Institution
Moorfields Eye Hospital
Healthcare•London, United Kingdom•
About: Moorfields Eye Hospital is a healthcare organization based out in London, United Kingdom. It is known for research contribution in the topics: Visual acuity & Glaucoma. The organization has 3721 authors who have published 6790 publications receiving 246004 citations.
Papers published on a yearly basis
Papers
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University of Leeds1, Radboud University Nijmegen2, Alberta Children's Hospital3, University of Washington4, University College Dublin5, University of Mainz6, University of Tübingen7, Howard Hughes Medical Institute8, St James's University Hospital9, University Medical Center Utrecht10, Children's Hospital of Eastern Ontario11, University of Erlangen-Nuremberg12, Alfaisal University13, King Saud University14, University of Western Ontario15, University of Chicago16, University of Manitoba17, University of California, San Francisco18, Leeds Teaching Hospitals NHS Trust19, Queen's University Belfast20, UCL Institute of Ophthalmology21, Moorfields Eye Hospital22, University of Liverpool23, Protein Sciences24, University College London25
TL;DR: A whole-genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium is described and insights into ciliogenesis complexity and roles for unanticipated pathways in human genetic disease are provided.
Abstract: Defects in primary cilium biogenesis underlie the ciliopathies, a growing group of genetic disorders. We describe a whole-genome siRNA-based reverse genetics screen for defects in biogenesis and/or maintenance of the primary cilium, obtaining a global resource. We identify 112 candidate ciliogenesis and ciliopathy genes, including 44 components of the ubiquitin-proteasome system, 12 G-protein-coupled receptors, and 3 pre-mRNA processing factors (PRPF6, PRPF8 and PRPF31) mutated in autosomal dominant retinitis pigmentosa. The PRPFs localize to the connecting cilium, and PRPF8- and PRPF31-mutated cells have ciliary defects. Combining the screen with exome sequencing data identified recessive mutations in PIBF1, also known as CEP90, and C21orf2, also known as LRRC76, as causes of the ciliopathies Joubert and Jeune syndromes. Biochemical approaches place C21orf2 within key ciliopathy-associated protein modules, offering an explanation for the skeletal and retinal involvement observed in individuals with C21orf2 variants. Our global, unbiased approaches provide insights into ciliogenesis complexity and identify roles for unanticipated pathways in human genetic disease.
201 citations
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TL;DR: The risk of visual loss in the second eye is documented as being between 7% and 10% per year in patients with unilateral visual loss related to age-related macular disease.
200 citations
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TL;DR: The findings suggest that the lack of Ccl2 leads to a monocyte/macrophage-trafficking defect during aging and to an impaired recruitment of these cells to sites of laser injury.
Abstract: PURPOSE. Drusen, which are defined clinically as yellowish white spots in the outer retina, are cardinal features of age-related macular degeneration (AMD). Ccl2-knockout (Ccl2(-/-)) mice have been reported to develop drusen and phenotypic features similar to AMD, including an increased susceptibility to choroidal neovascularization (CNV). This study was conducted to investigate the nature of the drusenlike lesions in vivo and further evaluate the Ccl2(-/-) mouse as a model of AMD.METHODS. The eyes of 2- to 25-month-old Ccl2(-/-) and C57Bl/6 mice were examined in vivo by autofluorescence scanning laser ophthalmoscopy (AF-SLO) and electroretinography, and the extent of laser-induced CNV was measured by fluorescein fundus angiography. The retinal morphology was also assessed by immunohistochemistry and quantitative histologic and ultrastructural morphometry.RESULTS. The drusenlike lesions of Ccl2(-/-) mice comprised accelerated accumulation of swollen CD68(+), F4/80(+) macrophages in the subretinal space that were apparent as autofluorescent foci on AF-SLO. These macrophages contained pigment granules and phagosomes with outer segment and lipofuscin inclusions that may account for their autofluorescence. Only age-related retinal pigment epithelium (RPE) damage, photoreceptor loss, and sub-RPE deposits were observed but, despite the accelerated accumulation of macrophages, we identified no spontaneous development of CNV in the senescent mice and found a reduced susceptibility to laser-induced CNV in the Ccl2(-/-) mice.CONCLUSIONS. These findings suggest that the lack of Ccl2 leads to a monocyte/macrophage-trafficking defect during aging and to an impaired recruitment of these cells to sites of laser injury. Other, previously described features of Ccl2(-/-) mice that are similar to AMD may be the result of aging alone. (Invest Ophthalmol Vis Sci. 2009;50:5934-5943) DOI:10.1167/iovs.09-3462
200 citations
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TL;DR: The use of 95% ranges for TRV to establish the smallest measured visual acuity change that can be reliably detected ensures a high specificity but does not take account of sensitivity.
Abstract: Purpose: To determine the sensitivity to change and specificity achieved when published test–retest variability (TRV) data are used to determine whether measured changes in ETDRS logarithm of the minimum angle of resolution (logMAR) visual acuity reflect true clinical change or are attributable to measurement error alone.
Methods: Various degrees of change in visual acuity were simulated in a group of normal subjects by adjusting test difficulty through manipulation of viewing distance. Sensitivity to simulated change and specificity were determined with change criteria derived from published Bland-Altman 95% ranges for TRV.
Results: The relationship between viewing distance and measured acuity was as predicted theoretically. Simulated acuity change of 0.2 logMAR (two lines of letters) or greater can be reliably distinguished from no change (both sensitivity and specificity >95%) with the ETDRS chart, but a change of 0.1 logMAR or less cannot.
Conclusions: The use of 95% ranges for TRV to establish the smallest measured visual acuity change that can be reliably detected ensures a high specificity but does not take account of sensitivity. Use of change criteria derived from published 95% ranges results in a sensitivity of approximately 50% (assuming identical levels of TRV). Sensitivity may be improved by using a change criterion that is smaller than the minimum change sought, providing the change criterion is still at least as large as the 95% range for TRV, so that specificity is maintained. Reducing TRV allows smaller changes in acuity to be reliably detected.
200 citations
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TL;DR: For confirmed ocular hypertension, findings suggest that there is no clear benefit from intensive monitoring, and the best available glaucoma risk prediction model estimated the 5-year risk based on age and ocular predictors.
Abstract: Objectives: To determine effective and efficient monitoring criteria for ocular hypertension [raised intraocular pressure (IOP)] through (i) identification and validation of glaucoma risk prediction models; and (ii) development of models to determine optimal surveillance pathways. Design: A discrete event simulation economic modelling evaluation. Data from systematic reviews of risk prediction models and agreement between tonometers, secondary analyses of existing datasets (to validate identified risk models and determine optimal monitoring criteria) and public preferences were used to structure and populate the economic model. Setting: Primary and secondary care. Participants: Adults with ocular hypertension (IOP > 21mmHg) and the public (surveillance preferences). Interventions: We compared five pathways: two based on National Institute for Health and Clinical Excellence (NICE) guidelines with monitoring interval and treatment depending on initial risk stratification, 'NICE intensive' (4-monthly to annual monitoring) and 'NICE conservative' (6-monthly to biennial monitoring); two pathways, differing in location (hospital and community), with monitoring biennially and treatment initiated for a ≥ 6% 5-year glaucoma risk; and a 'treat all' pathway involving treatment with a prostaglandin analogue if IOP > 21 mmHg and IOP measured annually in the community. Main outcome measures: Glaucoma cases detected; tonometer agreement; public preferences; costs; willingness to pay and quality-adjusted life-years (QALYs). Results: The best available glaucoma risk prediction model estimated the 5-year risk based on age and ocular predictors (IOP, central corneal thickness, optic nerve damage and index of visual field status). Taking the average of two IOP readings, by tonometry, true change was detected at two years. Sizeable measurement variability was noted between tonometers. There was a general public preference for monitoring; good communication and understanding of the process predicted service value. 'Treat all' was the least costly and 'NICE intensive' the most costly pathway. Biennial monitoring reduced the number of cases of glaucoma conversion compared with a 'treat all' pathway and provided more QALYs, but the incremental cost-effectiveness ratio (ICER) was considerably more than £30,000. The 'NICE intensive' pathway also avoided glaucoma conversion, but NICE-based pathways were either dominated (more costly and less effective) by biennial hospital monitoring or had a ICERs > £30,000. Results were not sensitive to the risk threshold for initiating surveillance but were sensitive to the risk threshold for initiating treatment, NHS costs and treatment adherence. Limitations: Optimal monitoring intervals were based on IOP data. There were insufficient data to determine the optimal frequency of measurement of the visual field or optic nerve head for identification of glaucoma. The economic modelling took a 20-year time horizon which may be insufficient to capture long-term benefits. Sensitivity analyses may not fully capture the uncertainty surrounding parameter estimates. Conclusions: For confirmed ocular hypertension, findings suggest that there is no clear benefit from intensive monitoring. Consideration of the patient experience is important. A cohort study is recommended to provide data to refine the glaucoma risk prediction model, determine the optimum type and frequency of serial glaucoma tests and estimate costs and patient preferences for monitoring and treatment. Funding: The National Institute for Health Research Health Technology Assessment Programme. © Queen's Printer and Controller of HMSO 2012.
200 citations
Authors
Showing all 3754 results
Name | H-index | Papers | Citations |
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Rakesh K. Jain | 200 | 1467 | 177727 |
David Baker | 173 | 1226 | 109377 |
Nilesh J. Samani | 149 | 779 | 113545 |
Paul Mitchell | 146 | 1378 | 95659 |
Andrew J. Lees | 140 | 877 | 91605 |
Nick C. Fox | 139 | 748 | 93036 |
Alan J. Thompson | 131 | 718 | 82324 |
Martin N. Rossor | 128 | 670 | 95743 |
Nicholas W. Wood | 123 | 614 | 66270 |
Peter J. Goadsby | 123 | 946 | 73783 |
James A. Wells | 112 | 462 | 50847 |
Simon Cousens | 102 | 361 | 54579 |
Kailash P. Bhatia | 102 | 892 | 44372 |
Stafford L. Lightman | 98 | 714 | 36735 |
Simon Shorvon | 98 | 485 | 30672 |