Article Date: 5/1/2006

SUBSPECIALTY NEWS
Dr. Charles Schepens: Retina Pioneer
His Innovations Revolutionized Retinal Reattachment.

Dr. Charles Schepens

Charles Schepens, MD, considered the father of modern retinal surgery and honored for his heroic actions during World War II, died on March 28 after suffering a stroke. He was 94 years old and remained active in ophthalmology until his passing.  

Dr. Schepens' innovations helped improve retinal reattachment success rates from a lowly 40% to today's 90%. He was able to achieve this through his development of the binocular indirect ophthalmoscope, his technique for better observing the retina and locating the detachment, and his development of the scleral buckling surgical procedure, according to J. Wallace McMeel, MD, president of Schepens Retina Associates Foundation in Boston.

"He improved the diagnosis and treatment of a relatively common devastating ophthalmic disease, detached retina," says Dr. McMeel.

In the 1960s, Dr. McMeel completed his fellowship under Dr. Schepens and worked under him on what
Dr. McMeel characterizes as "seminal research papers" on the subject.

Before Dr. Schepens' work on retina reattachment, the treatment was to perform surgery, followed by patients being in bed for 3 to 4 weeks with sandbags on either side of their eyes in hopes of the retina reattaching. If success was not realized, the surgery was attempted again. As many as 60% of retinal detachment patients went blind in their affected eyes before Dr. Schepens' innovations.

Years before his retinal innovations, Dr. Schepens helped numerous people escape from the Nazis during World War II. His WW II actions were described in the book, The Surgeon and the Shepherd. In the book, author Meg Ostrum details Dr. Schepens' work in the French resistance and his role in helping downed Allied pilots, prisoners of war, Belgian government officials, and resistance leaders escape from the Nazis. He was able to do this by using a lumber business in the Pyrenees mountains in France to help ferry people through his mill into Spain, and then to England.

While the lumber mill was a real operation, its main purpose was to smuggle enemies of the Nazis out of France. Dr. Schepens himself had to escape from the Germans when they learned of his link to the resistance and appeared at the mill to confront him about his activities.

After the war, Dr. Schepens and his family emigrated to Massachusetts, where in 1950 he established The Retina Foundation, the first research facility dedicated to the study of the retina. This evolved over the years into the Schepens Eye Research Institute, which later affiliated with Harvard Medical School.

Dr. Schepens also founded The Retina Associates, which was the first subspecialty group dedicated to caring for retina patients and training retina specialists. This has evolved into the Schepens Retina Associates Foundation, a non-profit organization, dedicated to retina patient care, fellowship training, and clinical eye research.

Prior to his passing, Dr. Schepens was still working at the foundation that bears his name. He was seeing patients, assisting in fund-raising, and overseeing research.

Carolyn Bellefeuille, director of development at the Schepens Retina Associates Foundation, worked closely with Dr. Schepens for 18 years. She often marveled at his personal touch with patients.

"He had an excellent bedside manner," says Bellefeuille. "I can't think of anybody who had a better relationship with his patients. Patients would come from all over the world to come see him for check-ups."

Dr. Schepens is survived by his wife, Marie, 3 children, 8 grandchildren, and 4 great grandchildren.

IN BRIEF

►AAO and Avastin. The American Academy of Ophthalmology has asked CMS to reimburse intravitreal injections of Avastin for the treatment of wet AMD. In a letter to CMS, the Academy said Avastin is being used by "a large number of retinal specialists (who) believe that it is reasonable and medically necessary for treatment of some patients with neovascular AMD." The Academy cautioned that while "the scientific studies related to the use of intravitreal injections of bevacizumab (Avastin) for the treatment of neovascular AMD are supportive," they are not conclusive of its safety and efficacy.

"This is not an endorsement of intravitreal Avastin," said H. Dunbar Hoskins, M.D., Academy executive vice president. "It is a recommendation that those physicians who choose to use it should be reimbursed as they are with other off-label therapies."

The Academy's support for coverage is limited to "such patients who are deemed by their treating physician to have failed FDA-approved therapies, or in the judgment of their treating physician, based on his/her experience, are likely to have greater benefit from the use of intravitreal bevacizumab." It issued the letter in response to its members' and Medicare carriers' requests for clarification on the coverage issue.

►Priority review. Eli Lilly Company said the FDA has granted priority review status for Arxxant, a potential first-in-class oral treatment for diabetic retinopathy. There are no prescription products approved to treat diabetic retinopathy, says the company.

►Macugen label change. Reports of rare allergic reactions associated with injections of Macugen for the treatment of wet AMD have led to an addition to the Macugen label, advising doctors of the possibility of such reactions. The reactions have primarily taken the form of swelling around the eyes and lips and/or other anaphylactic symptoms.

OSI (Eyetech) and Pfizer, which make and market Macugen, said a direct relationship to Macugen or any of the various medications administered as part of the injection preparation procedure has not been established in these cases. The companies also cautioned doctors to evaluate patients for a history of hypersensitivity reactions before giving the drug.

►Lucentis priority review. The FDA has accepted the Biologics License Application (BLA) for the use of Lucentis in the treatment of wet AMD. As part of the BLA filing, Lucentis developer Genentech requested and has been granted a 6-month Priority Review.

Study: Diet Can Reduce AMD Risk
Researchers Cite Foods Rich in Antioxidants.

A recently released Dutch study that followed more than 4,000 at-risk seniors for 8 years indicates that a diet rich in foods containing antioxidant vitamins C and E, plus zinc and beta carotene, can reduce the chance of developing AMD by as much as 35%.

Previously, the AREDS I study undertaken by the National Eye Institute in the Unites States led to a recommendation that at-risk seniors could reduce the chance of developing AMD by as much as 25% by taking a supplement formulation containing vitamins C and E, plus zinc and beta carotene. A new AREDS II study will refine the original AREDS formulation while adding lutein and omega-3 fatty acids.

The Dutch study relied on foods alone to reduce risk.

"It's great news," said Robert Cykiert, MD, a professor of ophthalmology at New York University School of Medicine. "Up to now, we thought you needed to take heavy doses of supplements to achieve the benefits of these antioxidants. Now we know that if you eat a diet rich in these substances you achieve the same benefit, and possibly even more.

"If people start eating these things now, it may prevent problems 10, 15, or 20 years later," he added.

The new Dutch study, whose results were first reported in the Journal of the American Medical Association, sought to evaluate whether antioxidants that occur in everyday foods could play a role in preventing AMD.

The study began with 5,836 at-risk residents of Rotterdam. A total of 4,170 of those who initially began the study participated in the full 8-year follow-up. Participants filled out food questionnaires and were given regular eye exams.

Forum Brings Retina Fellows Together
Event Provides an Opportunity to Meet and Learn.

Eighty second-year vitreoretinal fellows recently got together in Chicago at the 6th Annual Retinal Fellows Forum, a weekend program that gave attendees an opportunity to meet their peers, hear from companies that provide vital products and services, and receive professional advice from leading retina specialists.

The Fellows Forum was organized by Carl C. Awh, MD, of Retina Vitreous Associates, Nashville, Tenn. Course co-directors were David Chow, MD, and Tarek Hassan, MD. Bausch & Lomb served as the major sponsor, along with 13 additional sponsors representing a cross-section of industry. The purpose of the program is to provide an expenses-paid educational and social opportunity for all North American vitreoretinal fellows in their final year of training.

"The fellows benefit by the opportunity to interact with the entire 'graduating class' of their professional peers, by introduction to representatives of companies that provide vital devices and services, and by participating in academic sessions devoted to the major clinical challenges they will face in practice. We also spend time discussing practice management issues relevant to new practitioners," says Dr. Awh.

This year, the fellows heard formal presentations on such topics as management of macular edema, 25-gauge vitrectomy, management of AMD, retinal detachment, practice pearls, highlights from the American Society of Retina Specialists Practices and Trends (PAT) survey, new instrumentation, and future trends in retinal services.

"Of note is that the entire faculty is assembled on stage throughout the meeting and each speaker acts as a moderator to solicit opinions from the faculty and the fellows," says Dr. Awh.

Neurotech Tackles Tough Retinal Diseases
The Company is Developing Treatments for RP and Dry AMD.
BY JOHN PARKINSON, ASSOCIATE EDITOR

With its potentially patient-blinding implications, the wet form of AMD has seen major investments in research and development. Consequently, new treatments have been made available. Dry AMD can also cause severe visual impairment, but as yet no serious treatment options are available to combat its effects.

One relatively young biotech company is looking to change that while also taking on another tough assignment — developing a treatment for retinitis pigmentosa (RP).

Neurotech USA, Inc., a subsidiary of Paris-based Neurotech, recently initiated a phase 2 clinical trial for dry AMD with its unique encapsulated cell technology (ECT) product, NT-501, after conducting a promising phase 1 clinical trial using an ECT implant for RP. In the RP trial, which involved 10 patients, the ECT safely delivered the medication into the vitreous, with some patients gaining more than 1 line of visual acuity.

The company says its decision to begin a dry AMD trial in addition to initiating a phase 2 RP trial was based largely on the fact that atrophic AMD and late-stage RP often exhibit similar retinal degeneration patterns in the macula. Thus, the company believes NT-501 may be able to treat both diseases.

Nonetheless, Neurotech's President and CEO, Ted Danse, says the company's main long-term goal for NT-501 is to achieve an RP treatment indication.

"Our key focus has to be on attaining approval and launch of NT-501 for retinitis pigmentosa," says Danse.

He notes the prevailing lack of available treatment and NT-501's orphan status as primary factors in the company's decision to pursue NT-501 for RP. Neurotech plans to soon begin 2 phase 2 RP studies that will be split between patients in early and late stages of the disease.

NT-501 is a polymer implant that contains genetically modified human retinal epithelial cells, which upon intraocular insertion deliver ciliary neurotrophic factor (CNTF) for sustained periods of time to the posterior segment. CNTF is a natural neuroprotective protein that has been shown in animal studies to protect against the loss of photoreceptors.

Over the long term, Neurotech is looking to convert its present NT-501 implant from a surgical procedure to an injectable implant. The company is developing a micro-sized injectable implant that will eventually be utilized in human trials, notes Danse.

Overall, he believes the ECT platform has 2 distinct, inherent strengths: its ability to deliver small amounts of protein over extended periods of time without the bolus drug release that occurs in intraocular injections, and the versatility to treat a number of retinal diseases.

Neurotech was formed in 2000 and is backed by an international group of venture capital firms. The company plans to pursue a growth strategy in looking for "follow-on products" within the ECT platform that could be developed for other retinal indications, and will break ground on a new manufacturing facility in Rhode Island this year.

Having held various positions with ophthalmic companies such as Coopervision, Bausch & Lomb, Allergan, and ISTA, Danse sees an industry shift towards the posterior segment of the eye.

"It's almost as if a whole new specialty was born. What we are seeing is the tip of the iceberg," asserts Danse. "There is going to be continued in-depth research and development behind new drugs and devices for the back of the eye. We are excited to be in the forefront of posterior-segment research."

Cataract Prevention for Vitrectomy Patients?
Othera Eye Drop is in Phase 2 Trials
BY JOHN PARKINSON, ASSOCIATE EDITOR

A small, privately held company is looking to break into the ophthalmic market with a cataract-preventing drug that may also be effective against dry AMD and other ocular diseases.

Othera Pharmaceuticals, based in Exton, Pa, recently announced it has initiated 2 phase 2 clinical trials for its eye drop formulation, OT-551. One study is as a treatment for prevention of cataract formation that can result from vitrectomy and the other is in collaboration with the National Eye Institute as a treatment for geographic atrophy associated with dry AMD.

David Joseph, Othera's chairman and CEO, asserts that there is a real need to address cataract prevention. "Eighty percent of patients who have vitrectomies will get a nuclear cataract within 9 to 12 months," says Joseph.

The company says its OT-551 is made up of a modified antioxidant molecule, Tempol-H (TP-H). The molecule emerged from a research program at the National Institutes of Health. Othera acquired the patent rights to TP-H, and modified the molecule to develop OT-551.

The drop's structure allows it to pass the corneal barrier into the eye before the drug metabolizes into its active form of TP-H.

"This molecule is lipophilic and is able to penetrate cell membranes quite efficiently. In some studies, we have shown we can not only get the drug into the anterior chamber but also into the vitreous and the retina," says Joseph.

The topical eye drop has been shown to deliver TP-H to the anterior and posterior segments, leading Othera to plan additional studies for OT-551, including as a possible treatment for both wet AMD and dry eye syndrome. Joseph says there is a link between cataracts and AMD. "There is a commonality in terms of the pathogenesis between cataract formation and AMD and oxidative stress," he notes. "This (OT-551) is a potent free-radical scavenger."

With OT-551 now a candidate for additional indications, Joseph says the drug's future has taken a serendipitous turn. His business experience in the medical field has shown that this is not an uncommon occurrence.

"There is always an interesting phenomenon that takes place in which you start with one [indication], and the potential exists for many others," he notes.

In addition to OT-551, the company has developed a glaucoma drug for which it expects to complete a phase 1 safety trial later this year. That drug, OT-730, is being studied to lower IOP, but at the same time avoid some of the systemic side effects associated with traditional beta-blockers. Overall, the company expects to be in 4 or 5 phase 2 clinical trials in 2006.

To help the company navigate the regulatory process for its leading drugs, Othera recently named Al Reaves, PhD, as senior vice president of clinical development. Dr. Reaves has experience in drug development, specifically bringing drugs from their inception stage to market introduction. Most recently, he led the global clinical development of Visudyne at Novartis.

The establishment of Othera was a marriage of Joseph's entrepreneurial background with his fellow founders' science backgrounds. Together, they wanted to explore the potential of OT-551. Joseph had previously cofounded 3 companies, including Surgical Laser Technologies, SITE Microsurgical Systems, and Orthovita. Othera has been financed with the assistance of several venture capital firms, including a venture arm of Johnson & Johnson. Joseph says Othera is open to partnering with other pharmaceutical or ophthalmic companies in its quest to bring its new drugs to market.

IN BRIEF

Pre-filled Avastin. Wedgewood Pharmacy, a large compounding pharmacy, is now offering Avastin pre-filled syringes. Sold as individual syringes, each 25 mg/ml syringe is drawn up in a Class-100 laminar flow hood to assure sterility and quality. Pre-filled with
0.12 ml for accurate 0.05 ml dosing, Wedgewood says these syringes are a cost-effective therapy option when treating individual patients.

"When physicians cannot easily obtain the medication they need, a capable compounding pharmacy becomes the best source for the desired treatment," says George Malmberg, RPH, CEO of Wedgewood Pharmacy. "We are glad we can offer retinal specialists convenient, pre-filled syringes for their patients."

Ethnicity in AMD. After fundus images were taken of 6,176 randomly selected people ages 45 to 85 representing 4 ethnicities, researchers led by Ronald Klein, MD, MPH, of the University of Wisconsin, found that blacks had the lowest prevalence of any form of AMD at 2.4%. Hispanics were at 4.2%, Chinese at 4.6%, and whites at 5.4%. However, Chinese had the highest rate of exudative AMD at 4.3%. In the 75-84 age group, whites had the highest rate of any form of AMD at 15.8%, while blacks in this age group had AMD prevalence of 7.4%.

Researchers noted that differences in age, gender, pupil size, body mass index, smoking, alcohol consumption, diabetes, and hypertension did not explain the variability among the 4 racial/ethnic groups.

The report first appeared in the March issue of Ophthalmology.

Lpath AMD initiatave. Lpath, Inc., a leader in therapeutic agents against bioactive lipids, has created an ocular division that will initially focus on a drug for the treatment of AMD and other eye diseases.

The company believes its lead drug candidate, Sphingomab, has multiple applications in the treatment of retinal diseases.

In addition to AMD, Lpath will immediately begin investigating the use of Sphingomab in animal models of diabetic retinopathy, glaucoma, and ocular diseases characterized by scar formation, such as proliferative vitreoretinopathy.



Retinal Physician, Issue: May 2006