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1. The long-term effects of Kerala Diabetes Prevention Program on diabetes incidence and cardiometabolic risk: a study protocol

Author

Tilahun Haregu, T. R. Lekha, Smitha Jasper, Nitin Kapoor, Thirunavukkarasu Sathish, Jeemon Panniyammakal, Robyn Tapp, Kavumpurathu Raman Thankappan, Ajay Mahal, Pilvikki Absetz, Edwin B. Fisher, and Brian Oldenburg

Subjects
Diabetes, India, Kerala, Peer support, Long-term effects, Cardiometabolic, Public aspects of medicine, RA1-1270
Abstract

Abstract Introduction India currently has more than 74.2 million people with Type 2 Diabetes Mellitus (T2DM). This is predicted to increase to 124.9 million by 2045. In combination with controlling blood glucose levels among those with T2DM, preventing the onset of diabetes among those at high risk of developing it is essential. Although many diabetes prevention interventions have been implemented in resource-limited settings in recent years, there is limited evidence about their long-term effectiveness, cost-effectiveness, and sustainability. Moreover, evidence on the impact of a diabetes prevention program on cardiovascular risk over time is limited. Objectives The overall aim of this study is to evaluate the long-term cardiometabolic effects of the Kerala Diabetes Prevention Program (K-DPP). Specific aims are 1) to measure the long-term effectiveness of K-DPP on diabetes incidence and cardiometabolic risk after nine years from participant recruitment; 2) to assess retinal microvasculature, microalbuminuria, and ECG abnormalities and their association with cardiometabolic risk factors over nine years of the intervention; 3) to evaluate the long-term cost-effectiveness and return on investment of the K-DPP; and 4) to assess the sustainability of community engagement, peer-support, and other related community activities after nine years. Methods The nine-year follow-up study aims to reach all 1007 study participants (500 intervention and 507 control) from 60 randomized polling areas recruited to the original trial. Data are being collected in two phases. In phase 1 (Survey), we are admintsering a structured questionnaire, undertake physical measurements, and collect blood and urine samples for biochemical analysis. In phase II, we are inviting participants to undergo retinal imaging, body composition measurements, and ECG. All data collection is being conducted by trained Nurses. The primary outcome is the incidence of T2DM. Secondary outcomes include behavioral, psychosocial, clinical, biochemical, and retinal vasculature measures. Data analysis strategies include a comparison of outcome indicators with baseline, and follow-up measurements conducted at 12 and 24 months. Analysis of the long-term cost-effectiveness of the intervention is planned. Discussion Findings from this follow-up study will contribute to improved policy and practice regarding the long-term effects of lifestyle interventions for diabetes prevention in India and other resource-limited settings. Trial registration Australia and New Zealand Clinical Trials Registry–(updated from the original trial)ACTRN12611000262909; India: CTRI/2021/10/037191.

Published
2023
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2. Omega-3 polyunsaturated fatty acids favourably modulate cardiometabolic biomarkers in type 2 diabetes: a meta-analysis and meta-regression of randomized controlled trials

Author

Lauren L. O’Mahoney, Jamie Matu, Oliver J. Price, Karen M. Birch, Ramzi A. Ajjan, Diane Farrar, Robyn Tapp, Daniel J. West, Kevin Deighton, and Matthew D. Campbell

Subjects
Type 2 diabetes, Omega-3 polyunsaturated fatty acids, Eicosapentaenoic acid, Docosahexaenoic acid, Cardiovascular disease, Meta-analysis, Diseases of the circulatory (Cardiovascular) system, RC666-701
Abstract

Abstract Background Randomized controlled trials (RCTs) suggest that supplementation with omega-3 polyunsaturated fatty acids (n-3PUFAs) may favourably modify cardiometabolic biomarkers in type 2 diabetes (T2DM). Previous meta-analyses are limited by insufficient sample sizes and omission of meta-regression techniques, and a large number of RCTs have subsequently been published since the last comprehensive meta-analysis. Updated information regarding the impact of dosage, duration or an interaction between these two factors is therefore warranted. The objective was to comprehensively assess the effect of n-3PUFAs supplementation on cardiometabolic biomarkers including lipid profiles, inflammatory parameters, blood pressure, and indices of glycaemic control, in people with T2DM, and identify whether treatment dosage, duration or an interaction thereof modify these effects. Methods Databases including PubMed and MEDLINE were searched until 13th July 2017 for RCTs investigating the effect of n-3PUFAs supplementation on lipid profiles, inflammatory parameters, blood pressure, and indices of glycaemic control. Data were pooled using random-effects meta-analysis and presented as standardised mean difference (Hedges g) with 95% confidence intervals (95% CI). Meta-regression analysis was performed to investigate the effects of duration of supplementation and total dosage of n-3PUFAs as moderator variables where appropriate. Results A total of 45 RCTs were identified, involving 2674 people with T2DM. n-3PUFAs supplementation was associated with significant reductions in LDL [ES: − 0.10, (95% CI − 0.17, − 0.03); p = 0.007], VLDL (ES: − 0.26 (− 0.51, − 0.01); p = 0.044], triglycerides (ES: − 0.39 (− 0.55, − 0.24; p ≤ 0.001] and HbA1c (ES: − 0.27 (− 0.48, − 0.06); p = 0.010]. Moreover, n-3PUFAs supplementation was associated with reduction in plasma levels of TNF-α [ES: − 0.59 (− 1.17, − 0.01); p = 0.045] and IL-6 (ES: − 1.67 (− 3.14, − 0.20); p = 0.026]. All other lipid markers, indices of glycaemic control, inflammatory parameters, and blood pressure remained unchanged (p > 0.05). Conclusions n-3PUFAs supplementation produces favourable hypolipidemic effects, a reduction in pro-inflammatory cytokine levels and improvement in glycaemia. Neither duration nor dosage appear to explain the observed heterogeneity in response to n-3PUFAs. Trial registration This trial was registered at http://www.crd.york.ac.uk as CRD42016050802

Published
2018
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3. A new polygenic score for refractive error improves detection of children at risk of high myopia but not the prediction of those at risk of myopic macular degeneration

Author

Rosie Clark, Samantha Sze-Yee Lee, Ran Du, Yining Wang, Sander C.M. Kneepkens, Jason Charng, Yu Huang, Michael L. Hunter, Chen Jiang, J.Willem L. Tideman, Ronald B. Melles, Caroline C.W. Klaver, David A. Mackey, Cathy Williams, Hélène Choquet, Kyoko Ohno-Matsui, Jeremy A. Guggenheim, Joan E. Bailey-Wilson, Paul N. Baird, Veluchamy A. Barathi, Ginevra Biino, Kathryn P. Burdon, Harry Campbell, Li Jia Chen, Ching-Yu Cheng, Emily Y. Chew, Jamie E. Craig, Margaret M. Deangelis, Cécile Delcourt, Xiaohu Ding, Qiao Fan, Maurizio Fossarello, Paul J. Foster, Puya Gharahkhani, Xiaobo Guo, Annechien E.G. Haarman, Toomas Haller, Christopher J. Hammond, Xikun Han, Caroline Hayward, Mingguang He, Alex W. Hewitt, Quan Hoang, Pirro G. Hysi, Adriana I. Iglesias, Robert P. Igo, Sudha K. Iyengar, Jost B. Jonas, Mika Kähönen, Jaakko Kaprio, Anthony P. Khawaja, Barbara E. Klein, Jonathan H. Lass, Kris Lee, Terho Lehtimäki, Deyana Lewis, Qing Li, Shi-Ming Li, Leo-Pekka Lyytikäinen, Stuart MacGregor, Nicholas G. Martin, Akira Meguro, Andres Metspalu, Candace Middlebrooks, Masahiro Miyake, Nobuhisa Mizuki, Anthony Musolf, Stefan Nickels, Konrad Oexle, Chi Pui Pang, Olavi Pärssinen, Andrew D. Paterson, Norbert Pfeiffer, Ozren Polasek, Jugnoo S. Rahi, Olli Raitakari, Igor Rudan, Srujana Sahebjada, Seang-Mei Saw, Claire L. Simpson, Dwight Stambolian, E-Shyong Tai, Milly S. Tedja, J. Willem L. Tideman, Akitaka Tsujikawa, Cornelia M. van Duijn, Virginie J.M. Verhoeven, Veronique Vitart, Ningli Wang, Ya Xing Wang, Juho Wedenoja, Wen Bin Wei, Katie M. Williams, James F. Wilson, Robert Wojciechowski, Jason C.S. Yam, Kenji Yamashiro, Maurice K.H. Yap, Seyhan Yazar, Shea Ping Yip, Terri L. Young, Xiangtian Zhou, Naomi Allen, Tariq Aslam, Denize Atan, Sarah Barman, Jenny Barrett, Paul Bishop, Graeme Black, Catey Bunce, Roxana Carare, Usha Chakravarthy, Michelle Chan, Sharon Chua, Valentina Cipriani, Alexander Day, Parul Desai, Bal Dhillon, Andrew Dick, Alexander Doney, Cathy Egan, Sarah Ennis, Paul Foster, Marcus Fruttiger, John Gallacher, David Garway-Heath, Jane Gibson, Dan Gore, Jeremy Guggenheim, Chris Hammond, Alison Hardcastle, Simon Harding, Ruth Hogg, Pirro Hysi, Pearse A. Keane, Peng Tee Khaw, Anthony Khawaja, Gerassimos Lascaratos, Thomas Littlejohns, Andrew Lotery, Phil Luthert, Tom MacGillivray, Sarah Mackie, Bernadette McGuinness, Gareth McKay, Martin McKibbin, Danny Mitry, Tony Moore, James Morgan, Zaynah Muthy, Eoin O'Sullivan, Chris Owen, Praveen Patel, Euan Paterson, Tunde Peto, Axel Petzold, Nikolas Pontikos, Jugnoo Rahi, Alicja Rudnicka, Jay Self, Panagiotis Sergouniotis, Sobha Sivaprasad, David Steel, Irene Stratton, Nicholas Strouthidis, Cathie Sudlow, Robyn Tapp, Caroline Thaung, Dhanes Thomas, Emanuele Trucco, Adnan Tufail, Stephen Vernon, Ananth Viswanathan, Katie Williams, Jayne Woodside, Max Yates, Jennifer Yip, Yalin Zheng, Neurology, Ophthalmology, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Neuroinfection & -inflammation, Epidemiology, Clinical Genetics, and Erasmus MC other

Subjects
All institutes and research themes of the Radboud University Medical Center, General Medicine, General Biochemistry, Genetics and Molecular Biology, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12]
Abstract

Contains fulltext : 292919.pdf (Publisher’s version ) (Open Access) BACKGROUND: High myopia (HM), defined as a spherical equivalent refractive error (SER) ≤ -6.00 diopters (D), is a leading cause of sight impairment, through myopic macular degeneration (MMD). We aimed to derive an improved polygenic score (PGS) for predicting children at risk of HM and to test if a PGS is predictive of MMD after accounting for SER. METHODS: The PGS was derived from genome-wide association studies in participants of UK Biobank, CREAM Consortium, and Genetic Epidemiology Research on Adult Health and Aging. MMD severity was quantified by a deep learning algorithm. Prediction of HM was quantified as the area under the receiver operating curve (AUROC). Prediction of severe MMD was assessed by logistic regression. FINDINGS: In independent samples of European, African, South Asian and East Asian ancestry, the PGS explained 19% (95% confidence interval 17-21%), 2% (1-3%), 8% (7-10%) and 6% (3-9%) of the variation in SER, respectively. The AUROC for HM in these samples was 0.78 (0.75-0.81), 0.58 (0.53-0.64), 0.71 (0.69-0.74) and 0.67 (0.62-0.72), respectively. The PGS was not associated with the risk of MMD after accounting for SER: OR = 1.07 (0.92-1.24). INTERPRETATION: Performance of the PGS approached the level required for clinical utility in Europeans but not in other ancestries. A PGS for refractive error was not predictive of MMD risk once SER was accounted for. FUNDING: Supported by the Welsh Government and Fight for Sight (24WG201).

Published
2023

4. The Association of Alcohol Consumption with Glaucoma and Related Traits

Author

Kelsey V. Stuart, Robert N. Luben, Alasdair N. Warwick, Kian M. Madjedi, Praveen J. Patel, Mahantesh I. Biradar, Zihan Sun, Mark A. Chia, Louis R. Pasquale, Janey L. Wiggs, Jae H. Kang, Jihye Kim, Hugues Aschard, Jessica H. Tran, Marleen A.H. Lentjes, Paul J. Foster, Anthony P. Khawaja, Mark Chia, Sharon Chua, Ron Do, Paul Foster, Jae Kang, Alan Kastner, Anthony Khawaja, Marleen Lentjes, Robert Luben, Kian Madjedi, Giovanni Montesano, Louis Pasquale, Kelsey Stuart, Alasdair Warwick, Janey Wiggs, Naomi Allen, Tariq Aslam, Denize Atan, Sarah Barman, Jenny Barrett, Paul Bishop, Graeme Black, Tasanee Braithwaite, Roxana Carare, Usha Chakravarthy, Michelle Chan, Alexander Day, Parul Desai, Bal Dhillon, Andrew Dick, Alexander Doney, Cathy Egan, Sarah Ennis, Marcus Fruttiger, John Gallacher, David (Ted) Garway-Heath, Jane Gibson, Jeremy Guggenheim, Chris Hammond, Alison Hardcastle, Simon Harding, Ruth Hogg, Pirro Hysi, Pearse Keane, Peng Tee Khaw, Gerassimos Lascaratos, Thomas Littlejohns, Andrew Lotery, Phil Luthert, Tom MacGillivray, Sarah Mackie, Bernadette McGuinness, Gareth McKay, Martin McKibbin, Tony Moore, James Morgan, Eoin O'Sullivan, Richard Oram, Chris Owen, Praveen Patel, Euan Paterson, Tunde Peto, Axel Petzold, Nikolas Pontikos, Jugnoo Rahi, Alicja Rudnicka, Naveed Sattar, Jay Self, Panagiotis Sergouniotis, Sobha Sivaprasad, David Steel, Irene Stratton, Nicholas Strouthidis, Cathie Sudlow, Robyn Tapp, Dhanes Thomas, Emanuele Trucco, Adnan Tufail, Ananth Viswanathan, Veronique Vitart, Mike Weedon, Katie Williams, Cathy Williams, Jayne Woodside, Max Yates, Jennifer Yip, Yalin Zheng, Tin Aung, Kathryn Burdon, Li Chen, Ching-Yu Cheng, Jamie Craig, Angela Cree, Victor de Vries, Sjoerd Driessen, John Fingert, Puya Gharahkhani, Christopher Hammond, Caroline Hayward, Alex Hewitt, Nomdo Jansonius, Fridbert Jonansson, Jost Jonas, Michael Kass, Chiea Khor, Caroline Klaver, Jacyline Koh, Stuart MacGregor, David Mackey, Paul Mitchell, Calvin Pang, Francesca Pasutto, Norbert Pfeiffer, Ozren Polašek, Wishal Ramdas, Alexander Schuster, Ayellet Segrè, Einer Stefansson, Kári Stefánsson, Gudmar Thorleifsson, Unnur Thorsteinsdottir, Cornelia van Duijn, Joëlle Vergroesen, Eranga Vithana, James Wilson, Robert Wojciechowski, Tien Wong, and Terri Young

Subjects
General Medicine
Published
2022

5. Increased High-Density Lipoprotein Levels Associated with Age-Related Macular Degeneration

Author

Johanna M. Colijn, Anneke I. den Hollander, Ayse Demirkan, Audrey Cougnard-Grégoire, Timo Verzijden, Eveline Kersten, Magda A. Meester-Smoor, Benedicte M.J. Merle, Grigorios Papageorgiou, Shahzad Ahmad, Monique T. Mulder, Miguel Angelo Costa, Pascale Benlian, Geir Bertelsen, Alain M. Bron, Birte Claes, Catherine Creuzot-Garcher, Maja Gran Erke, Sascha Fauser, Paul J. Foster, Christopher J. Hammond, Hans-Werner Hense, Carel B. Hoyng, Anthony P. Khawaja, Jean-Francois Korobelnik, Stefano Piermarocchi, Tatiana Segato, Rufino Silva, Eric H. Souied, Katie M. Williams, Cornelia M. van Duijn, Cécile Delcourt, Caroline C.W. Klaver, Niyazi Acar, Lebriz Altay, Eleftherios Anastosopoulos, Augusto Azuara-Blanco, Tos Berendschot, Arthur Bergen, Christine Binquet, Alan Bird, Martin Bobak, Morten Bøgelund Larsen, Camiel Boon, Rupert Bourne, Lionel Brétillon, Rebecca Broe, Alain Bron, Gabrielle Buitendijk, Maria Luz Cachulo, Vittorio Capuano, Isabelle Carrière, Usha Chakravarthy, Michelle Chan, Petrus Chang, Johanna Colijn, Angela Cree, Phillippa Cumberland, José Cunha-Vaz, Vincent Daien, Eiko De Jong, Gabor Deak, Marie-Noëlle Delyfer, Anneke den Hollander, Martha Dietzel, Pedro Faria, Claudia Farinha, Robert Finger, Astrid Fletcher, Paul Foster, Panayiota Founti, Theo Gorgels, Jakob Grauslund, Franz Grus, Christopher Hammond, Thomas Heesterbeek, Manuel Hermann, René Hoehn, Ruth Hogg, Frank Holz, Carel Hoyng, Nomdo Jansonius, Sarah Janssen, Eiko de Jong, Anthony Khawaja, Caroline Klaver, Jean-François Korobelnik, Julia Lamparter, Mélanie Le Goff, Terho Lehtimäki, Irene Leung, Andrew Lotery, Matthias Mauschitz, Magda Meester, Bénédicte Merle, Verena Meyer zu Westrup, Edoardo Midena, Stefania Miotto, Alireza Mirshahi, Sadek Mohan-Saïd, Michael Mueller, Alyson Muldrew, Joaquim Murta, Stefan Nickels, Sandrina Nunes, Christopher Owen, Tunde Peto, Norbert Pfeiffer, Elena Prokofyeva, Jugnoo Rahi, Olli Raitakari, Franziska Rauscher, Luisa Ribeiro, Marie-Bénédicte Rougier, Alicja Rudnicka, José Sahel, Aggeliki Salonikiou, Clarisa Sanchez, Tina Schick, Steffen Schmitz-Valckenberg, Alexander Schuster, Cédric Schweitzer, Jasmin Shehata, Giuliana Silvestri, Christian Simader, Eric Souied, Martynas Speckauskas, Henriet Springelkamp, Robyn Tapp, Fotis Topouzis, Elisa van Leeuwen, Virginie Verhoeven, Hans Vingerling, Therese Von Hanno, Katie Williams, Christian Wolfram, Jennifer Yip, Jennyfer Zerbib, Soufiane Ajana, Blanca Arango-Gonzalez, Verena Arndt, Vaibhav Bhatia, Shomi S. Bhattacharya, Marc Biarnés, Anna Borrell, Sebastian Bühren, Sofia M. Calado, Sascha Dammeier, Eiko K. de Jong, Berta De la Cerda, Francisco J. Diaz-Corrales, Sigrid Diether, Eszter Emri, Tanja Endermann, Lucia L. Ferraro, Míriam Garcia, Thomas J. Heesterbeek, Sabina Honisch, Ellen Kilger, Hanno Langen, Imre Lengyel, Phil Luthert, Cyrille Maugeais, Magda Meester-Smoor, Bénédicte M.J. Merle Inserm, Jordi Monés, Everson Nogoceke, Frances M. Pool, Eduardo Rodríguez, Marius Ueffing, Karl U. Ulrich Bartz-Schmidt, Elisabeth M. van Leeuwen, and Markus Zumbansen

Subjects
genetic structures, Blood lipids, Physiology, Drusen, 03 medical and health sciences, Rotterdam Study, 0302 clinical medicine, Cholesterylester transfer protein, medicine, media_common.cataloged_instance, European union, 030304 developmental biology, media_common, 2. Zero hunger, 0303 health sciences, biology, business.industry, Lipid metabolism, Odds ratio, Macular degeneration, medicine.disease, eye diseases, 3. Good health, Ophthalmology, 030221 ophthalmology & optometry, biology.protein, lipids (amino acids, peptides, and proteins), sense organs, business
Abstract

PURPOSE: Genetic and epidemiologic studies have shown that lipid genes and High Density Lipoproteins (HDL) are implicated in age-related macular degeneration (AMD). We studied circulating lipid levels in relation to AMD in a large European dataset, and investigated whether this relationship is driven by certain sub fractions. DESIGN: (Pooled) analysis of cross-sectional data. PARTICIPANTS: 30,953 individuals aged 50+ participating in the E3 consortium; and 1530 individuals from the Rotterdam Study with lipid sub fraction data. METHODS: In E3, AMD features were graded per eye on fundus photographs using the Rotterdam Classification. Routine blood lipid measurements were available from each participant. Data on genetics, medication and confounders such as body mass index, were obtained from a common database. In a subgroup of the Rotterdam Study, lipid sub fractions were identified by the Nightingale biomarker platform. Random-intercepts mixed-effects models incorporating confounders and study site as a random-effect were used to estimate the associations. MAIN OUTCOME MEASURES: early, late or any AMD, phenotypic features of early AMD, lipid measurements. RESULTS: HDL was associated with an increased risk of AMD, corrected for potential confounders (Odds Ratio (OR) 1.21 per 1mmol/L increase (95% confidence interval[CI] 1.14-1.29); while triglycerides were associated with a decreased risk (OR 0.94 per 1mmol/L increase [95%CI 0.91-0.97]). Both were associated with drusen size, higher HDL raises the odds of larger drusen while higher triglycerides decreases the odds. LDL-cholesterol only reached statistical significance in the association with early AMD (p=0.045). Regarding lipid sub fractions: the concentration of extra-large HDL particles showed the most prominent association with AMD (OR 1.24 [95%CI 1.10-1.40]). The CETP risk variant (rs17231506) for AMD was in line with increased-HDL levels (p=7.7x10-7); but LIPC risk variants (rs2043085, rs2070895) were associated in an opposite way (p=1.0x10-6 and 1.6x10-4). CONCLUSIONS: Our study suggests that HDL-cholesterol is associated with increased risk of AMD and triglycerides negatively associated. Both show the strongest association with early AMD and drusen. Extra-large HDL sub fractions seem to be drivers in the relation with AMD, variants in lipid genes play a more ambiguous role in this association. Whether systemic lipids directly influence AMD or represent lipid metabolism in the retina remains a question to be answered.

Published
2019

6. Systemic and Ocular Determinants of Peripapillary Retinal Nerve Fiber Layer Thickness Measurements in the European Eye Epidemiology (E3) Population

Author

Matthias M. Mauschitz, Pieter W.M. Bonnemaijer, Kersten Diers, Franziska G. Rauscher, Tobias Elze, Christoph Engel, Markus Loeffler, Johanna Maria Colijn, M. Arfan Ikram, Johannes R. Vingerling, Katie M. Williams, Christopher J. Hammond, Catherine Creuzot-Garcher, Alain M. Bron, Rufino Silva, Sandrina Nunes, Cécile Delcourt, Audrey Cougnard-Grégoire, Frank G. Holz, Caroline C.W. Klaver, Monique M.B. Breteler, Robert P. Finger, Niyazi Acar, Eleftherios Anastosopoulos, Augusto Azuara-Blanco, Tos Berendschot, Arthur Bergen, Geir Bertelsen, Christine Binquet, Alan Bird, Martin Bobak, Morten Bøgelund Larsen, Camiel Boon, Rupert Bourne, Lionel Brétillon, Rebecca Broe, Alain Bron, Gabrielle Buitendijk, Maria Luz Cachulo, Vittorio Capuano, Isabelle Carrière, Usha Chakravarthy, Michelle Chan, Petrus Chang, Johanna Colijn, Angela Cree, Phillippa Cumberland, José Cunha-Vaz, Vincent Daien, Eiko De Jong, Gabor Deak, Marie-Noëlle Delyfer, Anneke den Hollander, Martha Dietzel, Maja Gran Erke, Pedro Faria, Claudia Farinha, Sascha Fauser, Robert Finger, Astrid Fletcher, Paul Foster, Panayiota Founti, Theo Gorgels, Jakob Grauslund, Franz Grus, Christopher Hammond, Hans-Werner Hense, Manuel Hermann, René Hoehn, Ruth Hogg, Frank Holz, Carel Hoyng, Nomdo Jansonius, Sarah Janssen, Eveline Kersten, Anthony Khawaja, Caroline Klaver, Jean-François Korobelnik, Julia Lamparter, Mélanie Le Goff, Yara Lechanteur, Terho Lehtimäki, Irene Leung, Andrew Lotery, Matthias Mauschitz, Magda Meester, Bénédicte Merle, Verena Meyer zu Westrup, Edoardo Midena, Stefania Miotto, Alireza Mirshahi, Sadek Mohan-Saïd, Michael Mueller, Alyson Muldrew, Joaquim Murta, Stefan Nickels, Christopher Owen, Tunde Peto, Norbert Pfeiffer, Stefano Piermarocchi, Elena Prokofyeva, Jugnoo Rahi, Olli Raitakari, Franziska Rauscher, Luisa Ribeiro, Marie-Bénédicte Rougier, Alicja Rudnicka, José Sahel, Aggeliki Salonikiou, Clarisa Sanchez, Steffen Schmitz-Valckenberg, Alexander Schuster, Cédric Schweitzer, Tatiana Segato, Jasmin Shehata, Giuliana Silvestri, Christian Simader, Eric Souied, Martynas Speckauskas, Henriet Springelkamp, Robyn Tapp, Fotis Topouzis, Elisa van Leeuwen, Virginie Verhoeven, Timo Verzijden, Therese Von Hanno, Peter Wiedemann, Katie Williams, Christian Wolfram, Jennifer Yip, Jennyfer Zerbib, OEil, nutrition et signalisation cellulaire [CSGA], Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Service d'Ophtalmologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Bordeaux population health (BPH), Université de Bordeaux (UB)-Institut de Santé Publique, d'Épidémiologie et de Développement (ISPED)-Institut National de la Santé et de la Recherche Médicale (INSERM), Neuropsychiatrie : recherche épidémiologique et clinique, Université Montpellier 1 (UM1)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Neuropsychiatrie : recherche épidémiologique et clinique (PSNREC), Université Montpellier 1 (UM1)-Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM), Montrachet Study: Funding was provided by an Inter-regional grant (PHRC) and the Regional Council of Burgundy. Funded by INRA, CNRS, Université de Bourgogne, Regional Council of Burgundy France (PARI Agrale 1), FEDER (European Funding for Regional Economic Development), and French Government grant managed by the French National Research Agency (ANR) as part of the 'Investissements d’Avenir' program (reference ANR-11-LABX-0021-01-LipSTIC Labex)., Human Genetics, ANS - Cellular & Molecular Mechanisms, RS: NUTRIM - R1 - Obesity, diabetes and cardiovascular health, RS: MHeNs - R3 - Neuroscience, Oogheelkunde, MUMC+: MA UECM Oogartsen MUMC (9), Perceptual and Cognitive Neuroscience (PCN), Epidemiology, and Ophthalmology

Subjects
Retinal Ganglion Cells, Cross-Sectional Studies, Disease Progression, Europe, Glaucoma, Humans, Intraocular Pressure, Nerve Fibers, Optic Disk, Population Surveillance, Tomography, Optical Coherence, methods [Tomography, Optical Coherence], Intraocular pressure, OPTICAL COHERENCE TOMOGRAPHY, Cross-sectional study, Nerve Fibers/pathology, ANYANG CHILDHOOD EYE, AXIAL LENGTH, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], INTRAOCULAR-PRESSURE, Tomography, Optical Coherence/methods, Rotterdam Study, 0302 clinical medicine, physiopathology [Glaucoma], GLAUCOMA, epidemiology [Glaucoma], Tomography, education.field_of_study, GANGLION-CELL LAYER, epidemiology [Europe], pathology [Nerve Fibers], ASSOCIATION, 3. Good health, ALZHEIMERS-DISEASE, Population Surveillance/methods, pathology [Optic Disk], methods [Population Surveillance], Optic Disk/pathology, Cohort study, Glaucoma/diagnosis, medicine.medical_specialty, Population, physiology [Intraocular Pressure], Retinal Ganglion Cells/pathology, pathology [Retinal Ganglion Cells], Europe/epidemiology, 03 medical and health sciences, Ophthalmology, medicine, ddc:610, Intraocular Pressure/physiology, education, business.industry, diagnosis [Glaucoma], CONSORTIUM, medicine.disease, Confidence interval, ta3125, Optical Coherence, 030221 ophthalmology & optometry, DISC SIZE, business, Body mass index, 030217 neurology & neurosurgery, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract

Purpose: To investigate systemic and ocular determinants of peripapillary retinal nerve fiber layer thickness (pRNFLT) in the European population.Design: Cross-sectional meta-analysis.Participants: A total of 16 084 European adults from 8 cohort studies (mean age range, 56.9 +/- 12.3-82.1 +/- 4.2 years) of the European Eye Epidemiology (E3) consortium.Methods: We examined associations with pRNFLT measured by spectral-domain OCT in each study using multivariable linear regression and pooled results using random effects meta-analysis.Main Outcome Measures: Determinants of pRNFLT.Results: Mean pRNFLT ranged from 86.8 +/- 21.4 mu m in the Rotterdam Study I to 104.7 +/- 12.5 mu m in the Rotterdam Study III. We found the following factors to be associated with reduced pRNFLT: Older age (beta = -0.38 mu m/year; 95% confidence interval [CI], -0.57 to -0.18), higher intraocular pressure (10P) (beta = -0.36 mu m/mmHg; 95% CI, -0.56 to -0.15), visual impairment (beta = -5.50 mu m; 95% CI, -9.37 to -1.64), and history of systemic hypertension (beta = -0.54 mu m; 95% CI, -1.01 to -0.07) and stroke (beta = -1.94 mu m; 95% CI, -3.17 to -0.72). A suggestive, albeit nonsignificant, association was observed for dementia (beta = -3.11 mu m; 95% CI, -6.22 to 0.01). Higher pRNFLT was associated with more hyperopic spherical equivalent (beta = 1.39 mu m/diopter; 95% CI, 1.19-1.59) and smoking (beta = 1.53 mu m; 95% CI, 1.00-2.06 for current smokers compared with never-smokers).Conclusions: In addition to previously described determinants such as age and refraction, we found that systemic vascular and neurovascular diseases were associated with reduced pRNFLT. These may be of clinical relevance, especially in glaucoma monitoring of patients with newly occurring vascular comorbidities. (C) 2018 by the American Academy of Ophthalmology

Published
2018

7. Prevalence of Age-Related Macular Degeneration in Europe

Author

Johanna M. Colijn, Gabriëlle H.S. Buitendijk, Elena Prokofyeva, Dalila Alves, Maria L. Cachulo, Anthony P. Khawaja, Audrey Cougnard-Gregoire, Bénédicte M.J. Merle, Christina Korb, Maja G. Erke, Alain Bron, Eleftherios Anastasopoulos, Magda A. Meester-Smoor, Tatiana Segato, Stefano Piermarocchi, Paulus T.V.M. de Jong, Johannes R. Vingerling, Fotis Topouzis, Catherine Creuzot-Garcher, Geir Bertelsen, Norbert Pfeiffer, Astrid E. Fletcher, Paul J. Foster, Rufino Silva, Jean-François Korobelnik, Cécile Delcourt, Caroline C.W. Klaver, Soufiane Ajana, Blanca Arango-Gonzalez, Verena Arndt, Vaibhav Bhatia, Shomi S. Bhattacharya, Marc Biarnés, Anna Borrell, Sebastian Bühren, Sofia M. Calado, Audrey Cougnard-Grégoire, Sascha Dammeier, Eiko K. de Jong, Berta De la Cerda, Anneke I. den Hollander, Francisco J. Diaz-Corrales, Sigrid Diether, Eszter Emri, Tanja Endermann, Lucia L. Ferraro, Míriam Garcia, Thomas J. Heesterbeek, Sabina Honisch, Carel B. Hoyng, Eveline Kersten, Ellen Kilger, Hanno Langen, Imre Lengyel, Phil Luthert, Cyrille Maugeais, Magda Meester-Smoor, Jordi Monés, Everson Nogoceke, Tunde Peto, Frances M. Pool, Eduardo Rodríguez, Marius Ueffing, Karl U. Ulrich Bartz-Schmidt, Elisabeth M. van Leeuwen, Timo Verzijden, Markus Zumbansen, Niyazi Acar, Eleftherios Anastosopoulos, Augusto Azuara-Blanco, Arthur Bergen, Christine Binquet, Alan Bird, Lionel Brétillon, Gabrielle Buitendijk, Maria Luz Cachulo, Usha Chakravarthy, Michelle Chan, Petrus Chang, Johanna Colijn, Philippa Cumberland, José Cunha-Vaz, Vincent Daien, Gabor Deak, Marie-Noëlle Delyfer, Anneke den Hollander, Martha Dietzel, Maja Gran Erke, Sascha Fauser, Robert Finger, Astrid Fletcher, Paul Foster, Panayiota Founti, Arno Göbel, Theo Gorgels, Jakob Grauslund, Franz Grus, Christopher Hammond, Catherine Helmer, Hans-Werner Hense, Manuel Hermann, René Hoehn, Ruth Hogg, Frank Holz, Carel Hoyng, Nomdo Jansonius, Sarah Janssen, Anthony Khawaja, Caroline Klaver, Julia Lamparter, Mélanie Le Goff, Sergio Leal, Yara Lechanteur, Terho Lehtimäki, Andrew Lotery, Irene Leung, Matthias Mauschitz, Bénédicte Merle, Verena Meyer zu Westrup, Edoardo Midena, Stefania Miotto, Alireza Mirshahi, Sadek Mohan-Saïd, Michael Mueller, Alyson Muldrew, Sandrina Nunes, Konrad Oexle, Jugnoo Rahi, Olli Raitakari, Luisa Ribeiro, Marie-Bénédicte Rougier, José Sahel, Aggeliki Salonikiou, Clarisa Sanchez, Steffen Schmitz-Valckenberg, Cédric Schweitzer, Jasmin Shehata, Giuliana Silvestri, Christian Simader, Eric Souied, Henriet Springelkamp, Robyn Tapp, Virginie Verhoeven, Therese Von Hanno, Stela Vujosevic, Katie Williams, Christian Wolfram, Jennifer Yip, Jennyfer Zerbib, Isabella Zwiener, Erasmus University Rotterdam, Scientific Institute for Public Health, Federal Agency for Medicines and Health Products, Partenaires INRAE, Association for Innovation and Biomedical Research on Light and Image (AIBILI), Universidade de Coimbra, Coimbra University Hospital (CHUC), University of Cambridge [UK] (CAM), Moorfields Eye Hospital NHS Foundation Trust, Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Bordeaux (UB), Mainz University Medical Center, Oslo University Hospital [Oslo], Centre des Sciences du Goût et de l'Alimentation [Dijon] (CSGA), Institut National de la Recherche Agronomique (INRA)-Université de Bourgogne (UB)-AgroSup Dijon - Institut National Supérieur des Sciences Agronomiques, de l'Alimentation et de l'Environnement-Centre National de la Recherche Scientifique (CNRS), Department of Ophthalmology, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Aristotle University of Thessaloniki, Universitad de Padua, Univ Padua, Dept Ophthalmol, Padua, Italy, Royal Netherlands Academy of Arts and Sciences (KNAW), University Hospital of North Norway [Tromsø] (UNN), London School of Hygiene and Tropical Medicine (LSHTM), Institute of Ophthalmology, University of Messina, CHU Bordeaux [Bordeaux], Radboud University Medical Center [Nijmegen], The European Eye Epidemiology (E3) Consortium, Epidemiology, Ophthalmology, Erasmus MC other, Other departments, ANS - Complex Trait Genetics, Human Genetics, and Genome Analysis

Subjects
0301 basic medicine, medicine.medical_specialty, Visual acuity, OPTICAL COHERENCE TOMOGRAPHY, MACULOPATHY, genetic structures, Population, Prevalence, HEART-DISEASE, choroidal neovascularization, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], 03 medical and health sciences, Rotterdam Study, 0302 clinical medicine, All institutes and research themes of the Radboud University Medical Center, BEAVER DAM EYE, Epidemiology, geographic atrophy, medicine, VISUAL IMPAIRMENT, [SDV.MHEP.OS]Life Sciences [q-bio]/Human health and pathology/Sensory Organs, education, POPULATION, education.field_of_study, BIRTH COHORT, business.industry, Macular degeneration, medicine.disease, TRENDS, Confidence interval, eye diseases, 3. Good health, European Prospective Investigation into Cancer and Nutrition, Ophthalmology, 030104 developmental biology, Age-related Macular Degeneration, ENDOTHELIAL GROWTH-FACTOR, BLINDNESS, 030221 ophthalmology & optometry, Optometry, Age-related Macular Degeneration, choroidal neovascularization, geographic atrophy, sense organs, medicine.symptom, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Demography
Abstract

Manuscript no. 2016-1147 Supplemental material is available at www.aaojournal.org/; International audience; [u]Purpose:[/u] Age-related macular degeneration (AMD) is a frequent, complex disorder in elderly of European ancestry. Risk profiles and treatment options have changed considerably over the years, which may have affected disease prevalence and outcome. We determined the prevalence of early and late AMD in Europe from 1990 to 2013 using the European Eye Epidemiology (E3) consortium, and made projections for the future. [u]Design:[/u] Meta-analysis of prevalence data. [u]Participants:[/u] A total of 42 080 individuals 40 years of age and older participating in 14 population-based cohorts from 10 countries in Europe. [u]Methods:[/u] AMD was diagnosed based on fundus photographs using the Rotterdam Classification. Prevalence of early and late AMD was calculated using random-effects meta-analysis stratified for age, birth cohort, gender, geographic region, and time period of the study. Best-corrected visual acuity (BCVA) was compared between late AMD subtypes; geographic atrophy (GA) and choroidal neovascularization (CNV). [u]Main Outcome Measures:[/u] Prevalence of early and late AMD, BCVA, and number of AMD cases. [u]Results:[/u] Prevalence of early AMD increased from 3.5% (95% confidence interval [CI] 2.1% -5.0%) in those aged 55-59 years to 17.6% (95% CI 13.6%-21.5%) in those aged >= 85 years; for late AMD these figures were 0.1% (95% CI 0.04%-0.3%) and 9.8% (95% CI 6.3%-13.3%), respectively. We observed a decreasing prevalence of late AMD after 2006, which became most prominent after age 70. Prevalences were similar for gender across all age groups except for late AMD in the oldest age category, and a trend was found showing a higher prevalence of CNV in Northern Europe. After 2006, fewer eyes and fewer >= 80-year-old subjects with CNV were visually impaired (P = 0.016). Projections of AMD showed an almost doubling of affected persons despite a decreasing prevalence. By 2040, the number of individuals in Europe with early AMD will range between 14.9 and 21.5 million, and for late AMD between 3.9 and 4.8 million. [u]Conclusion:[/u] We observed a decreasing prevalence of AMD and an improvement in visual acuity in CNV occuring over the past 2 decades in Europe. Healthier lifestyles and implementation of anti-vascular endothelial growth factor treatment are the most likely explanations. Nevertheless, the numbers of affected subjects will increase considerably in the next 2 decades. AMD continues to remain a significant public health problem among Europeans.

Published
2017

8. Retinal arteriolar caliber predicts incident retinopathy: the Australian Diabetes, Obesity and Lifestyle (AusDiab) study

Author

Sophie Louise, Rogers, Gabriella, Tikellis, Ning, Cheung, Robyn, Tapp, Jonathan, Shaw, Paul Z, Zimmet, Paul, Mitchell, Jie Jin, Wang, and Tien Yin, Wong

Subjects
Blood Glucose, Male, Arterioles, Diabetic Retinopathy, Retinal Artery, Incidence, Multivariate Analysis, Australia, Odds Ratio, Humans, Blood Pressure, Female
Abstract

Changes in retinal vascular caliber may reflect subclinical microvascular disease and provide prognostic information regarding risk of retinopathy. In this study, we examined the prospective association of retinal vascular caliber with retinopathy risk in an Australian population-based cohort. A total of 906 participants without retinopathy at baseline had retinal vascular caliber measured from photographs and were followed-up for 5 years for incident retinopathy. After adjusting for age, sex, systolic blood pressure, A1C, and other risk factors, individuals with wider retinal arteriolar caliber (widest 25% vs. the remaining three-quarters of the population) were more likely to develop incident retinopathy (odds ratio 4.79 [95% CI 1.57-14.58]). This association was not significant in individuals without diabetes. Venular caliber did not predict incident retinopathy. Our findings suggest that retinal arteriolar dilatation is a specific sign of diabetic microvascular dysfunction and may be a preclinical marker of diabetic retinopathy.

Published
2008

9. Ethnicity and left ventricular diastolic function in hypertension an ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial) substudy

Author

Andrew, Sharp, Robyn, Tapp, Darrel P, Francis, Simon A, McG Thom, Alun D, Hughes, Alice V, Stanton, Andrew, Zambanini, Nish, Chaturvedi, Sheila, Byrd, Neil R, Poulter, Peter S, Sever, and Jamil, Mayet

Subjects
Adult, Male, West Indies, Black People, Middle Aged, Echocardiography, Doppler, Ventricular Function, Left, White People, Diastole, Hypertension, Multivariate Analysis, Humans, Female, Aged
Abstract

We investigated whether diastolic function differs between hypertensive patients of African-Caribbean or white European origin and established whether differences could be explained by confounding variables.African Caribbeans are known to have a higher prevalence of heart failure than white Europeans but it is unclear whether this is a result of known risk factors. Tissue Doppler technology now allows accurate quantification of diastolic function, which is recognized as an important factor in the development of heart failure.Participants from a single center participating in the ASCOT (Anglo-Scandinavian Cardiac Outcomes Trial), composed of patients with hypertension but no evidence of heart failure, were studied. Left ventricular structure and function were measured in 509 patients using conventional and tissue Doppler echocardiography. Diastolic function was assessed using the tissue Doppler early diastolic velocity E' (averaged from 3 left ventricular segments) and the ratio of this and the transmitral early filling velocity E (E/E').In African-Caribbean patients, mean E' was significantly lower (7.7 cm/s vs. 8.6 cm/s, p = 0.003) and mean E/E' was significantly higher (8.85 vs. 7.93, p = 0.003). After adjustment for confounding variables-age, gender, systolic blood pressure, pulse pressure, cholesterol, smoking, ejection fraction, left ventricular mass index, and diabetes mellitus-the effect of African-Caribbean ethnicity on diastolic function remained highly significant (E': 7.52 vs. 8.51; p0.001; E/E': 8.89 vs. 7.93; p = 0.003; African Caribbeans vs. white Europeans for both comparisons).Diastolic function is significantly worse in hypertensive patients of African-Caribbean origin than in white Europeans. This difference in diastolic performance is not due to known confounding variables.

Published
2007

10. Abstract 2746: Left Ventricular Diastolic Function Assessed By Tissue Doppler Echocardiography Is Impaired By β-blocker + Diuretic-based Therapy Compared With Calcium Antagonist + Ace Inhibitor-based Therapy: An ASCOT Substudy

Author

Robyn Tapp, Andrew Sharp, Alice Stanton, Eoin O’Brien, Nish Chaturvedi, Peter Sever, Neil Poulter, Alun Hughes, Simon Thom, and Jamil Mayet

Subjects
Physiology (medical), cardiovascular diseases, Cardiology and Cardiovascular Medicine
Abstract

Background: Different anti-hypertensive therapies may vary in their effect on left ventricular diastolic function. The Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) randomized patients to β-blocker (atenolol) + diuretic (bendroflumethiazide-K)-based therapy (BB/D) or calcium antagonist (amlodipine) + ACE inhibitor (perindopril)-based therapy (CA/ACEI). We compared left ventricular diastolic function in the two treatment groups. Methods: Echocardiography including Tissue Doppler Imaging was performed on 977 subjects at two centres participating in ASCOT (St Mary’s Hospital, London, UK & Beaumont Hospital, Dublin, Eire) to assess left ventricular diastolic function after 12 months of treatment. Data are means (SD). Results: Systolic blood pressure (SBP) was similar in both treatment groups (BB/D = 137(17), CA/ACEI = 136(14); p = 0.3), but heart rate was significantly lower in BB/D group (BB/D = 57(10), CA/ACEI = 73(12); p Conclusions: BB/D based therapy is associated with impaired diastolic function compared with CA/ACEI therapy. Differences in the effect of anti-hypertensive therapy on diastolic function could influence the risk of heart failure and other cardiovascular events in hypertensive patients with preserved systolic function.

Published
2007

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