Month: June 2014

Research to Prevent Blindness (RPB), a New York-based foundation and the world’s leading voluntary health organization supporting eye research, awarded 81 grants, totaling more than $7.9 million in 2005.

“RPB remains committed to fueling the vision research engine that we, in our earlier years, helped to build in departments of ophthalmology across the country,” said Diane S. Swift, President, RPB. “Basic and clinical researchers, at every stage of their careers, continue to make significant inroads into the understanding, prevention, treatment and eventual cures of all diseases of the human visual system. Recent breakthroughs in uncovering the genetic origins and molecular mechanisms of vision loss give us all reason to hope that we can more effectively help the increasing number of people suffering from these conditions.”

Across the nation, RPB-supported laboratories investigate the entire spectrum of eye disease, from cataracts, glaucoma, and diabetic retinopathy to macular degeneration, retinitis pigmentosa and eye movement disorders. The 2005 RPB awards include research grants to departments of ophthalmology at 46 medical schools throughout the United States, plus individual awards such as the Lew R. Wasserman Merit Award, Research Professorships, and Senior Scientific Investigator, Physician-Scientist and Career Development Awards. A total of 174 individual ophthalmic scientists received RPB grant support in 2005. A total of 54 departments of ophthalmology at U.S. medical schools are currently receiving RPB support.

Since it was founded in 1960, RPB has channeled more than $240 million to medical institutions throughout the United States. As a result, RPB has been identified with nearly every major breakthrough in eye research in that time, including the development of laser surgery now used to treat diabetic retinopathy, glaucoma, macular degeneration, myopia, retinal detachment and astigmatism.

RPB’s comprehensive grants program operates with economy and efficiency. Historically, 81% of RPB expenditures have gone directly for eye research.

Matthew Levine
mlevinerpbusa
Research to Prevent Blindness
www.rpbusa

OPKO Health, Inc. (Amex: OPK) announced that a study published in the peer-reviewed journal
Molecular Vision demonstrates that bevasiranib, its siRNA (small
interfering RNA) agent is distributed throughout the eye, including
extensive uptake into the retina. In two tissue distribution and
pharmacokinetic studies in rabbits, results showed that bevasiranib was
present in the retina and in targeted retinal pigment epithelium (RPE)
cells following intravitreal injection. Bevasiranib is a gene-silencing
agent designed to shut down the production of vascular endothelial growth
factor (VEGF), a primary cause of the new blood vessel growth, or
neovascularization, associated with vision loss in patients with wet
age-related macular degeneration, or wet AMD. The efficacy and safety of
bevasiranib are currently being assessed in the COBALT study, an
international Phase III trial for the treatment of wet AMD.

“Importantly, these data indicate that following intravitreal
injection, bevasiranib distributes to the ocular structures relevant to the
VEGF-induced neovascularization associated with vision loss in wet AMD, and
we believe this animal data provides support for the use of bevasiranib in
our ongoing pivotal Phase III trial for the treatment of wet AMD,” said
Samuel Reich, Executive Vice President of OPKO Ophthalmics. “It is
noteworthy that bevasiranib was distributed to the RPE cells, since we
believe that even a fraction of the tissue-associated bevasiranib entering
the RPE cell is likely to be effective in specifically suppressing VEGF
production.”

“Ocular biodistribution of bevasiranib following a single intravitreal
injection to rabbit eyes,” NS Dejneka, S Wan, OS Bond, DJ Kornbrust, SJ
Reich, Molecular Vision, Volume 14, May 28, 2008

About OPKO Health, Inc.

Miami-based OPKO is a specialty healthcare company. Its lead
investigational drug, the pioneering gene silencing agent bevasiranib, has
entered a pivotal Phase III trial after successfully completing Phase II
trials for wet age-related macular degeneration and diabetic macular edema.
OPKO is developing a preclinical pipeline of novel agents for ophthalmic
diseases, and it markets innovative diagnostic imaging systems that
complement the company’s therapeutic products. For more information visit
the company’s website at opko.

This press release contains “forward-looking statements,” as that term
is defined under the Private Securities Litigation Reform Act of 1995
(PSLRA), which statements may be identified by words such as “expects,”
“plans,” “projects,” “will,” “may,” “anticipates,” “believes,” “should,”
“intends,” “estimates,” and other words of similar meaning, including
statements regarding the potential benefits and effectiveness of
bevasiranib in suppressing the production of VEGF and reducing ocular
neovascularization, our ability to establish OPKO’s leadership position,
our ability to aggressively engage in R&D activities and advance clinical
testing of bevasiranib and our ability to develop a preclinical pipeline of
novel agents for ophthalmic diseases, as well as other non-historical
statements about our expectations, beliefs or intentions regarding our
business, technologies and products, financial condition, strategies or
prospects. Many factors could cause our actual activities or results to
differ materially from the activities and results anticipated in
forward-looking statements. These factors include those factors described
in our filings with the Securities and Exchange Commission, as well as
risks inherent in funding, developing and obtaining regulatory approvals of
new, commercially-viable and competitive products and treatments, including
the risks that enrollment of patients for the Phase III clinical trial for
bevasiranib, may not be successful, that the Phase III clinical trial
itself may not be completed on a timely basis or at all, that any of our
compounds under development, including bevasiranib, may fail, may not
achieve the expected results or effectiveness and may not generate data
that would support the approval or marketing of products for the
indications being studied or for other indications. In addition,
forward-looking statements may also be adversely affected by general market
factors, competitive product development, product availability, federal and
state regulations and legislation, the regulatory process for new products
and indications, manufacturing issues that may arise, patent positions and
litigation, among other factors. The forward-looking statements contained
in this press release speak only as of the date the statements were made,
and we do not undertake any obligation to update forward-looking
statements. We intend that all forward-looking statements be subject to the
safe-harbor provisions of the PSLRA.

OPKO Health, Inc.
opko

1. Broccoli and the Blood Brain Barrier
Jing Zhao, Anthony N. Moore, John B. Redell, and Pramod K. Dash

As if there weren’t enough reasons to eat your vegetables, this week Zhao et al. report that a substance in broccoli helps to maintain the integrity of the blood-brain barrier (BBB) following a cortical contusion injury. Systemic administration of sulforaphane, contained in broccoli and other cruciferous vegetables, increased activity of NF-E2-related factor-2 (Nrf2). Nrf2 binds to the antioxidant response element (ARE), influencing expression of so-called cytoprotective proteins. Sulforaphane treatment of uninjured and brain-injured rats increased cortical expression of Nrf2-driven genes. Infusion of NR decoy oligonucleotides containing the ARE binding site for Nrf2 prevented sulforaphane-induced, Nrf2-driven gene expression. Tight junction proteins are key to maintaining BBB integrity, and they decline after brain injury. Sulforaphane attenuated the loss of these proteins as well as the loss of endothelial cells and also reduced the injury-related increase in BBB permeability and brain edema. OK, OK, pass the broccoli.

2. Nuclear Position and Neurogenesis in the Retina
Lisa M. Baye and Brian A. Link

Proliferating cells of the developing retina divide either symmetrically into two daughter cells that remain proliferative or neurogenically with at least one of the daughter cells exiting the cell cycle to become a postmitotic neuron. This week, Baye and Link took a close look at interkinetic nuclear migration, the apical-basal movements of progenitor cell nuclei. The authors tracked nuclear movements in zebrafish retinal neuroepithelial cells. As expected, nuclear position was apical in cells during M-phase, but varied in G1- or S-phase. Progenitor cells varied in total cell cycle period, basal-most nuclear position, and time spent in that position. To watch nuclear movements of single cells, the authors used time-lapse confocal images of transgenic zebrafish in which GFP was expressed at cell cycle exit. The nuclei of cells that produced postmitotic neurons showed greater maximum basal migration and shorter cell cycle periods.

3. Feature Maps in the Ferret Visual Cortex
Brandon J. Farley, Hongbo Yu, Dezhe Jin, and Mriganka Sur

Neurons of the visual cortex are organized into multiple feature maps according to parameters including receptive field, ocular dominance, orientation selectivity, and spatial frequency. Each of these complex maps is spatially interrelated, but it is unclear what guides the development of these relationships. Experimental and modeling data point to a dimension-reduction system in which feature maps obey the principles of continuity and uniform coverage. This week, Farley et al. removed the ocular dominance map from the equation by removing sensory input from one eye of newborn ferrets. They reasoned that if the maps were interdependent, removal of the ocular dominance map would affect the shape and relatedness of the other maps. Indeed, modeling of a three-feature as opposed to a four-feature map predicted these shifts. In vivo optical imaging showed that enucleation eliminated the ocular dominance map but not orientation or spatial frequency maps. However, the structure and spatial relationships of the remaining maps was altered.

4. PARP Activity and Photoreceptor Death in the rd1 Mouse
Fran?�ois Paquet-Durand, Jos?� Silva, Tanuja Talukdar, Leif E. Johnson, Seifollah Azadi, Theo van Veen, Marius Ueffing, Stefanie M. Hauck, and Per A. R. Ekstr?�m

Retinitis pigmentosa (RP) is a general term for photoreceptor neurodegeneration that results from any of > 100 genetic mutations. This week, Paquet-Durand et al. make a case for poly(ADP-ribose) polymerase (PARP) in the photoreceptor cell death. In the rd1 mouse model of RP, a loss-of-function mutation in phosphodiesterase 6 (PDE6-??) leads to cGMP accumulation and excessive calcium entry through cGMP-gated channels. PARP normally kick-starts DNA repair, but overactive PARP may promote cell death. Although PARP expression was similar in rd1 and wild-type mouse retinas, activated PARP and its by-product PAR were elevated considerably in rd1 mice by postnatal day 11. Apoptotic markers revealed a cell-death pattern that matched the central-to-peripheral retinal gradient of PARP activity. Some cells with elevated PARP activity also displayed signs of DNA damage and expression of apoptosis inducing factor. In retinal explants, a PARP inhibitor reduced PARP activity and the ensuing photoreceptor cell death.

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Source: Sara Harris

Society for Neuroscience

The American Academy of Ophthalmology has joined the Blinded Veterans Association (BVA) and other veteran’s service organizations in support of legislation that would establish a Center of Excellence within the Department of Defense (DoD) to improve the tracking, diagnosis, treatment and follow-up for service members who have incurred eye injuries while serving on active duty. The “Military Eye Trauma Treatment Act of 2007,” (H.R. 3558) introduced in the House today by Rep. John Boozman, R-Ark., would also create a formal registry that would house electronic records and enable the DoD and Department of Veterans Affairs (VA) to share patient information. The Academy worked closely with the BVA, ophthalmology leaders in the DoD and VA, and members of Congress to draft this important legislation.

This legislation would require ophthalmologists in the DoD to report surgeries or other procedures to the registry within 30 days. Information relating to additional treatments, surgical procedures, and eventual visual outcomes would be accessible by the DoD ophthalmologist who initially treated the patient as well as any future ophthalmologist in the VA. The Walter Reed Army Medical Center in Washington, D.C., is a potential location for the Center.

Between October 2001 and June 2006, more than 1,000 service members with combat eye trauma were evacuated from military operations overseas; with no official mechanism to document or track these injuries, resulting in transition problems. This legislation would provide a record of eye injuries and streamline services by alleviating administrative errors such as record transfer duplications and effectively identifying eye injuries during the crucial period when soldiers under treatment are in transition from the DoD to the VA.

“The Academy’s efforts as this legislation was drafted once again demonstrates our commitment to ensuring that our soldiers and our veterans are provided with excellent eye care and resources” said Michael X. Repka, MD, the Academy’s federal affairs secretary. “This legislation will create an invaluable resource for ophthalmologists working in the armed forces and those that will ultimately treat these patients in the VA.”

U.S. veterans seeking information on eye care and where to get it are encouraged to visit Academy-sponsored Web site. VeteransEyeCare.

The American Academy of Ophthalmology is the voice for ophthalmologists and their patients in Washington D.C., and is the world’s largest organization of eye physicians and surgeons, with more than 27,000 members.

aao

An international research collaboration including research teams from the Children’s Hospital in Boston (USA), King’s College London and the Peninsula Medical School, has identified a gene that, when mutated, causes Duane syndrome.

The research is published in the latest edition of Science.

Duane syndrome is a congenital eye movement disorder that causes eye muscles to contract and relax when they should not. It develops in the womb where it affects nerve growth in the eye. Sufferers of the syndrome have limited eye movement sideways towards the ear or nose. When the eye moves towards the nose the eyeball pulls into the socket, closing the eyelids and sometimes forcing the eye movement up or down.

Duane syndrome usually causes vision problems. It can be accompanied by malformations of the skeleton, eyes, ears, kidneys and nervous system but more commonly occurs in isolation.

Most sufferers of the condition are diagnosed by the age of 10. It is more prevalent in women and in the left eye. It is believed to affect around half a million people worldwide.

Until now, scientists have been unable to pinpoint a genetic mutation that causes isolated Duane syndrome. By isolating the gene from affected families, the research team introduced the mutation into chick embryos (which have a visual system very similar to that of humans) and produced similar defects in nerve growth.

Dr. John Chilton, RCUK Academic Fellow in Clinical Neuroscience and Molecular Biology at the Peninsula Medical School, commented: “By understanding how this gene causes Duane syndrome, we can begin to achieve a wider understanding of how the visual system develops in the womb. This raises the possibility of better diagnosis and even genetic treatments for visual conditions such as Duane syndrome’.”

He added: “We also discovered that the gene responsible for Duane syndrome is widely expressed throughout the nervous system, so the next question to be answered is why only the nerves that control the eye muscles are affected.”

The international research collaboration includes Dr. Elizabeth Engle at the Children’s Hospital in Boston, USA; Dr. Chilton at the Peninsula Medical School (PMS); Dr. Nick Gutowski, Professor Sian Ellard and Dr. Beth Young at both PMS and the Royal Devon and Exeter Hospital; Professor Sarah Guthrie at King’s College London.

Case Study

Ami Ryder, aged 8 from West Park, Plymouth, UK, was diagnosed with Duane syndrome as a small baby at the Royal Eye Infirmary, Plymouth Hospitals NHS Trust.

Since then Ami, who is a pupil at Knowle Primary School, has undergone a series of treatments at the Royal Eye Infirmary for type B Duane syndrome in her left eye. Although Ami does not have a full range of eye movement, she turns her head to maintain vision and it has not stopped her enjoying skipping and football.

Her doctors say she is doing very well and, at age 8, her vision is not likely to deteriorate any further.

Her mum, Sarah Ryder, said: “Ami is great, she just gets on with it and thinks it is actually quite funny. It certainly hasn’t stopped her enjoying all the activities that every little girl of her age enjoys.”

Sarah continued: “We are very pleased with her treatment and we are delighted to have been told that there will be no lasting damage to her eyesight. She has taken the regular visits to hospital in her stride, and she has now been told that all she needs is one final examination and that’s it.”

Lizzy Padgett, Head Orthoptist at the Royal Eye Infirmary, commented: “Although the eye muscle balance of patient’s with Duane syndrome is affected in such a way that the patient does not have the full range of eye movement, the majority of patients are in fact often asymptomatic and control any squint by turning their head to maintain binocular vision. The concern with children who have a squint due to Duane syndrome is the risk of developing amblyopia (where the brain favours one eye over the other), but this is usually treatable during childhood.”

She added: “The breakthrough made by colleagues at the Peninsula Medical School and their research partners in the US and UK is extremely welcome and should lead to more advances in our knowledge of how the eye and visual system develops.”

The Peninsula Medical School is a joint entity of the University of Exeter, the University of Plymouth and the NHS in the South West of England, and a partner of the Combined Universities in Cornwall. The Peninsula Medical School has created for itself an excellent national and international reputation for groundbreaking research in the areas of diabetes and obesity, neurological disease, child development and ageing, clinical education and health technology assessment.

Source: Andrew Gould

The Peninsula College of Medicine and Dentistry

Columbia University Medical Center’s Department of Ophthalmology announces the opening of its new comprehensive eye care center in midtown Manhattan, the Gloria and Louis Flanzer Vision Care Center. Occupying the entire second floor of 880 Third Avenue at East 53rd Street, the new site will offer patients expert care in a beautiful and spacious setting, equipped with the latest in diagnostic and treatment technologies.

The new center is funded by Gloria and Louis Flanzer, a gift from Robert L. Burch III, and donations from other supporters.

“We are pleased to bring academic medical center-based eye care treatment to the midtown Manhattan area in a comprehensive vision care center,” said Stanley Chang, M.D., the Edward S. Harkness Professor of Ophthalmology, and chair of the Department of Ophthalmology, Columbia University Medical Center. “In today’s rapid-paced lifestyle, we recognize that people have limited time for health checkups and other physician visits, so this location meets the needs of those who live and work in midtown, as a complement to our primary location in Washington Heights in Upper Manhattan.”

“The Gloria and Louis Flanzer Vision Care Center will increase access for all patients to the outstanding clinical services of the Columbia University ophthalmology faculty,” said Lee Goldman, M.D., executive vice president and dean of the Faculties of Health Sciences and Medicine at Columbia University Medical Center. “The availability of linked specialty care and an enhanced diagnostics program will provide efficient, high-quality care for all patients, those who live in the New York metropolitan region and those who come from other parts of the United States and foreign countries.”

The new center consolidates and expands Columbia’s several ophthalmology practices located around midtown into one location and will give patients access to general ophthalmologists and specialists, who focus on cornea, cataract, glaucoma, oculoplastics (rebuilding the eye following major trauma or tumors), and retina diagnosis and treatment.

This comprehensive center will provide many conveniences for patients, in terms of efficiencies of care and scheduling referrals for follow-up treatment, expanded access to clinical trials in a modern, easily accessible location.

Ophthalmic examinations, consultative services, and eye surgeries, which are best conducted in a hospital setting, will continue to be provided at Columbia University Medical Center’s primary location in Washington Heights.

Columbia University Department of Ophthalmology is an established leader in the study and practice of ophthalmologic medicine. Its research, educational and clinical care programs have helped define the standard of care offered to individuals affected by vision disorders across the country and across the world. Since its founding in 1933, it has been recognized as a center of excellence for vision care and research.

Columbia University Medical Center provides international leadership in basic, pre-clinical and clinical research, in medical and health sciences education, and in patient care. The medical center trains future leaders and includes the dedicated work of many physicians, scientists, public health professionals, dentists, and nurses at the College of Physicians and Surgeons, the Mailman School of Public Health, the College of Dental Medicine, the School of Nursing, the biomedical departments of the Graduate School of Arts and Sciences, and allied research centers and institutions. Established in 1767, Columbia’s College of Physicians and Surgeons was the first institution in the country to grant the M.D. degree and is now among the most selective medical schools in the country. Columbia University Medical Center is home to the most comprehensive medical research enterprise in New York City and State and one of the largest in the United States. Columbia University Medical Center is affiliated with NewYork-Presbyterian Hospital, the nation’s largest not-for-profit hospital provider.

Source: Columbia University Medical Center

When the idea appeared several years ago, it sounded persuasive: How about implanting electrodes at the defective retina of blind subjects and connecting them with a mini camera in order to re-establish vision.

However, the first clinical tests yielded quite sobering results: Following the surgery, the patients could not even distinguish simple shapes. Neural computation scientists at Bonn University will introduce a software system at the Hanover Fair that is hoped to change this: with the aid of this software, the visual prosthesis “learns” to generate exactly those signals, which are expected and can be interpreted by the brain. The learning visual prosthesis will be exhibited between April 16th and April 20th at the community booth of the Science Region Bonn (hall 2, booth D35).

Nearly two dozens of patients in Germany and the U.S. have so far been implanted with a visual prosthesis. For this purpose, clinicians open the eye ball and attach a thin foil at the retina. Small protruding contacts reach neurons, which form the ganglion cell layer of the retina. These electrical stimulation contacts feed camera signals into the optic nerve. The camera may be attached to a frame of glasses and transmits its signals in a wireless fashion to the implant.

Currently, the results do not meet the high expectations. “The camera generates electrical signals, which are almost useless for the brain,” comments Rolf Eckmiller, a professor at the Department of Computer Science at Bonn University. “Our own system translates the camera signals into a language, which the central visual system in the brain understands”. Unfortunately, the central visual system of each individual speaks a different dialect; this poses a difficulty for the translator function. For this reason, the computer- and neural scientist developed the “Retina Encoder” together with his graduate students Oliver Baruth and Rolf Schatten. At the Hanover Fair he is looking for commercial partners for the next step into clinical trials.

Translator in the Spectacles

“In principle, the Retina Encoder is a computer program that converts the camera signals and forwards them to the retinal implant,” explains Oliver Baruth the function. “The encoder learns in a continuous process how to change the camera output signal so that the respective patient can perceive the image.” Currently, tests of the learning dialog process are being performed with normally sighted volunteers. The camera images are translated by the Retina Encoder and subsequently forwarded to a kind of “virtual central visual system.” This simulation mimics the brain function for the interpretation of the converted camera data.

Initially, the Retina Encoder does not know which language the virtual central visual system speaks. Therefore the software translates the original picture – for example a ring – in different, randomly selected “dialects”. This way, variations of the picture emerge, which are more or less similar to a ring. The volunteer sees these variations on a small screen that is integrated in a frame of glasses. By means of head movements, the person selects those variations that appear most similar to a ring. From these choices, the learning software draws conclusions how to improve the translation. In the next learning cycle, several new picture variations are being presented, which look already more similar to the original: during this process, the Retina Encoder becomes adapted step-by-step to the language of the virtual central visual system. In the current tests it works very well; however, the scientists have not yet tested their system in patients. The scientists emphasize that in principle, the Retina Encoder could be integrated in implanted visual prostheses within a few months.

In normally sighted humans, a kind of natural Retina Encoder is already integrated in the retina: specifically, four layers of nerve cells are positioned in front of the photoreceptor cells. “The retina is a transparent biocomputer,” Eckmiller says. “It transforms the electrical signals of rod and cone photoreceptors into a complex signal.” This signal reaches the brain via the optic nerve.

Don’t expect Miracles

In the brain, the complex information is being decoded. The brain acquires the corresponding ability within the first months of life. During this time, the central visual system becomes individually adjusted to the retinal signals: the brain learns how to interpret the data from the optic nerve. In adults, however, who become blind later in life, the central visual system is already matured: it is not able anymore to change easily. “If the central visual system is not as flexible anymore, the artificial retina has to be,” Eckmiller points out. “The artificial retina must learn to generate signals that are useful for the brain. And exactly this learning ability distinguishes our Retina Encoder”.

Nevertheless, he warns against too high expectations,” Nobody should think that one could read again ones favorite detective stories with a visual prosthesis. One may perhaps be able to recognize the ‘Gestalt’ of larger objects and to perceive contours; a higher vision quality can not be expected in the near future. However, for a blind subject this represents a major improvement. He will be able to orient himself again in his environment. This gain in independence is our goal!”

Contact: Rolf Eckmiller

University of Bonn

German researcher Claus Cursiefen, MD, also affiliated with Harvard School of Medicine, reports good results with a surgical strategy that uses a single donor cornea to help two patients with differing corneal diseases. In the United States keeping pace with demand for donated corneal tissue for use in transplant surgery is a cause for concern, while in Europe and Asia shortages lead to treatment delays. Dr. Cursiefen’s new approach restored good vision to patients who had Fuchs’ dystrophy (degeneration of certain corneal cells) or keratoconus (thin, cone-shaped cornea) while also addressing the supply problem. The study appears in February’s Ophthalmology, the journal of the American Academy of Ophthalmology.

Advanced keratoconus (and other diseases of the anterior portion of the cornea) is often treated with a surgery called deep anterior lamellar keratoplasty (DALK). Fuchs’ dystrophy and similar diseases can be treated via several surgical techniques, including the recently developed Descemet’s membrane endothelial keratoplasty (DMEK). Dr. Cursiefen and his colleagues noted that, once the tissues needed for DALK were removed from a donor cornea, the precise tissues needed for DMEK remained. They reasoned that scheduling two patients for surgery on the same day, with the DALK patient always scheduled first, would make it possible to use one cornea for two patients. Since about 80 percent of the cornea diseases that require transplants can be treated with DALK or DMEK, this approach might potentially nearly double the available corneal tissue supply and make timely treatment available to many more patients.

“In this exploratory study, we were able to use one cornea to successfully treat two patients, for 10 of 12 consecutive donor corneas,” Dr. Cursiefen said. “Only twice during surgery did we find that a full corneal transplant, rather than DALK, was needed. Our early follow-up with all patients shows good visual outcomes and few complications,” he added.

At their six-month follow up, successful DALK patients achieved, on average, 20/35 vision, and DMEK patients achieved 20/31 vision, on average. The two patients scheduled for DALK who instead received full transplants achieved 20/50 vision, on average. All surgeries were performed at the University Eye Hospital, Friedrich-Alexander University Erlangen-Nurnberg, Germany, in 2009.

Drawbacks of this approach are that both DALK and DMEK are demanding surgeries that at present can only be performed at leading-edge ophthalmic hospitals, and, because both techniques are relatively new, longer-term outcomes and effectiveness remain to be determined. Also preparation and care of the split corneas requires sophisticated planning and preparation, and access to additional corneas is essential in case full transplants becomes necessary. Further research will determine whether the approach will be widely accepted.

Source:

American Academy of Ophthalmology

The New Zealand Branch of the Royal Australian and New Zealand College of Ophthalmologists (RANZCO) has expressed concern about recently highlighted shortages of ophthalmologists in Dunedin and elsewhere in New Zealand.

There are currently 16 unfilled public hospital vacancies nationally for ophthalmologists, says RANZCO NZ Chairman Dr Jim Stewart, who is attending the Pan Professional Medical Forum Workforce Summit today.

“This national shortage of ophthalmologists is not due to a reduction in the numbers of specialists being trained, except temporarily in Dunedin where trainee numbers have had to be reduced because of the shortage of consultant ophthalmologists,” he said.

“The College wishes to establish more training posts and has done the preparatory work for this, but new positions are dependant on the funding of salaries, and provision of clinic space and operating theatre time in our public hospitals.

“We have a steady loss of New Zealand-trained ophthalmologists to Australia, where they can earn twice as much,” he said. “For instance, there have been recent departures from Auckland, Palmerston North and Timaru.”

nzma.nz
ranzco.edu

Resolvyx Pharmaceuticals, Inc., the leading resolvin therapeutics company, announced positive data from a Phase 2 clinical study evaluating RX-10045, a resolvin administered as a topical eye drop for the treatment of patients with chronic dry eye syndrome. In this 28-day, randomized, placebo-controlled, 232-patient trial, RX-10045 produced dose-dependent, statistically significant improvement on the primary endpoints for both the signs and symptoms of dry eye, and was generally shown to be safe and well tolerated. These Phase 2 results represent the first demonstration of clinical efficacy for the novel class of resolvin compounds and suggest that resolvins have the potential to treat a broad range of inflammatory diseases.

“There is an urgent need for new treatment options in dry eye and the results of this Phase 2 study are as strong as any I have seen,” said Stephen Pflugfelder, MD, an expert in dry eye at Baylor College of Medicine. “Based both on these clinical results and on its unique mode of action, I am confident that RX-10045 can be an important new treatment modality for these patients.”

The 28-day, randomized, multi-center, placebo-controlled study in 232 patients with moderate dry eye patients was designed to evaluate the safety, tolerability and efficacy of RX-10045 administered twice daily. The Phase 2 study examined three doses of RX-10045 and utilized a controlled adverse environment (CAE) to measure corneal staining in a stressful drying environment, as well as daily patient diaries using a standard visual analog scale to assess symptom improvement over the course of the study.

RX-10045 produced a significant dose-dependent improvement from baseline in symptoms recorded in daily patient diaries. The improvement was observed across all symptoms evaluated in the study, including dryness, stinging, burning, grittiness, ocular discomfort and the composite of each patient’s most severe symptom (Worst Symptom Score). RX-10045 was superior to placebo on the primary symptomatic endpoint of Worst Symptom Score (p < 0.02), as well as on several individual symptoms. The onset of symptom relief occurred within the first week of treatment, and symptoms continued to improve over the course of the 28-day study, suggesting the potential for even greater benefit with longer treatment durations. “I am very encouraged by the symptom relief achieved with RX-10045,” said Ira Udell, M.D., Chairman of the Department of Ophthalmology at the North Shore-Long Island Jewish Health System and Professor of Ophthalmology and Visual Sciences, Albert Einstein College of Medicine. “Symptomatic improvement is what really matters to patients.” RX-10045 also produced a 75% reduction from baseline in CAE-induced staining of the central cornea (p < 0.00001), the primary sign endpoint in the study. This improvement was greater than that observed for placebo, the difference approaching statistical significance (p = 0.11). RX-10045 also produced a significant improvement in CAE-induced staining in the inferior cornea and in the composite of central and inferior cornea, which also approached statistical significance over placebo (p = 0.09). “We are very enthusiastic about the results of this Phase 2 study which, in only a 28-day study, achieved what we believe is unprecedented dose-dependent improvement in the symptoms of dry eye, as well as strong improvement in the signs of dry eye. The results of this study will help Resolvyx design the pivotal trials for RX-10045, which are currently targeted to begin in the first half of 2010,” said Greg Weinhoff, Executive Chairman of Resolvyx. “In addition to demonstrating the potential of RX-10045 to treat dry eye patients, this study also shows the potential of the entire resolvin class to treat a range of inflammatory diseases.” Resolvyx is also currently conducting a Phase 1 study with a second resolvin, RX-10001, an orally-administered drug candidate for the treatment of systemic inflammatory diseases such as asthma, inflammatory bowel disease and other inflammatory diseases. About RX-10045 RX-10045 is Resolvyx’s lead resolvin therapeutic, and is a synthetic analog of RvE1, a naturally occurring resolvin. RX-10045 has been shown to have potent anti-inflammatory and cell-survival benefits in laboratory testing. In preclinical studies, RX-10045 was highly effective in preventing signs of dry eye, including decreasing corneal inflammation, reducing corneal epithelial damage, preventing loss of goblet cells (cells that play an important role in maintaining tear film integrity) and improving tear volume. In addition, those studies demonstrated that RX-10045 potently inhibited the release of several key pro-inflammatory mediators from corneal epithelial cells and accelerated corneal tissue repair with an effect level comparable to that seen with epidermal growth factor, the most potent previously-known mediator of corneal tissue repair. RX-10045 is formulated as a clear, aqueous, preservative-free solution for ocular administration. About Dry Eye Syndrome Dry eye syndrome is one of the most common problems treated by eye physicians; an estimated 25-30 million Americans suffer from dry eye and the worldwide prevalence closely parallels that of the United States. Dry eye is a chronic, multifactorial disease of the tears and ocular surface that results in symptoms of discomfort, visual disturbance, and tear film instability with potential damage to the ocular surface. It is accompanied by increased osmolarity of the tear film and inflammation of the ocular surface. Dry eye can make it more difficult to perform some visual activities for an extended period of time, and it can decrease tolerance for dry environments. About Resolvins Resolvins are a recently discovered family of naturally-occurring, small molecule lipid mediators that can be targeted to treat a wide range of diseases. In particular, resolvins act to protect healthy tissue during an inflammatory response to infection, injury or other environmental challenge, and then act to resolve inflammation and promote healing after the insult has passed. Resolvins are shown to be highly potent and efficacious in pre-clinical models of asthma, atherosclerosis, rheumatoid arthritis, inflammatory bowel disease, dry eye and retinal disease, among others. Resolvins are potential drug candidates to treat a broad range of acute and chronic diseases caused by a failure to resolve the inflammatory response and restore immune homeostasis. Such diseases include auto-immune diseases (like Crohn’s disease, psoriasis and rheumatoid arthritis), allergic diseases (like asthma) and chronic inflammatory diseases (like atherosclerosis, degenerative retinal diseases, chronic dry eye and Alzheimer’s disease). Resolvins offer an entirely novel biological approach to treating significant inflammatory diseases, with a decreased potential for immuno-suppression. Source
Resolvyx Pharmaceuticals