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CRSToday Europe News – July 2009
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 patients achieved and maintained a 30% improvement in motor function for 6 to 12 months.
Cataract & Refractive Surgery Today Europe 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 Lenti-Vector and EncorStat prevent corneal graft rejection.
The LentiVector technology is a proprietary gene transfer system based on the lentivirus equine infectious anemia virus (EIAV). Applications for the gene vector system include gene therapy, transgenesis, stem cell manipulation, somatic disease models, target validation, and gene discovery. 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. 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 ex vivo treatment of donor corneas prior to transplant; the lentivirus is not directly introduced 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 4¼ C. The vectors implant themselves into the tissue, 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 on surgical time and expenses as well as extend the viability and visual abilities of those patients who would otherwise need multiple grafts and eventually be unable 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 CRST Europe. 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 collaboration agreement with Sanofi-Aventis SA (Paris) 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 results of 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."
Preloaded Injector for Acrylic Lens Receives CE Mark
STAAR Surgical (Monrovia, California) received the Conformité Européene (CE) Mark for the KS-X Preloaded Hydrophobic Acrylic Injector for use in minimally invasive cataract surgery procedures, according to a news release. The KS-X, which allows single or bimanual injection, delivers foldable IOLs through a 2.8-mm incision. According to STAAR, the first shipments of the KS-X in key European and Australian markets are expected to begin in late June. The injector is not approved for sale in the United States.
Morcher Receives FDA Approval for Three Products
The US Food and Drug Administration (FDA) recently approved three capsular tension ring products by Morcher GmbH (Stuttgart, Germany) for marketing in the United States. According to a news release, FCI Ophthalmics, Inc. (Marshfield Hills, Massachusetts), is the US importer and distributor.
Designed by Bonnie An Henderson, MD, of Ophthalmic Consultants of Boston, the Henderson Ring is an open C-shaped loop made of a single piece of PMMA. The ring performs the same basic function as standard capsular tension rings, stabilizing the capsular bag before, during, and after cataract surgery. The Henderson Ring, however, features eight equally spaced indentations that span its circumference to create a sinusoidal shape. The indentations reportedly allow easier nuclear and cortical material removal while maintaining the desired stretch of the capsular bag.
The Ahmed Capsular Tension Segments, designed by Iqbal "Ike" K. Ahmed, MD, FRCSC, an Assistant Professor at the University of Toronto, Canada, is a modified design of the Cionni Capsular Tension Ring (Morcher GmbH). Each segment is a partial ring of clear PMMA that covers approximately one capsular quadrant and includes a hole for temporary or permanent fixation. A single iris retractor hooked into the hole can reportedly support the segment during surgery. The broad, polished ring segments have no sharp points or edges, so they will not tear the capsulorrhexis perioperatively. Following surgery, the segments can be either removed or sutured to the sclera for permanent support. Additionally, one or more segments may be used to support areas of the capsule that have been damaged or have insufficient zonular support. According to Dr. Ahmed, stripping cortex from under and around a capsular tension segment is also easy, and a segment can be used when anterior or posterior capsular tears are present.
The EyeJet Capsular Tension Ring is a disposable injector preloaded with one of three Type 14 capsular tension rings (14, 14A, or 14C) and is available in both left and right versions to accommodate the surgeon's desired direction of implantation. The EyeJet Capsular Tension Ring is most useful for cataract procedures involving zonular dehiscence, pseudoexfoliation, or other anomalies of the capsular bag.
Crystalens HD Available Across Europe
Bausch & Lomb (Rochester, New York) announced that the company has fully launched the Crystalens HD across Europe. This multipiece, silicone, posterior chamber accommodating IOL is indicated for the treatment of cataracts. Designed to mimic the natural crystalline lens, the Crystalens also treats presbyopia using 100% of available light rays at all distances. The HD is the fourth-generation Crystalens IOL.
One-Use Plus Produced Good Visual Outcomes
A large-scale study concluded that flaps created with the One Use-Plus microkeratome with a 130-µm head (Moria SA, Antony, France) yielded highly effective, predictable, and safe outcomes in myopic eyes.1 The results of the study were presented by Mark Wevill, MD, of UltraLase, Birmingham, United Kingdom, at the Royal College of Ophthalmology Annual Congress in May.
The study included 1,008 eyes (529 patients; mean age, 37.2 ±8.6 years). All patients were treated with wavefront-guided LASIK (Zyoptix 217z100; Bausch & Lomb, Rochester, New York). At baseline, mean spherical equivalent was -3.27 ±1.41. Over 18 months, logMAR UCVA and BCVA were assessed at day 1, week 1, months 1 and 6, and at discharge.
Mean UCVA (logMAR) was +0.06 ±0.16 at discharge. Defocus equivalent shifted from 3.22 ±1.47 preoperatively to 0.18 ±0.20 at discharge. In terms of postoperative Snellen UCVA, 96.2% achieved 6/12, and 77.3% achieved 6/6. Only nine eyes (0.83%) experienced a loss of two lines of BCVA.
Of 421 patients who responded to a patient satisfaction questionnaire, 41.3% claimed that the results could not be better, 38.6% were satisfied, 14.3% hoped for better results, and 1.2% regretted having the procedure.
Correction Safe, Predictable With AcrySof Phakic IOL
One-year interim analysis of a phase 3, prospective, multicenter European clinical study showed that the AcrySof phakic angle-supported IOL (Alcon Laboratories, Inc.) yielded positive refractive correction and predictability with acceptable safety in patients with moderate to high myopia.1
Thomas Kohnen, MD, a Professor of Ophthalmology and Deputy Chairman at the Johann Wolfgang Goethe-University Clinic, in Frankfurt, Germany, and a Visiting Professor at the Baylor College of Medicine, in Houston, and colleagues implanted the AcrySof phakic angle-supported IOL in 190 eyes (190 patients). The preoperative mean manifest refraction spherical equivalent was -10.38 ±2.43 D.
Of 190 patients enrolled, 161 completed 1-year follow-up. According to investigators, no patient lost two or more lines of BCVA. A UCVA of 20/20 or better was achieved by 57.8% of participants; 99.4% achieved 20/40 or better. A BCVA of 20/32 or better was achieved by 100% of patients, and 85.7% achieved 20/20 or better.
The mean postoperative manifest refraction spherical equivalent was -0.23 ±0.50 D (range, -2.50 to 0.75 D), the study reported. Residual refractive error was within ±1.00 D from the target for 95.7% of patients and within ±0.50 D for 72.7% of patients. The overall mean percentage change in central endothelial cell density 1 year after surgery was
-4.77 ±8.04% (n=139). No pupil ovalization, pupillary block, or retinal detachment were reportedly observed.
Evidence of Accommodation With Synchrony Dual-Optic IOL
An analysis of five patients implanted with the Synchrony Dual-Optic accommodating IOL (Visiogen, Inc., Irvine, California) confirmed that the lens provides a good amplitude of accommodation. The results of the study were presented by Douglas D. Koch, MD, of the Cullen Eye Institute in Houston, Texas, at the American Society of Cataract and Refractive Surgery (ASCRS) meeting in San Francisco.1
Dr. Koch compared objective and subjective measurements of accommodation, including distance-corrected near visual acuity (only used twice), ultrasound biomicroscopy, and wavefront aberrometry. Patients' distance-corrected near visual acuity ranged from 20/20 to 20/32, and their push-down accommodative amplitude ranged from 2.76 to 3.22 D. Ultrasound biomicroscopy images confirmed the position of the anterior optic and forward axial movement of the front of the optic during accommodation. Dr. Koch noted that the optic's movement changed the refractive power of the lens, a finding that confirmed that the Synchrony is truly an accommodating IOL.
"It is gratifying to see this clear evidence of true accommodation," Dr. Koch said in an e-mail to CRST Europe. "I suspect that the amount of actual movement may be greater than was measured, as testing conditions with ultrasound biomicroscopy are challenging to the patient and may not elicit maximal accommodative effort."
Patient-Harvested Stem Cells Healed Damaged Corneas
A stem-cell transplantation procedure in which patient-harvested cells were expanded on therapeutic contact lenses, rehabilitated corneas damaged by limbal stem cell deficiency (LSCD), according to results of a small study conducted by researchers at the University of New South Wales, Sydney, Australia.1
The trial included three patients. Two patients had extensive corneal damage resulting from multiple surgeries to remove ocular melanomas, and one patient was aniridic. The patients' own limbal or conjunctival stem cells were cultured on therapeutic contact lenses, which were then placed onto the damaged corneas for 10 days. During this period, the cells recolonized the eye surface. Follow-up ranged from 8 to 13 months.
BCVA significantly improved in all eyes within weeks of the procedure. A stable, transparent corneal epithelium was restored in each patient, and there was no recurrence of conjunctivalization or corneal vascularization. Patients reported significant improvements in symptoms.
Correction
The article, Top Products of the Year, by Robert H. Osher, MD, (May 2009, pages 74-76), wrongly reported that preloaded injectors are available in Europe from Hoya Vision Care Europe (Uithoorn, Netherlands). Preloaded injectors are available in Europe from Hoya Surgical Optics GmbH (Frankfurt, Germany).
– Compiled by Jennifer Kreatsoulas, PhD, News and Contributing Editor
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