Volume 8, Number 35
Monday, September 8, 2008



In this issue: (click heading to view article)
RNAi Therapy May Be Related to Geographic Atrophy in Some Patients
Ocular and Systemic Factors Related to IOP in Japanese Adults
Prevalence of Amblyopia and Strabismus in African-American and Hispanic Children
New Technique for Repair of Combined Orbital Floor and Medial Wall Fractures
Briefly










RNAi Therapy May Be Related to Geographic Atrophy in Some Patients

It is known that advanced AMD consists of geographic atrophy and choroidal neovascularization; however, the specific genetic variants that predispose patients to geographic atrophy are largely unknown. In this study, researchers from Johns Hopkins University tested for an association between the functional toll-like receptor 3 gene (TLR3) variant rs3775291 and AMD in Americans of European descent. They also tested for the effect of TLR3 Leu and Phe variants on the viability of human retinal pigment epithelial (RPE) cells in vitro and on apoptosis of RPE cells from wild-type mice and Tlr3-knockout (Tlr3[-/-]) mice.

The Phe variant (encoded by the T allele at rs3775291) was associated with protection against geographic atrophy. This association was replicated in two independent case-control series of geographic atrophy. No association was found between TLR3 variants and choroidal neovascularization. A prototypic TLR3 ligand induced apoptosis in a greater fraction of human RPE cells with the Leu-Leu genotype than those with the Leu-Phe genotype and in a greater fraction of wild-type mice than Tlr3(-/-) mice.

Based on these results, the investigators believe that the TLR3 412Phe variant confers protection against geographic atrophy, probably by suppressing the death of RPE cells. Because double-stranded RNA (dsRNA) can activate TLR3-mediated apoptosis, the data suggest a role of viral dsRNA in the development of geographic atrophy and point to potential toxic effects of short-interfering RNA (siRNA) therapies in the eye for some patients.

SOURCE: Yang Z, Stratton C, Francis PJ, et al. Toll-like receptor 3 and geographic atrophy in age-related macular degeneration. N Engl J Med 2008 Aug 27 [Epub ahead of print].		 Table of Contents






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Ocular and Systemic Factors Related to IOP in Japanese Adults

Because IOP and age are consistent risk factors of glaucoma, it is of special interest to know the association between IOP and possibly relating factors, including age, in Japan, where a high prevalence of normal-tension glaucoma has been reported. The aim of this study by investigators at Japan"s Gifu University Graduate School of Medicine was to evaluate the distribution of and factors related to applanation IOP in a population-based group.

Investigators performed screening exams, including measurements of IOP with Goldmann applanation tonometry and central corneal thickness, on a randomly sampled group of 3,021 residents (response rate 78.1 percent) of Tajimi City, Japan, aged 40 years or older. Among right eyes without glaucoma, suspected glaucoma or other disorders that could affect correct IOP measurements, IOP averaged 14.6 (SD 2.7) in men and 14.5 (2.5) mmHg in women, with no significant intergender difference. Multiple regression analyses revealed that age was significantly negatively correlated with IOP. Higher body mass index (B = 0.14/BMI), higher mean blood pressure (B = 0.022/mmHg), history of diabetes, thicker cornea (B = 0.014/µm), higher myopia (B = 0.055/diopters) and steeper corneal curvature (B = -0.72/mm) were also significantly correlated with higher IOP.

Based on these results, investigators concluded that in the adult Japanese population, applanation IOP was negatively correlated with age after adjusting for other related factors, and that IOP and myopia are positively correlated in this population.

SOURCE: Kawase K, Tomidokoro A, Araie M, et al. (Tajimi Study Group, Japan Glaucoma Society). Ocular and systemic factors related to intraocular pressure in Japanese adults: the Tajimi study. Br J Ophthalmol 2008;92(9):1175â€"1179.		 Table of Contents

 



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Prevalence of Amblyopia and Strabismus in African-American and Hispanic Children

The Doheny Eye Institute conducted this cross-sectional Multi-Ethnic Pediatric Eye Disease Study to determine the age- and ethnicity-specific prevalences of strabismus in African-American and Hispanic/Latino children ages 6 to 72 months and of amblyopia in African-American and Hispanic/Latino children ages 30 to 72 months.

The study was conducted in Los Angeles County, California. A total of 77 percent of eligible children completed a comprehensive eye examination; this report focuses on results from 3,007 African-American and 3,007 Hispanic/Latino children. Eligible children in all enumerated households in 44 census tracts were identified. Participants underwent an in-home interview and were scheduled for a comprehensive eye examination and in-clinic interview. The examination included evaluation of ocular alignment, refractive error and ocular structures, as well as determination of optotype visual acuity (VA) in children 30 months and older. Main outcome measures included the proportion of 6-month-olds to 72-month-olds with strabismus on ocular examination and the proportion of 30-month-olds to 72-month-olds with optotype VA deficits and amblyopia risk factors consistent with predetermined definitions of amblyopia.

Strabismus was detected in 2.4 percent of Hispanic/Latino children and 2.5 percent of African-American children, and was more prevalent in older children than in younger children. Amblyopia was detected in 2.6 percent of Hispanic/Latino children and 1.5 percent of African-American children (a statistically significant difference) and 78 percent of cases of amblyopia were attributable to refractive error. Amblyopia prevalence did not vary with age.

The authors concluded that among Hispanic/Latino and African-American children in Los Angeles County, strabismus prevalence increases with age, but amblyopia prevalence appears stable by three years. They believe that these findings may help to optimize the timing and modality of preschool vision screening programs.

SOURCE: Tarczy-Hornoch K, Varma R, Cotter S, et al. (Multi-ethnic Pediatric Eye Disease Study Group). Prevalence of amblyopia and strabismus in African American and Hispanic children ages 6 to 72 months: the Multi-Ethnic Pediatric Eye Disease Study. Ophthalmol 2008;115(7):1229â€"1236.e1.		 Table of Contents






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New Technique for Repair of Combined Orbital Floor and Medial Wall Fractures

Researchers in Indianapolis report on a new technique of implanting a single 0.4-mm-thick nylon foil (Supramid) continuously across combined medial wall and floor fractures within weeks of orbital trauma in this retrospective interventional case series.

The study included patients with combined medial wall and floor fractures with or without external orbital and facial fractures, without prior surgery; all patients were in the early post-trauma phase. A total of 102 orbits in 98 consecutive patients were treated with a "wraparound" technique, which is explained in detail in the study. Comatose patients and those with cranial nerve palsies, severe globe injury, anophthalmia or previous repair of the same fractures were excluded. Patients underwent surgery from five to 21 days after trauma. Postoperatively (average, 6.2 months), patients were evaluated for enophthalmos, extraocular motility and diplopia.

Normal globe position and full extraocular motility without diplopia was accomplished in 101 of 102 orbits. One orbit had persistent enophthalmos, requiring a second procedure; the same patient had ipsilateral restriction in extreme upgaze, but no diplopia symptoms. This orbit had complete loss of inferomedial strut support. Overall, strut loss was not a risk factor for subsequent enophthalmos.

No other patient had globe malposition, restrictive myopathy or diplopia. No implant migration, hemorrhage, fistula or infection was observed. The transconjunctival and canthal wounds were hidden and tolerated by all patients with no eyelid cicatrization, webbing or malposition.

The authors maintain that the "wraparound" technique for 0.4-mm nylon foil implantation continuously across orbital floor and medial wall fractures, which was associated with almost no enophthalmos and diplopia in this series, is an effective technique for repair of combined orbital floor and medial wall fractures.

SOURCE: Nunery WR, Tao JP, Johl S. Nylon foil "wraparound" repair of combined orbital floor and medial wall fractures. Ophthal Plast Reconstr Surg 2008;24(4):271â€"275.		 Table of Contents






BRIEFLY
  • NEW TREATMENT OPTION FOR GLAUCOMA RECEIVES FDA EXPANDED 510K INDICATION. The FDA has granted 510k clearance for iScience Interventional"s canaloplasty microcatheter, for catheterization and viscodilation of Schlemm’s canal to reduce IOP in adult patients with primary open-angle glaucoma. The minimally invasive surgical technique, called canaloplasty, uses a 250-µm microcatheter to access the drainage channels; it uses the eye’s natural drainage system to remove fluid from the eye. During the 30-minute procedure, the surgeon inserts the microcatheter through a small incision, enlarges the main drainage channel and places a small suture inside the canal to maintain the opening so it can function normally. Once completed successfully, this procedure rejuvenates the native drainage system and lowers IOP. For more information, go to www.iscienceinterventional.com.

  • ALCON RESEARCH INSTITUTE PROVIDES UNRESTRICTED GRANTS TO SEVEN RESEARCHERS. The Alcon Research Institute (ARI) has recognized seven outstanding researchers in vision and eye health, nominated by previous winners and selected by ARI"s independent Scientific Selection Committee. Each will receive $100,000 in unrestricted grant money from the ARI to continue pursuing their research. The 2008 ARI Award winners are: Vadim Y. Arshavsky, PhD, Professor of ophthalmology and pharmacology and Scientific Director, Department of Ophthalmology, Duke University, for his research on the behavior of G-proteins and photoreceptors in an effort to understand humans" response to light; Emily Y. Chew, MD, Deputy Director, Division of Epidemiology and Clinical Research, NEI/NIH and Frederick L. Ferris, MD, Director of Epidemiology and Clinical Research, NEI/NIH, who were jointly instrumental in designing, developing and executing the Age-Related Eye Disease Study; David R. Copenhagen, PhD, Professor and Vice Chair, Department of Ophthalmology, University of California, for his extensive work on visual system development; Reza Dana, MD, Professor in the Harvard Department of Ophthalmology, Director, Cornea Service, Massachusetts Eye & Ear Infirmary and senior scientist at Schepens Eye Research Institute, for his significant contributions in the area of corneal transplants; Elizabeth C. Engle, MD, Associate Professor of neurology, Harvard Medical School, investigator at Howard Hughes Medical Institute and senior research associate in ophthalmology at Children"s Hospital Boston, for her extensive research into the genetics of ocular defects; Simon W. John, PhD, Professor at the Jackson Laboratory, research assistant professor at Tufts University School of Medicine and investigator at Howard Hughes Medical Institute, for his distinguished career and groundbreaking research directed to understanding the underlying causes and potential treatments of glaucoma. In addition to the unrestricted grants, the awardees will join previous ARI winners in a biennial symposium in 2009 that will review, evaluate and discuss cutting-edge research into the causes and treatments of eye disease.

  • BAYER AND REGENERON ANNOUNCE POSITIVE PHASE II RESULTS FOR VEGF TRAP-EYE. Bayer HealthCare AG and Regeneron Pharmaceuticals, Inc. recently announced that patients with wet AMD who are receiving VEGF Trap-Eye in a Phase II extension study on a prn dosing schedule continued to show highly significant improvements at 52 weeks in the primary and key secondary endpoints of retinal thickness and vision gain. The 32-week results of the Phase II study were presented at the 2008 ARVO meeting; a full analysis of the 52-week results of the study will be presented at the 2008 meeting of the Retina Society on September 26-28, 2008 in Scottsdale, Ariz. In the trial, 157 patients were randomized to five dose groups and treated with VEGF Trap-Eye in one eye. Two groups initially received monthly doses of 0.5 mg or 2.0 mg of VEGF Trap-Eye at weeks 0, 4, 8 and 12, and three groups received quarterly doses of 0.5 mg, 2.0 mg or 4.0 mg of VEGF Trap-Eye at baseline and week 12. Following the initial 12-week fixed-dosing phase of the trial, patients continued to receive therapy at the same dose on a prn dosing schedule based upon the physician assessment of the need for re-treatment in accordance with pre-specified criteria. Patients were monitored for safety, retinal thickness and visual acuity. These data represent the final one-year analysis from the 52-week study. All dose cohorts combined showed a 5.3 mean letter gain in visual acuity versus baseline at the week 52 evaluation visit. The mean decrease in retinal thickness for all dose groups combined at week 52 was 130 µm vs. baseline. During the week 12 to week 52 prn dosing period, patients from all dose groups combined received, on average, only two additional injections. VEGF Trap-Eye was generally well tolerated, and there were no drug-related serious adverse events. One case of culture-negative endophthalmitis/uveitis was reported in a study eye, in addition to one arterial thrombotic event, but neither was deemed drug-related. The most common adverse events were those typically associated with intravitreal injections.


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