Volume 7, Number 9
Monday, March 5, 2007



In this issue: (click heading to view article)
Fifteen-Year Cumulative Incidence of AMD
Treatment of Central Retinal Vein Occlusion by Radial Optic Neurotomy
Corneal Epithelial Cell Line Spontaneously Derived from Human Limbal Cells
Genome-Wide Linkage Scan for Genes Contributing to Retinopathy Risk
Briefly





Fifteen-Year Cumulative Incidence of AMD

Investigators at the University of Wisconsin School of Medicine and Public Health conducted a population-based cohort study documenting the long-term incidence of signs of age-related macular degeneration (AMD) and a continuum from small hard drusen to late AMD in older persons in the population.

The study included 3,917 participants ages 43 to 86 at the time of a baseline examination in 1988 through 1990 and with information collected in follow-up in 1993 through 1995, and/or 1998 through 2000, and/or 2003 through 2005. Stereoscopic fundus photographs were graded using the Wisconsin Age-Related Maculopathy Grading System. Main outcome measures included cumulative incidence of drusen type and size, pigmentary abnormalities, geographic atrophy and exudative AMD accounting for competing risk of death.

The 15-year cumulative incidence was 14.3 percent for early AMD (the presence of either soft indistinct drusen or pigmentary abnormalities with any type of drusen) and 3.1 percent for late AMD (presence of exudative AMD or geographic atrophy). Results showed an increased incidence of AMD lesions with age. Participants 75 years or older at baseline had significantly higher 15-year incidences of the following characteristics than people 43 to 54 years of age: larger drusen (125 microns in diameter, 24.1 percent vs. 10.6 percent of younger participants), soft indistinct drusen (18.7 percent vs. 6.5 percent of younger participants), retinal pigmentary abnormalities (20.2 percent vs. 3.7 percent of younger participants), exudative macular degeneration (4.4 percent vs. 0.4 percent of younger participants) and pure geographic atrophy (3.2 percent vs. 0 percent of younger participants). Controlling for age, compared with those with small numbers of only small hard drusen (one to two), those with large numbers of only hard drusen (eight or more) had an increased 15-year age-adjusted incidence of both soft indistinct drusen (16.3 percent vs. 4.7 percent of those with small numbers of small hard drusen) and pigmentary abnormalities (10.6 percent vs. 2.7 percent of those with small numbers of small hard drusen). Eyes with soft indistinct drusen or pigmentary abnormalities at baseline were more likely to develop late AMD at follow-up than eyes without these lesions (17.8 percent with soft indistinct drusen vs. 1.2 percent without and 12.9 percent with soft indistinct drusen vs. 1.7 percent without).

The authors maintain that the 15-year cumulative incidence of late AMD in people 75 years or older in this study indicates a public health problem of significant proportions, especially because the percentage of the U.S. population who are in this age group is expected to increase by 54 percent between 2005 and 2025.

SOURCE: Klein R, Klein BE, Knudtson MD, et al. Fifteen-year cumulative incidence of age-related macular degeneration: the Beaver Dam Eye Study. Ophthalmol 2007;114(2):253-62.
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Treatment of Central Retinal Vein Occlusion by Radial Optic Neurotomy

To evaluate the potential role of radial optic neurotomy (RON), a new surgical technique has been recently proposed for treating central retinal vein occlusion (CRVO). In this study, German researchers investigate the hypothesis that CRVO constitutes a neurovascular compartment syndrome at the site of the lamina cribrosa, which can be alleviated by performing a radial incision at the nasal part of the optic nerve head, relaxing the cribriform plate and the adjacent sclera.

The study included 107 patients, 55.6 percent male, 44.4 percent female, with a median age of 68 years (range, 21 to 91 years) who were treated with RON for CRVO at five collaborating ophthalmologic centers. All patients were evaluated using standardized protocol. Investigators used reference images for analysis of the angiographic and fundus findings, then reviewed intraoperative and postoperative complications.

RON was performed on 55 right eyes and 52 left eyes of all patients. The median follow-up time was six months (range, 1 to 24 months). The median preoperative visual acuity (VA) was 0.05 (logMAR 1.3), increasing to a median postoperative VA of 0.08 (logMAR 1.1). Patients with an interval of more than 90 days between RON and onset of CRVO showed no significant change in VA at the six-month follow-up. Severe peripapillary swelling of the optic nerve head before RON resulted in an average increase of 4.2 lines in VA at the six-month follow-up. Angiographic findings of shunt vessels were seen in 18 of 30 cases after 12 months and were accompanied by an average improvement of VA of six lines. Visual field tests showed various defects in 86.8 percent of all cases. One patient (0.9 percent) had an iatrogenic injury of the central retinal artery.

The authors conclude that, despite the potential risk of visual field defects, RON seems to be a safe procedure. The majority of patients in this study showed rapid normalization of the morphologic fundus findings, with an improvement in VA uncommon for the natural history of CRVO. They suggest that a prospective study be conducted to further investigate.

SOURCE: Hasselbach HC, Ruefer F, Feltgen N, et al. Treatment of central retinal vein occlusion by radial optic neurotomy in 107 cases. Graefes Arch Clin Exp Ophthalmol 2007; Jan 12 [Epub ahead of print].
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Corneal Epithelial Cell Line Spontaneously Derived from Human Limbal Cells

The objective of this Chinese study was to establish a spontaneously derived human corneal epithelial cell line from a normal human limbus that retains differentiation potential and proliferative properties under continuous cell culture.

After 50 passages of epithelial cells obtained from human limbal tissue, a cell line spontaneously emerged. The immortalized cells showed a cobblestone appearance and displayed dense microvilli on their apical cell surface membrane. Colony-forming efficiency was 5 to 6 percent, and population doubling time was 19.6 hours. On the mRNA level, cytokeratin (CK) 3 and 12 were detected in this cell line. On the protein level, the cells expressed CK3, CK12, CK14, CK19, vimentin and some other proteins such as F-actin and beta-tubulin and beta(1)-integrin; however, they lacked p63.

The immortalized cells had a heteroploid karyotype but did not exhibit tumorigenic features. When cultured on an air-liquid interface, the cells were able to form stratified multilayer epithelia.

The authors believe that these results indicate the spontaneous establishment of a new human corneal epithelial cell line from normal limbal tissue through serial culture. They suggest that the cell line would be useful for studies of corneal epithelial biology and reconstructive corneal tissue engineering.

SOURCE: Liu J, Song G, Wang Z, et al. Establishment of a corneal epithelial cell line spontaneously derived from human limbal cells. Exp Eye Res 2007; Jan 11 [Epub ahead of print].
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Genome-Wide Linkage Scan for Genes Contributing to Retinopathy Risk

The Human Genetics Center at the University of Texas Health Science Center, Houston, conducted a genome-wide linkage scan for genes contributing to diabetic retinopathy risk using 794 diabetes cases from 393 Mexican-American families from Starr County, Texas, who have at least two diabetic siblings.

The sample included 567 retinopathy cases comprising 282 affected sibling pairs. Retinopathy was classified as none, early non-proliferative, moderate-to-severe nonproliferative or proliferative. Using 360 polymorphic markers (average spacing: 9.4 cM), the researchers conducted nonparametric linkage analysis, followed by ordered-subset analysis (OSA) ranking families by average age of diabetes diagnosis. For any retinopathy, the highest logarithm of the odds (LOD) scores including all families were on chromosomes 3 (2.41 at 117 cM) and 12 (2.47 at 15.5 cM). OSA LOD scores greater than 2 for any retinopathy occurred on chromosomes 12 (4.47 at 13.2 cM), 15 (3.65 at 100.6 cM) and 20 (2.67 at 54.1 cM). OSA LOD scores greater than 2 either for moderate-to-severe nonproliferative or proliferative retinopathy occurred on chromosomes 5 (2.53 at 11.2 cM), 6 (2.28 at 30.6 cM) and 19 (2.21 at 100.6 cM).

Results of the unconditional linkage analysis revealed suggestive evidence of linkage with diabetic retinopathy on two chromosomes, while ordered-subset analysis revealed strong evidence of linkage on two chromosomes and suggestive evidence on four chromosomes Candidate genes were identified in most implicated regions.

SOURCE: Hallman DM, Boerwinkle E, Gonzalez VH, et al. A genome-wide linkage scan for diabetic retinopathy susceptibility genes in Mexican Americans with type 2 diabetes from Starr County, Texas. Diabetes 2007; Jan 24 [Epub ahead of print].
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BRIEFLY
  • GLAUCOMA RESEARCH FOUNDATION AWARDS $200,000 TO FIVE PROMISING RESEARCH PROJECTS. Grants in the amount of $200,000 were awarded in January by the Glaucoma Research Foundation (GRF) to fund five Pilot Projects at Tel Aviv University, University of California at Irvine, University of Alabama at Birmingham, Dalhousie University and the Medical College of Wisconsin, according to GRF President and CEO Thomas M. Brunner. The Pilot Project grants provide essential seed money for research studies with breakthrough potential, according to Brunner. Results from the studies promise to accelerate the pace of discovery for improved glaucoma treatments and enhance the quality of life for people with glaucoma. Pilot Grant awardees included $40,000 to Ruth Ashery-Padan, PhD, Tel Aviv University, Israel, to study the roles of the Pax6 gene in the development of the trabecular meshwork and Schlemm"s canal; $40,000 to Donald J. Brown, PhD, University of California, Irvine, to study pressure-induced dynamic 3D changes in lamina cribrosa using second harmonic imaging microscopy; $40,000 to Christopher A. Girkin, MD MSPH, University of Alabama, Birmingham, to study the role of the lamina cribrosa in development and progression of glaucoma; $40,000 to Sharon A. Haymes, PhD, Dalhousie University, Nova Scotia, Canada, to study strategies used by glaucoma patients to view real-world scenes; and $40,000 to Brian A. Link, PhD, Medical College of Wisconsin, Milwaukee, to identify genes that promote retinal ganglion cell degeneration in the context of elevated intraocular pressure. Founded in 1978, the Glaucoma Research Foundation works to prevent vision loss from glaucoma by investing in innovative research, education and support with the ultimate goal of finding a cure. For more information, go to www.glaucoma.org.
  • INSPIRE LICENSES AZASITE FOR OCULAR INFECTIONS. Inspire Pharmaceuticals recently signed an exclusive licensing agreement with InSite Vision Incorporated for the U.S. and Canadian commercialization of AzaSite (1.0% azithromycin ophthalmic solution), a topical anti-infective product currently under review by the FDA for treating bacterial conjunctivitis. Under the terms of the agreement, Inspire has acquired from InSite exclusive rights to commercialize AzaSite for ocular infections in the United States and Canada. AzaSite contains the drug azithromycin, a broad-spectrum antibiotic, formulated with DuraSite, InSite"s patented drug-delivery vehicle. According to terms of the agreement, Inspire will pay InSite Vision an upfront license fee of $13 million and an additional $19 million milestone payment contingent upon regulatory approval by the FDA. Inspire will also pay a royalty of 20 percent in the first two years of commercialization and 25 percent thereafter on net sales of AzaSite for ocular infections in the United States and Canada, if approved by regulatory authorities. The two companies have also entered into a supply agreement for azithromycin. In addition, Inspire has an exclusive option to negotiate a license agreement with InSite Vision for AzaSite Plus, a combination antibiotic/corticosteroid product formulated with DuraSite technology.
  • ALCON HONORS LEADING SCIENTISTS FOR OUTSTANDING OPHTHALMIC RESEARCH. The independent Scientific Selection Committee of the Alcon Research Institute (ARI) recently announced the ARI’s 2007 award recipients, recognized for their outstanding research contributions to the field of ophthalmology. The ARI, established in 1981 and sponsored by Alcon Laboratories, Inc., a subsidiary of Alcon, identifies exceptional ophthalmic scientists and awards each with $100,000 unrestricted grants to further their research endeavors. Each year, five or six awards are granted based on the nominees’ research achievements. Many of the award recipients have also been recognized with awards from other leading organizations, including the Association for Research in Vision and Ophthalmology (ARVO), the American Academy of Ophthalmology (AAO), International Society for Eye Research (ISER) and the American Society of Cataract and Refractive Surgeons (ASCRS). The 2007 ARI Award winners are: Rando Allikmets, PhD, Acquavella Associate Professor and Research Director, Departments of Ophthalmology and Pathology & Cell Biology, Harkness Eye Institute, Columbia University; Dimitri Azar, MD, Billie Alexander Field Chair of Ophthalmologic Research, professor and department head, University of Illinois at Chicago; Paulus de Jong, MD, PhD, Clinical Ophthalmogenetics Department, Netherlands Institute for Neuroscience of the Royal Academy of Arts and Sciences, Amsterdam; Paul Lee, MD, JD, James Pitzer Gills III, MD and Joy Gills, Professor of Ophthalmology and vice chair, Department of Ophthalmology, Albert Eye Research Institute, Duke University; Lois Smith, MD, PhD, associate professor of ophthalmology, Harvard Medical School, Children"s Hospital, Boston; and Bernhard H.F. Weber, PhD, professor and head of the Institute of Human Genetics, University of Regensburg, Germany. For more information on the ARI, go to www.alcon.com/contact-alcon/alcon-res-inst.asp.


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