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News
Gene Vector Delivery Platform Targets Prevention of Corneal Graft Rejection
The LentiVector (Oxford BioMedica plc, Oxford, United Kingdom) is under evaluation as a mechanism to deliver EncorStat (Oxford BioMedica), a gene-based treatment that uses a lentivirus to prevent corneal graft rejection by blocking vascularization. For other indications, the LentiVector has been shown to efficiently and effectively deliver genes to a target site. For example, results from a phase 1/2 clinical trial using the LentiVector delivery system with ProSavin (Oxford BioMedica) in patients with Parkinson's disease showed that subjects achieved and maintained a 30% improvement in motor function for 6 to 12 months.
Cataract & Refractive Surgery Today recently spoke with Stuart Naylor, PhD, chief scientific officer and executive director of Oxford BioMedica, and his colleague Nick Woolf, chief business officer, about how the LentiVector and EncorStat prevent corneal graft rejection. The LentiVector technology is a proprietary gene transfer system based on the lentivirus equine infectious anemia virus. Applications for the gene vector system include gene therapy, transgenesis, stem cell manipulation, somatic disease models, target validation, and gene discovery, Dr. Naylor explained. In ocular indications, however, the primary application of the LentiVector system is either to establish a local factory to produce therapeutic molecules (eg, antiangiogenic factors) or, in the case of targeting retinal diseases, to reprogram pathology-causing parent retinal cells by neutralizing the effect of mutant genes with corrected versions of the appropriate gene. According to Dr. Naylor, the therapeutic genes are engineered into the viral vector genome that has been stripped of all of its native genetic information, and it is then packaged using the normal structural proteins of the lentivirus.
Currently, Oxford BioMedica's product candidate EncorStat is undergoing preclinical testing. Although the cornea is one of the most successfully transplanted tissues, a significant number of grafts are rejected due to neovascularization of the recipient corneal bed, the graft/host interface, or the graft itself.1 Once neovascularization has occurred in an eye, the likelihood that it will develop in subsequent transplants increases.
EncorStat is designed for the ex vivo treatment of donor corneas prior to transplantation; the lentivirus is not introduced directly into the body. The LentiVector delivers EncorStat, which is made of two antiangiogenic proteins—angiostatin and endostatin—to the donor corneas, which are stored at 4°C. The vectors reportedly implant themselves into the tissue, thereby engineering the transplanted corneas to block encroaching vessels from delivering the immune cells that cause the rejection response.
"With the LentiVector, EncorStat should be an effective approach to prevent graft rejection," Dr. Naylor said. "This therapy will save surgical time and expenses as well as extend the viability [of the graft] and visual abilities of patients who would otherwise need multiple grafts and eventually not be able to receive future ones," he added. EncorStat has been successful in large-animal studies.1 Oxford BioMedica anticipates that the gene-based therapy will progress through clinical studies fairly quickly.
"EncorStat is a groundbreaking therapy, because it is the first gene therapy designed to prevent corneal transplant rejection and corneal transplant neovascularization," said J. Timothy Stout, MD, PhD, MBA, in an interview with CRSToday. Dr. Stout is a professor of ophthalmology and the vice president for business development at the Oregon Health & Science University, Casey Eye Institute, in Portland. Dr. Stout is collaborating with Oxford BioMedica on the development of EncorStat.
"EncorStat ameliorates the imbalance of proangiogenic factors that leads to neovascularization," Dr. Stout added. "Blood vessel growth in the eye accounts for many serious problems, such as corneal rejection, diabetic retinopathy, age-related macular degeneration, and certain types of glaucoma. Being able to control when and where blood vessels grow is therapeutically a good thing."
Oxford BioMedica recently entered into a collaborative agreement with Sanofi-Aventis SA (Paris, France) to develop EncorStat and three ocular therapies that target eye diseases with an option for further development, manufacturing, and commercialization on a worldwide basis pending the results of the phase 1/2 human clinical trials. "We are delighted to be working with Sanofi-Aventis on the advancement of our LentiVector system in the field of ophthalmology," Mr. Woolf said. "This collaboration enables us to accelerate the development of four novel gene therapies that have the potential to benefit patients with debilitating ocular diseases."
Organization Calls for Universal Comprehensive Eye Examinations for Children
According to a report from the National Commission on Vision and Health, children may be more successful in school if they undergo mandatory universal comprehensive eye examinations before they return to school in the fall.
The report, "Building a Comprehensive Child Vision Care System," found that children have their eyes examined at low rates and that those who do often fail to receive necessary follow-up and treatment, particularly children without health insurance and those living in poverty. Although many states require that children receive some type of vision screening prior to entering public schools, most states do not use the most sophisticated screening tests and neglect to enforce follow-up for children who fail the examination, according to the report. Currently, Kentucky, Illinois, and Missouri are the only states that require comprehensive eye examinations for children entering school. Fifteen states do not require any form of eye screenings or examinations. The inconsistency among states is creating a public health emergency for millions of children, declared the commission.
The commission recommended that agencies at the federal, state, and local levels collaborate with academic institutions, businesses, providers, and the public to create a comprehensive vision care system that will ensure all children are assessed for potential ocular and visual problems, both before they enter school and throughout their education. In addition to universal access to vision care, the commission recommended a point of accountability within local public health agencies, a national educational campaign, and ongoing data collection to monitor the use and efficacy of vision examinations for children.
Akreos MICS IOL Launched in the United States
Bausch & Lomb Surgical (Rochester, NY) launched the Akreos AO Micro Incision Lens (model MI60L), also known as the Akreos MICS IOL, in the United States. According to a company news release, the spherical, aberration-free lens is designed for implantation through a 1.8-mm incision.
AcrySof IQ Toric Lens Approved for NTIOL Designation
The AcrySof IQ Toric IOL (Alcon, Inc., Huenenberg, Switzerland) was granted a New Technology Intraocular Lens (NTIOL) designation by the Centers for Medicare & Medicaid Services. The lens is included in the reduced spherical aberration class of NTIOLs, a news release said. Due to the lens' NTIOL status, Medicare will reimburse ambulatory surgery centers an additional $50 for every AcrySof IQ Toric IOL that is implanted. According to the company, the designation went into effect on July 31, 2009.
CareCredit Promotes 3D-Eye Home
CareCredit, Inc. (Costa Mesa, CA), announced that the company will support Eyemaginations, Inc. (Towson, MD), by promoting 3D-Eye Home to its patients. 3D-Eye Home combines Web-based technology with Eyemaginations' patient education tools for home use. According to a spokesperson for Eyemaginations, CareCredit is sponsoring the cost of 3D-Eye Home for associated practices as well as paying the doctor's fee for the program.
Preloaded IOL Injection System Introduced to the US Market
The iSert Preloaded IOL Injection System (Hoya Surgical Optics, Inc., Chino Hills, CA) has been approved for use in the United States. According to the company, the iSert, which has been available in Europe and Japan since 2007, provides predictable and safe insertion of glistening-free hydrophobic acrylic aspheric IOLs through a sub-2.4-mm incision. The preloaded device reportedly eliminates the risk of contamination from endotoxins associated with reusable instruments.
3D Training Video for Manual, Small-Incision Cataract Surgery
TrueVision Systems, Inc. (Santa Barbara, CA), partnered with the Mission Eyes Network and the Christian Ophthalmology Society to record a 3D, high-definition video of manual small-incision cataract surgery. According to a news release, the video will be used to train surgeons how to perform this surgical technique in developing countries. Manual small-incision cataract surgery is reportedly an effective, high-volume, low-cost procedure that does not require high-tech instrumentation.
"For cataract blindness in the developing world, manual, sutureless small-incision cataract surgery is the most cost effective method that must be increasingly adopted worldwide," stated David F. Chang, MD, in a news release. Dr. Chang is a clinical professor at the University of California, San Francisco, and he is in private practice in Los Altos, California. "For scalable skills transfer, 3D video can play a major role in educating and training more surgeons."
Glenn Strauss, MD, chief eye surgeon on the Mercy Ships, and Timothy R. Fincher, MD, an ophthalmic surgeon in Dallas, reportedly filmed the video in the Republic of Benin in West Africa.
Mydriatic, Anti-Inflammatory Agents Combined in Trial
The results of a phase 1/2 clinical trial of OMS302 (Omeros Corporation, Seattle, WA) suggest that the agent helped maintain mydriasis throughout cataract surgery and reduced pain in the early postoperative period. OMS302 is a proprietary combination of anti-inflammatory and mydriatic agents.
In a parallel-group, double-blind, vehicle-controlled study, 61 patients undergoing cataract extraction with lens replacement were divided among three treatment arms. In the first arm, OMS302 was added to a standard irrigating solution and delivered directly to the eye during surgery. In the second arm, patients received a standard irrigating solution plus a mydriatic agent. In the third arm, patients received a standard irrigating solution only. Pupillary size was monitored during surgery, and patients' pain and inflammation were monitored for 14 days after surgery.
According to the company, patients treated with OMS302 reported less postoperative pain and demonstrated statistically significantly improved maintenance of mydriasis during surgery compared with patients treated with a standard irrigating solution only. No serious adverse events were observed. Omeros is reportedly conducting additional studies to determine the optimal dosage of OMS302's mydriatic and anti-inflammatory agents.
In Memoriam—Jeffrey P. Gilbard, MD
A tribute by Eric D. Donnenfeld, MD.
Ophthalmology lost a truly unique individual on August 12, 2009, with the untimely death of Jeffrey P. Gilbard, MD, following a bicycle accident. Jeff was a gifted cornea specialist and expert on dry eye whose pioneering research led to new treatments for dry eye disease. He became interested in dry eye disease in 1976 as a medical student, and his research into this condition was supported by a grant from the National Eye Institute. To this day, he remains the youngest scientist to receive financial support from this institution.
The core of Jeff's research and multiple publications was the breakthrough concept that the osmolarity of tears played a large role in dry eye disease. This led to the development of a hypotonic artificial tear that contained bicarbonate and potassium—a landmark event in the management of ocular surface disease. Jeff then entered the next phase of his life with the founding of Advanced Vision Research (AVR; Woburn, MA) in 1995. For 14 years, he served as AVR's CEO and chief scientific officer. His first product, Theratears, was a great success and led to multiple additional advances. He is also considered one of the first ophthalmologists and researchers to understand the correlation between nutrition and the health of the eye, a discovery that led to the development of several holistic ophthalmic nutritional supplements.
In an era of large pharmaceutical corporations, Jeff was a refreshing maverick. He lectured tirelessly at any venue with people who would listen to his novel ideas. At major meetings, Jeff was the face of AVR. He would stand at his booth and speak with passion and conviction to anyone passing by about the importance of treating dry eye disease. Over the course of his professional career, Jeff led the charge to change dry eye from an inevitable complication of aging to a treatable disease. His discoveries offered relief to and improved the quality of life and vision of millions of dry eye patients.
Jeffrey Gilbard is survived by his beloved wife of 19 years, Liz, and his three children, whom he adored.
Eric D. Donnenfeld, MD, is a trustee of Dartmouth Medical School in Hanover, New Hampshire, and he is a partner in Ophthalmic Consultants of Long Island in Rockville Centre, New York.
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