Volume 4, Number 46

Monday, November 15, 2004

In this issue: (click heading to view article)
		Instrument for Assessing Vision-related Quality of Life in Young Children
		Vitreous Surgery With and Without ILM Peeling for Macular Hole Repair
		Directed Retinal Nerve Cell Growth in a Retinal Prosthesis Interface
		Using TOSCA Telescreening Procedures for Diabetic Retinopathy
		Cell Surface Protein Distinguishes Corneal Fibroblasts and Myofibroblasts from Keratocytes
		Briefly

Instrument for Assessing Vision-related Quality of Life in Young Children Quality of life (QOL) instruments are increasingly used in ophthalmological research. Measuring vision-related QOL in young children is complicated by constantly evolving abilities related to normal growth and development. Researchers at the Retina Foundation of the Southwest in Dallas, TX, aimed to develop vision-related QOL instruments for children in different age ranges and to provide initial validation of these instruments. The cross-sectional multicenter study involved 773 pediatric patients aged 7 years or younger with a wide range of ophthalmological diagnoses. A 61-item prototype questionnaire with a wide variety of items was applied to 403 consecutive patients. To derive two age group-specific instruments and to find the age limit dividing the groups, researchers evaluated the usefulness of the items as a function of age. Age-specific versions of a Children"s Visual Function Questionnaire (CVFQ) were thus defined for children aged less than 3 years and for children aged 3 years or older. These were applied to a convenience sample of patients. The investigators used factor analysis to help identify underlying dimensions of the data, and they defined corresponding subscales. Validation was provided by examining the internal consistency reliability and by exploring the associations between scores and clinical characteristics. Investigators defined subscales for General Health, General Vision, Competence, Personality, Family Impact and Treatment, with internal consistency reliabilities ranging from 0.60 to 0.86. The association between subscales scores and age was weak, but investigators saw strong correlations with the level of visual impairment and type of visual diagnosis. The authors of the study believe that the CVFQ they devised may be a useful tool for the pediatric vision research community.

SOURCE: Felius J, Stager DR Sr., Berry PM, et al. Development of an instrument to assess vision-related quality of life in young children. Am J Ophthalmol 2004;138(3):362-72.

Vitreous Surgery With and Without ILM Peeling for Macular Hole Repair Internal limiting membrane (ILM) peeling shows high closure and low reopening rates in macular hole surgery; it is beneficial in older holes but is limited in larger holes and does not significantly improve visual acuity, according to a recent Japanese study. In a retrospective, nonrandomized, comparative trial, researchers compared surgical results for idiopathic macular holes with (175 eyes) and without ILM peeling (417 eyes) in a series of consecutive patients during an eight-year period. All eyes underwent pars plana vitrectomy with intravitreous gas, followed by head-down positioning. No adjunctive therapies were used. Investigators analyzed the comparison of closure and reopening rates and visual acuity with and without ILM peeling. Results showed that initial success rate significantly improved from 81 percent to 92 percent with ILM peeling. ILM peeling significantly improved the initial success rates in all categories of preoperative features. Reopening rates significantly decreased from 7 percent to 0.6 percent with ILM peeling. Among successful cases, line improvement was 6.0 in ILM-reserved eyes and 5.8 in ILM-peeled eyes. Among all cases, line improvement was 5.4 in ILM-reserved eyes and 5.7 in ILM-peeled eyes. Initial success rate of holes measuring more than 400 millimicrons was significantly less than that of holes measuring less than 400 millimicrons with or without ILM peeling. Initial success rate of holes older than six months was significantly lower than that of holes less than six months old without ILM peeling.

SOURCE: Kumagai K, Furukawa M, Ogino N, et al. Vitreous surgery with and without internal limiting membrane peeling for macular hole repair. Retina 2004;24(5):721-7.

Directed Retinal Nerve Cell Growth in a Retinal Prosthesis Interface Retinal prosthetic devices that use microelectrode arrays to stimulate retinal nerve cells may provide a viable treatment for degenerative retinal diseases. Current devices are based on electrical field-effect stimulation of remaining functional neural elements. However, the distance between target neurons and electrodes limits the potential density of electrodes and the ability to stimulate specific types of retinal neurons that contribute to visual perceptions. Investigators at California’s Stanford University School of Medicine conducted a study to investigate the use of microcontact printing (MCP) to direct cultured or explant retinal ganglion cell (RGC) neurites to precise and close stimulation positions and to evaluate the cell types that grow from a retinal explant. RGCs and whole retinal explants were isolated from postnatal Day 7 Sprague-Dawley rats using immunopanning purification and microdissection, respectively. Researchers used aligned MCP to direct the growth of RGC neurites from 105 pure cultures and 64 retinal explants along laminin patterns and to individual microelectrodes. They used 39 immunofluorescence stains to determine the cell types that grew out from the retinal explants. RGC neurite growth was directed reproducibly along aligned laminin micropatterns to individual microelectrodes in pure RGC cultures and from full-thickness explanted rat retinas in 92 percent of experiments. Neurites from pure RGC cultures extended along the laminin lines with an average length of 263 +/- 118 µm (SD; 27 neurites) after 24 hours. Neurites from retinal explants extended in more than 80 percent of experiments and were observed to grow to an average length of 279 +/- 78 µm (64 neurites) after two days in culture. These neurites grew up to 3 mm after one month of culture on the laminin micropatterns. Immunohistochemical stains demonstrated that extended processes from both RGCs and glial cells grew out of retinal explants onto stamped laminin lines. The authors of the study conclude that using MCP to pattern surfaces with growth factors, individual neuronal processes from pure RGC culture and whole retinal explants can be directed to discrete sites on a microelectronic chip surface. By directing RGC neurite processes to specific sites, single cell stimulation becomes possible. They believe that this may allow discrete populations of retinal neurons to be addressed so that physiologic retinal processing of visual information can be achieved.

SOURCE: Leng T, Wu P, Mehenti NZ, et al. Directed retinal nerve cell growth for use in a retinal prosthesis interface. Invest Ophthalmol Vis Sci 2004;45(11):4132-7.

Using TOSCA Telescreening Procedures for Diabetic Retinopathy The TeleOphthalmological Services-Citizen-centered Applications (TOSCA) project was set up to establish a tele-ophthalmology service to screen for diabetic retinopathy (DR) in Europe. Investigators at the Diabetes Research Unit in Cardiff, United Kingdom, aimed to determine the feasibility of establishing telemedicine-based digital screening for detecting DR and to evaluate the satisfaction of patients and healthcare professionals with the screening procedures used within the TOSCA project. The non-randomized, multicenter study was carried out in four different countries over a period of three months and included 390 patients older than 12 years who had diabetes. Researchers took two digital retinal images per eye (macular and nasal) and exported them to a central server. Patients were asked to complete a questionnaire to assess satisfaction. Accredited graders carried out grading remotely, and these results were reported to the referring center. Previously graded patient data chosen randomly to represent examples of both DR and no DR were also sent anonymously to the grading center at a frequency of approximately every 10 patients. Ninety-nine percent of the images were assessable and thus enabled a retinopathy grade to be assigned to the patient. Patients found the retinal photography procedures acceptable; only 6 percent in one center said they would not recommend the procedure. Healthcare professionals (photographers and graders) were also satisfied with the overall procedures. The average time taken to grade each patient was approximately five minutes.

SOURCE: Luzio S, Hatcher S, Zahlmann G, et al. Feasibility of using the TOSCA telescreening procedures for diabetic retinopathy. Diabet Med 2004;21(10):1121-8.

Cell Surface Protein Distinguishes Corneal Fibroblasts and Myofibroblasts from Keratocytes After corneal injury, keratocytes become activated and transform into repair phenotypes (corneal fibroblasts or myofibroblasts). However, these important cells are difficult to identify histologically, so studies of stromal wound healing are often compromised. Recent studies have shown that expression of the cell surface protein Thy-1 is induced in fibroblast populations associated with wound healing and fibrosis in other tissues. Investigators at the University of Houston College of Optometry investigated whether keratocyte transformation to either repair-associated phenotype induced Thy-1 expression. Researchers isolated human corneal keratocytes by collagenase digestion. The cells were either processed immediately (i.e., they were freshly isolated keratocytes) or they were cultured in the presence of 10 percent fetal bovine serum or transforming growth factor-beta to induce transformation to the corneal fibroblast and myofibroblast phenotypes, respectively. Thy-1 messenger RNA (mRNA) and protein expression by freshly isolated keratocytes and corneal fibroblasts were assessed by reverse-transcriptase polymerase chain reaction (RT-PCR) and Western blotting. mRNA was also extracted from the whole intact stroma and assessed by RT-PCR. Thy-1 was localized immunocytochemically in cultured human corneal fibroblasts, myofibroblasts, and in keratocytes in normal human corneal tissue sections. Thy-1 mRNA and protein were detectable in cultured human corneal fibroblasts but not in freshly isolated keratocytes. Whole uninjured stroma showed no detectable Thy-1 mRNA expression. Cultured human corneal fibroblasts and myofibroblasts both labeled for Thy-1, but keratocytes in the stroma of normal human cornea did not. Investigators concluded that Thy-1 expression is induced by transformation of keratocytes to corneal fibroblasts and myofibroblasts, suggesting a potential functional role for Thy-1 in stromal wound healing and providing a surface marker to distinguish the normal keratocyte from its repair phenotypes.

SOURCE: Pei Y, Sherry DM, McDermott AM. Thy-1 distinguishes human corneal fibroblasts and myofibroblasts from keratocytes. Exp Eye Res 2004;79(5):705-12.

BRIEFLY AMO MERGES WITH VISX. Advanced Medical Optics, Inc. (AMO) has announced that it is acquiring laser vision correction giant VISX, Inc. The agreement was unanimously approved by both company"s boards. Under the terms of the merger agreement, VISX stockholders will receive a total value of $26.52 per share of VISX common stock, based on the closing price of AMO"s common stock on November 8, 2004. The total consideration will be approximately 29.0 million shares of AMO stock and $184 million in cash. Upon completion of the transaction, AMO"s stockholders will own approximately 58.5 percent of the combined company and VISX"s stockholders will own approximately 41.5 percent. The combined company will retain the Advanced Medical Optics name and be headquartered in Santa Ana, CA. For more information on the merger, go to www.amo-inc.com or www.visx.com. INSPIRE PHARMACEUTICALS LICENSES NOVEL GLAUCOMA TECHNOLOGY. Inspire Pharmaceuticals, Inc., has signed an agreement to license exclusively several patents from the Wisconsin Alumni Research Foundation (WARF) for use in developing and commercializing new glaucoma treatments. The patents are based on research that focuses on inhibitors of actomyosin contractility or actin microfilament assembly that can effectively relax and alter the shape of the cells and tissue architecture within the trabecular meshwork. The drugs act directly on the trabecular outflow pathway, the site of abnormal flow resistance in glaucoma. Under the terms of the agreement, Inspire undertakes the development of products covered by the licensed patents and funds all further research, development, testing, regulatory filings and potential marketing activities related to any product developed from the license. Inspire will pay WARF potential milestone payments during the development process, including a one-time upfront payment, and will also pay royalties on sales of any regulatory approved product developed from this technology and covered by the associated patents. For more information, go to www.inspirepharm.com. FIRST-EVER MANUFACTURING AGREEMENT SIGNED FOR AMD TRIAL DRUG. Acuity Pharmaceuticals, Inc., has signed a long-term manufacturing agreement with Avecia Biotechnology, Inc., for pharmaceutical-grade supplies of its lead product, Cand5. A small interfering RNA (siRNA), Cand5 uses RNAi technology to turn off genes that produce the growth factor VEGF, believed to be a primary cause of the excess leakage and blood vessel growth that lead to progressive blindness in AMD patients. The substance is currently in Phase I clinical trials in AMD patients--the first human clinical trials for an siRNA therapeutic. Under the terms of the agreement, Avecia will supply Acuity with Cand5 through the clinical development process up to commercial launch of the drug. Financial details of the agreement were not disclosed. BAUSCH & LOMB CELEBRATES EYECARE "VISIONARIES." Bausch & Lomb recently honored the achievements of five eyecare practitioners with the 2004 Bausch & Lomb Visionaries Recognition Award. The program was established to commemorate the Company’s 150th anniversary by honoring eyecare professionals who embody the highest ideals in vision care. Receiving the 2004 awards were: Eleanor E. Faye, MD, of Lighthouse International (New York); Bradley R. Staatsma, MD, of the Jules Stein Eye Institute (Los Angeles); Michael T. Trese, MD, of Associated Retinal Consultants (Royal Oak, MI); George O. Waring III, MD, of InView Vision (Atlanta); and Karla Zadnik, OD, PhD, of the Ohio State University College of Optometry. B&L will equally distribute a total of $150,000 in donations to vision-related, nonprofit organizations chosen by the five Visionaries. For more information on the award recipients, go to www.perfectingvision.com.

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