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