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Glaucoma: HELP
Articles by Paul J. Foster
Based on 89 articles published since 2008
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Between 2008 and 2019, P. Foster wrote the following 89 articles about Glaucoma.
 
+ Citations + Abstracts
Pages: 1 · 2 · 3 · 4
1 Review Topical Beta-Blockers and Cardiovascular Mortality: Systematic Review and Meta-Analysis with Data from the EPIC-Norfolk Cohort Study. 2016

Pinnock, Claude / Yip, Jennifer L Y / Khawaja, Anthony P / Luben, Robert / Hayat, Shabina / Broadway, David C / Foster, Paul J / Khaw, Kay-Tee / Wareham, Nick. ·a Department of Public Health and Primary Care , University of Cambridge , Cambridge , UK. · b NIHR Biomedical Research Centre for Ophthalmology , Moorfields Eye Hospital and UCL Institute of Ophthalmology , London , UK. · c Department of Ophthalmology , Norfolk and Norwich University Hospital , Norwich , UK. · d MRC Epidemiology Unit , University of Cambridge School of Clinical Medicine , Cambridge , UK. ·Ophthalmic Epidemiol · Pubmed #27551956.

ABSTRACT: PURPOSE: To determine if topical beta-blocker use is associated with increased cardiovascular mortality, particularly among people with self-reported glaucoma. METHODS: All participants who participated in the first health check (N = 25,639) of the European Prospective Investigation into Cancer (EPIC) Norfolk cohort (1993-2013) were included in this prospective cohort study, with a median follow-up of 17.0 years. We determined use of topical beta-blockers at baseline through a self-reported questionnaire and prescription check at the first clinical visit. Cardiovascular mortality was ascertained through data linkage with the Office for National Statistics mortality database. Hazard ratios (HRs) were estimated using multivariable Cox regression models. Meta-analysis of the present study's results together with other identified literature was performed using a random effects model. RESULTS: We did not find an association between the use of topical beta-blockers and cardiovascular mortality (HR 0.93, 95% confidence interval, CI, 0.67-1.30). In the 514 participants with self-reported glaucoma, no association was found between the use of topical beta-blockers and cardiovascular mortality (HR 0.89, 95% CI 0.56-1.40). In the primary meta-analysis of four publications, there was no evidence of an association between the use of topical beta-blockers and cardiovascular mortality (pooled HR estimate 1.10, 95% CI 0.84-1.36). CONCLUSION: Topical beta-blockers do not appear to be associated with excess cardiovascular mortality. This evidence does not indicate that a change in current practice is warranted, although clinicians should continue to assess individual patients and their cardiovascular risk prior to commencing topical beta-blockers.

2 Review Global variations and time trends in the prevalence of primary open angle glaucoma (POAG): a systematic review and meta-analysis. 2016

Kapetanakis, Venediktos V / Chan, Michelle P Y / Foster, Paul J / Cook, Derek G / Owen, Christopher G / Rudnicka, Alicja R. ·Population Health Research Institute, St George's, University of London, London, UK. · Division of Genetics and Epidemiology, UCL Institute of Ophthalmology, London, UK. · Division of Genetics and Epidemiology, UCL Institute of Ophthalmology, London, UK NIHR Biomedical Research Centre Moorfields Eye Hospital NHS Foundation Trust, London, UK. ·Br J Ophthalmol · Pubmed #26286821.

ABSTRACT: Systematic review of published population based surveys to examine the relationship between primary open angle glaucoma (POAG) prevalence and demographic factors. A literature search identified population-based studies with quantitative estimates of POAG prevalence (to October 2014). Multilevel binomial logistic regression of log-odds of POAG was used to examine the effect of age and gender among populations of different geographical and ethnic origins, adjusting for study design factors. Eighty-one studies were included (37 countries, 216 214 participants, 5266 POAG cases). Black populations showed highest POAG prevalence, with 5.2% (95% credible interval (CrI) 3.7%, 7.2%) at 60 years, rising to 12.2% (95% CrI 8.9% to 16.6%) at 80 years. Increase in POAG prevalence per decade of age was greatest among Hispanics (2.31, 95% CrI 2.12, 2.52) and White populations (1.99, 95% CrI 1.86, 2.12), and lowest in East and South Asians (1.48, 95% CrI 1.39, 1.57; 1.56, 95% CrI 1.31, 1.88, respectively). Men were more likely to have POAG than women (1.30, 95% CrI 1.22, 1.41). Older studies had lower POAG prevalence, which was related to the inclusion of intraocular pressure in the glaucoma definition. Studies with visual field data on all participants had a higher POAG prevalence than those with visual field data on a subset. Globally 57.5 million people (95% CI 46.4 to 73.1 million) were affected by POAG in 2015, rising to 65.5 million (95% CrI 52.8, 83.2 million) by 2020. This systematic review provides the most precise estimates of POAG prevalence and shows omitting routine visual field assessment in population surveys may have affected case ascertainment. Our findings will be useful to future studies and healthcare planning.

3 Review The prevalence of primary angle closure glaucoma in European derived populations: a systematic review. 2012

Day, Alexander C / Baio, Gianluca / Gazzard, Gus / Bunce, Catey / Azuara-Blanco, Augusto / Munoz, Beatriz / Friedman, David S / Foster, Paul J. ·Department of Genetics and Epidemiology, UCL Institute of Ophthalmology, London, UK. alex.day@ucl.ac.uk ·Br J Ophthalmol · Pubmed #22653314.

ABSTRACT: AIM: To estimate the prevalence of primary angle closure glaucoma (PACG) in European derived populations. METHOD: Systematic review and modelling of PACG prevalence data from population studies. PACG was defined according to the ISGEO definition requiring structural and/or functional evidence of glaucomatous optic neuropathy. Prevalence estimates were applied to the 2010 United Nations projected population figures to estimate case numbers. RESULTS: The prevalence of PACG in those 40 years or more is 0.4% (95% CI 0.3% to 0.5%). Age-specific prevalence values are 0.02% (CI 0.00 to 0.08) for those 40-49 years, 0.60% (0.27 to 1.00) for those 50-59 years, 0.20% (0.06 to 0.42) for those 60-69 years and 0.94% (0.63 to 1.35) for those 70 years and older. Three-quarters of all cases occur in female subjects (3.25 female to 1 male; CI 1.76 to 5.94). CONCLUSION: This analysis provides a current evidence-based estimate of PACG prevalence in European derived populations and suggests there are 130,000 people in the UK, 1.60 million people in Europe and 581,000 people in the USA with PACG today. Accounting for ageing population structures, cases are predicted to increase by 19% in the UK, 9% in Europe and 18% in the USA within the next decade. PACG is more common than previously thought, and all primary glaucoma cases should be considered to be PACG until the anterior chamber angle is shown to be open on gonioscopy.

4 Review Angle closure and angle-closure glaucoma: what we are doing now and what we will be doing in the future. 2012

Friedman, David S / Foster, Paul J / Aung, Tin / He, Mingguang. ·Wilmer Eye Institute, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA. ·Clin Exp Ophthalmol · Pubmed #22356460.

ABSTRACT: Primary angle-closure glaucoma (PACG) frequently leads to severe vision loss. Prevalence among older Asian populations is high and given global demographics, the number of persons with PACG will increase dramatically in the coming decades. Improvements in imaging of the anterior segment will help us to identify more of those with angle closure, and important clinical trials that are currently underway will provide important evidence to support screening and treatment approaches for PACG. In this manuscript, we intend to review the existing evidences, to introduce some important on-going studies on PACG and to share the experience and viewpoints of the authors.

5 Review Pharmacological and environmental factors in primary angle-closure glaucoma. 2010

Subak-Sharpe, Ian / Low, Sancy / Nolan, Winifred / Foster, Paul J. ·Moorfields Eye Hospital, London, UK. ·Br Med Bull · Pubmed #19933218.

ABSTRACT: INTRODUCTION OR BACKGROUND: A large number of drug classes have now been reported to provoke angle closure in high-risk individuals. The mechanism of action can be generalized into three main categories: sympathomimetic, parasympatholytic and idiosyndratic reactions. SOURCES OF DATA: This review of the ophthalmic literature provides a clinical summary of primary angle-closure glaucoma (PACG) and its management. AREAS OF AGREEMENT: External stimuli (pharmacological and environmental) may induce acute, and more often, asymptomatic angle closure, which carries a significant risk of glaucoma. GROWING POINTS: Whenever in doubt, patients at risk of PACG who are starting on drug therapy known to provoke angle closure or aggravate the condition should be referred for detailed gonioscopic examination of the anterior chamber by an ophthalmologist. AREAS FOR DEVELOPING RESEARCH: The use of new imaging methods such as anterior segment optical coherence tomography to assess the presence or risk of angle closure is gaining popularity, and may offer a more rapid method of identifying people who are at risk of sight loss from angle-closure glaucoma precipitated by non-ophthalmological medication.

6 Clinical Trial Appositional closure identified by ultrasound biomicroscopy in population-based primary angle-closure glaucoma suspects: the Liwan eye study. 2011

Kong, Xiangbin / Foster, Paul J / Huang, Qunxiao / Zheng, Yingfeng / Huang, Wenyong / Cai, Xiaoyu / He, Mingguang. ·State Key Laboratory of Ophthalmology, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China. ·Invest Ophthalmol Vis Sci · Pubmed #21357394.

ABSTRACT: PURPOSE: To describe the characteristics of the iridocorneal angle using ultrasound biomicroscopy (UBM) in Chinese people classified gonioscopically as having suspected primary angle-closure (PACS) glaucoma. METHODS: PACS were defined as not having visible posterior (usually pigmented) trabecular meshwork in two or more quadrants examined by static gonioscopy. The PACS and 1 of 10 those who did not meet this criterion were identified from a population-based survey. Iridotrabecular meshwork contact (ITC) was identified and further classified into low and high, according to standard UBM images. Those with high ITC were further classified according the configuration of ITC: B-type, with contiguous ITC from the base of the angle, and S-type, with ITC localized to the region of Schwalbe's line. RESULTS: ITC was identified in 78.6% of the superior, 40.2% of the nasal, 59.8% of the inferior, and 25.6% of the temporal quadrants in the PACS (n = 117). These proportions were 43.9%, 15.8%, 29.8%, and 14.0% in the controls (n = 57), respectively. About two thirds of the eyes with ITC were classified as high. In those with high ITC, the number with B- and S-type ITC was very similar. The proportions of any high ITCs increased substantially from 15.4% in those with Shaffer angle grade 4 and 45.0% in grade 3, to 71.0% in grade 2, 70.2% in grade 1, and 86.4% in grade 0. CONCLUSIONS: More ITC is identified on UBM imaging than by gonioscopy. Careful consideration should be given to the assessment modality regarded as the reference standard in defining anatomic risk factors for glaucomatous visual loss and the need for treatment.

7 Article Laser peripheral iridotomy for the prevention of angle closure: a single-centre, randomised controlled trial. 2019

He, Mingguang / Jiang, Yuzhen / Huang, Shengsong / Chang, Dolly S / Munoz, Beatriz / Aung, Tin / Foster, Paul J / Friedman, David S. ·State Key Laboratory of Ophthalmology, Clinical Research Center, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China; Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, East Melbourne, VIC, Australia; National Institute for Health Research Biomedical Research Centre, Moorfields Eye Hospital, London, UK; UCL Institute of Ophthalmology, London, UK. Electronic address: mingguang_he@yahoo.com. · National Institute for Health Research Biomedical Research Centre, Moorfields Eye Hospital, London, UK; UCL Institute of Ophthalmology, London, UK. · State Key Laboratory of Ophthalmology, Clinical Research Center, Zhongshan Ophthalmic Center, Sun Yat-Sen University, Guangzhou, China. · Dana Center for Preventive Ophthalmology, Wilmer Eye Institute and Department of International Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore Yong Loo Lin School of Medicine, National University of Singapore, Singapore. · National Institute for Health Research Biomedical Research Centre, Moorfields Eye Hospital, London, UK; UCL Institute of Ophthalmology, London, UK. Electronic address: p.foster@ucl.ac.uk. ·Lancet · Pubmed #30878226.

ABSTRACT: BACKGROUND: Primary angle-closure glaucoma affects 20 million people worldwide. People classified as primary angle closure suspects have a higher but poorly quantified risk of developing glaucoma. We aimed to assess efficacy and safety of laser peripheral iridotomy prophylaxis against primary angle-closure glaucoma in Chinese people classified as primary angle closure suspects. METHODS: In this randomised controlled trial, bilateral primary angle closure suspects aged 50-70 years were enrolled at the Zhongshan Ophthalmic Center, a tertiary specialised hospital in Guangzhou, China. Eligible patients received laser peripheral iridotomy in one randomly selected eye, with the other remaining untreated. The primary outcome was incident primary angle closure disease as a composite endpoint of elevation of intraocular pressure, peripheral anterior synechiae, or acute angle-closure during 72 months of follow-up in an intention-to-treat analysis between treated eyes and contralateral controls. This trial is registered with the ISRCTN registry, number ISRCTN45213099. FINDINGS: Of 11 991 screened individuals, 889 individuals were randomly assigned from June 19, 2008 (889 treated and 889 untreated eyes). Incidence of the primary outcome was 4·19 per 1000 eye-years in treated eyes compared with 7·97 per 1000 eye-years in untreated eyes (hazard ratio 0·53; 95% CI 0·30-0·92; p=0·024). A primary outcome event occurred in 19 treated eyes and 36 untreated eyes with a statistically significant difference using pair-wise analysis (p=0·0041). No serious adverse events were observed during follow-up. INTERPRETATION: Incidence of angle-closure disease was very low among individuals classified as primary angle closure suspects identified through community-based screening. Laser peripheral iridotomy had a modest, albeit significant, prophylactic effect. In view of the low incidence rate of outcomes that have no immediate threat to vision, the benefit of prophylactic laser peripheral iridotomy is limited; therefore, widespread prophylactic laser peripheral iridotomy for primary angle-closure suspects is not recommended. FUNDING: Fight for Sight, the Sun Yat-Sen University 5010 Project Fund, Moorfields Eye Charity, and the National Natural Science Foundation of China.

8 Article Ascorbic acid metabolites are involved in intraocular pressure control in the general population. 2019

Hysi, Pirro G / Khawaja, Anthony P / Menni, Cristina / Tamraz, Bani / Wareham, Nick / Khaw, Kay-Tee / Foster, Paul J / Benet, Leslie Z / Spector, Tim D / Hammond, Chris J. ·Section of Academic Ophthalmology, Faculty of Life Sciences and Medicine, Kings' College London, UK; King's College London Department of Twin Research and Genetic Epidemiology, London, UK. Electronic address: pirro.hysi@kcl.ac.uk. · Department of Public Health & Primary Care, University of Cambridge, UK; NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital and University College London, UK. · King's College London Department of Twin Research and Genetic Epidemiology, London, UK. · University of California, San Francisco, School of Pharmacy, San Francisco, CA, USA. · Department of Public Health & Primary Care, University of Cambridge, UK. · NIHR Biomedical Research Centre for Ophthalmology, Moorfields Eye Hospital and University College London, UK. · University of California, San Francisco, School of Pharmacy, Department of Bioengineering and Therapeutic Sciences, San Francisco, CA, USA. · Section of Academic Ophthalmology, Faculty of Life Sciences and Medicine, Kings' College London, UK; King's College London Department of Twin Research and Genetic Epidemiology, London, UK. ·Redox Biol · Pubmed #30391827.

ABSTRACT: Elevated intraocular pressure (IOP) is an important risk factor for glaucoma. Mechanisms involved in its homeostasis are not well understood, but associations between metabolic factors and IOP have been reported. To investigate the relationship between levels of circulating metabolites and IOP, we performed a metabolome-wide association using a machine learning algorithm, and then employing Mendelian Randomization models to further explore the strength and directionality of effect of the metabolites on IOP. We show that O-methylascorbate, a circulating Vitamin C metabolite, has a significant IOP-lowering effect, consistent with previous knowledge of the anti-hypertensive and anti-oxidative role of ascorbate compounds. These results enhance understanding of IOP control and may potentially benefit future IOP treatment and reduce vision loss from glaucoma.

9 Article Genome-wide analyses identify 68 new loci associated with intraocular pressure and improve risk prediction for primary open-angle glaucoma. 2018

Khawaja, Anthony P / Cooke Bailey, Jessica N / Wareham, Nicholas J / Scott, Robert A / Simcoe, Mark / Igo, Robert P / Song, Yeunjoo E / Wojciechowski, Robert / Cheng, Ching-Yu / Khaw, Peng T / Pasquale, Louis R / Haines, Jonathan L / Foster, Paul J / Wiggs, Janey L / Hammond, Chris J / Hysi, Pirro G / Anonymous1621138 / Anonymous1631138. ·NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK. · Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK. · Department of Population and Quantitative Health Sciences, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, OH, USA. · MRC Epidemiology Unit, University of Cambridge School of Clinical Medicine, Institute of Metabolic Science, Cambridge Biomedical Campus, Cambridge, UK. · Department of Ophthalmology, King's College London, St. Thomas' Hospital, London, UK. · Department of Twin Research & Genetic Epidemiology, King's College London, St. Thomas' Hospital, London, UK. · Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. · Johns Hopkins Wilmer Eye Institute, Baltimore, MD, USA. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore. · Department of Ophthalmology, National University of Singapore and National University Health System, Singapore, Singapore. · Ophthalmology & Visual Sciences Academic Clinical Program (Eye-ACP), Duke-NUS Medical School, Singapore, Singapore. · Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA. · Division of Genetics and Epidemiology, UCL Institute of Ophthalmology, London, UK. · Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, MA, USA. janey_wiggs@meei.harvard.edu. · Department of Ophthalmology, King's College London, St. Thomas' Hospital, London, UK. chris.hammond@kcl.ac.uk. · Department of Ophthalmology, King's College London, St. Thomas' Hospital, London, UK. pirro.hysi@kcl.ac.uk. · Department of Twin Research & Genetic Epidemiology, King's College London, St. Thomas' Hospital, London, UK. pirro.hysi@kcl.ac.uk. ·Nat Genet · Pubmed #29785010.

ABSTRACT: Glaucoma is the leading cause of irreversible blindness globally

10 Article Cross-ancestry genome-wide association analysis of corneal thickness strengthens link between complex and Mendelian eye diseases. 2018

Iglesias, Adriana I / Mishra, Aniket / Vitart, Veronique / Bykhovskaya, Yelena / Höhn, René / Springelkamp, Henriët / Cuellar-Partida, Gabriel / Gharahkhani, Puya / Bailey, Jessica N Cooke / Willoughby, Colin E / Li, Xiaohui / Yazar, Seyhan / Nag, Abhishek / Khawaja, Anthony P / Polašek, Ozren / Siscovick, David / Mitchell, Paul / Tham, Yih Chung / Haines, Jonathan L / Kearns, Lisa S / Hayward, Caroline / Shi, Yuan / van Leeuwen, Elisabeth M / Taylor, Kent D / Anonymous9241162 / Bonnemaijer, Pieter / Rotter, Jerome I / Martin, Nicholas G / Zeller, Tanja / Mills, Richard A / Souzeau, Emmanuelle / Staffieri, Sandra E / Jonas, Jost B / Schmidtmann, Irene / Boutin, Thibaud / Kang, Jae H / Lucas, Sionne E M / Wong, Tien Yin / Beutel, Manfred E / Wilson, James F / Anonymous9251162 / Anonymous9261162 / Uitterlinden, André G / Vithana, Eranga N / Foster, Paul J / Hysi, Pirro G / Hewitt, Alex W / Khor, Chiea Chuen / Pasquale, Louis R / Montgomery, Grant W / Klaver, Caroline C W / Aung, Tin / Pfeiffer, Norbert / Mackey, David A / Hammond, Christopher J / Cheng, Ching-Yu / Craig, Jamie E / Rabinowitz, Yaron S / Wiggs, Janey L / Burdon, Kathryn P / van Duijn, Cornelia M / MacGregor, Stuart. ·Department of Ophthalmology, Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands. · Department of Epidemiology, Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands. · Department of Clinical Genetics, Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands. · University of Bordeaux, Bordeaux Population Health Research Center, INSERM UMR 1219, F-33000, Bordeaux, France. · Institute of Genetics and Molecular Medicine, Medical Research Council Human Genetics Unit, University of Edinburgh, EH42XU, Edinburgh, UK. · Regenerative Medicine Institute and Department of Surgery, Cedars-Sinai Medical Center, CA 90048, Los Angeles, CA, USA. · Cornea Genetic Eye Institute, CA 90048, Los Angeles, CA, USA. · Department of Ophthalmology, University Medical Center Mainz, 55131, Mainz, Germany. · Department of Ophthalmology, Inselspital, University Hospital Bern, University of Bern, Bern, CH-3010, Switzerland. · Statistical Genetics, QIMR Berghofer Medical Research Institute, QLD 4029, Brisbane, Australia. · Department of Population and Quantitative Health Sciences, Case Western Reserve University, OH 44106, Cleveland, OH, USA. · Institute for Computational Biology, Case Western Reserve University, Cleveland, OH, 44106, USA. · Biomedical Sciences Research Institute, Ulster University, BT52 1SA, Belfast, Northern Ireland, UK. · Royal Victoria Hospital, Belfast Health and Social Care Trust, BT12 6BA, Belfast, Northern Ireland, UK. · Institute for Translational Genomics and Population Sciences and Department of Pediatrics, Los Angeles Biomedical Research Institute at Harbor-UCLA Medical Center, Torrance, CA 90509, CA, USA. · Division of Genomic Outcomes, Departments of Pediatrics and Medicine, Harbor-UCLA Medical Center, Torrance, CA 90502, CA, USA. · Centre for Ophthalmology and Visual Science, University of Western Australia, Lions Eye Institute, WA 6009, Perth, WA, Australia. · Department of Twin Research and Genetic Epidemiology, King's College London, WC2R 2LS, London, UK. · Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, CB2 0SR, Cambridge, UK. · NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, EC1V 9EL, London, UK. · Faculty of Medicine, University of Split, HR-21000, Split, Croatia. · Departments of Medicine and Epidemiology and Cardiovascular Health Research Unit, University of Washington, WA 98101, Washington, USA. · The New York Academy of Medicine, NY 10029, New York, NY, USA. · Centre for Vision Research, Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney, NSW 2145, Sydney, NSW, Australia. · Singapore Eye Research Institute, Singapore National Eye Centre, 168751, Singapore, Singapore. · Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, VIC 3002, East Melbourne, Australia. · Department of Genetics and Computational Biology, QIMR Berghofer Medical Research Institute, QLD 4029, Brisbane, Australia. · Department of General and Interventional Cardiology, University Heart Center Hamburg, 20251, Hamburg, Germany. · German Center for Cardiovascular Research (DZHK), Partner Site Hamburg/Kiel/Lübeck, 20246, Hamburg, Germany. · Department of Ophthalmology, Flinders University, SA 5042, Adelaide, Australia. · Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University of Heidelberg, 68167, Mannheim, Germany. · Institute for Medical Biostatistics, Epidemiology and Informatics, University Medical Center Mainz, 55131, Mainz, Germany. · Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA 02115, MA, USA. · Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7005, TAS, Australia. · Ophthalmology & Visual Sciences Academic Clinical Program (Eye ACP), Duke-NUS Medical School, 169857, Singapore, Singapore. · Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, 117549, Singapore. · Department of Psychosomatic Medicine and Psychotherapy, University Medical Center Mainz, Mainz, 55131, Germany. · Centre for Global Health Research, Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, EH16 4UX, Edinburgh, UK. · Department of Internal Medicine, Erasmus Medical Center, 3000 CA, Rotterdam, The Netherlands. · Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, 2593 HW, The Hague, The Netherlands. · School of Medicine, Menzies Institute for Medical Research, University of Tasmania, Hobart, TAS 7005, TAS, Australia. · Genome Institute of Singapore, 60 Biopolis Street, Singapore, 138672, Singapore. · Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, MA 02114, MA, USA. · Institute for Molecular Bioscience, University of Queensland, QLD 4067, Brisbane, Australia. · Department of Ophthalmology, Radboud University Medical Center, 6525 GA, Nijmegen, The Netherlands. · Statistical Genetics, QIMR Berghofer Medical Research Institute, QLD 4029, Brisbane, Australia. Stuart.MacGregor@qimrberghofer.edu.au. ·Nat Commun · Pubmed #29760442.

ABSTRACT: Central corneal thickness (CCT) is a highly heritable trait associated with complex eye diseases such as keratoconus and glaucoma. We perform a genome-wide association meta-analysis of CCT and identify 19 novel regions. In addition to adding support for known connective tissue-related pathways, pathway analyses uncover previously unreported gene sets. Remarkably, >20% of the CCT-loci are near or within Mendelian disorder genes. These included FBN1, ADAMTS2 and TGFB2 which associate with connective tissue disorders (Marfan, Ehlers-Danlos and Loeys-Dietz syndromes), and the LUM-DCN-KERA gene complex involved in myopia, corneal dystrophies and cornea plana. Using index CCT-increasing variants, we find a significant inverse correlation in effect sizes between CCT and keratoconus (r = -0.62, P = 5.30 × 10

11 Article Analysing barriers to service improvement using a multi-level theory of innovation: the case of glaucoma outpatient clinics. 2018

Turner, Simon / Vasilakis, Christos / Utley, Martin / Foster, Paul / Kotecha, Aachal / Fulop, Naomi J. ·Centre for Primary Care, Division of Population Health, Health Services Research and Primary Care, School of Health Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK. · Centre for Healthcare Innovation & Improvement, School of Management, University of Bath, Bath, UK. · Clinical Operational Research Unit, University College London, London, UK. · NIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK. · Department of Applied Health Research, University College London, London, UK. ·Sociol Health Illn · Pubmed #29441595.

ABSTRACT: The development and implementation of innovation by healthcare providers is understood as a multi-determinant and multi-level process. Theories at different analytical levels (i.e. micro and organisational) are needed to capture the processes that influence innovation by providers. This article combines a micro theory of innovation, actor-network theory, with organisational level processes using the 'resource based view of the firm'. It examines the influence of, and interplay between, innovation-seeking teams (micro) and underlying organisational capabilities (meso) during innovation processes. We used ethnographic methods to study service innovations in relation to ophthalmology services run by a specialist English NHS Trust at multiple locations. Operational research techniques were used to support the ethnographic methods by mapping the care process in the existing and redesigned clinics. Deficiencies in organisational capabilities for supporting innovation were identified, including manager-clinician relations and organisation-wide resources. The article concludes that actor-network theory can be combined with the resource-based view to highlight the influence of organisational capabilities on the management of innovation. Equally, actor-network theory helps to address the lack of theory in the resource-based view on the micro practices of implementing change.

12 Article Developing standards for the development of glaucoma virtual clinics using a modified Delphi approach. 2018

Kotecha, Aachal / Longstaff, Simon / Azuara-Blanco, Augusto / Kirwan, James F / Morgan, James Edwards / Spencer, Anne Fiona / Foster, Paul J. ·NIHR Biomedical Research Centre (BRC) at Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, UK. · Ophthalmology department, Royal Hallamshire Hospital, Sheffield, UK. · Institute of Clinical Science, Queen's University Belfast, Belfast, UK. · Queen Alexandra Hospital, Portsmouth, UK. · Department of Ophthalmology, University of Wales College of Medicine, Cardiff, UK. · Department of Ophthalmology, Manchester Royal Eye Hospital and Manchester Academic and Health Science Centre, Central Manchester University Hospitals NHS Foundation Trust, Manchester, UK. ·Br J Ophthalmol · Pubmed #28821554.

ABSTRACT: PURPOSE: To obtain consensus opinion for the development of a standards framework for the development and implementation of virtual clinics for glaucoma monitoring in the UK using a modified Delphi methodology. METHODS: A modified Delphi technique was used that involved sampling members of the UK Glaucoma and Eire Society (UKEGS). The first round scored the strength of agreement to a series of standards statements using a 9-point Likert scale. The revised standards were subjected to a second round of scoring and free-text comment. The final standards were discussed and agreed by an expert panel consisting of seven glaucoma subspecialists from across the UK. A version of the standards was submitted to external stakeholders for a 3-month consultation. RESULTS: There was a 44% response rate of UKEGS members to rounds 1 and 2, consisting largely of consultant ophthalmologists with a specialist interest in glaucoma. The final version of the standards document was validated by stakeholder consultation and contains four sections pertaining to the patient groups, testing methods, staffing requirements and governance structure of NHS secondary care glaucoma virtual clinic models. CONCLUSIONS: Use of a modified Delphi approach has provided consensus agreement for the standards required for the development of virtual clinics to monitor glaucoma in the UK. It is anticipated that this document will be useful as a guide for those implementing this model of service delivery.

13 Article Glaucoma and intraocular pressure in EPIC-Norfolk Eye Study: cross sectional study. 2017

Chan, Michelle P Y / Broadway, David C / Khawaja, Anthony P / Yip, Jennifer L Y / Garway-Heath, David F / Burr, Jennifer M / Luben, Robert / Hayat, Shabina / Dalzell, Nichola / Khaw, Kay-Tee / Foster, Paul J. ·Division of Genetics and Epidemiology, UCL Institute of Ophthalmology, London EC1V 9EL, UK. · University of East Anglia, Norwich NR4 7TJ, UK. · Department of Public Health and Primary Care, University of Cambridge, Cambridge CB1 8RN, UK. · NIHR Biomedical Research Centre Moorfields Eye Hospital NHS Foundation Trust, London EC1V 2PD, UK. · UCL Institute of Ophthalmology, London EC1V 9EL, UK. · School of Medicine, Medical and Biological Sciences, University of St Andrews, St Andrews KY16 9TF, Scotland, UK. ·BMJ · Pubmed #28903935.

ABSTRACT:

14 Article Residual Angle Closure One Year After Laser Peripheral Iridotomy in Primary Angle Closure Suspects. 2017

Baskaran, Mani / Yang, Elizabeth / Trikha, Sameer / Kumar, Rajesh S / Wong, Hon Tym / He, Mingguang / Chew, Paul T K / Foster, Paul J / Friedman, David / Aung, Tin. ·Singapore Eye Research Institute and Singapore National Eye Center, Singapore; Duke-NUS Medical School, Singapore. · Singapore Eye Research Institute and Singapore National Eye Center, Singapore; The Queen's College, Oxford University, United Kingdom. · Singapore Eye Research Institute and Singapore National Eye Center, Singapore; King's College, London, United Kingdom. · Narayana Nethralaya, Bangalore, India. · Tan Tock Seng Hospital, Singapore. · Zhongshan Ophthalmic Centre, Guangzhou, China. · National University Hospital, Singapore, and the Yong Loo Lin School of Medicine, National University of Singapore, Singapore. · National Biomedical Research Centre for Ophthalmology, UCL Institute of Ophthalmology and Moorfields Eye Hospital, London, United Kingdom. · Dana Center for Preventive Ophthalmology, Wilmer Eye Institute and Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland. · Singapore Eye Research Institute and Singapore National Eye Center, Singapore; Duke-NUS Medical School, Singapore; National University Hospital, Singapore, and the Yong Loo Lin School of Medicine, National University of Singapore, Singapore. Electronic address: aung.tin@singhealth.com.sg. ·Am J Ophthalmol · Pubmed #28887116.

ABSTRACT: PURPOSE: To determine the incidence and baseline clinical and anterior segment optical coherence tomography (AS-OCT) predictors associated with residual angle closure as assessed by gonioscopy 1 year after laser peripheral iridotomy (LPI) in primary angle closure suspects (PACS). DESIGN: Subanalysis of randomized controlled trial data. METHODS: AS-OCT images from 181 PACS subjects ≥50 years of age were analyzed using customized software before and 1 year after LPI. Other parameters assessed were intraocular pressure (IOP) and axial length (Axl). Residual angle closure was defined as the inability to see the posterior trabecular meshwork for at least 2 quadrants on gonioscopy after LPI. Multivariate regression analysis determined the baseline predictors of residual angle closure 1 year after LPI. RESULTS: The mean age of participants was 62.4 (standard deviation 9.9) years. The majority were female (137, 75.7%) and Chinese (174, 96.1%). At 1 year post LPI, 148 (81.8%) subjects had gonioscopic residual angle closure. Univariate analysis showed that baseline Axl, anterior chamber area, anterior chamber volume, angle opening distance at 750 μm from the scleral spur, and angle recess area were smaller while baseline lens vault and iris curvature were larger in residual angle closure subjects (all P < .05). Multivariate analysis revealed that baseline iris volume (B = -0.08, P = .035) and baseline IOP (B = 0.23, P = .032) were predictors for residual angle closure. CONCLUSIONS: One year after LPI, >80% of PACS had gonioscopic residual angle closure. Greater baseline iris volume and higher IOP at baseline are independent risk factors for residual gonioscopic angle closure.

15 Article A technician-delivered 'virtual clinic' for triaging low-risk glaucoma referrals. 2017

Kotecha, A / Brookes, J / Foster, P J. ·Glaucoma Service, Moorfields Eye Hospital NHS Foundation Trust, London, UK. · NIHR Biomedical Research Centre (BRC) at Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, UK. ·Eye (Lond) · Pubmed #28211881.

ABSTRACT: PurposeThe purpose of this study is to describe the outcomes of a technician-delivered glaucoma referral triaging service with 'virtual review' of resultant data by a consultant ophthalmologist.Patients and methodsThe Glaucoma Screening Clinic reviewed new optometrist or GP-initiated glaucoma suspect referrals into a specialist ophthalmic hospital. Patients underwent testing by three ophthalmic technicians in a dedicated clinical facility. Data were reviewed at a different time and date by a consultant glaucoma ophthalmologist. Approximately 10% of discharged patients were reviewed in a face-to-face consultant-led clinic to examine the false-negative rate of the service.ResultsBetween 1 March 2014 and 31 March 2016, 1380 patients were seen in the clinic. The number of patients discharged following consultant virtual review was 855 (62%). The positive predictive value of onward referrals was 84%. Three of the 82 patients brought back for face-to-face review were deemed to require treatment, equating to negative predictive value of 96%.ConclusionsOur technician-delivered glaucoma referral triaging clinic incorporates consultant 'virtual review' to provide a service model that significantly reduces the number of onward referrals into the glaucoma outpatient department. This model may be an alternative to departments where there are difficulties in implementing optometrist-led community-based referral refinement schemes.

16 Article New insights into the genetics of primary open-angle glaucoma based on meta-analyses of intraocular pressure and optic disc characteristics. 2017

Springelkamp, Henriët / Iglesias, Adriana I / Mishra, Aniket / Höhn, René / Wojciechowski, Robert / Khawaja, Anthony P / Nag, Abhishek / Wang, Ya Xing / Wang, Jie Jin / Cuellar-Partida, Gabriel / Gibson, Jane / Bailey, Jessica N Cooke / Vithana, Eranga N / Gharahkhani, Puya / Boutin, Thibaud / Ramdas, Wishal D / Zeller, Tanja / Luben, Robert N / Yonova-Doing, Ekaterina / Viswanathan, Ananth C / Yazar, Seyhan / Cree, Angela J / Haines, Jonathan L / Koh, Jia Yu / Souzeau, Emmanuelle / Wilson, James F / Amin, Najaf / Müller, Christian / Venturini, Cristina / Kearns, Lisa S / Kang, Jae Hee / Anonymous1171064 / Tham, Yih Chung / Zhou, Tiger / van Leeuwen, Elisabeth M / Nickels, Stefan / Sanfilippo, Paul / Liao, Jiemin / van der Linde, Herma / Zhao, Wanting / van Koolwijk, Leonieke M E / Zheng, Li / Rivadeneira, Fernando / Baskaran, Mani / van der Lee, Sven J / Perera, Shamira / de Jong, Paulus T V M / Oostra, Ben A / Uitterlinden, André G / Fan, Qiao / Hofman, Albert / Tai, E-Shyong / Vingerling, Johannes R / Sim, Xueling / Wolfs, Roger C W / Teo, Yik Ying / Lemij, Hans G / Khor, Chiea Chuen / Willemsen, Rob / Lackner, Karl J / Aung, Tin / Jansonius, Nomdo M / Montgomery, Grant / Wild, Philipp S / Young, Terri L / Burdon, Kathryn P / Hysi, Pirro G / Pasquale, Louis R / Wong, Tien Yin / Klaver, Caroline C W / Hewitt, Alex W / Jonas, Jost B / Mitchell, Paul / Lotery, Andrew J / Foster, Paul J / Vitart, Veronique / Pfeiffer, Norbert / Craig, Jamie E / Mackey, David A / Hammond, Christopher J / Wiggs, Janey L / Cheng, Ching-Yu / van Duijn, Cornelia M / MacGregor, Stuart. ·Department of Epidemiology, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Ophthalmology, Erasmus Medical Center, Rotterdam, the Netherlands. · Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, the Netherlands. · Statistical Genetics, QIMR Berghofer Medical Research Institute, Royal Brisbane Hospital, Brisbane, Australia. · Department of Complex Trait Genetics, VU University, Center for Neurogenomics and Cognitive Research, Amsterdam, the Netherlands. · Department of Ophthalmology, Inselspital, University Hospital Bern, University of Bern, Bern, Switzerland. · Department of Ophthalmology, University Medical Center Mainz, Mainz, Germany. · Computational and Statistical Genomics Branch, National Human Genome Research Institute (NIH), Baltimore, MD, USA. · Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, MD, USA. · Wilmer Eye Institute, Johns Hopkins School of Medicine, Baltimore, MD, USA. · NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK. · Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. · Beijing Institute of Ophthalmology, Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing, China. · Beijing Ophthalmology and Visual Science Key Lab, Beijing, China. · Centre for Vision Research, Department of Ophthalmology and Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia. · Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, University of Southampton, Southampton, UK. · Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore, Singapore. · Duke-National University of Singapore Graduate Medical School, Singapore, Singapore. · Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. · Medical Research Council Human Genetics Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK. · Clinic for General and Interventional Cardiology, University Heart Center Hamburg, Hamburg, Germany. · German Center for Cardiovascular Research (DZHK), Partner Site Hamburg, Luebeck, Kiel, Hamburg/Germany. · Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK. · Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia. · Clinical and Experimental Sciences, Faculty of Medicine, University of Southampton, Southampton, UK. · Department of Ophthalmology, Flinders University, Adelaide, Australia. · Centre for Global Health Research, The Usher Institute for Population Health Sciences and Informatics, University of Edinburgh, Scotland, UK. · Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia. · Division of Network Medicine, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Division of Human Genetics, Genome Institute of Singapore, Singapore, Singapore. · Department of Internal Medicine, Erasmus Medical Center, Rotterdam, the Netherlands. · Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, the Hague, the Netherlands. · Department of Ophthalmology, Academic Medical Center, Amsterdam, the Netherlands. · Department of Ophthalmology, Leiden University Medical Center, Leiden, the Netherlands. · The Netherlands Institute of Neuroscience KNAW, Amsterdam, the Netherlands. · Department of Medicine, National University of Singapore and National University Health System, Singapore, Singapore. · Saw Swee Hock School of Public Health, National University of Singapore and National University Health System, Singapore, Singapore. · Department of Statistics and Applied Probability, National University of Singapore, Singapore, Singapore. · Glaucoma Service, The Rotterdam Eye Hospital, Rotterdam, the Netherlands. · Department of Biochemistry, Yong Loo Lin School of Medicine, National University of Singapore. · Institute of Clinical Chemistry and Laboratory Medicine, University Medical Center Mainz, Mainz, Germany. · Department of Ophthalmology, University of Groningen, University Medical Center Groningen, Groningen, the Netherlands. · Department of Molecular Epidemiology, Queensland Institute of Medical Research, Herston, Brisbane, Queensland, Australia. · Preventive Cardiology and Preventive Medicine/Center for Cardiology, University Medical Center Mainz, Mainz, Germany. · Center for Thrombosis and Hemostasis, University Medical Center Mainz, Mainz, Germany. · German Center for Cardiovascular Research (DZHK), partner site RhineMain, Mainz, Germany. · Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin, USA. · School of Medicine, Menzies Research Institute Tasmania, University of Tasmania, Hobart, Australia. · Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA and. · Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht-Karls-University of Heidelberg, Heidelberg, Germany. ·Hum Mol Genet · Pubmed #28073927.

ABSTRACT: Primary open-angle glaucoma (POAG), the most common optic neuropathy, is a heritable disease. Siblings of POAG cases have a ten-fold increased risk of developing the disease. Intraocular pressure (IOP) and optic nerve head characteristics are used clinically to predict POAG risk. We conducted a genome-wide association meta-analysis of IOP and optic disc parameters and validated our findings in multiple sets of POAG cases and controls. Using imputation to the 1000 genomes (1000G) reference set, we identified 9 new genomic regions associated with vertical cup-disc ratio (VCDR) and 1 new region associated with IOP. Additionally, we found 5 novel loci for optic nerve cup area and 6 for disc area. Previously it was assumed that genetic variation influenced POAG either through IOP or via changes to the optic nerve head; here we present evidence that some genomic regions affect both IOP and the disc parameters. We characterized the effect of the novel loci through pathway analysis and found that pathways involved are not entirely distinct as assumed so far. Further, we identified a novel association between CDKN1A and POAG. Using a zebrafish model we show that six6b (associated with POAG and optic nerve head variation) alters the expression of cdkn1a. In summary, we have identified several novel genes influencing the major clinical risk predictors of POAG and showed that genetic variation in CDKN1A is important in POAG risk.

17 Article Virtual clinics in glaucoma care: face-to-face versus remote decision-making. 2017

Clarke, Jonathan / Puertas, Renata / Kotecha, Aachal / Foster, Paul J / Barton, Keith. ·Glaucoma Service, Moorfields Eye Hospital London, London, UK. · NIHR BRC at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK. ·Br J Ophthalmol · Pubmed #27729310.

ABSTRACT: BACKGROUND/AIMS: To examine the agreement in clinical decisions of glaucoma status made in a virtual glaucoma clinic with those made during a face-to-face consultation. METHODS: A trained nurse and technicians entered data prospectively for 204 patients into a proforma. A subsequent face-to-face clinical assessment was completed by either a glaucoma consultant or fellow. Proformas were reviewed remotely by one of two additional glaucoma consultants, and 12 months later, by the clinicians who had undertaken the original clinical examination. The interobserver and intraobserver decision-making agreements of virtual assessment versus standard care were calculated. RESULTS: We identified adverse disagreement between face-to-face and virtual review in 7/204 (3.4%, 95% CI 0.9% to 5.9%) patients, where virtual review failed to predict a need to accelerated follow-up identified in face-to-face review. Misclassification events were rare, occurring in 1.9% (95% CI 0.3% to 3.8%) of assessments. Interobserver κ (95% CI) showed only fair agreement (0.24 (0.04 to 0.43)); this improved to moderate agreement when only consultant decisions were compared against each other (κ=0.41 (0.16 to 0.65)). The intraobserver agreement κ (95% CI) for the consultant was 0.274 (0.073 to 0.476), and that for the fellow was 0.264 (0.031 to 0.497). CONCLUSIONS: The low rate of adverse misclassification, combined with the slowly progressive nature of most glaucoma, and the fact that patients will all be regularly reassessed, suggests that virtual clinics offer a safe, logistically viable option for selected patients with glaucoma.

18 Article Effectiveness of early lens extraction for the treatment of primary angle-closure glaucoma (EAGLE): a randomised controlled trial. 2016

Azuara-Blanco, Augusto / Burr, Jennifer / Ramsay, Craig / Cooper, David / Foster, Paul J / Friedman, David S / Scotland, Graham / Javanbakht, Mehdi / Cochrane, Claire / Norrie, John / Anonymous9770883. ·Centre for Public Health, Queen's University Belfast, Belfast, UK. Electronic address: a.azuara-blanco@qub.ac.uk. · School of Medicine, University of St Andrews, St Andrews, UK. · Health Services Research Unit, University of Aberdeen, Aberdeen, UK. · NIHR Biomedical Research Centre, Moorfields Eye Hospital and University College London, UK. · Johns Hopkins Wilmer Eye Institute, Baltimore, MD, USA. · Health Services Research Unit, University of Aberdeen, Aberdeen, UK; Health Economics Research Unit, University of Aberdeen, Aberdeen, UK. · Health Economics Research Unit, University of Aberdeen, Aberdeen, UK. · Health Services Research Unit, University of Aberdeen, Aberdeen, UK; Centre for Health Care Randomised Trials, University of Aberdeen, Aberdeen, UK. ·Lancet · Pubmed #27707497.

ABSTRACT: BACKGROUND: Primary angle-closure glaucoma is a leading cause of irreversible blindness worldwide. In early-stage disease, intraocular pressure is raised without visual loss. Because the crystalline lens has a major mechanistic role, lens extraction might be a useful initial treatment. METHODS: From Jan 8, 2009, to Dec 28, 2011, we enrolled patients from 30 hospital eye services in five countries. Randomisation was done by a web-based application. Patients were assigned to undergo clear-lens extraction or receive standard care with laser peripheral iridotomy and topical medical treatment. Eligible patients were aged 50 years or older, did not have cataracts, and had newly diagnosed primary angle closure with intraocular pressure 30 mm Hg or greater or primary angle-closure glaucoma. The co-primary endpoints were patient-reported health status, intraocular pressure, and incremental cost-effectiveness ratio per quality-adjusted life-year gained 36 months after treatment. Analysis was by intention to treat. This study is registered, number ISRCTN44464607. FINDINGS: Of 419 participants enrolled, 155 had primary angle closure and 263 primary angle-closure glaucoma. 208 were assigned to clear-lens extraction and 211 to standard care, of whom 351 (84%) had complete data on health status and 366 (87%) on intraocular pressure. The mean health status score (0·87 [SD 0·12]), assessed with the European Quality of Life-5 Dimensions questionnaire, was 0·052 higher (95% CI 0·015-0·088, p=0·005) and mean intraocular pressure (16·6 [SD 3·5] mm Hg) 1·18 mm Hg lower (95% CI -1·99 to -0·38, p=0·004) after clear-lens extraction than after standard care. The incremental cost-effectiveness ratio was £14 284 for initial lens extraction versus standard care. Irreversible loss of vision occurred in one participant who underwent clear-lens extraction and three who received standard care. No patients had serious adverse events. INTERPRETATION: Clear-lens extraction showed greater efficacy and was more cost-effective than laser peripheral iridotomy, and should be considered as an option for first-line treatment. FUNDING: Medical Research Council.

19 Article Genome-wide association study identifies five new susceptibility loci for primary angle closure glaucoma. 2016

Khor, Chiea Chuen / Do, Tan / Jia, Hongyan / Nakano, Masakazu / George, Ronnie / Abu-Amero, Khaled / Duvesh, Roopam / Chen, Li Jia / Li, Zheng / Nongpiur, Monisha E / Perera, Shamira A / Qiao, Chunyan / Wong, Hon-Tym / Sakai, Hiroshi / Barbosa de Melo, Mônica / Lee, Mei-Chin / Chan, Anita S / Azhany, Yaakub / Dao, Thi Lam Huong / Ikeda, Yoko / Perez-Grossmann, Rodolfo A / Zarnowski, Tomasz / Day, Alexander C / Jonas, Jost B / Tam, Pancy O S / Tran, Tuan Anh / Ayub, Humaira / Akhtar, Farah / Micheal, Shazia / Chew, Paul T K / Aljasim, Leyla A / Dada, Tanuj / Luu, Tam Thi / Awadalla, Mona S / Kitnarong, Naris / Wanichwecharungruang, Boonsong / Aung, Yee Yee / Mohamed-Noor, Jelinar / Vijayan, Saravanan / Sarangapani, Sripriya / Husain, Rahat / Jap, Aliza / Baskaran, Mani / Goh, David / Su, Daniel H / Wang, Huaizhou / Yong, Vernon K / Yip, Leonard W / Trinh, Tuyet Bach / Makornwattana, Manchima / Nguyen, Thanh Thu / Leuenberger, Edgar U / Park, Ki-Ho / Wiyogo, Widya Artini / Kumar, Rajesh S / Tello, Celso / Kurimoto, Yasuo / Thapa, Suman S / Pathanapitoon, Kessara / Salmon, John F / Sohn, Yong Ho / Fea, Antonio / Ozaki, Mineo / Lai, Jimmy S M / Tantisevi, Visanee / Khaing, Chaw Chaw / Mizoguchi, Takanori / Nakano, Satoko / Kim, Chan-Yun / Tang, Guangxian / Fan, Sujie / Wu, Renyi / Meng, Hailin / Nguyen, Thi Thuy Giang / Tran, Tien Dat / Ueno, Morio / Martinez, Jose Maria / Ramli, Norlina / Aung, Yin Mon / Reyes, Rigo Daniel / Vernon, Stephen A / Fang, Seng Kheong / Xie, Zhicheng / Chen, Xiao Yin / Foo, Jia Nee / Sim, Kar Seng / Wong, Tina T / Quek, Desmond T / Venkatesh, Rengaraj / Kavitha, Srinivasan / Krishnadas, Subbiah R / Soumittra, Nagaswamy / Shantha, Balekudaru / Lim, Boon-Ang / Ogle, Jeanne / de Vasconcellos, José P C / Costa, Vital P / Abe, Ricardo Y / de Souza, Bruno B / Sng, Chelvin C / Aquino, Maria C / Kosior-Jarecka, Ewa / Fong, Guillermo Barreto / Tamanaja, Vania Castro / Fujita, Ricardo / Jiang, Yuzhen / Waseem, Naushin / Low, Sancy / Pham, Huan Nguyen / Al-Shahwan, Sami / Craven, E Randy / Khan, Muhammad Imran / Dada, Rrima / Mohanty, Kuldeep / Faiq, Muneeb A / Hewitt, Alex W / Burdon, Kathryn P / Gan, Eng Hui / Prutthipongsit, Anuwat / Patthanathamrongkasem, Thipnapa / Catacutan, Mary Ann T / Felarca, Irene R / Liao, Chona S / Rusmayani, Emma / Istiantoro, Vira Wardhana / Consolandi, Giulia / Pignata, Giulia / Lavia, Carlo / Rojanapongpun, Prin / Mangkornkanokpong, Lerprat / Chansangpetch, Sunee / Chan, Jonathan C H / Choy, Bonnie N K / Shum, Jennifer W H / Than, Hlaing May / Oo, Khin Thida / Han, Aye Thi / Yong, Victor H / Ng, Xiao-Yu / Goh, Shuang Ru / Chong, Yaan Fun / Hibberd, Martin L / Seielstad, Mark / Png, Eileen / Dunstan, Sarah J / Chau, Nguyen Van Vinh / Bei, Jinxin / Zeng, Yi Xin / Karkey, Abhilasha / Basnyat, Buddha / Pasutto, Francesca / Paoli, Daniela / Frezzotti, Paolo / Wang, Jie Jin / Mitchell, Paul / Fingert, John H / Allingham, R Rand / Hauser, Michael A / Lim, Soon Thye / Chew, Soo Hong / Ebstein, Richard P / Sakuntabhai, Anavaj / Park, Kyu Hyung / Ahn, Jeeyun / Boland, Greet / Snippe, Harm / Stead, Richard / Quino, Raquel / Zaw, Su Nyunt / Lukasik, Urszula / Shetty, Rohit / Zahari, Mimiwati / Bae, Hyoung Won / Oo, Nay Lin / Kubota, Toshiaki / Manassakorn, Anita / Ho, Wing Lau / Dallorto, Laura / Hwang, Young Hoon / Kiire, Christine A / Kuroda, Masako / Djamal, Zeiras Eka / Peregrino, Jovell Ian M / Ghosh, Arkasubhra / Jeoung, Jin Wook / Hoan, Tung S / Srisamran, Nuttamon / Sandragasu, Thayanithi / Set, Saw Htoo / Doan, Vi Huyen / Bhattacharya, Shomi S / Ho, Ching-Lin / Tan, Donald T / Sihota, Ramanjit / Loon, Seng-Chee / Mori, Kazuhiko / Kinoshita, Shigeru / Hollander, Anneke I den / Qamar, Raheel / Wang, Ya-Xing / Teo, Yik Y / Tai, E-Shyong / Hartleben-Matkin, Curt / Lozano-Giral, David / Saw, Seang Mei / Cheng, Ching-Yu / Zenteno, Juan C / Pang, Chi Pui / Bui, Huong T T / Hee, Owen / Craig, Jamie E / Edward, Deepak P / Yonahara, Michiko / Neto, Jamil Miguel / Guevara-Fujita, Maria L / Xu, Liang / Ritch, Robert / Liza-Sharmini, Ahmad Tajudin / Wong, Tien Y / Al-Obeidan, Saleh / Do, Nhu Hon / Sundaresan, Periasamy / Tham, Clement C / Foster, Paul J / Vijaya, Lingam / Tashiro, Kei / Vithana, Eranga N / Wang, Ningli / Aung, Tin. ·Genome Institute of Singapore, A-STAR, Singapore. · Singapore Eye Research Institute, Singapore National Eye Centre and Eye ACP, Duke-National University of Singapore, Singapore. · Department of Biochemistry, National University of Singapore, Singapore. · Vietnam National Institute of Ophthalmology, Hanoi, Vietnam. · Beijing Tongren Eye Center, Beijing Tongren Hospital, Capital Medical University, Beijing Ophthalmology and Visual Science Key Laboratory, Beijing, China. · Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, Kyoto, Japan. · Jadhavbhai Nathamal Singhvi Department of Glaucoma, Medical Research Foundation, Sankara Nethralaya, Chennai, India. · Department of Ophthalmology, College of Medicine, King Saud University, Riyadh, Saudi Arabia. · Department of Ophthalmology, College of Medicine, University of Florida, Jacksonville, Florida, USA. · Department of Genetics, Aravind Medical Research Foundation, Madurai, India. · Department of Ophthalmology and Visual Sciences, Chinese University of Hong Kong, Hong Kong, China. · Department of Ophthalmology, Tan Tock Seng Hospital, NHG Eye Institute, Singapore. · Department of Ophthalmology, University of the Ryukyus, Okinawa, Nishihara, Japan. · Center of Molecular Biology and Genetic Engineering, University of Campinas, Campinas, Brazil. · Department of Ophthalmology, School of Medical Sciences, Health Campus, Universiti Sains Malaysia and Hospital Universiti Sains Malaysia, Kelantan, Malaysia. · Department of Ophthalmology, Kyoto Prefectural University of Medicine, Kyoto, Japan. · Instituto de Glaucoma y Catarata, Lima, Peru. · Department of Diagnostics and Microsurgery of Glaucoma, Medical University, Lublin, Poland. · NIHR Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital and University College London Institute of Ophthalmology, London, UK. · Glaucoma Service, Moorfields Eye Hospital NHS Foundation Trust, London, UK. · Division of Genetics, UCL Institute of Ophthalmology, London, UK. · Department of Ophthalmology, Medical Faculty Mannheim of the Ruprecht Karls University Heidelberg, Heidelberg, Germany. · Ho Chi Minh City Eye Hospital, Ho Chi Minh City, Vietnam. · Department of Biosciences, COMSATS Institute of Information Technology, Islamabad, Pakistan. · Pakistan Institute of Ophthalmology, Al-Shifa Trust Eye Hospital, Rawalpindi, Pakistan. · Department of Ophthalmology, Radboud University Medical Centre, Nijmegen, the Netherlands. · Department of Ophthalmology, National University Health System, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. · King Khaled Eye Specialist Hospital, Riyadh, Saudi Arabia. · All India Institute of Medical Sciences, New Delhi, India. · Department of Glaucoma, Da Nang Eye Hospital, Da Nang City, Vietnam. · Department of Ophthalmology, Flinders University, Flinders Medical Centre, Adelaide, South Australia, Australia. · Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. · Glaucoma Services, Department of Ophthalmology, Rajavithi Hospital, Bangkok, Thailand. · College of Medicine, Rangsit University, Bangkok, Thailand. · Mandalay Eye Department, Mandalay Eye ENT Hospital, University of Medicine Mandalay, Mandalay, Myanmar. · Department of Ophthalmology, Hospital Kuala Lumpur, Kuala Lumpur, Malaysia. · Vision Research Foundation, Sankara Nethralaya, Chennai, India. · Division of Ophthalmology, Changi General Hospital, Singapore. · Department of Ophthalmology, Thammasat University Faculty of Medicine, Rangsit, Thailand. · Eye Department, Viet Tiep General Hospital, Hai Phong, Vietnam. · Asian Eye Institute, Manila, Philippines. · Division of Ophthalmology, University of the East, Manila, Philippines. · Department of Ophthalmology, Seoul National University College of Medicine, Seoul, Republic of Korea. · Glaucoma Service Jakarta Eye Center, Jakarta, Indonesia. · Faculty of Medicine, University of Indonesia, Jakarta, Indonesia. · Narayana Nethralaya Eye Hospital, Bangalore, India. · Einhorn Clinical Research Center, New York Eye and Ear Infirmary of Mount Sinai, New York, New York, USA. · Department of Ophthalmology, Kobe City Medical Center General Hospital, Kobe, Japan. · Nepal Glaucoma Eye Clinic, Tilganga Institute of Ophthalmology, Kathmandu, Nepal. · Department of Ophthalmology, Faculty of Medicine, Chiang Mai University, Chiang Mai, Thailand. · Oxford Eye Hospital, John Radcliffe Hospital, Oxford University Hospitals NHS Trust, Oxford, UK. · Department of Ophthalmology, Konyang University, Kim's Eye Hospital, Myung-Gok Eye Research Institute, Seoul, Republic of Korea. · Dipartimento di Scienze Chirurgiche, Università di Torino, Turin, Italy. · Ozaki Eye Hospital, Hyuga, Japan. · Department of Ophthalmology, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan. · Department of Ophthalmology, University of Hong Kong, Hong Kong, China. · Department of Ophthalmology, Faculty of Medicine, Chulalongkorn University, Bangkok, Thailand. · Department of Ophthalmology, No. 1 Defence Services General Hospital, Yangon, Myanmar. · Mizoguchi Eye Hospital, Sasebo, Japan. · Department of Ophthalmology, Oita University Faculty of Medicine, Oita, Japan. · Department of Ophthalmology, Yonsei University College of Medicine, Seoul, Republic of Korea. · Shijiazhuang First Eye Hospital, Shijiazhuang, China. · Handan Eye Hospital, Handan, China. · Eye Institute and Affiliated Xiamen Eye Center, Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, Xiamen, China. · Anyang Eye Hospital, Anyang, China. · Department of Ophthalmology, Pasig City General Hospital, Pasig City, Philippines. · University of Malaya, Eye Research Centre, Kuala Lumpur, Malaysia. · Department of Ophthalmology, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia. · Myanmar Eye Centre, Pun Hlaing Silom Hospital, Yangon, Myanmar. · Myanmar Eye Centre, Shwe La Min Hospital, Yangon, Myanmar. · Department of Ophthalmology/Glaucoma Section, Asian Hospital and Medical Center, Muntinlupa City, Philippines. · Binan Doctors Eye Center, Binan Doctors Hospital, Laguna, Philippines. · Department of Ophthalmology, University Hospital Nottingham, University of Nottingham, Nottingham, UK. · BMI Park Hospital Nottingham, Nottingham, UK. · International Specialist Eye Centre, Kuala Lumpur, Malaysia. · Glaucoma Clinic, Aravind Eye Hospital, Pondicherry, India. · Glaucoma Clinic, Aravind Eye Hospital, Madurai, India. · Department of Ophthalmology, Faculty of Medical Sciences, University of Campinas, Campinas, Brazil. · Instituto de Ciencias Médicas, Lima, Peru. · Hospital Nacional Arzobispo Loayza, Lima, Peru. · Centro de Genética y Biología Molecular, Universidad de San Martín de Porres, Lima, Peru. · Wilmer Eye Institute, Johns Hopkins Hospital School of Medicine, Baltimore, Maryland, USA. · Department of Human Genetics, Radboud University Medical Centre, Nijmegen, the Netherlands. · Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia. · Centre for Eye Research Australia, University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia. · Department of Ophthalmology, King Chulalongkorn Memorial Hospital, Bangkok, Thailand. · Department of Ophthalmology, Queen Mary Hospital, Hong Kong, China. · Department of Ophthalmology, North Okkalarpa General Hospital, Yangon, Myanmar. · Institute for Human Genetics, University of California, San Francisco, San Francisco, California, USA. · Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. · Peter Doherty Institute for Infection and Immunity, University of Melbourne, Melbourne, Victoria, Australia. · Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam. · Sun Yat-Sen University Cancer Center, State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangzhou, China. · Department of Experimental Research, Sun Yat-sen University Cancer Center, Guangzhou, China. · Peking Union Medical College, Beijing, China. · Oxford University Clinical Research Unit-Nepal, Patan Academy of Health Sciences, Patan Hospital, Patan, Nepal. · Institute of Human Genetics, Friedrich Alexander Universität Erlangen-Nürnberg (FAU), Erlangen, Germany. · Department of Ophthalmology, Monfalcone Hospital, Gorizia, Italy. · Department of Surgery, Section of Ophthalmology, University of Siena, Siena, Italy. · Centre for Vision Research, Department of Ophthalmology, Westmead Institute for Medical Research, University of Sydney, Sydney, New South Wales, Australia. · Department of Ophthalmology and Visual Sciences, Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA. · Wynn Institute for Vision Research, University of Iowa, Iowa City, Iowa, USA. · Department of Ophthalmology, Duke University Eye Center, Durham, North Carolina, USA. · Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA. · Division of Medical Oncology, National Cancer Centre, Singapore. · Department of Economics, National University of Singapore, Singapore. · Department of Psychology, National University of Singapore, Singapore. · Institut Pasteur, Functional Genetics of Infectious Diseases Unit, Department of Genomes and Genetics, Paris, France. · Centre National de la Recherche Scientifique, Unité de Recherche Associée 3012, Paris, France. · Department of Ophthalmology, Seoul National University Bundang Hospital, Gyeonggi, Republic of Korea. · Department of Ophthalmology, Seoul Metropolitan Government Seoul National University Boramae Medical Center, Seoul, Republic of Korea. · Department of Medical Microbiology and Virology, University Medical Center Utrecht, Utrecht, the Netherlands. · GROW Research Laboratory, Narayana Nethralaya Foundation, Bangalore, India. · Department of Biochemistry, Al-Nafees Medical College and Hospital, Isra University, Islamabad, Pakistan. · Beijing Institute of Ophthalmology, Beijing Tongren Hospital, Capital Medical University, Beijing, China. · Saw Swee Hock School of Public Health, National University of Singapore, Singapore. · Life Sciences Institute, National University of Singapore, Singapore. · National University of Singapore Graduate School for Integrative Science and Engineering, National University of Singapore, Singapore. · Department of Statistics and Applied Probability, National University of Singapore, Singapore. · Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. · Department of Glaucoma, Institute of Ophthalmology 'Conde de Valenciana', Mexico City, Mexico. · Department of Genetics, Institute of Ophthalmology 'Conde de Valenciana', Mexico City, Mexico. · Department of Biochemistry, Faculty of Medicine, Universidad Nacional Autónoma de México, Mexico City, Mexico. ·Nat Genet · Pubmed #27064256.

ABSTRACT: Primary angle closure glaucoma (PACG) is a major cause of blindness worldwide. We conducted a genome-wide association study (GWAS) followed by replication in a combined total of 10,503 PACG cases and 29,567 controls drawn from 24 countries across Asia, Australia, Europe, North America, and South America. We observed significant evidence of disease association at five new genetic loci upon meta-analysis of all patient collections. These loci are at EPDR1 rs3816415 (odds ratio (OR) = 1.24, P = 5.94 × 10(-15)), CHAT rs1258267 (OR = 1.22, P = 2.85 × 10(-16)), GLIS3 rs736893 (OR = 1.18, P = 1.43 × 10(-14)), FERMT2 rs7494379 (OR = 1.14, P = 3.43 × 10(-11)), and DPM2-FAM102A rs3739821 (OR = 1.15, P = 8.32 × 10(-12)). We also confirmed significant association at three previously described loci (P < 5 × 10(-8) for each sentinel SNP at PLEKHA7, COL11A1, and PCMTD1-ST18), providing new insights into the biology of PACG.

20 Article Genome-wide association analysis identifies TXNRD2, ATXN2 and FOXC1 as susceptibility loci for primary open-angle glaucoma. 2016

Bailey, Jessica N Cooke / Loomis, Stephanie J / Kang, Jae H / Allingham, R Rand / Gharahkhani, Puya / Khor, Chiea Chuen / Burdon, Kathryn P / Aschard, Hugues / Chasman, Daniel I / Igo, Robert P / Hysi, Pirro G / Glastonbury, Craig A / Ashley-Koch, Allison / Brilliant, Murray / Brown, Andrew A / Budenz, Donald L / Buil, Alfonso / Cheng, Ching-Yu / Choi, Hyon / Christen, William G / Curhan, Gary / De Vivo, Immaculata / Fingert, John H / Foster, Paul J / Fuchs, Charles / Gaasterland, Douglas / Gaasterland, Terry / Hewitt, Alex W / Hu, Frank / Hunter, David J / Khawaja, Anthony P / Lee, Richard K / Li, Zheng / Lichter, Paul R / Mackey, David A / McGuffin, Peter / Mitchell, Paul / Moroi, Sayoko E / Perera, Shamira A / Pepper, Keating W / Qi, Qibin / Realini, Tony / Richards, Julia E / Ridker, Paul M / Rimm, Eric / Ritch, Robert / Ritchie, Marylyn / Schuman, Joel S / Scott, William K / Singh, Kuldev / Sit, Arthur J / Song, Yeunjoo E / Tamimi, Rulla M / Topouzis, Fotis / Viswanathan, Ananth C / Verma, Shefali Setia / Vollrath, Douglas / Wang, Jie Jin / Weisschuh, Nicole / Wissinger, Bernd / Wollstein, Gadi / Wong, Tien Y / Yaspan, Brian L / Zack, Donald J / Zhang, Kang / Study, Epic-Norfolk Eye / Anonymous3990854 / Weinreb, Robert N / Pericak-Vance, Margaret A / Small, Kerrin / Hammond, Christopher J / Aung, Tin / Liu, Yutao / Vithana, Eranga N / MacGregor, Stuart / Craig, Jamie E / Kraft, Peter / Howell, Gareth / Hauser, Michael A / Pasquale, Louis R / Haines, Jonathan L / Wiggs, Janey L. ·Department of Epidemiology and Biostatistics, Institute for Computational Biology, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA. · Department of Ophthalmology, Harvard Medical School, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA. · Channing Division of Network Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. · Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA. · QIMR Berghofer Medical Research Institute, Brisbane, Queensland, Australia. · Division of Human Genetics, Genome Institute of Singapore, Singapore. · Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore. · Menzies Institute for Medical Research, University of Tasmania, Hobart, Tasmania, Australia. · Department of Ophthalmology, Flinders University, Adelaide, South Australia, Australia. · Department of Epidemiology, Harvard School of Public Health, Boston, Massachusetts, USA. · Division of Preventive Medicine, Brigham and Women's Hospital, Harvard Medical School, Boston, Massachusetts, USA. · Department of Twin Research and Genetic Epidemiology, King's College London, London, UK. · Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA. · Center for Human Genetics, Marshfield Clinic Research Foundation, Marshfield, Wisconsin, USA. · Department of Genetic Medicine and Development, University of Geneva Medical School, Geneva, Switzerland. · Department of Ophthalmology, University of North Carolina, Chapel Hill, North Carolina, USA. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. · Eye Academic Clinical Program, Duke-National University of Singapore Graduate Medical School, Singapore. · Section of Rheumatology and Clinical Epidemiology Unit, Boston University School of Medicine, Boston, Massachusetts, USA. · Renal Division, Department of Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Department of Ophthalmology, University of Iowa, College of Medicine, Iowa City, Iowa, USA. · Department of Anatomy and Cell Biology, University of Iowa, College of Medicine, Iowa City, Iowa, USA. · National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital, London, UK. · Department of Ophthalmology, University College London, London, UK. · Department of Medical Oncology, Dana-Farber Cancer Institute, Harvard Medical School, Boston, Massachusetts, USA. · Eye Doctors of Washington, Chevy Chase, Maryland, USA. · Scripps Genome Center, University of California at San Diego, San Diego, California, USA. · Centre for Eye Research Australia, University of Melbourne, Melbourne, Victoria, Australia. · Department of Ophthalmology, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia. · Department of Nutrition, Harvard School of Public Health, Boston, Massachusetts, USA. · Program in Genetic Epidemiology and Statistical Genetics, Harvard School of Public Health, Boston, Massachusetts, USA. · Department of Public Health and Primary Care, Institute of Public Health, University of Cambridge School of Clinical Medicine, Cambridge, UK. · Bascom Palmer Eye Institute, University of Miami Miller School of Medicine, Miami, Florida, USA. · Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA. · Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Western Australia, Australia. · Medical Research Council Social Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College London, London, UK. · Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Westmead, New South Wales, Australia. · Duke-National University of Singapore Graduate Medical School, Singapore. · The Jackson Laboratory, Bar Harbor, Maine, USA. · Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, New York, USA. · Department of Ophthalmology, West Virginia University Eye Institute, Morgantown, West Virginia, USA. · Department of Epidemiology, University of Michigan, Ann Arbor, Michigan, USA. · Einhorn Clinical Research Center, Department of Ophthalmology, New York Eye and Ear Infirmary of Mount Sinai, New York, New York, USA. · Center for Systems Genomics, Pennsylvania State University, University Park, Pennsylvania, USA. · Department of Ophthalmology, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. · Institute for Human Genomics, University of Miami Miller School of Medicine, Miami, Florida, USA. · Department of Ophthalmology, Stanford University School of Medicine, Palo Alto, California, USA. · Department of Ophthalmology, Mayo Clinic, Rochester, Minnesota, USA. · Department of Ophthalmology, School of Medicine, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece. · Department of Genetics, Stanford University School of Medicine, Palo Alto, California, USA. · Institute for Ophthalmic Research, Centre for Ophthalmology, University of Tübingen, Tübingen, Germany. · Genentech, San Francisco, California, USA. · Wilmer Eye Institute, Johns Hopkins University Hospital, Baltimore, Maryland, USA. · Hamilton Glaucoma Center, Shiley Eye Institute, University of California, San Diego, San Diego, California, USA. · Department of Cellular Biology and Anatomy, Georgia Regents University, Augusta, Georgia, USA. · James and Jean Culver Vision Discovery Institute, Georgia Regents University, Augusta, Georgia, USA. ·Nat Genet · Pubmed #26752265.

ABSTRACT: Primary open-angle glaucoma (POAG) is a leading cause of blindness worldwide. To identify new susceptibility loci, we performed meta-analysis on genome-wide association study (GWAS) results from eight independent studies from the United States (3,853 cases and 33,480 controls) and investigated the most significantly associated SNPs in two Australian studies (1,252 cases and 2,592 controls), three European studies (875 cases and 4,107 controls) and a Singaporean Chinese study (1,037 cases and 2,543 controls). A meta-analysis of the top SNPs identified three new associated loci: rs35934224[T] in TXNRD2 (odds ratio (OR) = 0.78, P = 4.05 × 10(-11)) encoding a mitochondrial protein required for redox homeostasis; rs7137828[T] in ATXN2 (OR = 1.17, P = 8.73 × 10(-10)); and rs2745572[A] upstream of FOXC1 (OR = 1.17, P = 1.76 × 10(-10)). Using RT-PCR and immunohistochemistry, we show TXNRD2 and ATXN2 expression in retinal ganglion cells and the optic nerve head. These results identify new pathways underlying POAG susceptibility and suggest new targets for preventative therapies.

21 Article Qualitative investigation of patients' experience of a glaucoma virtual clinic in a specialist ophthalmic hospital in London, UK. 2015

Kotecha, Aachal / Bonstein, Karen / Cable, Richard / Cammack, Jocelyn / Clipston, Jane / Foster, Paul. ·NIHR Biomedical Research Centre for Ophthalmology at Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK. ·BMJ Open · Pubmed #26671959.

ABSTRACT: OBJECTIVES: To explore how patients felt about delivery of care in a novel technician-delivered virtual clinic compared with delivery of care in a doctor-delivered model. DESIGN: A qualitative investigation using one-to-one interviews before and after patients' appointments at either the standard outpatient glaucoma clinic or the new technician-delivered virtual glaucoma clinic (Glaucoma Screening and Stable Monitoring Service, GSMS). SETTING: A glaucoma clinic based in a tertiary ophthalmic specialist hospital in London. PARTICIPANTS: 43 patients (38 Caucasian, 5 African/Afro-Caribbean) were interviewed prior to their glaucoma appointment; 38 patients were interviewed between 4 and 6 weeks after their appointment. Consecutive patients were identified from patient reception lists and telephoned prior to their appointment inviting them to participate. RESULTS: Trust in the patient-provider relationship emerged as a key theme in patients' acceptance of not being seen in a traditional doctor-delivered service. Patients who were well informed regarding their glaucoma status and low risk of progression to sight loss were more accepting of the GSMS. Patients valued the reassurance received through effective communication with their healthcare practitioner at the time of their appointment. CONCLUSIONS: This study suggests that patients are accepting of moving to a model of service delivery whereby the doctor is removed from the consultation as long as they are informed about the status of their condition and reassured by the interaction with staff they meet. This study highlights the importance of patient engagement when introducing new models of service delivery.

22 Article Measures of socioeconomic status and self-reported glaucoma in the U.K. Biobank cohort. 2015

Shweikh, Y / Ko, F / Chan, M P Y / Patel, P J / Muthy, Z / Khaw, P T / Yip, J / Strouthidis, N / Foster, P J / Anonymous6890840. ·Division of Genetics and Epidemiology, NIHR Biomedical Research Centre, Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, UK. · Department of Public Health and Primary Care, University of Cambridge, Cambridge, UK. · Singapore Eye Research Institute, Singapore, Singapore. · Discipline of Clinical Ophthalmology and Eye Health, University of Sydney, Sydney, NSW, Australia. ·Eye (Lond) · Pubmed #26315700.

ABSTRACT: PURPOSE: To determine ocular, demographic, and socioeconomic associations with self-reported glaucoma in the U.K. Biobank. METHODS: Biobank is a study of U.K. residents aged 40-69 years registered with the National Health Service. Data were collected on visual acuity, intraocular pressure (IOP), corneal biomechanics, and questionnaire from 112,690 participants. Relationships between ocular, demographic, and socioeconomic variables with reported diagnosis of glaucoma were examined. RESULTS: In all, 1916 (1.7%) people in U.K. Biobank reported glaucoma diagnosis. Participants reporting glaucoma were more likely to be older (mean 61.4 vs. 56.7 years, P<0.001) and male (2.1% vs. 1.4%, P=0.001). The rate of reported glaucoma was significantly higher in Black (3.28%, P<0.001) and Asian (2.14%, P=0.009) participants compared with White participants (1.62%, reference). Cases of reported glaucoma had a higher mean IOP (18 mm Hg both eyes, P<0.001), lower corneal hysteresis (9.96 right eye, 9.89 left eye, P<0.001), and lower visual acuity (0.09 logMAR right eye, 0.08 logMAR left eye, P<0.001) compared with those without (16 mm Hg both eyes, hysteresis 10.67 right eye, 10.63 left eye, 0.03 logMAR right eye, 0.02 logMAR left eye). The mean Townsend deprivation index was -0.72 for those reporting glaucoma and -0.95 for those without (P<0.001), indicating greater relative deprivation in those reporting glaucoma. Multivariable logistic regression showed that people in the lowest income group (<£18,000/year) were significantly more likely to report a diagnosis of glaucoma compared with any other income level (P<0.01). We observed increasing glaucoma risk across the full range of income categories, with highest risk among those of lowest income, and no evidence of a threshold effect. CONCLUSIONS: In a large U.K. cohort, individuals reporting glaucoma had more adverse socioeconomic characteristics. Study of the mechanisms explaining these effects may aid our understanding of health inequality and will help inform public health interventions.

23 Article The Prevalence and Types of Glaucoma in an Urban Chinese Population: The Singapore Chinese Eye Study. 2015

Baskaran, Mani / Foo, Reuben C / Cheng, Ching-Yu / Narayanaswamy, Arun K / Zheng, Ying-Feng / Wu, Renyi / Saw, Seang-Mei / Foster, Paul J / Wong, Tien-Yin / Aung, Tin. ·Singapore Eye Research Institute, Singapore National Eye Centre, Singapore2Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore2Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore3Academic Clinical Program for Ophthalmo. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore4Zhongshan Ophthalmic Center, State Key Laboratory of Ophthalmology, Sun Yat-sen University, Guangzhou, China. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore5Xiamen Eye Center of Xiamen University, Xiamen, China. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore2Department of Ophthalmology, Yong Loo Lin School of Medicine, National University of Singapore, National University Health System, Singapore6Saw Swee Hock School of Public Health. · National Institute for Health Research Biomedical Research Centre, Moorfields Eye Hospital, University College of London Institute of Ophthalmology, London, England. · Singapore Eye Research Institute, Singapore National Eye Centre, Singapore3Academic Clinical Program for Ophthalmology and Visual Sciences, Office of Clinical, Academic and Faculty Affairs, Duke-National University of Singapore Graduate Medical School, Si. ·JAMA Ophthalmol · Pubmed #25974263.

ABSTRACT: IMPORTANCE: Glaucoma represents a major public health challenge in an aging population. The Tanjong Pagar Eye Study reported the prevalence and risk factors of glaucoma in a Singapore Chinese population in 1997, which established the higher rates of blindness in this population. OBJECTIVES: To determine the prevalence and associated risk factors for glaucoma among Chinese adults in Singapore and to compare the results with those of the 1997 study. DESIGN, SETTING, AND PARTICIPANTS: In a population-based survey of 4605 eligible individuals, we selected 3353 Chinese adults 40 years or older from the southwestern part of Singapore. Participants underwent examination at a single tertiary care research institute from February 9, 2009, through December 19, 2011. EXPOSURES: All participants underwent slitlamp ophthalmic examination, applanation tonometry, measurement of central corneal thickness, gonioscopy, and a dilated fundus examination. MAIN OUTCOMES AND MEASURES: Glaucoma as defined by the International Society of Geographical and Epidemiological Ophthalmology guidelines and age-standardized prevalence estimates computed as per the 2010 Singapore Chinese census. Blindness was defined as logMAR visual acuity of 1.00 (Snellen equivalent, 20/200 or worse). RESULTS: Of the 3353 respondents, 134 (4.0%) had glaucoma, including primary open-angle glaucoma (POAG) in 57 (1.7%), primary angle-closure glaucoma (PACG) in 49 (1.5%), and secondary glaucoma in 28 (0.8%). The age-standardized prevalence (95% CI) of glaucoma was 3.2% (2.7%-3.9%); POAG, 1.4% (1.1%-1.9%); and PACG, 1.2% (0.9%-1.6%). In a multivariate model, POAG was associated with being older and male and having a higher intraocular pressure. Of the 134 participants with glaucoma, 114 (85.1%; 95% CI, 78.1%-90.1%) were not aware of their diagnosis. Prevalence (95% CI) of blindness caused by secondary glaucoma was 14.3% (5.7%-31.5%), followed by 10.2% (4.4%-21.8%) for PACG and 8.8% (3.8%-18.9%) for POAG. We could not identify a difference in the prevalence of glaucoma compared with the 3.2% reported in 1997 (difference, -0.04%; 95% CI, -1.2 to 1.2; P = .97). CONCLUSIONS AND RELEVANCE: The prevalence of glaucoma among Singapore Chinese likely ranges from 2.7% to 3.9%, with secondary glaucoma being the most visually debilitating type. We could not identify a difference compared with previous studies approximately 12 years earlier. We report a high proportion of previously undiagnosed disease, suggesting the need to increase public awareness of this potentially blinding condition.

24 Article Crowdsourcing as a screening tool to detect clinical features of glaucomatous optic neuropathy from digital photography. 2015

Mitry, Danny / Peto, Tunde / Hayat, Shabina / Blows, Peter / Morgan, James / Khaw, Kay-Tee / Foster, Paul J. ·NIHR Biomedical Research Centre, Moorfields Eye Hospital and UCL Institute of Ophthalmology, London, United Kingdom. · Department of Public Health and Primary Care, University of Cambridge, Strangeways Research Laboratory, Cambridge, United Kingdom. · School of Optometry and Vision Sciences, Cardiff University, Cardiff, United Kingdom. · Department of Clinical Gerontology, Addenbrookes Hospital, University of Cambridge, Cambridge, United Kingdom. ·PLoS One · Pubmed #25692287.

ABSTRACT: AIM: Crowdsourcing is the process of simplifying and outsourcing numerous tasks to many untrained individuals. Our aim was to assess the performance and repeatability of crowdsourcing in the classification of normal and glaucomatous discs from optic disc images. METHODS: Optic disc images (N = 127) with pre-determined disease status were selected by consensus agreement from grading experts from a large cohort study. After reading brief illustrative instructions, we requested that knowledge workers (KWs) from a crowdsourcing platform (Amazon MTurk) classified each image as normal or abnormal. Each image was classified 20 times by different KWs. Two study designs were examined to assess the effect of varying KW experience and both study designs were conducted twice for consistency. Performance was assessed by comparing the sensitivity, specificity and area under the receiver operating characteristic curve (AUC). RESULTS: Overall, 2,540 classifications were received in under 24 hours at minimal cost. The sensitivity ranged between 83-88% across both trials and study designs, however the specificity was poor, ranging between 35-43%. In trial 1, the highest AUC (95%CI) was 0.64(0.62-0.66) and in trial 2 it was 0.63(0.61-0.65). There were no significant differences between study design or trials conducted. CONCLUSIONS: Crowdsourcing represents a cost-effective method of image analysis which demonstrates good repeatability and a high sensitivity. Optimisation of variables such as reward schemes, mode of image presentation, expanded response options and incorporation of training modules should be examined to determine their effect on the accuracy and reliability of this technique in retinal image analysis.

25 Article Common variants near ABCA1, AFAP1 and GMDS confer risk of primary open-angle glaucoma. 2014

Gharahkhani, Puya / Burdon, Kathryn P / Fogarty, Rhys / Sharma, Shiwani / Hewitt, Alex W / Martin, Sarah / Law, Matthew H / Cremin, Katie / Bailey, Jessica N Cooke / Loomis, Stephanie J / Pasquale, Louis R / Haines, Jonathan L / Hauser, Michael A / Viswanathan, Ananth C / McGuffin, Peter / Topouzis, Fotis / Foster, Paul J / Graham, Stuart L / Casson, Robert J / Chehade, Mark / White, Andrew J / Zhou, Tiger / Souzeau, Emmanuelle / Landers, John / Fitzgerald, Jude T / Klebe, Sonja / Ruddle, Jonathan B / Goldberg, Ivan / Healey, Paul R / Anonymous4351063 / Mills, Richard A / Wang, Jie Jin / Montgomery, Grant W / Martin, Nicholas G / RadfordSmith, Graham / Whiteman, David C / Brown, Matthew A / Wiggs, Janey L / Mackey, David A / Mitchell, Paul / MacGregor, Stuart / Craig, Jamie E. ·QIMR Berghofer Medical Research Institute, Brisbane, QLD 4029, Australia. · Department of Ophthalmology, Flinders University, Adelaide, SA 5042, Australia. · Menzies Research Institute Tasmania, University of Tasmania, Hobart, TAS, 7000, Australia. · Centre for Eye Research Australia (CERA), University of Melbourne, Royal Victorian Eye and Ear Hospital, Melbourne, Victoria, Australia. · University of Queensland Diamantina Institute, Brisbane, QLD 4102, Australia. · Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee, USA. · Department of Epidemiology and Biostatistics, Case Western Reserve University, Cleveland, Ohio, USA. · Department of Ophthalmology, Harvard Medical School and Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA. · Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, Massachusetts, USA. · Department of Ophthalmology, Duke University Medical Center, Durham, North Carolina, USA. · Department of Medicine, Duke University Medical Center, Durham, North Carolina, USA. · NIHR Biomedical Research Centre, Moorfields Eye Hospital NHS Foundation Trust and UCL Institute of Ophthalmology, London, UK. · MRC Social Genetic and Developmental Psychiatry Research Centre, Institute of Psychiatry, King's College, De Crespigny Park, London, UK. · Department of Ophthalmology, School of Medicine, Aristotle University of Thessaloniki, AHEPA Hospital, Thessaloniki, Greece. · Ophthalmology and Vision Science, Macquarie University, Sydney, New South Wales, Australia. · South Australian Institute of Ophthalmology, University of Adelaide, Adelaide, South Australia, Australia. · Centre for Vision Research, Westmead Millennium Institute, University of Sydney, Westmead, NSW 2145, Australia. · Department of Anatomical Pathology, Flinders University, Flinders Medical Centre, South Australia. · Department of Ophthalmology, University of Sydney, Sydney Eye Hospital, Sydney, Australia. · School of Medicine, University of Queensland, Herston Campus, Brisbane, QLD, Australia. · Centre for Ophthalmology and Visual Science, Lions Eye Institute, University of Western Australia, Perth, Australia. · South Australian Health and Medical Research Institute, Adelaide, South Australia. ·Nat Genet · Pubmed #25173105.

ABSTRACT: Primary open-angle glaucoma (POAG) is a major cause of irreversible blindness worldwide. We performed a genome-wide association study in an Australian discovery cohort comprising 1,155 cases with advanced POAG and 1,992 controls. We investigated the association of the top SNPs from the discovery stage in two Australian replication cohorts (932 cases and 6,862 controls total) and two US replication cohorts (2,616 cases and 2,634 controls total). Meta-analysis of all cohorts identified three loci newly associated with development of POAG. These loci are located upstream of ABCA1 (rs2472493[G], odds ratio (OR) = 1.31, P = 2.1 × 10(-19)), within AFAP1 (rs4619890[G], OR = 1.20, P = 7.0 × 10(-10)) and within GMDS (rs11969985[G], OR = 1.31, P = 7.7 × 10(-10)). Using RT-PCR and immunolabeling, we show that these genes are expressed within human retina, optic nerve and trabecular meshwork and that ABCA1 and AFAP1 are also expressed in retinal ganglion cells.

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