Month: June 2014

In the United States, the management of glaucoma costs about $2.5 billion per year. Of the $1.9 billion in direct costs, glaucoma medications account for an estimated 38% to 52% of the total. In an article published in the January 2008 issue of the American Journal of Ophthalmology, researchers from The Texas A&M University System Health Science Center College of Medicine, Temple, Texas; analyzed the economics of medically managing glaucoma. The yearly costs to patients of various topical glaucoma medications were calculated and significant price differences and increases in cost over time were found.

The researchers looked at four classes of pharmaceuticals; ??-blockers, prostaglandins, ?�2-agonists and carbonic anhydrase inhibitors. They compared both brand-name and generic formulations, evaluated how accurately the bottles were filled and how accurately the medications could be dispensed by patients. Using results from earlier studies, the increases in Average Wholesale Prices (AWP) were also evaluated from 1999 through 2006.

Nonselective ??-blockers remain the most inexpensive class of glaucoma medications. For all categories of drugs, calculated yearly cost ranged from $150.81 for generic timolol maleate 0.5% (??-blocker), to $697.42 for Cosopt (combination formulation), to as high as $873.98 for a three-times-daily dose of Alphagan P 0.15% (?�2-agonist). Among brand name ??-blockers, yearly cost ranged between $203.47 for Timoptic 0.5% and $657.24 for Betoptic S. Generic ??-blockers consistently were more economical than their brand-name counterparts. Yearly cost of prostaglandin analogs ranged from $427.69 for Travatan to $577.62 for Lumigan. The two carbonic anhydrase inhibitors, Azopt and Trusopt, yielded similar economic profiles. The generic selective ?�2-agonist brimonidine tartrate 0.2% costs approximately $352.89 and $529.34 per year for the respective two and three drops daily per eye regimens.

AWP trends through two periods, 1999 to 2006 and 2002 to 2006, showed significant increases, even within a category. For example, in the ??-blockers, Betoptic S increased nearly 100 % from 1999 to 2006, while Timoptic, increased only 11.7 %. In the period 2002 to 2006, the AWP of Timoptic remained constant.

Writing in the article, Steven D. Vold states, “Physicians consider many factors when treating patients with glaucoma. Ultimately, the goal of eye care providers is to give the best, most cost-effective care to their patients. Our study addresses the calculated cost per year passed on to the patient for single medication treatment plans??�As newer medications and treatment schemes are introduced, future studies will be needed to update the rapidly changing economic information pertaining to the medical management of glaucoma.”

The article is “Cost Analysis of Glaucoma Medications” by Nathan R. Rylander and Steven D. Vold. It appears in the American Journal of Ophthalmology, Volume 145, Issue 1, (January 2008), and is published by Elsevier.

About The American Journal Of Ophthalmology
The American Journal of Ophthalmology is a peer-reviewed, scientific publication that welcomes the submission of original, previously unpublished manuscripts directed to ophthalmologists and visual science specialists describing clinical investigations, clinical observations and clinically relevant laboratory investigations. Published monthly since 1884, the full text of the American Journal of Ophthalmology and supplementary material are also presented on the Internet at AJO.

The American Journal of Ophthalmology publishes Original Articles, Brief Reports, Perspectives, Editorials, Abstracts, Correspondence, Book Reports and Announcements. Perspectives, Editorials and Abstracts (from other journals) are published by invitation.

About Elsevier

Elsevier is a world-leading publisher of scientific, technical and medical information products and services. Working in partnership with the global science and health communities, Elsevier’s 7,000 employees in over 70 offices worldwide publish more than 2,000 journals and 1,900 new books per year, in addition to offering a suite of innovative electronic products, such as ScienceDirect, MD Consult, Scopus, bibliographic databases, and online reference works.

Elsevier is a global business headquartered in Amsterdam, The Netherlands and has offices worldwide. Elsevier is part of Reed Elsevier Group plc , a world-leading publisher and information provider. Operating in the science and medical, legal, education and business-to-business sectors, Reed Elsevier provides high-quality and flexible information solutions to users, with increasing emphasis on the Internet as a means of delivery. Reed Elsevier’s ticker symbols are REN (Euronext Amsterdam), REL (London Stock Exchange), RUK and ENL (New York Stock Exchange).

Elsevier

View drug information on Alphagan; Cosopt; Lumigan.

According to a new CNIB survey released this week for World Glaucoma Week (March 7-13), few Canadians are as informed as they need to be about their family history of glaucoma, a serious and incurable eye condition that affects 250,000 Canadians.

Despite the fact that glaucoma tends to run in families, the survey found that almost half of Canadians (47 per cent) do not feel well-informed about their family history of the disease. In fact, only one-third of Canadians (33 per cent) have spoken to their immediate families to learn whether glaucoma could be a hereditary concern.

But astonishingly, among the group that reported having had that conversation, almost half (47 per cent) learned that glaucoma was in the family, indicating they could be at an elevated risk.

“People forget that learning about your family history of glaucoma is an important step to protecting your eyesight. Family history, particularly having a parent or sibling with the disease, is considered one of the primary risk factors of glaucoma,” said Dr. Keith Gordon, Vice-President of Research and Service Quality, CNIB.

The survey also revealed that most Canadians (71 per cent) are unaware that you could have glaucoma, but still be able to see perfectly well.

Eye Remember

To educate Canadians about the importance of detecting glaucoma early, CNIB has launched its third annual awareness campaign and photo contest called “Eye Remember.” From March 8 to May 18, Canadians can visit www.eyeremember to get the facts on glaucoma and upload a photograph that represents a cherished memory from their past – whether it’s a summer with family at the cottage, a shot from your honeymoon, or an old black and white picture from grandma’s albums – along with a brief description of why it is close to their heart and reminds them to be proactive about their vision health.

All uploaded photos will be entered for a chance to win a once-in-a-lifetime trip for two to one of four popular Canadian destinations, including Banff (Alberta), Quebec City (Quebec), Niagara Falls (Ontario) and the Okanagan Valley (British Columbia).

Glaucoma: The “silent thief”

Caused by damage to the optic nerve, glaucoma usually progresses slowly and painlessly; therefore it’s possible to have glaucoma without noticing any symptoms or major changes to your eyesight. In fact, 125,000 Canadians are living with glaucoma today and don’t know it.

“Because glaucoma has no symptoms, it can only be picked up by regular eye examinations with an eye doctor,” said Dr. Neeru Gupta, Professor, Dorothy Pitts Chair of Ophthalmology and Vision Sciences, and Director of the Glaucoma Unit at St. Michael’s Hospital, University of Toronto. “If someone in your family has glaucoma, you are at a much higher risk for the disease. Get your eye pressure and optic nerves checked for glaucoma. Early treatment is a powerful way to prevent vision loss.”

In addition to family history, risk factors for glaucoma include having elevated eye pressure, being over the age of 40, being of African, Asian or Inuit descent and having myopia.

Over time, glaucoma may cause loss of peripheral (side) vision, followed by “tunnel” vision or complete vision loss. There is no cure for glaucoma and, once you begin to lose your vision, it can’t be restored. Fortunately, vision loss from glaucoma can be controlled if detected early.

About the survey

This survey was conducted as part of CNIB’s Eye Remember campaign in order to determine how much Canadians know about glaucoma and its risk factors. A random sample of 1,003 Canadians aged 18 and older answered an online survey. Survey results from a sample of Canadians of this size can be considered accurate to +/- 3.1 per cent, 19 times out of 20. The survey was undertaken by CNIB, with data collection by Ipsos Public Affairs. Eye Remember is supported by an unrestricted educational grant from Pfizer Canada Inc.

Source:

CNIB

“Primates and humans have three photoreceptors and can only see four basic colors, red, green, blue and yellow,” says Jay Neitz, Ph.D. “Birds, fish and reptiles have four photoreceptors, allowing them to see things we cannot. They must see an entire dimension of color, including ultraviolet, infrared and all the combinations thereof, which we miss.”

He is the R.D. and Linda Peters Professor in Ophthalmology at the Medical College. Maureen E. Neitz, Ph.D., is the Richard O. Schultz/Ruth Works Professor in Ophthalmology Research.

Two of the world’s leading color vision researchers, the Neitzes are also pioneers in the field of functional genomics. Their studies of human color vision have not only identified the genes responsible for colorblindness, but also defined one of the first examples of a nervous system defect for which a person’s DNA can predict both the occurrence and the severity of the disorder.

“This has been an important breakthrough, because as scientists strive to understand the genetic basis of human disease, more than merely revealing the presence of a genetic defect, it is also important to forecast the severity of the impairment,” says Dr. Maureen Neitz.

They are currently studying gene therapy at the Froedtert & The Medical College of Wisconsin Eye Institute to evaluate the plasticity of the adult human visual system. Gene therapy has been demonstrated to correct deficits in the retina, but the major unanswered question is whether the brain can interpret new information it receives from the therapeutically-treated retina to restore vision. For humans to migrate around objects in their world requires that information about objects be transmitted from the retina to the brain, and that the brain recreate an image of the world.

Their color vision research has also provided them with unique opportunities to discover the steps in the causal chain from the gene, to protein function, to neural signal. They are applying these lessons to other genetic defects that cause visual impairment.

“We anticipate that our studies of the basic mechanisms controlling gene expression in the retina, and the structure/functional relationships among proteins involved in signal transduction, may lead to development of new methods for early diagnosis of retinal disorders, and ultimately extend our knowledge of the role genes play in construction of the nervous system,” she says.

The Neitzes are currently conducting several research studies involving human subjects including a study of color vision and a study of how eye growth is controlled to cause nearsightedness.

Contact: Eileen LaSusa

Medical College of Wisconsin

ReVision Optics, a leading company in the research, development and manufacture of custom optical products to correct and maintain vision, announced today that it has begun its US clinical trial of the PresbyLens® corneal inlay. The clinical trial will evaluate the PresbyLens® corneal inlay for the correction of presbyopia, the age-related loss of near vision. The study began on April 6th with the treatment of three subjects by clinical investigator Dr. Stephen Slade of the Slade & Baker Vision Center in Houston, Texas.

The PresbyLens® clinical study will evaluate 400 presbyopic subjects for three years. During the initial phase of enrollment, 30 eyes will be treated at two clinical sites. The first two investigators chosen are Dr. Stephen Slade of the Slade & Baker Vision Center in Houston, Texas, and Dr. Jon Dishler of the Dishler Laser Institute in Greenwood Village, Colorado.

Presbyopia is a common vision problem that affects everyone as they age. When people become older their eyes naturally lose the ability to focus, which typically happens around age 45. For people with good distance vision, symptoms of presbyopia can include difficulty seeing things close up like newspapers, menus and computer screens. Currently, more than 73 million people in the US are presbyopic.

ReVision Optics’ PresbyLens® has the potential to gently reshape the cornea to improve a patient’s near or reading vision. The lens is made from a proprietary, optically clear, biocompatible material that is similar to the material used in a soft contact lens.

“We are pleased to begin our US clinical trials for the PresbyLens®. Our research and development studies strongly indicate that we may be able to provide a solution for one of the most common vision issues, presbyopia,” said J. Randy Alexander, President and CEO of ReVision Optics.

Source
ReVision Optics™, Inc.

Retinal detachment, a condition that afflicts about 10,000 Americans each year, puts an individual at risk for vision loss or blindness. In a new study in today’s issue of the New England Journal of Medicine, a leading ophthalmologist at NewYork-Presbyterian Hospital/Weill Cornell Medical Center writes, however, that a high probability of reattachment and visual improvement is possible by using one of three currently available surgical techniques.

“Although no randomized trials have been conducted that show definitively that one procedure is best for every situation, improvements in these surgical techniques have led to effective treatments for most patients,” says Dr. Donald J. D’Amico, ophthalmologist-in-chief at NewYork-Presbyterian Hospital/Weill Cornell Medical Center, professor and chairman of ophthalmology at Weill Cornell Medical College, and an international leader in vitreoretinal surgery.

Although relatively rare, retinal detachment can occur when holes, tears or breaks appear in the light-sensitive retina as a result of trauma or pulling away of the gelatinous mass, known as the vitreous, that fills the back of the eye. Retinal tears occur most often in adults over age 60, but may occur much earlier, particularly in those with high myopia. The sudden onset of light flashes and “floaters” could be the warning signs of an impending retinal detachment, although these symptoms do not always mean that a retinal tear has occurred. Surgery is the only treatment for a retinal detachment.

In the article “Primary Retinal Detachment,” Dr. D’Amico offers his recommendations for treating a 57-year-old man who experiences sudden flashes and floaters in one eye, progressive loss of vision and a retinal detachment.

The three surgical options currently in use to treat such a case are:

— Scleral Buckling. A common way to treat a retinal detachment, scleral buckling surgery has been performed with success for several decades. In this procedure, a piece of silicone is sutured onto the outside wall of the eyeball and left in place permanently to create an indentation, or buckle, that restores contact with the detached retina. The individual tears are then closed by a localized scar that is induced with a freezing probe or laser. According to Dr. D’Amico, scleral buckling is a relatively involved procedure and requires the use of a hospital operating room. It is usually performed on an outpatient basis with local anesthesia with intravenous sedation, and the overall success rate for reattachment is about 90 percent.

— Pneumatic Retinopexy. A newer and less invasive procedure than scleral buckling, pneumatic retinopexy is usually done in the retina specialist’s office under local anesthesia. The procedure involves injecting a gas bubble into the vitreous cavity of the eye, then positioning the patient’s head so that the bubble floats to the break in the detached retina. The bubble spans and closes the retinal break, and this allows the natural forces in the eye to reattach the retina. The break is permanently sealed by the application of a freezing probe or laser to create a scar around the break. The gas bubble then resolves over several days, and in successful cases, the retina is left reattached without a trip to the operating room, and with no permanent buckling material applied to the eye. According to Dr. D’Amico, pneumatic retinopexy is not suitable for every patient and has a somewhat lower success rate with initial treatment than does scleral buckling or vitrectomy. Nevertheless, he says, because of its minimally invasive attributes, and the fact that an attempted pneumatic does not reduce the ultimate chance for success if additional surgery is required for recurrent detachment, patient and surgeons increasingly select pneumatic retinopexy for suitable primary retinal detachments after a careful discussion of the limitations.

— Vitrectomy. In contrast to scleral buckling, vitrectomy is a surgery within the eye in which the vitreous gel is removed. Because vitreous traction is the typical cause of the retinal tears in a detachment, this approach has the advantage of directly attacking the underlying cause of the detachment. Vitrectomy surgery — a few decades old — is a newer surgery than scleral buckling, and it is continually improving due to innovations in instrumentation and technique. Recent studies have shown success rates comparable to those of scleral buckling. Dr. D’Amico notes that there is a very strong shift toward vitrectomy, and away from buckling, for retinal detachment, particularly by younger surgeons and for patients that have detachment after cataract surgery. Vitrectomy for detachment may be associated with a higher risk of postoperative cataract, and this appears to be its main disadvantage compared to buckling, which has lower risk of cataract but higher risk of other complications. In cases where bleeding in the vitreous gel is present with the detachment, a vitrectomy approach is clearly preferred to remove the vitreous hemorrhage in order to gain better visualization to find and repair tears or holes in the retina. Vitrectomy, like scleral buckling, is typically done on an outpatient basis with local anesthesia with intravenous sedation.

For the patient described in the vignette who went to his ophthalmologist with classic symptoms of primary retinal detachment, including flashing lights, floaters and progressive loss of vision, Dr. D’Amico’s first recommendation would be to perform a pneumatic retinopexy. “I would select this option for this patient because this specific detachment is well-suited to pneumatic retinopexy by virtue of the retinal breaks being located close together in the superior retina, which is the easiest location to treat with an intraocular gas bubble. Furthermore, the procedure can be done immediately in the doctor’s office at lower cost and with fewer risks of complications, compared to buckling or vitrectomy, and it also compares quite favorably with the other procedures with having a 75 percent chance of restoring vision to 20/50 or better after this minimally invasive procedure,” Dr. D’Amico says.

As with any surgery, there are risks associated with each of these techniques. For example, vitrectomy can cause cataract or elevated pressure inside the eye, especially in people with glaucoma; scleral buckling can cause a change in the shape of the eye that may require alteration of the eyeglass prescription; and pneumatic retinopexy often requires more than one surgery to reattach the retina.

“The benefits of surgery, however, far outweigh the risks,” says Dr. D’Amico, who performs all of these procedures. “No matter which procedure the surgeon chooses, there is a very good chance today that a patient’s retina can be reattached and his or her vision preserved.”

NewYork-Presbyterian Hospital/Weill Cornell Medical Center

NewYork-Presbyterian Hospital/Weill Cornell Medical Center, located in New York City, is one of the leading academic medical centers in the world, comprising the teaching hospital NewYork-Presbyterian and Weill Cornell Medical College, the medical school of Cornell University. NewYork-Presbyterian/Weill Cornell provides state-of-the-art inpatient, ambulatory and preventive care in all areas of medicine, and is committed to excellence in patient care, education, research and community service. Weill Cornell physician-scientists have been responsible for many medical advances — from the development of the Pap test for cervical cancer to the synthesis of penicillin, the first successful embryo-biopsy pregnancy and birth in the U.S., the first clinical trial for gene therapy for Parkinson’s disease, the first indication of bone marrow’s critical role in tumor growth, and, most recently, the world’s first successful use of deep brain stimulation to treat a minimally conscious brain-injured patient. NewYork-Presbyterian, which is ranked sixth on the U.S.News & World Report list of top hospitals, also comprises NewYork-Presbyterian Hospital/Columbia University Medical Center, Morgan Stanley Children’s Hospital of NewYork-Presbyterian, NewYork-Presbyterian Hospital/Westchester Division and NewYork-Presbyterian Hospital/The Allen Pavilion. Weill Cornell Medical College is the first U.S. medical college to offer a medical degree overseas and maintains a strong global presence in Austria, Brazil, Haiti, Tanzania, Turkey and Qatar. For more information, visit nyp and medrnell.edu.

NewYork-Presbyterian Hospital
425 E 61st St., Fl. 7
New York
NY 10021
United States
nyp

Inotek Pharmaceuticals Corp., a leader in the development of innovative drug candidates to address significant diseases of the eye, announced that it has initiated dosing in a multiple-dose Phase 2 clinical trial to evaluate the efficacy and safety of its novel eye-drop INO-8875 in patients with glaucoma. In an earlier Phase 1/2 single ocular dose clinical trial, INO-8875 was shown to significantly reduce intraocular pressure (IOP) in glaucoma patients. As a highly-selective adenosine-1 receptor agonist, INO-8875 reduces IOP by enhancing a natural mechanism for clearing protein material that clogs the major outflow pathway — the trabecular meshwork — as the eye with glaucoma ages.

“Currently available first-line treatment options for glaucoma do not adequately reduce IOP in up to 40% of glaucoma patients,” said Paul G. Howes, President and Chief Executive Officer of Inotek. “In addition, there exist no approved products for glaucoma that act on the major pathway for outflow — the trabecular meshwork. Based on our promising clinical and preclinical data, we believe INO-8875 has significant potential to be the first trabecular meshwork outflow enhancer to lower IOP in glaucoma, and with an excellent safety profile.”

Thomas K. Mundorf, M.D. of the Mundorf Eye Center in Charlotte, NC and investigator for the Phase 2 trial, stated, “We are excited to evaluate the ability of INO-8875 to reduce IOP as a new class of agent for glaucoma, with its unique mechanism to improve outflow in the trabecular meshwork. As there is a clear unmet need for novel treatments that are both well tolerated and effective for lowering IOP in glaucoma patients, we believe INO-8875 is an exceptional candidate based on its profile to date.”

The Phase 2 trial is a randomized, double-blind, placebo-controlled, dose-ranging study to evaluate the safety, tolerability, pharmacokinetics, and efficacy of INO-8875 delivered as an eye-drop formulation in patients with primary open-angle glaucoma or ocular hypertension. The trial includes multiple centers in the United States. For a more detailed description of the clinical trial protocol, please visit here.

In an earlier Phase 1/2 single ascending ocular dose study of 84 patients with primary open-angle glaucoma or ocular hypertension, INO-8875 was well tolerated up to the highest dose tested, with no serious adverse events or observed dose-limiting toxicities. While the trial was not powered to achieve statistical significance, statistically significant reductions in IOP compared to placebo were attained at the two highest doses of INO-8875 tested.

About INO-8875 for Glaucoma

Glaucoma is a leading cause of blindness globally, and it is broadly accepted that lowering intraocular pressure (IOP) in glaucoma patients is the only clinically reliable means of slowing the progression of vision loss. Current products for glaucoma, such as prostaglandins and beta blockers, lower IOP by reducing inflow of fluid in the eye or increasing its drainage through a secondary pathway in the eye — the uveoscleral pathway. As glaucoma advances with age, the eye’s trabecular meshwork grows increasingly clogged with protein debris, and the eye can become less responsive to these mechanisms. As such, a significant percentage of patients do not respond adequately to currently approved products, and up to 40% of patients are treated with a combination of products in the hope of achieving targeted reductions in IOP. There remains an unmet need for innovative glaucoma products acting on the trabecular meshwork to provide improved IOP-lowering efficacy.

The Company believes INO-8875 has significant potential as an IOP-lowering medicine, either as monotherapy or in combination with other glaucoma products, because it restores outflow of aqueous humor through the trabecular meshwork. As validation of its complementary mechanism to other glaucoma products, INO-8875 has shown substantial additivity of IOP-lowering efficacy when combined with the leading glaucoma product (Xalatan®, Pfizer) in a preclinical model. As a highly selective adenosine-1 receptor agonist, INO-8875 has a novel mechanism differentiating it from currently approved products and other candidates in development for glaucoma in that INO-8875 enhances a natural cellular signaling pathway to clear debris from the trabecular meshwork, resulting in improved outflow.

Source
Inotek Pharmaceuticals Corp.

Some unexpected effects of lead exposure that may one day help prevent and reverse blindness have been uncovered by a University of Houston (UH) professor and his team.

Donald A. Fox, a professor of vision sciences in UH’s College of Optometry (UHCO), described his team’s findings in a paper titled “Low-Level Gestational Lead Exposure Increases Retinal Progenitor Cell Proliferation and Rod Photoreceptor and Bipolar Cell Neurogenesis in Mice,” published recently online in Environmental Health Perspectives and soon to be published in the print edition of the prestigious peer-reviewed journal.

The study suggests that lead, or a new drug that acts like lead, could transform human embryonic retinal stem cells into neurons that would be transplanted into patients to treat retinal degenerations.

“We saw a novel change in the cellular composition of the retina in mice exposed to low levels of lead during gestation. The retina contained more cells in the rod vision pathway than normal or than we expected,” said Fox, who also is a professor of biology and biochemistry, pharmacology and health and human performance. “The rod photoreceptors and bipolar cells in this pathway are responsible for contrast and light/dark detection. These new findings directly relate to the supernormal retinal electrophysiological changes seen in children, monkeys and rats with low-level gestational lead exposure.”

Fox said these effects occur at blood lead levels at or below 10 micrograms per deciliter, the current low-level of concern by the Centers for Disease Control and Prevention. Because the effects occur below the “safe level,” Fox says it raises more questions about what should be considered the threshold level for an adverse effect of lead on the brain and retina.

Fox has studied lead toxicity for 35 years, specifically as it relates to its effects on the brain and retina of children. His interest in gestational lead exposure started in 1999, when he and colleague Stephen Rothenberg studied a group of children in Mexico City whose mothers had lead exposure throughout their pregnancies. The study was funded to measure the adverse effects of lead poisoning on the nervous system of children born in Mexico City – a city that has elevated levels of lead in the air due to the use of leaded gasoline, as well as continued use of lead-containing pottery and glassware for food preparation. The study was funded by the U.S. Environmental Protection Agency and the Mexican government and was published in 2002 in the journal Investigative Ophthalmology and Visual Sciences.

Supported by a $1.7 million National Institutes of Health (NIH) grant, Fox and his group set out to find possible reasons for this supernormal retinal response in children. The researchers employed rat and mice models that covered the three levels of lead found in the blood of the Mexico City mothers -some below, some right at and some higher than the CDC “safe level.” The researchers exposed rodents to lead throughout pregnancy and the first 10 days of life, which is a time period equivalent to human gestation.

Fox said that the early-born retinal progenitor cells give rise to four neuron types, which were not affected by lead exposure. The later-born retinal progenitor cells, he said, give rise to two types of neurons and a glial cell. Surprisingly, only the late-born neurons increased in number. The glial cells, which nurture neurons and sometimes protect them from disease, were not changed at all. The rats and mice both had “bigger, fatter retinas,” according to Fox. Interestingly, the lower and moderate doses of lead produced a larger increase in cell number than the high lead dose.

“This is really a novel and highly unexpected result, because lead exposure after birth or during adulthood kills retinal and brain cells, but our study showed that low-level lead exposure during gestation caused cells to proliferate, increased neurons and did not affect glia,” Fox said. “So, gestational exposure produces an exact opposite to what was previously shown by our lab and others. It also shows that the timing of chemical exposure during development is just as important as the amount of exposure.”

This brought the researchers to a crossroads. On the one hand, the retina is not built to have all these extra cells and, according to unpublished data from Fox’s mouse studies, the retinas will start to degenerate as the mice age. This suggests that the retinas of the children from the original Mexico City study should be examined as they might start to degenerate when they are 40 years of age.

“This work has long-term implications in retinal degeneration and diseases where photoreceptors die. If we can figure out how low-level lead increases the number of retinal progenitor cells and selectively produces photoreceptors and bipolar cells, then perhaps a drug can be created to help those with degenerative retinal diseases that eventually cause blindness,” Fox said. “Researchers may be able to use lead as tool in transforming embryonic retinal stem cells into rods and bipolar cells that could be transplanted into diseased retinas, ultimately saving sight and reversing blindness.”

Fox said that more research is needed before such a potential drug could be developed to mimic the effects of lead. Ideally, this drug would induce human embryonic retinal stem cells to form rods and bipolars that could be transplanted into patients to treat early stages of retinal degeneration.

In addition to Fox and research assistant professor Dr. Weimin Xiao in the UHCO, the research team consisted of a number of Fox’s current and former students, including Anand Giddabasappa, a former Ph.D. student and now UHCO alumnus; Jerry E. Johnson, a UH alumnus from the department of biology and biochemistry, former post-doctoral fellow in Fox’s lab and now an assistant professor at UH-Downtown; and current Ph.D. students W. Ryan Hamilton, Shawntay Chaney and Shradha Mukherjee.

Supplementing the NIH research project grant, this study also was funded by National Eye Institute training and core grants and a National Institute for Occupational Safety and Health educational resource grant.

Source:

University of Houston

UH College of Optometry

Sirion Therapeutics, Inc., an
ophthalmic-focused biopharmaceuticals company, announced today that it has
begun enrollment of two phase III clinical trials, which will evaluate
ST-601 (difluprednate) in the treatment of inflammation following ocular
surgery.

ST-601 (difluprednate) was acquired by Sirion last year through an
exclusive licensing agreement with Senju Pharmaceutical Co., Ltd. of Japan.
The agreement gives Sirion the U.S. rights to develop and market a topical
ophthalmic emulsion containing the steroid compound difluprednate for the
treatment of inflammatory eye diseases.

“Initiating patient enrollment in our phase III clinical trials for
difluprednate is another important milestone for Sirion,” said Barry
Butler, President and Chief Executive Officer of Sirion Therapeutics, Inc.
The company recently announced the initiation of a phase II proof of
concept trial for ST- 602 (fenretinide) for the treatment of geographic
atrophy. “Difluprednate is a good strategic fit with our company mission of
finding treatments for sight threatening diseases and conditions.
Inflammation of the eye that is untreated or undertreated can contribute to
loss of sight. We hope that difluprednate will offer help to the millions
of people in the U.S. that have eye surgery each year,” concluded Butler.

About Sirion Therapeutics, Inc. and Sirion Holdings, Inc.

Sirion Therapeutics is a Tampa, Florida based biopharmaceutical
company, with additional offices in La Jolla, California, dedicated to the
development and commercialization of innovative ophthalmic products. Sirion
Holdings, Inc. is Sirion’s parent company. For more information regarding
Sirion and the matters announced in this press release, please visit
Sirion’s website at siriontherapeutics/.

Forward-Looking Statements

This press release contains forward-looking statements and information
about Sirion Holdings, Inc.’s and Sirion Therapeutics, Inc.’s business,
product candidates, and product development schedule. These forward-looking
statements are only predictions, are uncertain and involve substantial
known and unknown risks, uncertainties and other factors which may cause
actual results to be materially different from the results anticipated,
expressed or implied by these forward-looking statements. Among the factors
that could cause actual results to differ materially are the following: the
success or failure of research, development and marketing activities,
decisions by regulatory authorities regarding whether and when to approve
our drug applications, and the speed with which regulatory authorizations
may be achieved. Please see Sirion Holdings, Inc.’s public filings with the
Securities and Exchange Commission for further discussion of these risks,
uncertainties and related cautionary statements regarding our business and
such forward-looking statements.

Sirion Therapeutics, Inc.
siriontherapeutics/

Although reports about the hazards lead presents in toys have attracted attention this holiday season, lead is not the only danger toys can present to children. December is Safe Toys and Celebrations Month and the American Academy of Ophthalmology reminds parents of the dangers that some toys may pose to children’s eyes.

“The holidays are supposed to be a time of happiness and celebration,” said David Coats, MD, clinical correspondent for the American Academy of Ophthalmology and pediatric ophthalmologist at Texas Children’s Hospital in Houston. “A serious eye injury can bring an abrupt end to the celebration. Parents should choose a toy that is appropriate for their child’s age, abilities, maturity, and the parent’s willingness to supervise use of the toy.”

Children receive all sorts of potentially unsafe presents during the holidays, including BB guns, darts, pellet guns and paintball guns. According to the Consumer Product Safety Commission, there were more than 210,000 toy-related injuries treated in U.S. emergency rooms in 2005, the most recent year for which data is available. About 6,000 of those were injuries to the eyes of children under age 15.

“Any toy that can eject or propel an object can lead to a serious eye injury if used incorrectly,” said Dr. Coats. “This includes innocuous appearing toys such as a popgun or a paddleball set.” Among the patients Dr. Coats’ has treated for injuries from toys is a boy who suffered a severe hemorrhage inside his eye after being shot with a potato gun.

Don’t forget that sports equipment, a popular gift, should also include protective eyewear. Sports-related eye injuries are common and can cause permanent vision loss, accounting for about 40,000 eye injuries annually. “If you plan to give sports equipment, provide appropriate protective gear, such as helmets, facemasks or goggles with polycarbonate lenses,” said Dr. Coats. Parents can check with their Eye MD to learn about protective gear recommended for their child’s sport.

For more information about eye safety, go to geteyesmart, the Academy’s public Web site.

About the American Academy of Ophthalmology

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

American Academy of Ophthalmology (AAO)
655 Beach St. P.O. Box 7424
San Francisco, CA 94120-7424
United States
aao

HOUSTON — (March, 2006) – When Dr. Rui Chen, assistant professor in the Baylor College of Medicine Human Genome Sequencing Center, sought to understand further the protein called Eyeless, he faced a dilemma.

Eyeless is a transcription factor, which means one of its major activities is to turn off or turn on other genes that have an effect on eye development later in the process. It is so powerful that when it is inserted into almost any tissues of the fruit fly, eyes grow – often in unexpected places.

Because Eyeless is a critical factor in the development of eyes in fruit flies or Drosophila, (a common model organism for studying how different organs grow), understanding the genes it affects could offer key clues into how the organs for sight actually develop in fruit flies and ultimately people.

One method for locating these genes is called a microarray, a tiny DNA chip used to identify specific sequences of genetic material. A microarray can provide hundreds of candidate genes – too many to be useful. Another method is to use bioinformatics and computers to predict where transcription factors bind, but this can give thousands of candidate genes. Again, that’s too much information to be valuable.

Chen, however, took a different tack. He used both methods. Then he dealt with only the genes and binding sequences that were found by both. Of the 300 genes found by microarray and 10,000 or more by the binding site technique, only 21 were found by both.

Because 11 of these were known to play a key role in eye development, he knew he was on the right track. A report of his work appears online today in the journal Genome Research.

“The reason I like this project is that it provides the possibility of doing this in almost any species,” said Chen. “It’s a combination of genomic and biologic techniques.”

“Finding specific targets of a transcription factor is the Holy Grail for many biologists,” said Dr. Graeme Mardon, senior co-author and a professor in the Program in Developmental Biology at BCM. In this case, he said, the researchers have shown that the genes they found are, in fact, targets of the Eyeless protein.

“We are now in the process of knocking out hundreds of genes predicted to be targets of this retinal network,” said Mardon. “This has opened the door to determining what are the critical targets of this gene for eye development. Others can use similar methods to do the same thing.”

Eventually, he said, the technique could be used to identify genes that are involved in similar processes that go wrong, leading to diseases. This will identify the areas where things go wrong so that researchers can target proposed therapies and drugs in the future.

In their area, the technique speeds the process of identifying those genes that are really important in identifying the genes critical to development of the eye.

“It also gives you a global picture of what the transcription factor does,” said Chen. “This is also a molecular screen” that will be valuable in studying mammals.

Funding for this project came from the National Eye Institute, the Retina Research Foundation, the Curtis & Doris K. Hankamer Foundation and The Robert and Janice McNair Foundation.

Contact: Ross Tomlin
htomlinbcm.edu
Baylor College of Medicine