Month: August 2014

Oraya Therapeutics, Inc., announced that enrollment is now underway for the first ever masked and sham-controlled study to demonstrate the efficacy and safety of radiation therapy for the treatment of wet age-related macular degeneration (AMD). The groundbreaking clinical trial is being conducted at seven European sites, and will include a minimum of 150 patients, with approximately one third of those receiving a sham exposure and the remainder receiving radiation dosing of either 16 or 24 Gray (GY).

All patients will have standard of care anti-VEGF drug therapy, and the trial is designed and powered to measure the effect of the radiation adjunct on vision outcomes and on the frequency of anti-VEGF injections. Trial endpoints will be evaluated one year post radiation treatment. The radiation dose is delivered using Oraya’s IRay™ system, a proprietary non-invasive low energy stereotactic X-ray platform that has been in development since early 2007. Over 60 patients have already been treated in a Phase 1 study of the device, and results from that study led to the design and initiation of this newly announced trial.

In commenting on the trial, Jim Taylor, president & CEO of Oraya says, “We are pleased to have reached this important milestone for the company, and even more excited to demonstrate conclusively the value of this promising new therapeutic approach for the treatment of AMD. Our employees, investors and clinical advisors have all made exceptional commitments and contributions to this endeavor, and it is gratifying to see that we now have the opportunity to conduct such an important and scientifically sound clinical study.”

The IRay system is an investigational stereotactic radiosurgical device designed specifically to treat diseases of the eye. The single organ focus of Oraya’s technology enables precise delivery of low-energy X-rays to treat wet AMD. Designed to maximize patient comfort and precision, the IRay system utilizes a vacuum-coupled contact lens interface, the I-Guide™, which holds the eye to maintain stability during treatment, while detecting eye motion. A gating system, which automatically shuts down the device in case of misalignment due to patient movement, is also featured. Because the radiation delivered is low-voltage, comparable to a chest or dental X-ray, the IRay is suitable for use in a typical ophthalmology office setting. The entire patient treatment process requires only a topical anesthetic, and lasts 15 to 20 minutes.

In discussing the European trial, Darius Moshfeghi, M.D., associate professor of ophthalmology at Stanford University, and a clinical advisor to Oraya, commented that “Data from the Phase 1 study, with over a year follow-up to date, clearly show potential effects that are outside those seen in current day to day practice. With an excellent safety profile so far, it will be very interesting to see how the [IRay] therapy performs in this well designed and controlled trial.”

Peter Kaiser, M.D., of the Cole Eye Institute at the Cleveland Clinic and a recognized expert on new therapies for AMD, notes that “Combination therapies as adjuncts to anti-VEGF therapy are showing great promise to improve the overall treatment options and outcomes for wet AMD patients. The growing body of data from radiation therapy studies during the last few years has become of significant interest, with results suggesting that both patient outcome and treatment burden and cost could be positively impacted.” Dr. Kaiser participated in the design of Oraya’s European protocol, and remains an active advisor to the company.

Additional information about Oraya’s randomized, masked, sham-controlled study of radiotherapy for wet AMD, currently enrolling in Europe, can be found orayainc/clinicaltrials.asp, and by searching clinicaltrials for identifier NCT01016873.

Source
Oraya Therapeutics

Results of the Comparison of AMD Treatments Trials (CATT) study were published online today in The New England Journal of Medicine (NEJM). The CATT study was designed to compare two drugs currently used to treat wet-AMD: Lucentis (ranibizumab) and Avastin (bevacizumab) — a drug that is used off label for ocular use in a number of countries around the world.

“As an organization representing more than 30 million people around the world living with age-related macular degeneration, we have been anxiously awaiting the results of the CATT study,” said AMD Alliance International CEO, Narinder Sharma. “Proven safety and efficacy should be the only concern of any treatment debate. With the guidance of our respected Science Panel Chair, Dr. Alan Cruess, we have reviewed the report and believe that it is important to put this high profile study into context and encourage frank and open dialogue between patients and doctors about all treatment options and potential risks.”

What Does CATT Tell Us?

The highly anticipated CATT study, sponsored by the National Eye Institute (NEI) is reporting non-inferiority of bevacizumab (Avastin®) monthly intravitreal injections in terms of efficacy for choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD) relative to the gold standard therapy, ranibizumab (Lucentis®) injected monthly.

As widely anticipated by the worldwide community of retina sub-specialist ophthalmologists, bevacizumab injected monthly appears to preserve vision in this disease as well as ranibizumab intravitreal injected monthly. Furthermore, it means secondarily that bevacizumab appears to reduce retinal thickness, reduce sub-retinal fluid and resolve sub-retinal bleeding as well as ranibizumab.

What CATT Does Not Tell Us.

Safety signals, of new medicines, especially for relatively uncommon events such as endophthalmitis, stroke or myocardial infarction are notoriously difficult to detect, oftentimes for years following the approval and licensing of a new drug therapy. Examples of this abound, such as the recall of Vioxx®, the black box safety warnings for systemic bevacizumab and rosiglitazone (Avandia®), to name some germane instances.

Fortunately, in this case, we do have access to a large amount of accumulated data concerning both the ocular and systemic safety of ranibizumab, through the pooling of results from many large clinical trials. In fact, stroke has been recognized with a label warning as a legitimate risk of intravitreal ranibizumab therapy, especially if a given patient has been afflicted with prior stroke before undertaking therapy. We do not have this information regarding intravitreal bevacizumab, and, unfortunately, CATT does not put these relevant safety concerns to rest.

Next in the Comparative Effectiveness Research (CER) pipeline is IVAN, and subsequently trials from around the world notably from Australia, France, Germany, Brazil, Norway and the Netherlands are due to report in the coming years. At a minimum these trials should all be brought to completion, regardless of the results of CATT and IVAN, because the accumulated data from these trials will be crucial to a better understanding of the relative safety risks of these two drugs. The accumulated CER clinical trial data of bevacizumab vs. ranibizumab will hopefully make possible a high quality meta-analysis to compare the safety signals mentioned.

Safety concerns are legitimate in the debate about off label use of unproven yet inexpensive and readily available alternatives to proven licensed therapies. Safety comparisons, notwithstanding efficacy similarities, are not yet powerful enough to make conclusions that should alter public policy.

The gold standard for the treatment of “wet” age-related macular degeneration remains intravitreal ranibizumab. Cost savings should not trump safety concerns in ocular disease any more than in cardiac disease.

Source:

AMD Alliance International

View drug information on Avandia; Avastin; Lucentis.

Scientists at Schepens Eye Research Institute have found that people with a certain low level of tear production are more likely to develop chronic dry eye syndrome after LASIK (laser-assisted in situ keratomileusis), laser refractive surgery to correct near- and far-sightedness than those with more plentiful tears. Their research, published in Investigative Ophthalmology and Vision Science, may offer reliable prescreening criteria for ophthalmologists and patients.

“These findings should help ophthalmologists determine if pretreatment is necessary before surgery or if surgery is appropriate at all for an individual,” says Dr. Darlene Dartt, director of the Military Vision Research Program at Schepens Eye Research Institute and the principal investigator of the study.

Dry eye syndrome is one of the most common problems treated by eye physicians. Affecting more than 10 million Americans, it is caused by problems with the tear film responsible for lubricating the eye. While it does not cause vision loss, dry eye syndrome can be painful and severely decrease quality of life for its victims who constantly search for relief with artificial tears and other medications.

LASIK surgery uses small laser cuts to reshape the surface of the cornea, eliminating far-sightedness or near-sightedness, and the need for glasses or contacts. Many people choose LASIK for cosmetic reasons. In recent years, thousands of military personnel have opted for LASIK surgery because it can help them see better and identify objects and people in the field more quickly. It also relieves them of the worry about lost or damaged glasses.

Usually, LASIK causes some dry eye syndrome directly after surgery, but the condition resolves within a few months. In a small number of cases, however, the dry eye condition following LASIK can become chronic and impact functioning of both civilian and military individuals for as long as nine months following surgery.

Dartt and her team were determined to find a way to prescreen for the chronic condition so that surgeons could prepare patients in advance with preventative artificial tears or opt against surgery for some patients.

Dartt and her team evaluated the eyes of 24 patients about to undergo LASIK at the Massachusetts Eye and Ear Infirmary. The patients were given a series of evaluations, including the Schirmer test with and without anesthesia, before and after surgery. Using a piece of paper on the corneal surface, the Schirmer test measures the amount of tears an eye is producing. Study subjects also filled out a dry eye questionnaire indicating their experience with dry eyes pre- and post-operatively.

The team discovered that if a patient had a presurgical tear production value greater than 20 mm of wetting of the Schrimer strip in 5 minutes, they were not likely to develop chronic dry eye syndrome. Patients who produced less tears were more likely to develop long-term dry eye syndrome.

According to Dartt, the next steps for her team include expanding this study to a larger number of individuals and examining patients who have the PRK (photorefractive keratectomy) type of refractive surgery. The PRK has the same goal as LASIK, but the procedures differ. In LASIK a flap of corneal epithelium is cut and lifted to allow the underlying stroma to be shaped by the laser. Then the flap is placed down on the eye. In PRK the corneal epithelium is mechanically removed to allow laser shaping of the stroma. The epithelium then grows back over several days. LASIK and PRK have different side effects.

Authors of the study included Keiko Konomi,1,2,3 Li-Li Chen,1,2,4 Rachel S. Tarko,1 Amy Scally,5 Debra A. Schaumberg,1,2,6; Dimitri Azar,1,2,7 and Darlene A. Dartt1,2

1 Schepens Eye Research Institute, Boston, Massachusetts

2 Department of Ophthalmology, Harvard Medical School, Boston, Massachusetts

5 Massachusetts Eye and Ear Infirmary, Boston, Massachusetts and

6 Division of Preventive Medicine, Brigham and Women’s Hospital, Boston, Massachusetts.

Present affiliations: 3 Department of Ophthalmology, Keio University School of medicine, Tokyo, Japan; 4 Department of Ophthalmology, Tokyo Women’s Medical University, Tokyo, Japan;
7 Department of Ophthalmology and Visual Sciences, University of Illinois at Chicago, Chicago, Illinois.

Schepens Eye Research Institute is an affiliate of Harvard Medical School and the largest independent eye research institute in the nation.

Source: Patti Jacobs

Schepens Eye Research Institute

A new Bluetooth system designed primarily for blind people places a layer of information technology over the real world to tell pedestrians about points of interest along their path as they pass them.

The Talking Points urban orientation system was developed at the University of Michigan. Researchers will present their work at two conferences on Sept. 24.

“Blind people can get from point A to point B. They learn to count steps if they have to, but they miss the journey because they don’t always know what they’re passing. The idea behind Talking Points is to enhance the journey,” said James Knox, adaptive technology coordinator for the University’s Information Technology Central Services and one of the system’s developers.

“Talking Points can be viewed as a first step in the direction of an audio virtual reality designed for people with blindness and very useful to the sighted community as well,” Knox said.

For the sighted community, the system could give passersby a peek at the specials or sales inside a business. It could offer on-the-go access to customer reviews. For blind pedestrians, it could do the same, but it would also fill those gaps in knowledge. Talking Points could help visually-impaired people find public restrooms, police stations, public transportation and restaurants with Braille menus, for example.

“If it caught on, this would be an effective way to tag the whole world,” said Jason Stewart, a master’s student in the School of Information who is involved in the project. “Anyone with a reader could use it to find out more information about where they are.”

Similar systems exist, but Talking Points is the first known to use Bluetooth, cater to both the sighted and the visually-impaired, allow people to operate it entirely with voice commands, and incorporate community-generated content through a website.

Knox and collaborators in the School of Information and the Department of Electrical Engineering and Computer Science created an early version of Talking Points years ago.

A group of master’s students and undergraduates has given the project new energy. They shrunk the receiver and switched the transmitting technology from RFID to the more popular Bluetooth. They are also exploring other technologies such as GPS.

Stewart and fellow School of Information master’s students Jakob Hilden and Michelle Escobar will present papers about Talking Points on Sept. 24. Stewart and Hilden will present at the Ubicomp 2008 conference in South Korea. Escobar will present at the Accessible Design in the Digital World conference in the United Kingdom.

The Talking Points system includes several components:

A mobile device picks up the Bluetooth signals and speaks or displays information to the user. In the future, a cell phone could be the receiver, but this prototype isn’t a phone. It is slightly larger, about the size of a paperback book. If a user wants more information about a beacon, she can tell the device by voice or touch.

Bluetooth beacons, or tags, would be located at points of interest where owners wish to give information to Talking Points users. Businesses could purchase these beacons, which cost less than $20. Cities could tag information centers, parks or other buildings, for example.

A website would allow Talking Points beacon owners to program their tags. They could update their messages regularly. Once a beacon is added, other community members could add their comments about the point of interest. Pedestrians using the system could then choose to get those comments.

“This project enables a type of augmented reality,” said Hilden, one of the students who will present the research at Ubicomp. “It shows how we can take user-generated information from the Internet and lay it over reality to help people make sense of where they are in their environment and what the possibilities are around them.”

In addition to developing a prototype receiver, the students tested their system in field simulations with visually-impaired and sighted people and conducted focus groups.

“Location-based guide systems of one kind or another have been built and re-built by academic researchers for over a decade now, but this is the first project that has really focused on the needs of the visually impaired and gone out to make sure the system is being developed to meet those needs,” said Mark Newman, an assistant professor in the School of Information and the Department of Electrical Engineering and Computer Science. Newman is a co-author of the papers that will be presented.

The students received a $10,000 grant from GROCS 2008 to undertake this project. GROCS stands for Grant Opportunities [Collaborative Spaces], a Digital Media Commons program to fund student research on digital media in collaborative learning.

The Ubicomp paper is called “Accessible Contextual Information for Urban Orientation.” The Accessible Design in the Digital World paper is called “Contextual information system for urban orientation of sighted and non-sighted users.” Authors of both are: School of Information master’s students Stewart, Escobar, Hilden and Kumud Bihani; recent sociology graduate Sara Baumann, as well as Newman, an assistant professor.

Developers of the current prototype software are engineering undergraduates Travis (Donggun) Yoo and Josh Rychlinksi, and recent engineering graduate Peter Kretschman.

Related Links:

Talking Points

School of Information

Mark Newman

Source: Nicole Casal Moore

University of Michigan

Patients seen at private facilities reimbursed by Medicare were more than 550 percent more likely to have routine cataract surgery than those who received their care from the Department of Veterans Affairs, a strong indication that the frequency of cataract surgery may be responsive to financial incentives to either or both the medical facility and the physicians who perform the procedure.

These findings from a large eight-year study are reported in the March 2010 issue of the American Journal of Medical Quality.

The authors are uncertain of the cause of the disparity in cataract surgery given that the vast majority of older veterans are enrolled in both Medicare and the VA health system, both government-funded systems.

“We don’t know yet what exactly accounts for the five and a half fold difference in surgery rates between the two systems. It may be related to how the two systems are funded by the government, it could be a difference between physician-driven decisions or it may be related to a lack of ophthalmologists within the VA system or it could be more than one of these factors,’ said first author Dustin French, Ph.D., Regenstrief Institute investigator and assistant professor of medicine at the Indiana University School of Medicine. Dr. French is a health economist who studies health outcomes.

VA physicians and hospitals do not have the same financial incentives to perform cataract surgery as physicians and medical facilities outside the VA system.

“The results of our study raise important questions about the possible existence of a two-tier, federally funded health-care system that may not be equivalent in terms of quality of care,” said Dr. French, who is also a research scientist with the Center of Excellence on Implementing Evidence Based Practice at the Richard A. Roudebush VA Medical Center.

The authors note that their findings provide ample reason to further investigate the determinants of cataract surgery rates. Nationwide, cataract surgery is the most common surgical procedure performed by ophthalmologists.

In addition to Dr. French, co-authors of “Cataract Surgery Among Veterans 65 Years and Older: Analysis of National Veterans Health Administration Databases” are Curtis E. Margo, M.D., MPH of the University of South Florida’s departments of ophthalmology and pathology; and Robert R. Campbell, J.D., MPH, Ph.D., of the Department of Veterans Affairs. The authors received no financial support for the research and authorship of the study.

Source:
Cindy Fox Aisen
Indiana University School of Medicine

In a world-first breakthrough, University of New South Wales (UNSW) medical researchers have used stem cells cultured on a simple contact lens to restore sight to sufferers of blinding corneal disease.

Sight was significantly improved within weeks of the procedure, which is simple, inexpensive and requires a minimal hospital stay.

The research team from UNSW’s School of Medical Sciences harvested stem cells from patients’ own eyes to rehabilitate the damaged cornea. The stem cells were cultured on a common therapeutic contact lens which was then placed onto the damaged cornea for 10 days, during which the cells were able to re-colonise the damaged eye surface.

While the novel procedure was used to rehabilitate damaged corneas, the researchers say it offers hope to people with a range of blinding eye conditions and could have applications in other organs.

A paper detailing the breakthrough appears in the high-impact journal Transplantation this week.

The trial was conducted on three patients; two with extensive corneal damage resulting from multiple surgeries to remove ocular melanomas, and one with the genetic eye condition aniridia. Other causes of cornea damage can include chemical or thermal burns, bacterial infection and chemotherapy.

“The procedure is totally simple and cheap,” said lead author of the study, UNSW’s Dr Nick Di Girolamo. “Unlike other techniques, it requires no foreign human or animal products, only the patient’s own serum, and is completely non-invasive.

“There’s no suturing, there is no major operation: all that’s involved is harvesting a minute amount – less than a millimeter – of tissue from the ocular surface,” Dr Di Girolamo said.

“If you’re going to be treating these sorts of diseases in third world countries all you need is the surgeon and a lab for cell culture. You don’t need any fancy equipment.”

Because the procedure uses the patient’s own stem cells harvested from their eye, it is ideal for sufferers of unilateral eye disease. However, it also works in patients who have had both eyes damaged, Dr Di Girolamo said.

“One of our patients had aniridia, a congenital condition affecting both eyes. In that case, instead of taking the stem cells from the other cornea, we took them from another part of the eye altogether – the conjunctiva – which also harbours stem cells.

“The stem cells were able to change from the conjunctival phenotype to a corneal phenotype after we put them onto the cornea. That’s the beauty of stem cells,” Dr Di Girolamo said.

The therapeutic contact lens used in the trial was of a type commonly used worldwide after ocular surface surgery. However, of the several brands on the market, only one was suitable for growing the stem cells.

“We don’t know why. It’s probably to do with the components the manufacturers have used in that particular lens,” Dr Di Girolamo said.

The researchers are hopeful the technique can be adapted for use in other parts of the eye, such as the retina, and even in other organs. “If we can do this procedure in the eye, I don’t see why it wouldn’t work in other major organs such as the skin, which behaves in a very similar way to the cornea,” Dr Di Girolamo said.

Dr Di Girolamo’s team included UNSW medical scientists Professor Denis Wakefield and Dr Stephanie Watson.

Source:
Steve Offner

University of New South Wales

The British Contact Lens Association (BCLA) and the General Optical Council (GOC) are today urging Britain’s 3.5 million contact lens wearers not to endanger their eye health and comfort during the recession through risky contact lens practices.

The warning follows a YouGov poll that reveals nearly one in four contact lens wearers would consider switching their contact lens brand to save money, and more than one in ten wearers would consider having less frequent check-ups. One in five would consider wearing the lenses for longer than recommended, such as using monthly lenses for more than a month, to cut costs.

Although, by law, contact lenses can only be supplied following a fitting by a registered eyecare or medical practitioner, recent reports suggest that some contact lens wearers are switching to cheaper lenses without having the new lenses fitted. When lenses are not properly fitted wearers may experience a range of side-effects, from minor discomfort and blurred vision to more serious adverse reactions such as red, inflamed eyes.

Professor Roger Buckley, clinical adviser to the GOC, commented: “In the current economic climate, it’s understandable that contact lens wearers are looking to save money. But without a proper fitting, patients could be putting their eye health and comfort at risk. It’s essential that patients follow the advice of their eyecare practitioner when it comes to contact lens care.”

A contact lens fitting should include an eye examination to make sure your eyes are healthy, and measurements of your eyes to ensure the best lens type, fit and vision. Your practitioner should also advise you when you should wear the lenses, how to look after them and how often they should be replaced. Contact lens wearers should not change their prescribed lens type, wearing schedule, replacement frequency, solutions or care procedures without the recommendation of their eyecare practitioner.

Other examples of high-risk contact lens practices include:

– Wearing a damaged or torn lens instead of replacing it.
– Cutting down on lens cleaning to save on solutions costs.
– Switching to solutions that may not be compatible with the eye or lens
– Sleeping in lenses not suitable for overnight wear to avoid buying solutions.

Source
British Contact Lens Association

The U.S. Food and Drug Administration announced it has approved the Implantable Miniature Telescope (IMT) to improve vision in some patients with end-stage age-related macular degeneration (AMD).

Surgically implanted in one eye, the IMT is a small telescope that replaces the natural lens and provides an image that has been magnified more than two times.

AMD, a condition that mainly affects older people, damages the center of the retina (macula) and results in a loss of vision in the center of the visual field. About 8 million people in the United States have AMD and nearly 2 million of them already have significant vision loss, according to the National Eye Institute. AMD can make it difficult or impossible to recognize faces or perform daily tasks such as reading or watching television.

“This innovation has the potential to provide many people with an improved quality of life,” said Jeffrey Shuren, M.D., J.D., director of the FDA’s Center for Devices and Radiological Health.

The IMT is available in two models: one that provides 2.2 times magnification and another 2.7 times magnification. The IMT is designed to magnify and project images onto a healthy portion of the retina. The IMT is intended to be implanted in only one eye; the non-implanted eye is used for peripheral vision.

The IMT is used in patients ages 75 years and older with stable severe to profound vision impairment (when vision impairment has not changed over time) caused by blind spots (bilateral central scotoma) associated with end-stage AMD. These patients also have evidence of a visually significant cataract.

Patients agree to undergo training with an external telescope with a low vision specialist prior to implantation to determine whether adequate improvement in vision with the external telescope can be obtained and to verify if the patient has adequate peripheral vision in the eye that would not be implanted. Patients also agree to participate in a post-operative visual training program.

In a 219-patient, multi-center clinical study of the IMT, 90 percent of patients achieved at least a 2-line gain in either their distance or best-corrected visual acuity, and 75 percent of patients improved their level of vision from severe or profound impairment to moderate impairment.

Because the IMT is a large device, implantation can lead to extensive loss of corneal endothelial cells (ECD), the layer of cells essential for maintaining the clarity of the cornea, and chronic endothelial cell loss. The chronic rate of endothelial cell loss is about 5 percent per year. Significant losses in ECD may lead to corneal edema, corneal decompensation, and the need for corneal transplant. In the study, 10 eyes had unresolved corneal edema, with five resulting in corneal transplants. The calculated five-year risk for unresolved corneal edema, corneal decompensation, and corneal transplant are 9.2 percent, 6.8 percent and 4.1 percent, respectively.

To ensure that the risks of IMT implantation are sufficiently and consistently communicated to patients, the FDA and the manufacturer created detailed labeling, including an Acceptance of Risk and Informed Decision Agreement, which patients must complete prior to IMT implantation. The agreement provides a guide for patients and their physicians to discuss the risks associated with IMT implantation. Patients should be given adequate time to review all of the information regarding the IMT.

As a condition of FDA approval, the manufacturer, VisionCare Ophthalmic Technologies Inc. of Saratoga, Calif., must conduct two post-approval studies. In one study, VisionCare must continue follow-up on the subjects from its long-term follow-up cohort for an additional two years. Another study of 770 newly enrolled subjects will include an evaluation of the endothelial cell density and related adverse events for five years after implantation.

Source: U.S. Food and Drug Administration

The popular dietary supplement vitamin E, loaded into special medicated contact lenses, can keep glaucoma medicine near the eye – where it can treat that common disease – almost 100 times longer than possible with current commercial lenses, scientists have reported.

In a presentation at the 239th National Meeting of the American Chemical Society (ACS), they described use of vitamin E to develop contact lenses that may deliver more medication for glaucoma and perhaps other diseases to the eye.

Anuj Chauhan, Ph.D., who headed the research team, explained that glaucoma is second only to cataracts as the leading cause of vision loss and blindness in the world. It affects almost 67 million people. Eye drops that relieve the abnormal build-up of pressure inside the eye that occurs in glaucoma, are a mainstay treatment.

“The problem is within about two to five minutes of putting drops in the eye, tears carry the drug away and it doesn’t reach the targeted tissue,” said Chauhan, who is with the University of Florida in Gainesville. “Much of the medicine gets absorbed into the bloodstream, which carries it throughout the body where it could cause side effects. Only about one to five percent of drugs in eye drops actually reach the cornea of the eye.”

Chauhan and colleagues have developed a new extended-release delivery approach incorporating vitamin E into contact lenses. The invisible clusters, or aggregates, of vitamin E molecules form what Chauhan describes as “transport barriers.” that slow down the elusion of the glaucoma medication from the lens into the eye. The drug released from the lens into the eye stays in the tears far longer than the 2-5 minutes with eye drops, leading to more effective therapy.

“These vitamin structures are like ‘nano-bricks’,” Chauhan said. “The drug molecules can’t go through the vitamin E. They must go around it. Because the nanobricks are so much bigger than the drug molecules – we believe about a few hundred times bigger – the molecules get diverted and must travel a longer path. This increases the duration of the drug release from the lenses.”

In research with laboratory animals, the lenses containing vitamin E nanobricks administered drugs up to 100 times longer than most commercial lenses. The lenses could be designed for continuous wear for up to a month, Chauhan said. In addition to treating glaucoma, the contacts could help other eye conditions, such as cataract and dry eye. Cataract is a clouding of the lens of the eye, and dry eye involves decreased production of tears. It affects about 2 in 10 people and can lead to more severe eye problems.

“Vitamin E is a proven nutraceutical that in small amounts is good for the eye because of its ant-oxidant properties. Also Vitamin E presence in the contact lenses blocks UV radiation, leading to increased protection against the UV light. Our research has shown that the vitamin can be loaded into the lenses without any reduction in transparency. We believe it could be helpful in disease treatment and in prevention as well,” he said.

Chauhan said that clinical trials of the new lenses could begin within a year to 2 years.

Excerpt from Chauhan’s ACS presentation:


We have developed a novel approach of extending the duration of drug release from contact lenses by including nanosized aggregates of Vitamin E in the lenses. The Vitamin E nano-aggregates force the drug molecules to travel in a tortuous path leading to increased drug release durations. Another benefit of Vitamin E incorporation is that Vitamin E is known to be an anti-oxidant, whose slow release from lenses could also help in prevention of ophthalmic diseases like cataract and glaucoma. Furthermore, Vitamin E blocks UV radiation, leading to reduced ocular damage from the UV light. Our research has shown that Vitamin E can be loaded into the lenses without any reduction in transparency. The drug release durations from Vitamin E loaded lenses are about 100 times longer than from commercial lenses for several ophthalmic drugs including glaucoma drug timolol, anti-inflammatory drug dexamethasone, and anti-viral drug flucanozole. Thus, Vitamin E loaded lenses could be highly effective in synergistic prevention and treatment of ophthalmic diseases through extended delivery of the desired drugs and the nutraceutical Vitamin E. Animal studies in beagle dogs are ongoing to explore glaucoma treatment through Vitamin E laden contact lenses.

Source:
Michael Bernstein

American Chemical Society

Movements in space create in humans and animals so-called optical flow fields which are characteristic for the movement in question. In a forward movement, the objects flow by laterally, objects at the front increase in size and objects further away hardly change at all. At a higher level in the visual centre in the brain, there must be a computation of the visual information, so that animals can differentiate between their own movement and movement of their environment and are able to correct their course if necessary. It is important for the analysis of flow fields that the movement information from both eyes is merged so that the whole flow field can be assessed. In their current study, Karl Farrow, Jurgen Haag and Alexander Borst have for the first time proved the direct link between two nerve cells, one in each half of the brain, combining the movement signals from both the facetted eyes of a fly.

In the blow fly, the nerve cells that analyse optical flow fields, called tangential cells, are located in the lobula plate. There are only 60 of these tangential cells for each half of the brain and each of these 60 cells can be identified individually. The scientists in Martinsried have looked closely at one cell, the H2 cell. This cell exhibits a strong preference for rotational flow fields such as that which arises when the fly turns around its body’s vertical axis. Interestingly, this cell seems initially to react only to the movements in front of its own eye (ipsilateral), but remain blind to movements in front of the other eye (contralateral). However, if the ipsilateral movement stimuli are combined with the contralateral, it is seen that the latter do indeed modulate the reactions to ipsilateral movement stimuli. “The preference of the H2 cell for rotational stimuli is due to a non-linear coordination of the movement stimuli from both eyes, and it was this non-linearity that we wanted to investigate further,” said Alexander Borst.

The next step was to analyse the circuit diagram of the tangential cells of the lobula plate in detail. This was based on a multitude of experiments in which the connections between the cells within one lobular plate and those between the two hemispheres were examined. In the end it turned out that there were two ways in which movement information from one half of the brain could reach the H2 cell in the other: firstly, directly from the so-called HSE cell, which is electrically linked to the H2 cell in the opposite hemisphere and secondly, indirectly via the CH cell, which receives information via several intermediate stops from the other half of the brain and which inhibits the H2 cell on the same side with chemical synapses. Both connections were in principle suitable for achieving the effect described; however the question remained: which of the two is the crucial one?

The Max Planck scientists therefore blocked the two possible routes selectively with laser ablation (the cell is filled with fluorescent dye which has a toxic effect when strongly stimulated) and tested sensitivity to rotation in the H2 cell. A long series of these technically very difficult experiments provided unambiguous proof: if the ipsilateral CH cell was destroyed, no effect was seen on the rotation sensitivity of the H2 cell. However, if the contralateral HSE cell was removed from the circuit, the rotation sensitivity of the H2 cell disappeared. It was blind to the movement stimuli in front of the other eye, irrespective of whether it was combined with the ipsilateral movement stimuli.

Alexander Borst enthused about the discovery: “The genius of this circuitry is in its simplicity: with a single electrical link between two cells from the halves of the brain, one cell is selective for rotation flow fields.” Whether nature has constructed similarly simple mechanisms in mammals is still unclear – the circuitry of the nerve cells in the relevant areas in the cerebral cortex has not yet been sufficiently explained to allow experiments of this nature to be carried out. And it is rather doubtful whether removing a single cell from the many billions of cells in the cerebral cortex would have an effect.

Clearly, however, this does not mean that the findings made by the fly researchers in Martinsried will be without consequence for other areas of science. For example, engineers developing navigating robots and driving assistance systems rely on simple and robust algorithms such as those realized by nature in insects. The mechanisms of optical flow field analysis are supremely suitable for technical implementation. As part of two projects supported by the Federal Ministry for Education and Research (the Bernstein Center in Munich and “Cognition in Technical Systems” (CoTeSys)) the neurobiologists in Martinsried, in collaboration with their colleagues from the Technical University in Munich, will be working more intensively on this area over the next few years. The Neuronal Information Processing department under the leadership of Alexander Borst has recently participated in the graduate training program “School of Systemic Neurosciences” at the Ludwig Maximilian University in Munich.

Original work:

Karl Farrow, Jurgen Haag & Alexander Borst
Nonlinear, binocular interactions underlying flow field selectivity of a motion-sensitive neuron
Nature Neuroscience, October 10, 2006

Contact: Eva Diehl

Max-Planck-Gesellschaft