced stable or improved vision at week 36, compared to 51 percent of patients who received sham (p=0.023). Among Macugen 0.3 mg patients: 59 percent reported vision gain of at least one line (5 letters) versus 34 percent of sham (p=0.010); 34 percent reported vision gain of at least two lines (10 letters) versus 10 percent of sham (p=0.003); and 18 percent reported vision gain of at least three lines (15 letters) versus seven percent of sham (p=0.12). In addition, 42 percent of patients receiving Macugen 0.3 mg showed a decrease in mean retinal thickness of at least 100 microns, compared to 16 percent of sham. As well, at the end of the study, only half as many patients who received Macugen needed additional laser therapy compared to those receiving usual care (25% vs. 48%).

About Diabetic Retinopathy

Diabetic retinopathy is a disease affecting the blood vessels of the retina, resulting in multiple abnormalities including retinal thickening or edema, hemorrhages, impeded blood flow (retinal ischemia), excessive leakage of fluid from blood vessels and, in the final stages, abnormal blood vessel growth. Such blood vessel growth (proliferative diabetic retinopathy) can lead to hemorrhages and severe retinal damage. When the blood vessel leakage causes swelling within the macula, it is referred to as DME.

According to the American Diabetes Association (ADA), there are at least 18 million people diagnosed with diabetes in the United States. After 10 years of disease duration, 75 percent of diabetics have developed some form of diabetic retinopathy. Diabetes is the leading cause of blindness in adults 20 to 74 years of age in the United States, and DME is the leading cause of vision loss for patients with diabetes. In the United States, there are approximately 500,000 people suffering from DME, with approximately 75,000 new cases each year. There is a significant unmet medical need for a new therapy for this disease.

About Macugen

Macugen is indicated in the United States for the treatment of neovascular age-related macular degeneration (neovascular AMD) and is administered in a 0.3 mg dose once every six weeks by intravitreal injection.

Macugen is a pegylated anti-VEGF aptamer, which binds to vascular endothelial growth factor (VEGF). VEGF is a protein that plays a critical role in angiogenesis (the formation of new blood vessels) and increased permeability (leakage from blood vessels), two pathological processes that contribute to the vision loss associated with neovascular AMD.

Important Safety Information

Macugen is contraindicated in patients with ocular or periocular infections.

Intravitreal injections including those with Macugen have been associated with endophthalmitis. Proper aseptic injection technique -- which includes use of sterile gloves, a sterile drape, and a sterile eyelid speculum (or equivalent) -- should always be utilized when administering Macugen. In addition, patients should be monitored during the week following the injection to permit early treatment, should an infection occur.

Increases in intraocular pressure (IOP) have been seen within 30 minutes of injection with Macugen. Therefore, IOP as well as the perfusion of the optic nerve head should be monitored and managed appropriately.

Serious adverse events related to the injection procedure occurring in less than 1% of intravitreal injections included endophthalmitis, retinal detachment, and iatrogenic traumatic cataract.

Most frequently reported adverse events in patients treated for up to two years were anterior chamber inflammation, blurred vision, cataract, conjunctival hemorrhage, corneal edema, eye discharge, eye irritation, eye pain, hypertension, increased IOP, ocular discomfort, punctate keratitis, reduced visual acuity, visual disturbance, vitreous floaters, and vitreous opacities. These events occurred in approximately 10% to 40% of patients.

New Laser Assisted Cornea Transplant Surgery

Wed, 04 May 2005 18:29:38 PST

( from http://www.rxpgnews.com ) A UC Irvine ophthalmologist and his team have invented a new laser-surgery technique to perform cornea-transplant surgery that can replace the use of traditional handheld surgical blades and potentially improve recovery time for patients.

The technique was developed by Dr. Roger F. Steinert, director of cornea, refractive and cataract surgery in UCI Health Sciences. Cornea transplants are performed on the front window of the eye, using living tissue from donors to replace corneas in which swelling, scars, distortions and degenerations are causing blindness.

The work will lead to human application of the high-tech procedure. Clinical trials are expected to begin by this summer at UCI.

While most transplants are successful in providing the patient with a clear cornea, the majority of cornea transplants take more than six months to provide good vision, and even then strong glasses or contact lenses are needed. In addition, stitches usually need to stay in place for years, because the cornea is slow to heal and, as a result, the transplant remains a weak spot, vulnerable to injury for the rest of the patients life. After the laser-based transplant, suture removal may be as soon as three months, and the strength of the repaired area may be nearly 10 times that of conventional transplants.

By using the laser, a highly precise incision is created, resulting in a perfect match of the donor and the patient, said Steinert, a professor of ophthalmology in the School of Medicine. In addition to precision that exceeds anything that can be duplicated by even a highly skilled surgeon, the laser can create complex shapes that are impossible to achieve with conventional surgery.

The study compared the results of conventional transplant surgical techniques to the results of the laser surgery. Utilizing 14 donated human corneas that were not medically suitable for transplantation, Steinert and his team performed simulated transplant surgery and then tested for the mechanical strength of the incisions and for induced distortion.

They found that the initial strength of the laser incision, even before any healing, measured almost seven times higher than that of the incision from the usual transplant technique performed by hand.

The laser used to cut the cornea is known as a femtosecond-pulsed laser, manufactured by Irvine-based IntraLase Corp. The laser fires 15,000 pulses per second, each pulse lasting only 400 quadrillionths of a second. (To understand how brief each laser pulse lasts, in one second a pulse of light would travel around the equator of the Earth seven times, but in one femtosecond a pulse of laser travels only the width of three human hairs.)

The location of the pulses in the cornea to create the incision is controlled by sophisticated optics and a computer, so that each pulse interconnects with the next, similar to the perforations in paper sheets that allow the paper to be torn cleanly.

Researchers Present Information on 'Artificial Retina'

Tue, 03 May 2005 13:17:38 PST

( from http://www.rxpgnews.com ) Researchers from the University of Southern California and the Doheny Eye Institute's Doheny Retina Institute will be presenting data on the first six patients implanted with an intraocular retinal prosthesis-more popularly referred to as an artificial retina-developed and manufactured in partnership with Second Sight Medical Products, Inc., of Sylmar, Calif.

According to Mark Humayun, professor of ophthalmology at the Keck School of Medicine and the lead investigator on the project, all six of the previously blind patients have been able to detect light, identify objects in their environment, and even perceive motion after implantation with the epiretinal device.

Data collected as of November of 2004 showed that the six patients-who had been implanted with a single prosthesis in their "worse eye" for between 5 and 33 months-were able to "localize the position of, or count the number of, high contrast objects with 74 to 99 percent accuracy," Humayun says. In addition, they could discriminate simple shapes-i.e., figure out the spatial orientation of a bar or the capital letter L-with 61 to 80 percent accuracy.

The researchers also noted that when there is no electricity running through the device, the subjects do not show any improvement in perceptual acuity, "suggesting that electrical stimulation did not improve the health or function of the retina."

Thus far, participants in the study have been people with little or no sight perception due to the degenerative eye disease retinitis pigmentosa (RP). Ultimately, however, the device is likely to be used for the millions of people suffering from age-related macular degeneration, or AMD, as well. In fact, notes Humayun, there are 25 million people across the globe, including 6 million in the United States alone, who have been blinded, or are severely visually impaired, due to disease like RP and AMD. By 2020, that figure is expected to double, creating a virtual vision-loss epidemic.

Both AMD and RP destroy vision by annihilating the retinal cells that allow light to be translated into recognizable images.

Second Sight's intraocular retinal prosthesis is taking the first step to replacing those cells with its device, a 4-by-4 grid of platinum electrodes embedded in silicone rubber. The electrodes are wirelessly stimulated through an external controller hooked up to a head-mounted video camera.

Encapsulated Cell Technology Brings New Hope for Patients with Retinitis Pigmentosa

Mon, 02 May 2005 10:27:38 PST

( from http://www.rxpgnews.com ) Neurotech SA, a specialist in the development of novel therapies for retinal diseases, today announced positive results from an open-label Phase I clinical trial (03-EI-0234) of its lead product, NT-501.

NT-501 uses Neurotech's patented Encapsulated Cell Technology (ECT) as a device to deliver ciliary neurotrophic factor (CNTF) to eyes of visually impaired patients with retinitis pigmentosa (RP).

Results confirm that CNTF can be safely delivered into the vitreous of patients with RP and that the ECT device was well tolerated by all patients.

Futhermore, some patients experienced more than one-line of improvement in their visual acuity score. These Phase I results were presented at the ARVO annual meeting and the trial was conducted at the National Eye Institute (NEI), Bethesda, USA. Neurotech has confirmed that it will now progress to a multi-center Phase II trial.

ECT, a technique developed and patented by Neurotech, allows for genetically-engineered specific protein delivery without manipulating the patient's genetic information or transferring new genetic information into the target tissue.

The Phase I study of NT-501 involved 10 patients with late- stage RP. The study was designed as an open-label safety and tolerability evaluation. Two doses of CNTF (5-fold difference in dose) were evaluated. Phase Ia treated 5 patients with a lower dose; Phase Ib treated 5 patients with a higher dose. The ECT device was implanted in one eye per patient and removed after six months. All explanted devices contained viable cells that continued to produce CNTF.

Commenting on the positive results, Weng Tao, MD, PhD, CSO and VP of R&D with Neurotech said:

"These safety and tolerability results are extremely encouraging and strengthen our confidence in pursuing NT-501 for treating RP and other retinal degenerative diseases. I would like to thank the National Eye Institute for conducting this milestone study and for its continued involvement with this technology."

Al Reaves, PhD, VP of Clinical Development with Neurotech confirmed: "This study represents the first use of ECT in human eyes and it is reassuring that the devices were safe and well-tolerated. We are planning Phase II development with well-designed and controlled multi-center clinical studies to help understand the role that NT-501 will play in treating patients with retinitis pigmentosa and other retinal degenerative conditions."

In this trial, the small ECT device was surgically-implanted into the vitreous cavity through the pars plana in one eye per patient.

The primary inclusion criteria for the study eye included visual acuity of 20/100 or worse, central visual field diameter of 40 degrees or less, and flicker ERG amplitude of 2 microV or less. The first 2 patients were also required to have visual acuity of 20/400 or worse. After surgical implantation of the device, each patient was followed for six months after which the device was explanted. Safety and tolerability was monitored by an independent Data and Safety Monitoring Committee. All 10 patients completed the study as planned and the devices have been explanted.

The ECT devices were well tolerated during the 6 months of implantation and the surgical procedure resulted in minimal or no observed inflammatory reaction. No serious adverse events were reported and in the untreated fellow-eye, there was little change from baseline in the visual acuity score during follow-up.

In the treated study-eye, however, the visual acuity score was more variable during follow-up: while some treated eyes showed little change from baseline, some patients experienced more than one-line of improvement in their visual acuity score.

Bernard Davitian, President of Neurotech, said: "We are extremely pleased that the Phase I trial has validated the safe use of the Encapsulated Cell Technology to deliver CNTF to the vitreous. In addition, the Phase I trial has validated ECT as a delivery platform for the back of the eye and the visual acuity outcomes observed in some patients are encouraging enough to pursue the clinical evaluation of NT-501 in Phase II trials. In addition to further studies with NT-501, we are evaluating other neurotrophic factors and agents that can be used with ECT for treating other retinal diseases."

In addition to NT-501 for the treatment of Retinitis Pigmentosa, Neurotech is applying ECT technology to deliver other protein factors for the treatment of other ophthalmic diseases, including anti-angiogenic factors for the treatment of the wet form of age-related macular degeneration (AMD) and diabetic macular edema (DME), and anti-inflammatory factors for the treatment of posterior uveitis.

About Retinitis Pigmentosa (RP)

RP is a group of inherited retinal diseases that affects about 100,000 Americans and 1.5 million people worldwide. It causes the progressive deterioration of specialized, light-absorbing cells in the retina, the paper- thin tissue that lines the back of the eye like film in a camera. As these cells slowly degenerate, people with RP develop night blindness and a gradual loss of peripheral vision. By about age 40, most have tunnel vision, although many may retain good central vision. Between the ages of 50 and 80, however, they typically lose their remaining sight. The extent of vision loss in people of the same age with RP may be different.

About Encapsulated Cell Technology (ECT)

ECT is a unique technology to overcome drug delivery problems into the back of the eye. ECT enables the controlled, continuous, long-term delivery of therapeutic proteins directly to the retina. In addition, the implants can be retrieved, providing an added level of safety as well as the ability to reverse or adjust therapy, if needed. ECT relies on the use of an immunoisolatory hollow fiber membrane technology to allow the implantation of genetically engineered cells that continuously produce the therapeutic protein at the site of implantation. The cells are loaded into the interior volume of the hollow fiber membrane and attach to a proprietary supportive matrix within this space. The genetically modified cells remain captive within the ECT device thus avoiding the risks associated with traditional gene therapy. Long term protein delivery (18 months) in the vitreous cavity of the eye has consistently been achieved when ECT devices containing human retinal pigmented epithelial (RPE) cells genetically engineered to secrete CNTF have been implanted in a highly disparate mammalian species (rabbits).

Distance (minus) Lenses Worsen Myopia

Mon, 02 May 2005 10:21:38 PST

( from http://www.rxpgnews.com ) The International Myopia Prevention Association (IMPA) has filed a Petition with the U.S. Food and Drug Administration (FDA) seeking enforcement action to require eye care professionals to advise parents of children with initial myopia that distance (minus) lenses worsen myopia and that myopia may be prevented by using reading (plus) lenses for computer usage and other prolonged close work.

The Petition is spearheaded by IMPA founder and author Donald Rehm in response to the absence of regulation for eye care professionals about what parents are told about the effect of distance (minus) lenses and the importance of using reading (plus) lenses for close work.

A copy of the 58-page Petition and an animation explaining the basis for the Petition can be found at www.preventmyopia.org. Rehm is the author of the book: The Myopia Myth, The Truth About Nearsightedness And How To Prevent It.

Myopia is a significant health problem affecting at least 25 percent of all adults in the United States. In addition to causing blurred distance vision, myopia is a predisposing factor for retinal detachment, myopic retinopathy and glaucoma. Myopia is increasing worldwide, in part due to the increased amount of time spent in front of computer monitors.

Commenting on the Petition, Rehm said: "No one is even questioning why parents are told virtually nothing when eye care professionals prescribe glasses or contact lenses for their children. Hopefully, this Petition will at the very least trigger a serious debate about what consumers should be told. Let the eye care professionals justify why consumers are not given the information that they need. The time for change has come. Ophthalmologists and optometrists have an ethical and legal responsibility to reduce and prevent myopia if they can."

Variation in immune response gene causes age-related macular degeneration

Sat, 30 Apr 2005 01:25:38 PST

( from http://www.rxpgnews.com ) Age-related macular degeneration, the leading cause of blindness in the elderly, occurs when a common inherited gene variation is triggered, possibly by an infection, according to a new study led by researchers at Columbia University Medical Center and the University of Iowa, with an international research team.

The gene, known as Factor H, encodes a protein that regulates immune defense against infection caused by bacteria and viruses. People who have an inherited variation in this gene are less able to control inflammation caused by these infections, which may spark age-related macular degeneration (AMD) later in life, the study finds.

Published in this week's Proceedings of the National Academy of Sciences, the results suggest that targeting the molecules involved in immune system response may provide powerful new therapies for treating and preventing AMD.

"We now understand the genetic variation that is behind age-related macular degeneration and are beginning to target the trigger that sets the process in motion," said Rando Allikmets, Ph.D., Acquavella Associate Professor in the department of ophthalmology and the department of pathology & cell biology at Columbia University College of Physicians and Surgeons. "By targeting the molecules involved in inflammation and its regulation we believe we can begin to develop therapies and diagnostic tools that could help countless people keep their sight."

Potential therapies could involve delivering healthy Factor H directly to the eye to short-circuit the disease process; extracting stem cells from the eye so they could be reengineered and re-implanted; or partial transplantation of the liver - the body's main source for Factor H.

Other research has recently established the link between the Factor H gene and AMD by scanning the human genome for variations in gene sequences, but this new research is the first to examine the roots of AMD from a biological perspective and to explore the role that immune response plays in triggering the disease.

More than 50 million people worldwide are estimated to have irreversible blindness as a result of macular degeneration, making it the most common cause of blindness for those over 60. It's estimated that 30 percent of the population will have some form of AMD by the time they reach the age of seventy-five. The disease is marked by a progressive loss of central vision due to degeneration of the macula--a region of the retina and the area responsible for fine, central vision.

The study was conducted in two parts biology and genetics. Dr. Allikmets, senior author on the paper, led the genetic analysis in the study, in collaboration with principal investigator Gregory Hageman, Ph.D., professor of ophthalmology and visual sciences at the University of Iowa Roy J. and Lucille A. Carver School of Medicine, who conducted the biological research. An international team of researchers was engaged in the project including scientists at the National Cancer Institute, the National Institutes of Health (NIH), the University of California at Santa Barbara (UCSB), and Queens University, Belfast, United Kingdom.

Dr. Allikmets began his career focusing on a different disease cancer. As an investigator for the National Cancer Institute, in 1997 Allikmets discovered the ABCR gene (also known as ABCA4), as the first gene involved in a substantial, but small fraction of age-related macular degeneration. This discovery set him on the path of pursuing research in the area of AMD genetics, and he joined Columbia University Medical Center in 1999 to pursue this groundbreaking research.

The researchers examined 900 AMD patients and 400 healthy controls and noticed that half of all AMD patients have an inherited pattern of genetic variants in the Factor H gene known as a haplotype that make them more susceptible to AMD. Different haplotypes in the Factor H gene in about one third of the population provide varied degrees of protection from acquiring AMD.

The Iowa team also examined a large collection of donated eye samples and observed that the activation of the immune system results in the formation of drusen - pockets of inflammation that are the precursors to AMD.

The new findings link variations on the Factor H gene which was found to be accumulated in drusen - directly to the process leading to AMD. The study found that compared to control subjects, patients with AMD were more likely to have single nucleotide polymorphisms that weaken the ability of Factor H to inhibit the immune response known as the alternative complement cascade - thus making them more susceptible to inflammation and the disease.

While it would seem that "anti-inflammatory" drugs could mitigate the inflammatory onslaught, the researchers say most do not work on this leg of the complement system.

The genetic pre-disposition to AMD exists in approximately half of the Caucasian population. But not everyone who has this genetic variant gets AMD, so what causes this mechanism to activate?

"We believe inflammation from infections might kick start the process that leads to AMD," said Dr. Hageman. "The variation in Factor H strengthens the immune response, keeping infections under control early, but ironically that may contribute to a chronic disease like AMD later in life." The Columbia and Iowa scientists were able to make this connection in large measure by studying a rare form of kidney disease called MPGN II. Patients with this condition often share the same kind of eye lesions as individuals with AMD. And, in fact, a genetic determinant of the two diseases had been previously linked to the same chromosome - chromosome 1. Thus, Factor H was thought to be a prime suspect in both diseases.

"It has been always assumed that AMD must have environmental triggers that turn on or aid the pathological process. Our research suggests that the trigger is a specific inducer of the alternative complement pathway, such as an infection, systemic disease, a vaccination, or another unusual agent. Interestingly, countries where the vaccination rate is highest also experience an elevated rate of AMD," said Dr. Allikmets.

The researchers continue to conduct new studies based on their results to further understand the triggers for this gene.

"This is an area for epidemiologists to study, but as our research progresses we should eventually be in a position to suggest treatment that could keep many people from going blind," he said.

Tobramycin and Prednisolone Combination for Inflammatory Ocular Conditions

Thu, 28 Apr 2005 10:24:38 PST

( from http://www.rxpgnews.com ) ISTA Pharmaceuticals, Inc. (Nasdaq: ISTA - News) announced today that the Company has filed an Investigational New Drug (IND) application with the U.S. Food & Drug Administration (FDA) to initiate a U.S. Phase III study of a new combination ophthalmic product containing tobramycin and prednisolone acetate for the treatment of steroid-responsive inflammatory ocular conditions where risk of bacterial infection exists.

Vicente Anido, Jr., Ph.D., ISTA's Chief Executive Officer, stated, "This new combination ophthalmic product was developed by ISTA and is a fixed combination of tobramycin and prednisolone acetate in a proprietary formulation that we believe will provide greater patient comfort in inflamed eyes. Both of the active ingredients in the product are approved drugs on their own. Based upon the timely commencement of the Phase III clinical trials this year, we would expect to submit a New Drug Application (NDA) to the FDA during the first half of 2006."

The tobramycin and prednisolone acetate combination product, if approved, will compete in the antibiotic steroid segment of the U.S. topical ophthalmic anti-inflammatory market. Based upon management estimates of sales and 2004 prescription data from IMS Health, 2004 sales in the U.S. topical ophthalmic anti-inflammatory market were approximately $400 MM, with total prescriptions of 8.6 million.

Common painkillers may play a role in preventing or slowing the progression of macular degeneration

Wed, 27 Apr 2005 01:33:38 PST

( from http://www.rxpgnews.com ) Rheumatoid arthritis patients treated with anti-inflammatory drugs are 10 times less likely to develop age-related macular degeneration (AMD), the most common form of blindness in people over 55, researchers at the University of British Columbia and University of Saskatchewan have found.

The study, recently published in the Neurobiology of Aging, is a joint effort of neurologist Dr. Patrick McGeer of UBC and rheumatologist Dr. John Sibley of the U of S.

The scientists found that that rheumatoid arthritis patients being treated with anti-inflammatory drugs were 10 times less likely to develop (AMD) than unaffected individuals in the United States, Australia, the Netherlands and the United Kingdom.

"Age-related macular degeneration is like Alzheimer's disease of the eye, with retinal deposits called drusen acting like amyloid deposits in the brain found in Alzheimer's," says McGeer, a UBC professor emeritus in the Kinsmen Laboratory of Neurological Research and expert in the use of non-steroidal anti-inflammatory drugs (NSAIDS).

The scientists reviewed 993 rheumatoid arthritis patients in Saskatchewan aged 65 years or older who, on average, had been living with the condition since age 51. Only three had developed AMD, where about 30 cases could be expected in a similarly-aged group from the general populace.

"It was natural for us to look at the rheumatoid arthritis population," says Sibley, a U of S professor of medicine and head of the division of rheumatology. "They have been followed closely for more than 40 years with particular attention paid to retinal changes because medication widely used for rheumatoid arthritis can create visual problems."

It is already accepted that NSAIDS reduce the incidence of bowel cancer. Fifteen years ago, McGeer and Sibley found the first of a growing body of evidence that NSAIDS may also help reduce the incidence of Alzheimer's. However, Sibley says this is the first time a link has been identified between anti-inflammatories and macular degeneration.

The researchers emphasize that further study is required to confirm their findings, but if they are corroborated, anti-inflammatories would be the first approach for this intractable disease. Related questions such as optimum dosage and when to begin treatment need to be answered. Also, since NSAIDS can have side effects such as stomach upset, ulcers and stress on kidneys, they are not appropriate for everyone and criteria for high-risk patients that would benefit from their use will need to be defined.

Macular degeneration is the most common cause of severe vision loss in Canada, especially among the elderly, according to the Canadian National Institute for the Blind. It causes one in three cases of reported vision loss. The condition causes light-sensitive cells in the macula, or central portion of the retina, to degenerate. The macula is responsible for perceiving fine visual detail. Early signs of macular degeneration include blurring of vision when performing detailed tasks like reading or sewing.

AMD is the most common form of the disease and causes permanent loss of central vision. There are two forms of AMD wet and dry with more than 85 per cent of cases being the dry form, for which there is no effective treatment.

FDA gives Clearance to Multicolor Laser Photocoagulator System for Retinal Applications

Sat, 16 Apr 2005 20:47:38 PST

( from http://www.rxpgnews.com ) NIDEK Inc., a U.S. leader in advanced ophthalmic laser technologies announced today that it received FDA marketing clearance for commercial release of its new MC-300 Multicolor Laser Photocoagulator System. The new laser will continue to establish NIDEK as a comprehensive laser provider for the fast growing retinal laser market. The MC-300 laser system has been commercially available in international markets and has received outstanding reviews and clinical results from retinal specialists in Asia and Europe.

The NIDEK MC-300 is an advanced multi-color (red, yellow and green) diode-pumped solid-state (DPSS) laser system. The new laser delivers three unique laser wavelengths - 659, 561 and 532 nm - ideal for retinal applications, disease treatments and management.

The new retinal photocoagulator features advanced software technologies for accurate and precise energy delivery to the retina. In addition, with advanced SOLIC Technology - the new system features digitally controlled instant duty cycles, permitting the laser to be used at rapid speeds and high powers for extended periods of time without failure and energy decay. The MC-300 laser can be mounted for slit-lamp delivery and requires a standard electric outlet, offering retinal surgeons with advanced delivery capabilities and versatility in either an operating room or in-office use.

NIDEK will launch the new MC-300 laser at the American Society For Cataract & Refractive Surgery - ASCRS Annual Meeting in Washington, DC, April 16th - 19th, 2005.

"The NIDEK MC-300 is an outstanding laser for retinal applications, delivering a suite of advanced technologies to the retinal specialist. With the introduction of the MC-300, NIDEK continues its long-standing commitment to delivering advanced solutions for all specialties of ophthalmology, including retinal applications. Together with the MC-300 and other diagnostics and laser solutions, NIDEK continues to forge ahead and build a solid franchise for delivering products and solutions that deliver on superior technology, product reliability, performance and outstanding clinical results, with a focus in the areas of cornea, cataract, glaucoma and retina," commented Mr. Hideo Ozawa, President and Founder of NIDEK, at a recent product release event.

Mr. Ted Shimomura, Vice-President & General Manager of NIDEK Inc. commented: "The NIDEK MC-300 is an innovative break-through in ophthalmic multi-wavelength laser technology, delivering a solution that retinal specialists have been asking for in the U.S. market for the last few years. Today there is only one other company that delivers a solution that is really not the ideal platform for retinal laser applications; now NIDEK is introducing a solution that is better in clinical results, more reliable, user-friendly and offers newer technology for the retinal specialist. In the months ahead, we look forward to having the MC-300 becoming the de facto standard for retinal lasers. With new lasers and diagnostic solutions being introduced at this year's ASCRS Meeting, NIDEK continues to forge ahead and make stronger in-roads into the U.S. ophthalmic laser and diagnostic instrumentation market."

Key to better-than-20/20 vision is in the Flap

Thu, 14 Apr 2005 16:09:38 PST

( from http://www.rxpgnews.com ) New scientific data being presented at this year's ASCRS meeting reveals the key to a better-than-20/20 outcome in LASIK surgery may depend on whether your doctor uses a blade or a laser to create the corneal flap in the first step of the procedure.

"It turns out that the flap that we make in LASIK is not an innocent bystander," says Roger F. Steinert, M.D., 2005 ASCRS president, professor of ophthalmology, professor of biomedical engineering, director of cornea, refractive and cataract surgery, and vice chair of clinical ophthalmology at University of California, Irvine.

"We now have data validating something we suspected for the past year but hadn't firmly proven, which is that the rate of achieving high levels of vision is better with the IntraLase laser than with the conventional metal microkeratome. On theoretical grounds we knew flap creation with IntraLase would be safer, and its performance bore that out. But we didn't anticipate seeing a difference in actual vision. Multiple studies now show higher rates of 20/20, higher rates of better than 20/20, and that Custom treatments show better results as well."

Older Children Can be Effectively Treated for Lazy Eye

Wed, 13 Apr 2005 20:04:38 PST

( from http://www.rxpgnews.com ) Surprising results from a nationwide clinical trial show that many children age seven through 17 with amblyopia (lazy eye) may benefit from treatments that are more commonly used on younger children.

Treatment improved the vision of many of the 507 older children with amblyopia studied at 49 eye centers. Previously, eye care professionals often thought that treating amblyopia in older children would be of little benefit. The study results, funded by the National Eye Institute (NEI), part of the National Institutes of Health (NIH), appear in the April issue of Archives of Ophthalmology.

"Doctors can now feel confident that traditional treatments for amblyopia will work for many older children," said Paul A. Sieving, M.D., Ph.D., director of the NEI. "This is important because it is estimated that as many as three percent of children in the United States have some degree of vision impairment due to amblyopia. Many of these children do not receive treatment while they are young," he said.

Amblyopia is a leading cause of vision impairment in children and usually begins in infancy or childhood. It is a condition resulting in poor vision in an otherwise healthy eye due to unequal or abnormal visual input while the brain is developing in infancy and childhood. The most common causes of amblyopia are crossed or wandering eye (strabismus) or significant differences between the eyes in refractive error, such as, astigmatism, farsightedness, or nearsightedness.

Children in the study were divided randomly into two groups. One group was fitted with new prescription glasses only. The other group was fitted with glasses as well as an eye patch, or the eye patch along with special eye drops, to limit use of the unaffected eye. These children were also asked to perform near vision activities. The patching, near activities, and eye drops force a child to use the eye with amblyopia. Patching was prescribed for periods of two to six hours daily, while the eye drops were administered daily for the children seven though twelve years of age.

The study investigators defined successful vision improvement as the ability to read (with the eye with amblyopia) at least two more lines on a standard eye chart. The study investigators found that 53 percent of children age seven through twelve years who received both glasses and treatment with patches and near activity met this standard, while only 25 percent of those children in this age group who received glasses alone met the standard. For children age 13 through 17 years who were treated with both glasses and patches (these children did not get drops), 25 percent met the standard while 23 percent of children of these ages who received only glasses met the standard.

The study also revealed that among children age 13 through 17 years who had not been previously treated for amblyopia, 47 percent of those who were treated with glasses, patching and near activities improved two lines or more compared with only 20 percent of those treated with glasses alone. Despite the benefits of the treatment, most children, including those who responded to treatment, were left with some visual impairment. They did not obtain
"20/20" vision.

"This study shows how important it is to screen children of all ages for amblyopia." said study co-chairman Richard W. Hertle, M.D., Children's Hospital of Pittsburgh.

Commented co-chairman Mitchell M. Scheiman, O.D., Pennsylvania College of Optometry, "This study shows that age alone should not be used as a factor to decide whether or not to treat a child for amblyopia. The opportunity to treat amblyopia does not end with the pre-school years."

It is not known, say the authors of the current study, whether vision improvement will be sustained in these children once treatment is discontinued. The NEI is supporting a one-year, follow-up study to determine the percentage of amblyopia that recurs among the children who responded well to treatment, as well as many other clinical studies of amblyopia at eye centers nationwide.

Dr. Sieving also commented that the current study results are "a wonderful example of the adaptability of the human visual system and brain. The NIH is exploring ways to take advantage of this adaptability in order to better understand and treat vision problems and other neurological conditions."

Smoking doubles risk of age related macular degeneration

Wed, 13 Apr 2005 01:36:38 PST

( from http://www.rxpgnews.com ) The risk of macular degeneration increases with age and is the most common cause of blindness in the UK, affecting around 200,000 elderly people.

The findings are based on a representative sample of over 4,000 people, aged 75 and older, from 49 general practices across Britain.

The participants all underwent a series of detailed eye tests and were asked about their smoking habits, and if they had given up, how long ago. After taking into account other risk factors, such as alcohol consumption and cardiovascular disease, the results showed that current smokers were twice as likely to be visually impaired as non-smokers.

Those who had kicked the habit more than 20 years previously were not at risk.

Based on the numbers of people in the UK who are blind or who are partially sighted as a result of macular degeneration, the authors calculated that smoking was likely to have caused up to 30,000 cases.

"An increased risk of [age related macular degeneration], which is the most commonly occurring cause of blindness in the United Kingdom, is yet another reason for people to stop smoking and governments to develop public health campaigns against this hazard," conclude the authors.

New Collaboration to discover genes responsible for Macular Degeneration

Fri, 01 Apr 2005 17:00:38 PST

( from http://www.rxpgnews.com ) ParAllele BioScience, Inc. announced today its joint collaboration agreement with the University of Iowa Cell Biology and Functional Genomics Laboratory, the UI Department of Ophthalmology and Visual Sciences and the UI Center for Macular Degeneration to accelerate the discovery of genes associated with age-related macular degeneration (AMD). The research initiative will be led by Gregory Hageman, Ph.D., professor at the UI Carver College of Medicine.

AMD is the leading cause of irreversible vision loss in the developed world, affecting 15 to 20 percent of individuals over the age of 60, or an estimated 50 million individuals.

"The molecular events leading to the development of AMD are poorly understood and no pharmacological treatment has been shown to be effective in preventing, arresting or reversing the loss of vision associated with early AMD," Hageman said.

Recent genome-wide linkage analyses have revealed loci on multiple chromosomes with the potential to harbor major AMD-associated genes. "We choose to collaborate with ParAllele because of their ability to comprehensively analyze those regions for both common and rare mutations that may be AMD-associated," he added. "Our long range goal is to identify new pathways and therapeutic targets that will hasten the development of pharmaceutical agents capable of delaying the onset and/or progression of AMD."

Hageman's studies are funded by the National Eye Institute at NIH and additional corporate entities.

"The agreement is an exciting opportunity for us to combine ParAllele's strengths in pharmacogenomics and high throughput gene mutation discovery with the acknowledged leadership of Dr. Hageman and his Institute in the field of AMD-associated pathways," said Nick Naclerio, CEO of ParAllele BioScience, Inc.

Stanford physicists and eye doctors to design a "Bionic Eye,"

Thu, 31 Mar 2005 16:47:38 PST

( from http://www.rxpgnews.com ) On Feb. 22 in the Journal of Neural Engineering, Daniel Palanker, Alexander Vankov and Phil Huie from the Department of Ophthalmology and the Hansen Experimental Physics Laboratory and Stephen Baccus from the Department of Neurobiology published a design of an optoelectronic retinal prosthesis system that can stimulate the retina with resolution corresponding to a visual acuity of 20/80sharp enough to orient yourself toward objects, recognize faces, read large fonts, watch TV and, perhaps most important, lead an independent life.

The researchers hope their device may someday bring artificial vision to those blind due to retinal degeneration. They are testing their system in rats, but human trials are at least three years away.

"This is basic research," said Palanker, a physicist whose primary appointment is in the Ophthalmology Department. "It's the essence of Bio-X," he said, referring to Stanford's interdisciplinary initiative to speed biomedical research from benchtop to bedside.

The project is funded in part by the U.S. Air Force and VISX Corp., which licensed the technology through Stanford's Office of Technology Licensing. Harvey Fishman, who is not an author of the current paper but directs the Stanford Ophthalmic Tissue Engineering Laboratory, pioneered the project.

Degenerative retinal diseases result in death of photoreceptorsrod-shaped cells at the retina's periphery responsible for night vision and cone-shaped cells at its center responsible for color vision. Worldwide, 1.5 million people suffer from retinitis pigmentosa (RP), the leading cause of inherited blindness. In the Western world, age-related macular degeneration (AMD) is the major cause of vision loss in people over age 65, and the issue is becoming more critical as the population ages. Each year, 700,000 people are diagnosed with AMD, with 10 percent becoming legally blind, defined by 20/400 vision. Many AMD patients retain some degree of peripheral vision.

"Currently, there is no effective treatment for most patients with AMD and RP," the researchers say in their paper. "However, if one could bypass the photoreceptors and directly stimulate the inner retina with visual signals, one might be able to restore some degree of sight."

To that end, the researchers plan to directly stimulate the layer underneath the dead photoreceptors using a system that looks like a cousin of the high-tech visor blind engineer Lt. Geordi La Forge wore in Star Trek: The Next Generation. It consists of a tiny video camera mounted on transparent "virtual reality" style goggles. There's also a wallet-sized computer processor, a solar-powered battery implanted in the iris and a light-sensing chip implanted in the retina.

The chip is the size of half a rice grain3 millimetersand allows users to perceive 10 degrees of visual field at a time. It's a flat rectangle of plastic (eventually a silicon version will be developed) with one corner snipped off to create asymmetry so surgeons can orient it properly during implantation. One design includes an orchard of pillars: One side of each pillar is a light-sensing pixel and the other side is a cell-stimulating electrode. Pillar density dictates image resolution, or visual acuity. The strip of orchard across the top third of the chip is densely planted. The strip in the middle is moderately dense, and the strip at the bottom is sparser still. Dense electrodes lead to better image resolution but may inhibit the desirable migration of retinal cells into voids near electrodes, so the different electrode densities of a current chip design allow the researchers to explore parameters and come up with a chip that performs optimally. Another designpore electrodesinvolves an array of cavities with stimulating electrodes located inside each of them.

How does the system work when viewing, say, a flower? First, light from the flower enters the video camera. (Keep in mind that camera technology is already pretty good at adjusting contrast and other types of image enhancement.) The video camera then sends the image of the flower to the wallet-sized computer for complex processing. The processor then wirelessly sends its image of the flower to an infrared LED-LCD screen mounted on the goggles. The transparent goggles reflect an infrared image into the eye and onto the retinal chip. Just as a person with normal vision cannot see the infrared signal coming out of a TV remote control, this infrared flower image is also invisible to normal photoreceptors. But for those sporting retinal implants, the infrared flower electrically stimulates the implant's array of photodiodes. The result? They may not have to settle for merely smelling the roses.

Complex processing: The eyes have it

The eye is a complex machine. It has more than 100 million photoreceptors. "If we compare it to modern digital cameras, for example, it will be 100 megapixels," Palanker said during an interview in the Hansen Experimental Physics Laboratory. "We buy cameras usually of three megapixels, maybe four."

And if electronic cameras do a good job of image processing, the eye does a spectacular job, compressing information before sending it to the brain through the 1 million axons that make up the optic nerve. "We have a built-in processor in the eye," Palanker said. "Before it goes into the brain, the image is significantly processed."

The bottom layer of photoreceptors is where rhodopsina protein pigment that converts light into an electrical signalexists. But as far as signal processing is concerned, the rubber meets the road where the signal enters the inner nuclear layer, which is populated with bipolar, amacrine and horizontal cells. These three cellular workhorses process the signals and transfer them to the ganglion cell layer, or "output cascade" of nerves that deliver signal pulses to the brain.

It's best to place an implant at the earliest accessible level of image processing, Palanker said. "The earliest [accessible level] in degenerated retina is in the nuclear layer, and the more you go along the chain of image processing, the more complex the signals become."

The Stanford researchers try to utilize most of the processing power remaining in the retina after retinal degeneration by placing their implant on the side of the retina facing the interior of the eye ("subretinal" placement), as opposed to several other groups in the United States, Germany and Japan that place retinal implants on the side of the retina facing the outside of the eyeball ("epiretinal" placement).

Signal processing allows the eye to detect direction of motion, perceive colors, enhance contrast and adjust to different levels of brightness. "Our eye is an amazingly adjustable machine," Palanker said. It operates in brightness levels that span eight orders of magnitude, meaning it can detect both dim objects and those 100 million times brighter, "from moonless night to bright day," he said.

It may seem counterintuitive that as it gets processed by the visual system, the signal travels from the back of the eye toward the eye's interior, rather than from the inner surface of the retina and out the back of the eye. But metabolically active photoreceptors need a lot of support. They are connected to a highly pigmented layer called retinal pigment epithelium (RPE) that grows atop a highly vascularized layer of tissue (choroid) carrying a heavy flow of blood. If the blood supply and the RPE were inside the eye, they would obscure light from the photosensitive cells. Explained Palanker: "That is why it's built upside down, because those cells on topthe bipolars and ganglionsdo not require as many nutrients and as much metabolic support as do photoreceptors."

A crucial aspect of visual perception is eye motion. Palanker said the Stanford system provides a powerful advantage over more basic devices now being tested in humans by a U.S. company because, besides making the most of the eye's natural image-processing strengths by subretinal placement of implants, the system tracks rapid intermittent eye movements required for natural image perception. Vankov, a physicist, designed the projection and tracking system.

"In reality, when you think you are fixating to a certain point, your eyes are not steady," Palanker said. "You are microscanning it all the time. So if you would be projecting an image not through the eye, but just deliver it from the camera to the implant, bypassing the moving eye, this will not be natural perception because you will completely eliminate this link."

Alon Asher, a graduate student in computer science at Tel Aviv University, spent a semester working with Palanker on the software that links image processing to motion detection. He now continues his work on the project from Israel. Assistant Professor of Neurobiology Stephen Baccus, a co-author of the paper who is an expert in retinal signal processing, advises the group about the details of image processing.

In the Stanford system, image amplification and other processing occur in the hardware, outside the eye. If amplification occurred inside the implant's pixels, as it does in one German design, there'd be no way short of surgery to make adjustments.

The Stanford system also makes new use of an old trick. By co-aligning real and enhanced images, it allows patients to utilize any remaining peripheral vision while making the most of the implant. Virtual reality systems that allow co-alignment of real and simulated views are already in use by pilots and surgeons, Palanker said. "This co-alignment of additional information with the normal view allows surgeons to see in the microscope the operating site, while the other eye is getting a projection of, say, a CT or MRI image of the same patient. So they can relate the information that they don't see in the operating site to anatomic findings and know exactly where the tumor or other problem is."

The amazing grace of physics

The new design answers major questions about what's feasible for bionic devices. Biology imposes limitations, such as the needs for a system that will not heat cells by more than 1 degree Celsius and for electrochemical interfaces that aren't corrosive.

Current retinal implants provide very low resolutionjust a few pixels. But several thousand pixels would be required for the restoration of functional sight. The Stanford design employs a pixel density of up to 2,500 pixels per millimeter, corresponding to a visual acuity of 20/80, which could provide functional vision for reading books and using the computer.

Physical limitations regarding electrical stimulation most likely make it impossible for implants to impart a visual acuity of 20/10 (the sharpness required to see the bottom line on an eye chart), 20/20 (the so-called standard of good vision) or even 20/40 (the level to which vision must be correctable to be eligible for a California driver's license).

A major limiting factor in achieving high resolution concerns the proximity of electrodes to target cells. A pixel density of 2,500 pixels per square millimeter corresponds to a pixel size of only 20 micrometers. But for effective stimulation, the target cell should not be more than 10 micrometers from the electrode. It is practically impossible to place thousands of electrodes so close to cells, Palanker said. With subretinal implants but not epiretinal ones, Stanford researchers discovered a phenomenonretinal migrationthat they now rely on to encourage retinal cells to move near electrodeswithin 7 to 10 microns. Within three days, cells migrate to fill the spaces between pillars and pores.

"If the mountain doesn't come to Muhammad, Muhammad goes to the mountain," Palanker said. "We cannot place electrodes that close to cells. We actually invite cells to come to the electrode site, and they do it happily and very quickly."

Currently the researchers are testing two designs in parallel because they aren't yet sure which will be best. One design uses electrodes that protrude up from the chip like pillars. The pillars allow retinal cells greater access to nutrients and let researchers affect specific cell layers by controlling the height of the pillars. But pillars expose more cells to current, potentially heating tissue and increasing the chance for "cross-talk"where many electrodes affect one cell. The second design has electrodes recessed into pores, which localizes currents and makes stimulation selective, perhaps allowing researchers to stimulate single cells.

Huie, a cell biologist and histologist, implants the chips in rats using a unique tool he and others developed. So far his short-term rat studies show no rejection of the implants. The next step will be longer tests in rats, as well as tests in larger animals for which models of retinal dystrophy exist. The researchers are currently shipping chips to Joseph Rizzo, a professor of ophthalmology at Harvard Medical School, for implantation into pigs.

Professor Mark Blumenkranz, chair of the Ophthalmology Department, advises the authors about surgical issues, and Professor Michael Marmor in that department, an expert in retinal physiology, provides advice about retinal electrophysiology. Graduate students Ke Wang in applied physics and Neville Mehenti in chemical engineering are currently working with Fishman of the Stanford Ophthalmic Tissue Engineering Laboratory on carbon nanotube electrodes and on chemical stimulation of the retinal cells. Medical student Ian Chan continues to develop lithographic fabrication technology for the implants. Alex Butterwick, a graduate student in applied physics, is studying the mechanisms of cellular damage and the safe limits of electrical stimulation.

FDA Approves Bromfenac ophthalmic solution for the Treatment of Ocular Inflammation Following Cataract Surgery

Tue, 29 Mar 2005 09:15:38 PST

( from http://www.rxpgnews.com ) ISTA Pharmaceuticals, Inc. has announced that the U.S. Food & Drug Administration (FDA) has approved the New Drug Application (NDA) for Xibrom(TM) (bromfenac ophthalmic solution) 0.09% for the treatment of ocular inflammation following cataract surgery. ISTA expects to launch Xibrom(TM), a topical, twice-daily, non-steroidal anti-inflammatory solution (NSAID), during the second quarter of 2005, after securing commercial quantities of the product from its manufacturer and completing the further expansion of its sales force.

Eric Donnenfeld, M.D.,Associate Professor of Ophthalmology, New York University Medical Center, New York and an investigator in the bromfenac ophthalmic solution Phase III clinical trials, commented, "Bromfenac ophthalmic solution is the first twice-daily ophthalmic NSAID to be approved in the United States. All other ophthalmic NSAIDS are dosed four times daily. Bromfenac ophthalmic solution represents an advance for ophthalmic care because of the improved patient compliance and its early onset of action, and I am pleased that patients will have this new treatment option."

Vicente Anido, Jr., Ph.D., President and Chief Executive Officer of ISTA stated, "We are excited to receive FDA approval of our third commercial product and anticipate launching bromfenac ophthalmic solution during the second quarter of 2005. We recently completed the interim expansion of our sales force which is now promoting Istalol(TM) and Vitrase®. With the bromfenac ophthalmic solution approval, we plan on hiring additional sales representatives in order to reach approximately 10,000 ophthalmologists in the U.S."

Xibrom (bromfenac ophthalmic solution) 0.09% is a sterile, topical, non- steroidal anti-inflammatory compound for the treatment of ocular inflammation following cataract surgery. Senju Pharmaceuticals Co. Ltd. has marketed this product in Japan since 2000. ISTA acquired U.S. marketing rights for bromfenac ophthalmic solution in May 2002 under a license from Senju. ISTA completed two pivotal Phase III clinical studies of bromfenac ophthalmic solution in the United States. In these studies involving 527 patients, a statistically significant proportion of patients treated with bromfenac ophthalmic solution achieved treatment success, defined as the complete absence of ocular inflammation, compared to those patients who received placebo. This effect was evident in the bromfenac ophthalmic solution group as early as Day 3 following initiation of treatment. ISTA filed its NDA for bromfenac ophthalmic solution with the FDA in May 2004.

According to company estimates and data compiled by IMS Health, the U.S. ophthalmic anti-inflammatory market, consisting of steroids, NSAIDS and other related products, is approximately $250 million per year.

Gene variation could be responsible for age-related macular degeneration

Sun, 27 Mar 2005 02:21:38 PST

( from http://www.rxpgnews.com ) Half of all cases of age-related macular degeneration, the leading cause of blindness among the elderly, could be caused by a variation in a particular gene, according to UT Southwestern Medical Center researchers involved in a multicenter study.

The National Eye Institute study which will appear in an upcoming edition of the journal Science and is available online links a mutation in the gene Complement Factor H to an increased risk of age-related macular degeneration (AMD).

Macular degeneration is a complex disease that is the leading cause of blindness in Americans over the age of 50. By age 75, an estimated 30 percent of Americans have some manifestation of AMD.

The macula is an area in the center of the retina where light is focused and changed into nerve signals to compose an image in the brain. This central or "macular" vision enables us to read, drive and do things requiring fine, sharp, straight-ahead vision.

"We've identified a gene that is implicated in the pathogenesis of AMD," said Robert Ritter, a UT Southwestern research scientist involved in the Science study. "It provides a starting point for future investigations that will help us understand what takes place during the breakdown of the visual process."

Scientists have long suspected a genetic role in the disease but previously were only able to narrow the culprit gene's location to one region of a particular chromosome.

"We know that one of the most significant factors in determining who gets macular degeneration is family history," said Dr. Albert Edwards, the study's lead author and an assistant professor of ophthalmology at UT Southwestern when he conducted his research. "A positive family history can increase a person's chances of developing macular degeneration several fold compared to people in the general population."

In the study, researchers analyzed genetic data from more than 200 patients who were at high risk for developing AMD or who already had AMD in one or both eyes, and from more than 130 healthy participants without a known family history of the disease. The genetic mutation of Complement Factor H was present in half of those with AMD or at high risk for the disease.

Researchers from the UT Southwestern Eugene McDermott Center for Human Growth and Development provided genotyping, technical advice and assistance.

"This is an important study that gives us new insight into a disease that impacts a growing population of aging Americans," said Dr. Helen Hobbs, director of the center and chief of Clinical Genetics at UT Southwestern. "Genetic studies such as this provide the basis for clinicians to identify those at risk and may lead to better treatment options."

These findings may help researchers develop new preventive and therapeutic strategies for managing AMD.

"By finding genes, we can understand where the biological pathways are and the processes involved in the disease," said Dr. Edwards, who is now the president of the Institute for Retina Research at Presbyterian Hospital of Dallas. "Once we determine which genes are responsible for macular degeneration, we can screen the population and manipulate biological pathways to develop treatments."

Infant vernier acuity is not as immature as previous research has indicated

Wed, 23 Mar 2005 23:15:38 PST

( from http://www.rxpgnews.com ) Infant vernier acuity is not as immature as previous research has indicated.

The data from this study also suggest that vernier testing could be a substitute for the traditional Snellen eye chart test for children or others who cannot read letters. Vernier acuity is tested by viewing nearly collinear stripes with varying amounts of spatial phase displacement between them and measuring an individual's ability to gauge the displacement between the stripes.

Angela M. Brown, Veena Adusumilli, and Delwin T. Lindsey of The Ohio State University conducted the study with major funding from the National Eye Institute and the National Science Foundation. The researchers first set out to establish a "benchmark" to which vernier acuity could be compared. The benchmark they chose was the ability to see small differences in contrast. Adults (ages 20 to 48) were tested 6.096 meters (20 feet) from the contrast stimuli, and healthy three-month-old infants were tested 45.72 centimeters (1.5 feet) from the contrast stimuli, to take into account the underdeveloped vision of infants. The experiment showed that under these conditions, infants see changes contrast almost as well as adults.

The vernier acuity of the infants and adults was then tested under the same conditions as the contrast discrimination had been tested. Under these conditions, infant vernier acuity (in degrees of spatial phase displacement) was almost as good as that of adults. Furthermore, the relation between "benchmark" contrast discrimination ability and vernier acuity was the same for infants and adults.

During the testing, an adult observer held an infant in her arms using a "baby sling," standing in a position that allowed the infant to see the stimulus display, but the adult observer could not. The adult observer watched the infant's looking behavior via closed-circuit video and judged whether the test stimulus (the modulation of stimulus displacement or contrast) was contained in the right- or left-side stripes. This is an objective measure of how well infants can see a stimulus, and is in common use in the laboratory and the clinic.

Angela Brown, lead researcher of the study, says the data suggest that vernier acuity of human infants and adults is quite similar, contrary to past studies conducted in this area. The similarity of infant and adult vernier acuity suggests that vernier acuity might be a sensitive test for strabismic amblyopia and other visual disorders that normally must be diagnosed using an eye chart. "The data from this study also suggest that vernier testing could be a substitute for eye chart testing for children and others who cannot read an eye chart," says Brown.