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2. The Association of Urinary Sodium Excretion with Glaucoma and Related Traits in a Large United Kingdom Population

Author

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

Published
2024
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3. Epidemiology and genetics of age-related macular degeneration

Author

Warwick, Alasdair Neil

Abstract

Background: Age-related macular degeneration (AMD) is the leading cause of blindness in developed countries. Advanced AMD has two main forms - neovascular AMD (nAMD) and geographic atrophy. While an effective treatment for nAMD is now available, there is still no cure for either form. There is therefore an urgent need to optimise visual outcomes and develop new treatments. Objectives: To (i) assess real world visual outcomes for treated nAMD patients (ii) further our understanding of both genetic and non-genetic risk factors for AMD, and (iii) evaluate different Mendelian randomisation (MR) approaches to drug target prioritisation. Methods and Outputs: To address objective (i) I analysed a multicentre ophthalmic electronic health records (EHR) dataset to show how visual outcomes have improved over the past decade for UK patients with nAMD, mainly because of earlier intervention. I furthermore developed a simulation model to estimate the national impact of delayed treatment during the global pandemic. For objective (ii) I characterised individuals in the UK Biobank (UKBB) cohort who were found to have AMD-associated features on retinal imaging. I then performed a genome-wide association study (GWAS) and a phenome-wide association study (PheWAS). The underlying R code for all UKBB analyses was developed as software packages to support future work. Finally, I approached objective (iii) by utilising publicly available GWAS summary statistics to undertake a MR PheWAS, assessing the causal relevance of C-reactive protein to a range of phenotypic traits, including AMD. Conclusions: I have demonstrated how large EHR, imaging and genetic datasets can be leveraged to provide important public health messages and novel insights to disease pathogenesis. I have also presented a new MR method for drug target prioritisation. This work adds to what is already known for AMD and much of the output has broader applications.

Published
2023

5. The Association of Alcohol Consumption with Glaucoma and Related Traits: Findings from the UK Biobank

Author

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

Published
2023
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9. Identifying and visualising multimorbidity and comorbidity patterns in patients in the English National Health Service: a population-based study

Author

Alexander, Daniel C, Asiimwe, Innocent G, Ball, Simon, Bennett, Frances, Borges, Maria Carolina, Butterworth, Adam, Chaturvedi, Nishi, Chopade, Sandesh, Clarkson, Christopher, Cox, Martin, Dale, Caroline, Denaxas, Spiros, Dunca, Diana, Engmann, Jorgen E, Fernandez-Sanles, Alba, Finan, Chris, Fitzpatrick, Natalie, Gallagher, Jean, Gonzalez-Izquierdo, Arturo, Gratton, Jasmine, Gross, Christian, Hemingway, Harry, Henry, Albert, Hidajat, Mira, Hingorani, Aroon, Hukerikar, Nikita, Jorgensen, Andrea, Joshi, Roshni, Katsoulis, Michail, Kuan, Valerie, Kumar, Rashmi, Lai, Alvina G, Langenberg, Claudia, Lawlor, Deborah, Mancini, Mary, Miller, Diane, Ogden, Margaret, Ozyigit, Eda B, Patel, Shilpa, Pirmohamed, Munir, Roberts, Amanda, Ryan, David, Schmidt, Amand F, Shah, Anoop D, Shah, Tina, Sofat, Reecha, Takhar, Rohan, Torralbo, Ana, Ullah, Ayath, Walker, Lauren E, Warwick, Alasdair, Wheeler, Eleanor, Wright, Victoria L, Wu, Honghan, Zwierzyna, Magdalena, Patalay, Praveetha, Nitsch, Dorothea, Mathur, Rohini, Partridge, Linda, Wong, Ian C K, Hingorani, Melanie, and Hingorani, Aroon D

Published
2023
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10. The Association of Urinary Sodium Excretion with Glaucoma and Related Traits in a Large United Kingdom Population

Author

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

Published
2024
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12. COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

Author

Abbasizanjani, Hoda, Ahmed, Nida, Ahmed, Badar, Akbari, Ashley, Akinoso-Imran, Abdul Qadr, Allara, Elias, Allery, Freya, Angelantonio, Emanuele Di, Ashworth, Mark, Ayyar-Gupta, Vandana, Babu-Narayan, Sonya, Bacon, Seb, Ball, Steve, Banerjee, Ami, Barber, Mark, Barrett, Jessica, Bennie, Marion, Berry, Colin, Beveridge, Jennifer, Birney, Ewan, Bojanić, Lana, Bolton, Thomas, Bone, Anna, Boyle, Jon, Braithwaite, Tasanee, Bray, Ben, Briffa, Norman, Brind, David, Brown, Katherine, Buch, Maya, Canoy, Dexter, Caputo, Massimo, Carragher, Raymond, Carson, Alan, Cezard, Genevieve, Chang, Jen-Yu Amy, Cheema, Kate, Chin, Richard, Chudasama, Yogini, Cooper, Jennifer, Copland, Emma, Crallan, Rebecca, Cripps, Rachel, Cromwell, David, Curcin, Vasa, Curry, Gwenetta, Dale, Caroline, Danesh, John, Das-Munshi, Jayati, Dashtban, Ashkan, Davies, Alun, Davies, Joanna, Davies, Gareth, Davies, Neil, Day, Joshua, Delmestri, Antonella, Denaxas, Spiros, Denholm, Rachel, Dennis, John, Denniston, Alastair, Deo, Salil, Dhillon, Baljean, Docherty, Annemarie, Dong, Tim, Douiri, Abdel, Downs, Johnny, Dregan, Alexandru, Ellins, Elizabeth A, Elwenspoek, Martha, Falck, Fabian, Falter, Florian, Fan, Yat Yi, Firth, Joseph, Fraser, Lorna, Friebel, Rocco, Gavrieli, Amir, Gerstung, Moritz, Gilbert, Ruth, Gillies, Clare, Glickman, Myer, Goldacre, Ben, Goldacre, Raph, Greaves, Felix, Green, Mark, Grieco, Luca, Griffiths, Rowena, Gurdasani, Deepti, Halcox, Julian, Hall, Nick, Hama, Tuankasfee, Handy, Alex, Hansell, Anna, Hardelid, Pia, Hardy, Flavien, Harris, Daniel, Harrison, Camille, Harron, Katie, Hassaine, Abdelaali, Hassan, Lamiece, Healey, Russell, Hemingway, Harry, Henderson, Angela, Herz, Naomi, Heyl, Johannes, Hidajat, Mira, Higginson, Irene, Hinchliffe, Rosie, Hippisley-Cox, Julia, Ho, Frederick, Hocaoglu, Mevhibe, Hollings, Sam, Horne, Elsie, Hughes, David, Humberstone, Ben, Inouye, Mike, Ip, Samantha, Islam, Nazrul, Jackson, Caroline, Jenkins, David, Jiang, Xiyun, Johnson, Shane, Kadam, Umesh, Kallis, Costas, Karim, Zainab, Kasan, Jake, Katsoulis, Michalis, Kavanagh, Kim, Kee, Frank, Keene, Spencer, Kent, Seamus, Khalid, Sara, Khawaja, Anthony, Khunti, Kamlesh, Killick, Richard, Kinnear, Deborah, Knight, Rochelle, Kolamunnage-Dona, Ruwanthi, Kontopantelis, Evan, Kurdi, Amanj, Lacey, Ben, Lai, Alvina, Lambarth, Andrew, Larzjan, Milad Nazarzadeh, Lawler, Deborah, Lawrence, Thomas, Lawson, Claire, Li, Qiuju, Li, Ken, Llinares, Miguel Bernabeu, Lorgelly, Paula, Lowe, Deborah, Lyons, Jane, Lyons, Ronan, Machado, Pedro, Macleod, Mary Joan, Macleod, John, Malgapo, Evaleen, Mamas, Mamas, Mamouei, Mohammad, Manohar, Sinduja, Mapeta, Rutendo, Martelli, Javiera Leniz, Martos, David Moreno, Mateen, Bilal, McCarthy, Aoife, Melville, Craig, Milton, Rebecca, Mizani, Mehrdad, Moncusi, Marta Pineda, Morales, Daniel, Mordi, Ify, Morrice, Lynn, Morris, Carole, Morris, Eva, Mu, Yi, Mueller, Tanja, Murdock, Lars, Nafilyan, Vahé, Nicholson, George, Nikiphorou, Elena, Nolan, John, Norris, Tom, Norris, Ruth, North, Laura, North, Teri-Louise, O'Connell, Dan, Oliver, Dominic, Oluyase, Adejoke, Olvera-Barrios, Abraham, Omigie, Efosa, Onida, Sarah, Padmanabhan, Sandosh, Palmer, Tom, Pasea, Laura, Patel, Riyaz, Payne, Rupert, Pell, Jill, Petitjean, Carmen, Pherwani, Arun, Pickrell, Owen, Pierotti, Livia, Pirmohamed, Munir, Priedon, Rouven, Prieto-Alhambra, Dani, Proudfoot, Alastair, Quinn, Terry, Quint, Jennifer, Raffetti, Elena, Rahimi, Kazem, Rao, Shishir, Razieh, Cameron, Roberts, Brian, Rogers, Caroline, Rossdale, Jennifer, Salim, Safa, Samani, Nilesh, Sattar, Naveed, Schnier, Christian, Schwartz, Roy, Selby, David, Seminog, Olena, Shabnam, Sharmin, Shah, Ajay, Shelton, Jon, Sheppard, James, Sinha, Shubhra, Skrypak, Mirek, Slapkova, Martina, Sleeman, Katherine, Smith, Craig, Sofat, Reecha, Sosenko, Filip, Sperrin, Matthew, Steeg, Sarah, Sterne, Jonathan, Stoica, Serban, Sudell, Maria, Sudlow, Cathie, Sun, Luanluan, Suseeladevi, Arun Karthikeyan, Sweeting, Michael, Sydes, Matt, Takhar, Rohan, Tang, Howard, Thygesen, Johan, Tilston, George, Tochel, Claire, Toit, Clea du, Tomlinson, Christopher, Toms, Renin, Torabi, Fatemeh, Torralbo, Ana, Townson, Julia, Tufail, Adnan, Tungamirai, Tapiwa, Varma, Susheel, Vollmer, Sebastian, Walker, Venexia, Wang, Tianxiao, Wang, Huan, Warwick, Alasdair, Watkinson, Ruth, Watson, Harry, Whiteley, William, Whittaker, Hannah, Wilde, Harry, Wilkinson, Tim, Williams, Gareth, Williams, Michelle, Williams, Richard, Withnell, Eloise, Wolfe, Charles, Wood, Angela, Wright, Lucy, Wu, Honghan, Wu, Jinge, Wu, Jianhua, Yates, Tom, Zaccardi, Francesco, Zhang, Haoting, Zhang, Huayu, Zuccolo, Luisa, Thygesen, Johan H, Mizani, Mehrdad A, Banerjee, Amitava, Lai, Alvina G, Li, Kezhi, Mateen, Bilal A, Sterne, Jonathan A C, Pagel, Christina, and Whiteley, William N

Published
2022
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14. The Association of Urinary Sodium Excretion with Glaucoma and Related Traits in a Large United Kingdom Population

Author

Stuart, Kelsey V., Biradar, Mahantesh I., Luben, Robert N., Dhaun, Neeraj, Wagner, Siegfried K., Warwick, Alasdair N., Sun, Zihan, Madjedi, Kian M., Pasquale, Louis R., Wiggs, Janey L., Kang, Jae H., Lentjes, Marleen, Aschard, Hugues, Kim, Jihye, Foster, Paul J., Khawaja, Anthony P., Stuart, Kelsey V., Biradar, Mahantesh I., Luben, Robert N., Dhaun, Neeraj, Wagner, Siegfried K., Warwick, Alasdair N., Sun, Zihan, Madjedi, Kian M., Pasquale, Louis R., Wiggs, Janey L., Kang, Jae H., Lentjes, Marleen, Aschard, Hugues, Kim, Jihye, Foster, Paul J., and Khawaja, Anthony P.

Abstract

OBJECTIVE: Excessive dietary sodium intake has known adverse effects on intravascular fluid volume and systemic blood pressure, which may influence intraocular pressure (IOP) and glaucoma risk. This study aimed to assess the association of urinary sodium excretion, a biomarker of dietary intake, with glaucoma and related traits, and to determine whether this relationship is modified by genetic susceptibility to disease. DESIGN: Cross-sectional observational and gene-environment interaction analyses in the population-based UK Biobank study. PARTICIPANTS: Up to 103 634 individuals (mean age 57 years, 51% women) with complete urinary, ocular, and covariable data. METHODS: Urine sodium:creatinine ratio (UNa:Cr; mmol:mmol) was calculated from a midstream urine sample. Ocular parameters were measured as part of a comprehensive eye examination and glaucoma case ascertainment was through a combination of self-report and linked national hospital records. Genetic susceptibility to glaucoma was calculated based on a glaucoma polygenic risk score (PRS) comprising 2 673 common genetic variants. Multivariable linear and logistic regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to model associations and gene-environment interactions. MAIN OUTCOME MEASURES: Corneal-compensated IOP, optical coherence tomography derived macular retinal nerve fiber layer (mRNFL) and ganglion cell-inner plexiform layer (GCIPL) thickness, and prevalent glaucoma. RESULTS: In maximally adjusted regression models, a one standard deviation increase in UNa:Cr was associated with higher IOP (0.14mmHg; 95% CI, 0.12 to 0.17; P<0.001) and greater prevalence of glaucoma (OR, 1.11; 95% CI, 1.07 to 1.14; P<0.001), but not mRNFL or GCIPL thickness. Compared to those with UNa:Cr in the lowest quintile, those in the highest quintile had significantly higher IOP (0.45mmHg; 95% CI, 0.36 to 0.53, P<0.001) and prevalence of glaucoma (OR, 1.30; 95% CI, 1.17 t

Published
2024
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16. Ethnic disparities in progression rates for sight-threatening diabetic retinopathy in diabetic eye screening: a population-based retrospective cohort study

Author

Olvera-Barrios, Abraham, primary, Owen, Christopher G, additional, Anderson, John, additional, Warwick, Alasdair N, additional, Chambers, Ryan, additional, Bolter, Louis, additional, Wu, Yue, additional, Welikala, Roshan, additional, Fajtl, Jiri, additional, Barman, Sarah A, additional, Remagnino, Paolo, additional, Chew, Emily Y, additional, Ferris, Frederick L, additional, Hingorani, Aroon D, additional, Sofat, Reecha, additional, Lee, Aaron Y, additional, Egan, Catherine, additional, Tufail, Adnan, additional, and Rudnicka, Alicja R, additional

Published
2023
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17. Two-year recall for people with no diabetic retinopathy: a multi-ethnic population-based retrospective cohort study using real-world data to quantify the effect

Author

Olvera-Barrios, Abraham, primary, Rudnicka, Alicja R, additional, Anderson, John, additional, Bolter, Louis, additional, Chambers, Ryan, additional, Warwick, Alasdair N, additional, Welikala, Roshan, additional, Fajtl, Jiri, additional, Barman, Sarah, additional, Remgnino, Paolo, additional, Wu, Yue, additional, Lee, Aaron Y, additional, Chew, Emily Y, additional, Ferris, Frederick L, additional, Hingorani, Aroon, additional, Sofat, Reecha, additional, A. Egan, Catherine, additional, Tufail, Adnan, additional, and Owen, Christopher G, additional

Published
2023
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18. Two-year recall for people with no diabetic retinopathy: a multiethnic population-based retrospective cohort study using real-world data to quantify the effect

Author

Olvera-Barrios, Abraham, primary, Rudnicka, Alicja R, additional, Anderson, John, additional, Bolter, Louis, additional, Chambers, Ryan, additional, Warwick, Alasdair N, additional, Welikala, Roshan, additional, Fajtl, Jiri, additional, Barman, Sarah, additional, Remagnino, Paolo, additional, Wu, Yue, additional, Lee, Aaron, additional, Chew, Emily Y, additional, Ferris, Frederick L., additional, Hingorani, Aroon D, additional, Sofat, Reecha, additional, Egan, Catherine, additional, Tufail, Adnan, additional, and Owen, Christopher G, additional

Published
2023
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19. The Association of Alcohol Consumption with Glaucoma and Related Traits

Author

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

Published
2022
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20. The association of alcohol consumption with glaucoma and related traits: Findings from the UK Biobank

Author

Stuart, Kelsey, Luben, Robert N., Warwick, Alasdair N., Madjedi, Kian, Patel, Praveen J., Biradar, Mahantesh I., Sun, Zihan, Chia, Mark, Pasquale, Louis, Wiggs, Janey, Kang, Jae H., Kim, Jihye, Aschard, Hugues, Tran, Jessica H., Lentjes, Marleen, Foster, Paul J., Khawaja, Anthony, Chua, Sharon, Do, Ron, Foster, Paul, Kang, Jae, Kastner, Alan, Luben, Robert, Montesano, Giovanni, Warwick, Alasdair, Allen, Naomi, Aslam, Tariq, Atan, Denize, Barman, Sarah, Barrett, Jenny, Bishop, Paul, Black, Graeme, Carare, Roxana, Ennis, Sarah, Gibson, Jane, Lotery, Andrew, Morgan, James, Self, Jay, Stratton, Irene, Chen, Li, Cheng, Ching Yu, Cree, Angela, and Wilson, James

Abstract

Purpose: To examine the associations of alcohol consumption with glaucoma and related traits, to assess whether a genetic predisposition to glaucoma modified these associations, and to perform Mendelian randomization (MR) experiments to probe causal effects. Design: Cross-sectional observational and gene–environment interaction analyses in the UK Biobank. Two-sample MR experiments using summary statistics from large genetic consortia. Participants: UK Biobank participants with data on intraocular pressure (IOP) (n = 109 097), OCT-derived macular inner retinal layer thickness measures (n = 46 236) and glaucoma status (n = 173 407). Methods: Participants were categorized according to self-reported drinking behaviors. Quantitative estimates of alcohol intake were derived from touchscreen questionnaires and food composition tables. We performed a 2-step analysis, first comparing categories of alcohol consumption (never, infrequent, regular, and former drinkers) before assessing for a dose-response effect in regular drinkers only. Multivariable linear, logistic, and restricted cubic spline regression, adjusted for key sociodemographic, medical, anthropometric, and lifestyle factors, were used to examine associations. We assessed whether any association was modified by a multitrait glaucoma polygenic risk score. The inverse-variance weighted method was used for the main MR analyses. Main Outcome Measures: Intraocular pressure, macular retinal nerve fiber layer (mRNFL) thickness, macular ganglion cell–inner plexiform layer (mGCIPL) thickness, and prevalent glaucoma. Results: Compared with infrequent drinkers, regular drinkers had higher IOP (+0.17 mmHg; P < 0.001) and thinner mGCIPL (-0.17 μm; P = 0.049), whereas former drinkers had a higher prevalence of glaucoma (odds ratio, 1.53; P = 0.002). In regular drinkers, alcohol intake was adversely associated with all outcomes in a dose-dependent manner (all P < 0.001). Restricted cubic spline regression analyses suggested nonlinear associations, with apparent threshold effects at approximately 50 g (∼6 UK or 4 US alcoholic units)/week for mRNFL and mGCIPL thickness. Significantly stronger alcohol–IOP associations were observed in participants at higher genetic susceptibility to glaucoma (Pinteraction < 0.001). Mendelian randomization analyses provided evidence for a causal association with mGCIPL thickness. Conclusions: Alcohol intake was consistently and adversely associated with glaucoma and related traits, and at levels below current United Kingdom (< 112 g/week) and United States (women, < 98 g/week; men, < 196 g/week) guidelines. Although we cannot infer causality definitively, these results will be of interest to people with or at risk of glaucoma and their advising physicians. Financial Disclosure(s): Proprietary or commercial disclosure may be found after the references.

Published
2022

23. Identifying and visualising multimorbidity and comorbidity patterns in patients in the English National Health Service: a population-based study

Author

Kuan, Valerie, primary, Denaxas, Spiros, additional, Patalay, Praveetha, additional, Nitsch, Dorothea, additional, Mathur, Rohini, additional, Gonzalez-Izquierdo, Arturo, additional, Sofat, Reecha, additional, Partridge, Linda, additional, Roberts, Amanda, additional, Wong, Ian C K, additional, Hingorani, Melanie, additional, Chaturvedi, Nishi, additional, Hemingway, Harry, additional, Hingorani, Aroon D, additional, Alexander, Daniel C, additional, Asiimwe, Innocent G, additional, Ball, Simon, additional, Bennett, Frances, additional, Borges, Maria Carolina, additional, Butterworth, Adam, additional, Chopade, Sandesh, additional, Clarkson, Christopher, additional, Cox, Martin, additional, Dale, Caroline, additional, Dunca, Diana, additional, Engmann, Jorgen E, additional, Fernandez-Sanles, Alba, additional, Finan, Chris, additional, Fitzpatrick, Natalie, additional, Gallagher, Jean, additional, Gratton, Jasmine, additional, Gross, Christian, additional, Henry, Albert, additional, Hidajat, Mira, additional, Hingorani, Aroon, additional, Hukerikar, Nikita, additional, Jorgensen, Andrea, additional, Joshi, Roshni, additional, Katsoulis, Michail, additional, Kuan, Valerie, additional, Kumar, Rashmi, additional, Lai, Alvina G, additional, Langenberg, Claudia, additional, Lawlor, Deborah, additional, Mancini, Mary, additional, Miller, Diane, additional, Ogden, Margaret, additional, Ozyigit, Eda B, additional, Patel, Shilpa, additional, Pirmohamed, Munir, additional, Ryan, David, additional, Schmidt, Amand F, additional, Shah, Anoop D, additional, Shah, Tina, additional, Takhar, Rohan, additional, Torralbo, Ana, additional, Ullah, Ayath, additional, Walker, Lauren E, additional, Warwick, Alasdair, additional, Wheeler, Eleanor, additional, Wright, Victoria L, additional, Wu, Honghan, additional, and Zwierzyna, Magdalena, additional

Published
2023
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24. UK Biobank retinal imaging grading: methodology, baseline characteristics and findings for common ocular diseases

Author

Warwick, Alasdair N., Curran, Katie, Hamill, Barbra, Stuart, Kelsey, Khawaja, A., Foster, Paul J., Lotery, Andrew J., Quinn, Michael, Madhusudhan, Savita, Balaskas, Konstantinos, Peto, Tunde, Allen, N., Aslam, T., Atan, D., Barman, S., Barrett, J., Bishop, P., Black, G., Braithwaite, T., Carare, R., Chakravarthy, U., Chan, M., Chua, S., Day, A., Desai, P., Dhillon, B., Dick, A., Doney, A., Egan, C., Ennis, S., Foster, P., Fruttiger, M., Gallacher, J., Garway-Heath, D., Gibson, J., Hammond, C., Hardcastle, A., Harding, S., Moore, T., Morgan, J., Owen, C., Patel, P., Self, J., Stratton, I., Sun, Z., Thomas, D., Williams, K., Williams, C., Zheng, Y., Neurology, Ophthalmology, APH - Mental Health, APH - Methodology, and Amsterdam Neuroscience - Neuroinfection & -inflammation

Subjects
Ophthalmology, SDG 3 - Good Health and Well-being
Abstract

Background/objectives This study aims to describe the grading methods and baseline characteristics for UK Biobank (UKBB) participants who underwent retinal imaging in 2009–2010, and to characterise individuals with retinal features suggestive of age-related macular degeneration (AMD), glaucoma and retinopathy. Methods Non-mydriatic colour fundus photographs and macular optical coherence tomography (OCT) scans were manually graded by Central Administrative Research Facility certified graders and quality assured by clinicians of the Network of Ophthalmic Reading Centres UK. Captured retinal features included those associated with AMD (≥1 drusen, pigmentary changes, geographic atrophy or exudative AMD; either imaging modality), glaucoma (≥0.7 cup-disc ratio, ≥0.2 cup-disc ratio difference between eyes, other abnormal disc features; photographs only) and retinopathy (characteristic features of diabetic retinopathy with or without microaneurysms; either imaging modality). Suspected cases of these conditions were characterised with reference to diagnostic records, physical and biochemical measurements. Results Among 68,514 UKBB participants who underwent retinal imaging, the mean age was 57.3 years (standard deviation 8.2), 45.7% were men and 90.6% were of White ethnicity. A total of 64,367 participants had gradable colour fundus photographs and 68,281 had gradable OCT scans in at least one eye. Retinal features suggestive of AMD and glaucoma were identified in 15,176 and 2184 participants, of whom 125 (0.8%) and 188 (8.6%), respectively, had a recorded diagnosis. Of 264 participants identified to have retinopathy with microaneurysms, 251 (95.1%) had either diabetes or hypertension. Conclusions This dataset represents a valuable addition to what is currently available in UKBB, providing important insights to both ocular and systemic health.

Published
2022

25. The association between serum lipids and intraocular pressure in two large UK cohorts

Author

Madjedi, Kian M., Stuart, Kelsey V., Chua, Sharon Y.L., Luben, Robert N., Warwick, Alasdair, Pasquale, Louis R., Kang, Jae H., Wiggs, Janey L., Lentjes, Marleen A.H., Aschard, Hugues, Sattar, Naveed, Foster, Paul J., and Khawaja, Anthony P.

Abstract

Purpose: \ud Serum lipids are modifiable, routinely collected blood test features associated with cardiovascular health. We examined the association of commonly collected serum lipid measures (total cholesterol [TC], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], and triglycerides) with intraocular pressure (IOP).\ud \ud Design: \ud Cross-sectional study in the UK Biobank and European Prospective Investigation into Cancer and Nutrition (EPIC)-Norfolk cohorts.\ud \ud Participants: \ud We included 94 323 participants from the UK Biobank (mean age, 57 years) and 6230 participants from the EPIC-Norfolk (mean age, 68 years) cohorts with data on TC, HDL-C, LDL-C, and triglycerides collected between 2006 and 2009.\ud \ud Methods: \ud Multivariate linear regression adjusting for demographic, lifestyle, anthropometric, medical, and ophthalmic covariables was used to examine the associations of serum lipids with corneal-compensated IOP (IOPcc).\ud \ud Main Outcome Measures: \ud Corneal-compensated IOP.\ud \ud Results: \ud Higher levels of TC, HDL-C, and LDL-C were associated independently with higher IOPcc in both cohorts after adjustment for key demographic, medical, and lifestyle factors. For each 1-standard deviation increase in TC, HDL-C, and LDL-C, IOPcc was higher by 0.09 mmHg (95% confidence interval [CI], 0.06–0.11 mmHg; P < 0.001), 0.11 mmHg (95% CI, 0.08–0.13 mmHg; P < 0.001), and 0.07 mmHg (95% CI, 0.05–0.09 mmHg; P < 0.001), respectively, in the UK Biobank cohort. In the EPIC-Norfolk cohort, each 1-standard deviation increase in TC, HDL-C, and LDL-C was associated with a higher IOPcc by 0.19 mmHg (95% CI, 0.07–0.31 mmHg; P = 0.001), 0.14 mmHg (95% CI, 0.03–0.25 mmHg; P = 0.016), and 0.17 mmHg (95% CI, 0.06–0.29 mmHg; P = 0.003). An inverse association between triglyceride levels and IOP in the UK Biobank (–0.05 mmHg; 95% CI, –0.08 to –0.03; P < 0.001) was not replicated in the EPIC-Norfolk cohort (P = 0.30).\ud \ud Conclusions: \ud Our findings suggest that serum TC, HDL-C, and LDL-C are associated positively with IOP in 2 United Kingdom cohorts and that triglyceride levels may be associated negatively. Future research is required to assess whether these associations are causal in nature.

Published
2022

26. The Association between Serum Lipids and Intraocular Pressure in 2 Large United Kingdom Cohorts

Author

Madjedi, Kian M., primary, Stuart, Kelsey V., additional, Chua, Sharon Y.L., additional, Luben, Robert N., additional, Warwick, Alasdair, additional, Pasquale, Louis R., additional, Kang, Jae H., additional, Wiggs, Janey L., additional, Lentjes, Marleen A.H., additional, Aschard, Hugues, additional, Sattar, Naveed, additional, Foster, Paul J., additional, Khawaja, Anthony P., additional, Chia, Mark, additional, Do, Ron, additional, Kastner, Alan, additional, Kim, Jihye, additional, Montesano, Giovanni, additional, Atan, Denize, additional, Aslam, Tariq, additional, Barman, Sarah A., additional, Barrett, Jenny H., additional, Bishop, Paul, additional, Blows, Peter, additional, Bunce, Catey, additional, Carare, Roxana O., additional, Chakravarthy, Usha, additional, Chan, Michelle, additional, Crabb, David P., additional, Cumberland, Philippa M., additional, Day, Alexander, additional, Desai, Parul, additional, Dhillon, Bal, additional, Dick, Andrew D., additional, Egan, Cathy, additional, Ennis, Sarah, additional, Foster, Paul, additional, Fruttiger, Marcus, additional, Gallacher, John E.J., additional, Garway-Heath, David F., additional, Gibson, Jane, additional, Gore, Dan, additional, Guggenheim, Jeremy A., additional, Hammond, Chris J., additional, Hardcastle, Alison, additional, Harding, Simon P., additional, Hogg, Ruth E., additional, Hysi, Pirro, additional, Keane, Pearse A., additional, Khaw, Sir Peng T., additional, Lascaratos, Gerassimos, additional, Lotery, Andrew J., additional, Macgillivray, Tom, additional, Mackie, Sarah, additional, Martin, Keith, additional, McGaughey, Michelle, additional, McGuinness, Bernadette, additional, McKay, Gareth J., additional, McKibbin, Martin, additional, Mitry, Danny, additional, Moore, Tony, additional, Morgan, James E., additional, Muthy, Zaynah A., additional, O’Sullivan, Eoin, additional, Owen, Chris G., additional, Patel, Praveen, additional, Paterson, Euan, additional, Peto, Tunde, additional, Petzold, Axel, additional, Rahi, Jugnoo S., additional, Rudnikca, Alicja R., additional, Self, Jay, additional, Sivaprasad, Sobha, additional, Steel, David, additional, Stratton, Irene, additional, Strouthidis, Nicholas, additional, Sudlow, Cathie, additional, Thomas, Dhanes, additional, Trucco, Emanuele, additional, Tufail, Adnan, additional, Vitart, Veronique, additional, Vernon, Stephen A., additional, Viswanathan, Ananth C., additional, Williams, Cathy, additional, Williams, Katie, additional, Woodside, Jayne V., additional, Yates, MaxM., additional, Yip, Jennifer, additional, and Zheng, Yalin, additional

Published
2022
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27. Alcohol, intra-ocular pressure and open angle glaucoma: A systematic review and meta-analysis (protocol)

Author

Stuart, Kelsey, Madjedi, Kian, Luben, Robert, Chua, Sharon, Warwick, Alasdair, Khawaja, Anthony, and Foster, Paul

Subjects
Ophthalmology, genetic structures, Epidemiology, Medicine and Health Sciences, Medical Specialties, Public Health, eye diseases
Abstract

This systematic review and meta-analysis aims to identify, summarise and quantitatively combine the existing evidence for the associations between alcohol use and both intra-ocular pressure (IOP) and open angle glaucoma (OAG). This registration reports the proposed study protocol. Findings from this study will be used to guide further original research into these associations by identifying current knowledge gaps and avenues which require additional study.

Published
2022
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28. COVID-19 trajectories among 57 million adults in England: a cohort study using electronic health records

Author

Thygesen, Johan H, primary, Tomlinson, Christopher, additional, Hollings, Sam, additional, Mizani, Mehrdad A, additional, Handy, Alex, additional, Akbari, Ashley, additional, Banerjee, Amitava, additional, Cooper, Jennifer, additional, Lai, Alvina G, additional, Li, Kezhi, additional, Mateen, Bilal A, additional, Sattar, Naveed, additional, Sofat, Reecha, additional, Torralbo, Ana, additional, Wu, Honghan, additional, Wood, Angela, additional, Sterne, Jonathan A C, additional, Pagel, Christina, additional, Whiteley, William N, additional, Sudlow, Cathie, additional, Hemingway, Harry, additional, Denaxas, Spiros, additional, Abbasizanjani, Hoda, additional, Ahmed, Nida, additional, Ahmed, Badar, additional, Akinoso-Imran, Abdul Qadr, additional, Allara, Elias, additional, Allery, Freya, additional, Angelantonio, Emanuele Di, additional, Ashworth, Mark, additional, Ayyar-Gupta, Vandana, additional, Babu-Narayan, Sonya, additional, Bacon, Seb, additional, Ball, Steve, additional, Banerjee, Ami, additional, Barber, Mark, additional, Barrett, Jessica, additional, Bennie, Marion, additional, Berry, Colin, additional, Beveridge, Jennifer, additional, Birney, Ewan, additional, Bojanić, Lana, additional, Bolton, Thomas, additional, Bone, Anna, additional, Boyle, Jon, additional, Braithwaite, Tasanee, additional, Bray, Ben, additional, Briffa, Norman, additional, Brind, David, additional, Brown, Katherine, additional, Buch, Maya, additional, Canoy, Dexter, additional, Caputo, Massimo, additional, Carragher, Raymond, additional, Carson, Alan, additional, Cezard, Genevieve, additional, Chang, Jen-Yu Amy, additional, Cheema, Kate, additional, Chin, Richard, additional, Chudasama, Yogini, additional, Copland, Emma, additional, Crallan, Rebecca, additional, Cripps, Rachel, additional, Cromwell, David, additional, Curcin, Vasa, additional, Curry, Gwenetta, additional, Dale, Caroline, additional, Danesh, John, additional, Das-Munshi, Jayati, additional, Dashtban, Ashkan, additional, Davies, Alun, additional, Davies, Joanna, additional, Davies, Gareth, additional, Davies, Neil, additional, Day, Joshua, additional, Delmestri, Antonella, additional, Denholm, Rachel, additional, Dennis, John, additional, Denniston, Alastair, additional, Deo, Salil, additional, Dhillon, Baljean, additional, Docherty, Annemarie, additional, Dong, Tim, additional, Douiri, Abdel, additional, Downs, Johnny, additional, Dregan, Alexandru, additional, Ellins, Elizabeth A, additional, Elwenspoek, Martha, additional, Falck, Fabian, additional, Falter, Florian, additional, Fan, Yat Yi, additional, Firth, Joseph, additional, Fraser, Lorna, additional, Friebel, Rocco, additional, Gavrieli, Amir, additional, Gerstung, Moritz, additional, Gilbert, Ruth, additional, Gillies, Clare, additional, Glickman, Myer, additional, Goldacre, Ben, additional, Goldacre, Raph, additional, Greaves, Felix, additional, Green, Mark, additional, Grieco, Luca, additional, Griffiths, Rowena, additional, Gurdasani, Deepti, additional, Halcox, Julian, additional, Hall, Nick, additional, Hama, Tuankasfee, additional, Hansell, Anna, additional, Hardelid, Pia, additional, Hardy, Flavien, additional, Harris, Daniel, additional, Harrison, Camille, additional, Harron, Katie, additional, Hassaine, Abdelaali, additional, Hassan, Lamiece, additional, Healey, Russell, additional, Henderson, Angela, additional, Herz, Naomi, additional, Heyl, Johannes, additional, Hidajat, Mira, additional, Higginson, Irene, additional, Hinchliffe, Rosie, additional, Hippisley-Cox, Julia, additional, Ho, Frederick, additional, Hocaoglu, Mevhibe, additional, Horne, Elsie, additional, Hughes, David, additional, Humberstone, Ben, additional, Inouye, Mike, additional, Ip, Samantha, additional, Islam, Nazrul, additional, Jackson, Caroline, additional, Jenkins, David, additional, Jiang, Xiyun, additional, Johnson, Shane, additional, Kadam, Umesh, additional, Kallis, Costas, additional, Karim, Zainab, additional, Kasan, Jake, additional, Katsoulis, Michalis, additional, Kavanagh, Kim, additional, Kee, Frank, additional, Keene, Spencer, additional, Kent, Seamus, additional, Khalid, Sara, additional, Khawaja, Anthony, additional, Khunti, Kamlesh, additional, Killick, Richard, additional, Kinnear, Deborah, additional, Knight, Rochelle, additional, Kolamunnage-Dona, Ruwanthi, additional, Kontopantelis, Evan, additional, Kurdi, Amanj, additional, Lacey, Ben, additional, Lai, Alvina, additional, Lambarth, Andrew, additional, Larzjan, Milad Nazarzadeh, additional, Lawler, Deborah, additional, Lawrence, Thomas, additional, Lawson, Claire, additional, Li, Qiuju, additional, Li, Ken, additional, Llinares, Miguel Bernabeu, additional, Lorgelly, Paula, additional, Lowe, Deborah, additional, Lyons, Jane, additional, Lyons, Ronan, additional, Machado, Pedro, additional, Macleod, Mary Joan, additional, Macleod, John, additional, Malgapo, Evaleen, additional, Mamas, Mamas, additional, Mamouei, Mohammad, additional, Manohar, Sinduja, additional, Mapeta, Rutendo, additional, Martelli, Javiera Leniz, additional, Martos, David Moreno, additional, Mateen, Bilal, additional, McCarthy, Aoife, additional, Melville, Craig, additional, Milton, Rebecca, additional, Mizani, Mehrdad, additional, Moncusi, Marta Pineda, additional, Morales, Daniel, additional, Mordi, Ify, additional, Morrice, Lynn, additional, Morris, Carole, additional, Morris, Eva, additional, Mu, Yi, additional, Mueller, Tanja, additional, Murdock, Lars, additional, Nafilyan, Vahé, additional, Nicholson, George, additional, Nikiphorou, Elena, additional, Nolan, John, additional, Norris, Tom, additional, Norris, Ruth, additional, North, Laura, additional, North, Teri-Louise, additional, O'Connell, Dan, additional, Oliver, Dominic, additional, Oluyase, Adejoke, additional, Olvera-Barrios, Abraham, additional, Omigie, Efosa, additional, Onida, Sarah, additional, Padmanabhan, Sandosh, additional, Palmer, Tom, additional, Pasea, Laura, additional, Patel, Riyaz, additional, Payne, Rupert, additional, Pell, Jill, additional, Petitjean, Carmen, additional, Pherwani, Arun, additional, Pickrell, Owen, additional, Pierotti, Livia, additional, Pirmohamed, Munir, additional, Priedon, Rouven, additional, Prieto-Alhambra, Dani, additional, Proudfoot, Alastair, additional, Quinn, Terry, additional, Quint, Jennifer, additional, Raffetti, Elena, additional, Rahimi, Kazem, additional, Rao, Shishir, additional, Razieh, Cameron, additional, Roberts, Brian, additional, Rogers, Caroline, additional, Rossdale, Jennifer, additional, Salim, Safa, additional, Samani, Nilesh, additional, Schnier, Christian, additional, Schwartz, Roy, additional, Selby, David, additional, Seminog, Olena, additional, Shabnam, Sharmin, additional, Shah, Ajay, additional, Shelton, Jon, additional, Sheppard, James, additional, Sinha, Shubhra, additional, Skrypak, Mirek, additional, Slapkova, Martina, additional, Sleeman, Katherine, additional, Smith, Craig, additional, Sosenko, Filip, additional, Sperrin, Matthew, additional, Steeg, Sarah, additional, Sterne, Jonathan, additional, Stoica, Serban, additional, Sudell, Maria, additional, Sun, Luanluan, additional, Suseeladevi, Arun Karthikeyan, additional, Sweeting, Michael, additional, Sydes, Matt, additional, Takhar, Rohan, additional, Tang, Howard, additional, Thygesen, Johan, additional, Tilston, George, additional, Tochel, Claire, additional, Toit, Clea du, additional, Toms, Renin, additional, Torabi, Fatemeh, additional, Townson, Julia, additional, Tufail, Adnan, additional, Tungamirai, Tapiwa, additional, Varma, Susheel, additional, Vollmer, Sebastian, additional, Walker, Venexia, additional, Wang, Tianxiao, additional, Wang, Huan, additional, Warwick, Alasdair, additional, Watkinson, Ruth, additional, Watson, Harry, additional, Whiteley, William, additional, Whittaker, Hannah, additional, Wilde, Harry, additional, Wilkinson, Tim, additional, Williams, Gareth, additional, Williams, Michelle, additional, Williams, Richard, additional, Withnell, Eloise, additional, Wolfe, Charles, additional, Wright, Lucy, additional, Wu, Jinge, additional, Wu, Jianhua, additional, Yates, Tom, additional, Zaccardi, Francesco, additional, Zhang, Haoting, additional, Zhang, Huayu, additional, and Zuccolo, Luisa, additional

Published
2022
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29. Alcohol, Intraocular Pressure, and Open-Angle Glaucoma

Author

Stuart, Kelsey V., primary, Madjedi, Kian, additional, Luben, Robert N., additional, Chua, Sharon Y.L., additional, Warwick, Alasdair N., additional, Chia, Mark, additional, Pasquale, Louis R., additional, Wiggs, Janey L., additional, Kang, Jae H., additional, Hysi, Pirro G., additional, Tran, Jessica H., additional, Foster, Paul J., additional, and Khawaja, Anthony P., additional

Published
2022
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30. Association of alcohol consumption with glaucoma and related traits

Author

Stuart, Kelsey Vernon, Luben, Robert, Warwick, Alasdair, Madjedi, Kian, Patel, Praveen, Lentjes, Marleen, Foster, Paul, Khawaja, Anthony, Stuart, Kelsey Vernon, Luben, Robert, Warwick, Alasdair, Madjedi, Kian, Patel, Praveen, Lentjes, Marleen, Foster, Paul, and Khawaja, Anthony

Abstract

Funding agencies:UCL Overseas Research ScholarshipDesmond Foundation

Published
2022

31. The Association between Serum Lipids and Intraocular Pressure in 2 Large United Kingdom Cohorts

Author

Madjedi, Kian M., Stuart, Kelsey V., Chua, Sharon Y. L., Luben, Robert N., Warwick, Alasdair, Pasquale, Louis R., Kang, Jae H., Wiggs, Janey L., Lentjes, Marleen, Aschard, Hugues, Sattar, Naveed, Foster, Paul J., Khawaja, Anthony P., Madjedi, Kian M., Stuart, Kelsey V., Chua, Sharon Y. L., Luben, Robert N., Warwick, Alasdair, Pasquale, Louis R., Kang, Jae H., Wiggs, Janey L., Lentjes, Marleen, Aschard, Hugues, Sattar, Naveed, Foster, Paul J., and Khawaja, Anthony P.

Abstract

PURPOSE: Serum lipids are modifiable, routinely collected blood tests associated with cardiovascular health. We examined the association of commonly collected serum lipid measures (total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL-C) and triglycerides (TG)) with intraocular pressure (IOP). DESIGN: Cross-sectional study in the UK Biobank and EPIC-Norfolk cohorts. PARTICIPANTS: We included 94 323 participants of UK Biobank (mean age 57 years) and 6 230 participants of EPIC-Norfolk (mean age 68 years) with data on TC, HDL-C, LDL-C, TG collected between 2006-2009. METHODS: Multivariable linear regression adjusting for demographic, lifestyle, anthropometric, medical and ophthalmic covariables was used to examine the associations of serum lipids with IOPcc. MAIN OUTCOME MEASURES: IOPcc. RESULTS: Higher levels of TC, HDL-C and LDL-C were independently associated with higher IOPcc in both cohorts after adjustment for key demographic, medical and lifestyle factors. For each standard deviation increase in TC, HDL-C, and LDL-C, IOPcc (mmHg) was higher by 0.09 (95% CI: 0.06-0.11; P<0.001), 0.11 (95% CI 0.08-0.13; P<0.001), 0.07 (95% CI: 0.05-0.09, P<0.001), respectively in the UK Biobank cohort. In the EPIC-Norfolk cohort, each additional standard deviation in TC, HDL-C, and LDL-C was associated with a higher IOPcc (mmHg) by 0.19 (95% CI 0.07-0.31, P=0.001), 0.14 (95% CI 0.03-0.25, P=0.016), and 0.17 (95% CI 0.06-0.29, P=0.003). An inverse association between TGs and IOP in the UK Biobank (-0.05, 95% CI -0.08 to -0.03, P<0.001) was not replicated in the EPIC cohort (P=0.30). CONCLUSION: Our findings suggest that serum TC, HDL-C and LDL-C are positively associated with IOP in two UK cohorts and TGs may be negatively associated. Future research is required to assess whether these associations are causal in nature., Funding agencies:UCL Overseas Research ScholarshipFight for Sight, London, United Kingdom 1956ADesmond FoundationNovartisUnited Kingdom Research and Innovation Future Leaders FellowshipMoorfields Eye Charity (Springboard Award)Career Development FellowshipUnited States Department of Health & Human ServicesNational Institutes of Health (NIH) - USANIH National Eye Institute (NEI) EY015473 EY032559 Research to Prevent Blindness (RPB)The Glaucoma Foundation, New York, New YorkBoehringer IngelheimRoche DiagnosticsAssociation for Research in Vision and Ophthalmology Foundation (David Epstein AwardUK Research and Innovation Future Leaders Fellowship (Medical Research Council MR/T040912/1United Kingdom Department of HealthNational Institute for Health Research (NIEye Hospital NHS Foundation TrustUCL Institute of Ophthalmology for a Biomedical Research Centre for OphthalmologyMoorfields Eye CharityNIHR Biomedical Research Centre at Moorfields Eye Hospital NHS Foundation TrustUCL Institute of OphthalmologyInternational Glaucoma Association (United Kingdom)UK Research & Innovation (UKRI)Medical Research Council UK (MRC) SP2024/0201 MR/N003284/1 Cancer Research UK G9502233 C864/A8257

Published
2022
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33. Evaluation of retinal nerve fibre layer thickness as a possible measure of diabetic retinal neurodegeneration in the EPIC-Norfolk Eye Study.

Author

Zafar, Sidra, Staggers, Kristen A., Jie Gao, Yao Liu, Patel, Praveen J., Foster, Paul J., Frankfort, Benjamin J., Abramoff, Michael, Minard, Charles G., Warwick, Alasdair, Khawaja, Anthony P., and Channa, Roomasa

Abstract

Background/aims Markers to clinically evaluate structural changes from diabetic retinal neurodegeneration (DRN) have not yet been established. To study the potential role of peripapillary retinal nerve fibre layer (pRNFL) thickness as a marker for DRN, we evaluated the relationship between diabetes, as well as glycaemic control irrespective of diabetes status and pRNFL thickness. Methods Leveraging data from a population-based cohort, we used general linear mixed models (GLMMs) with a random intercept for patient and eye to assess the association between pRNFL thickness (measured using GDx) and demographic, systemic and ocular parameters after adjusting for typical scan score. GLMMs were also used to determine: (1) the relationship between: (A) glycated haemoglobin (HbA1c) irrespective of diabetes diagnosis and pRNFL thickness, (B) diabetes and pRNFL thickness and (2) which quadrants of pRNFL may be affected in participants with diabetes and in relation to HbA1c. Results 7076 participants were included. After controlling for covariates, inferior pRNFL thickness was 0.94 µm lower (95% CI -1.28 µm to -0.60 µm), superior pRNFL thickness was 0.83 µm lower (95% CI -1.17 µm to -0.49 µm) and temporal pRNFL thickness was 1.33 µm higher (95% CI 0.99 µm to 1.67 µm) per unit increase in HbA1c. Nasal pRNFL thickness was not significantly associated with HbA1c (p=0.23). Similar trends were noted when diabetes was used as the predictor. Conclusion Superior and inferior pRNFL was significantly thinner among those with higher HbA1c levels and/or diabetes, representing areas of the pRNFL that may be most affected by diabetes. [ABSTRACT FROM AUTHOR]

Published
2023
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34. Estimating excess visual loss from neovascular age-related macular degeneration in the UK during the COVID-19 pandemic: a retrospective clinical audit and simulation model

Author

Thomas, Darren S, primary, Warwick, Alasdair, additional, Olvera-Barrios, Abraham, additional, Egan, Catherine, additional, Schwartz, Roy, additional, Patra, Sudeshna, additional, Eleftheriadis, Haralabos, additional, Khawaja, Anthony, additional, Lotery, Andrew, additional, Muller, Philipp L, additional, Hamilton, Robin, additional, Preston, Ella, additional, Taylor, Paul, additional, and Tufail, Adnan, additional

Published
2022
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36. Evaluation of retinal nerve fibre layer thickness as a possible measure of diabetic retinal neurodegeneration in the EPIC-Norfolk Eye Study

Author

Zafar, Sidra, primary, Staggers, Kristen A, additional, Gao, Jie, additional, Liu, Yao, additional, Patel, Praveen J, additional, Foster, Paul J, additional, Frankfort, Benjamin J, additional, Abramoff, Michael, additional, Minard, Charles G, additional, Warwick, Alasdair, additional, Khawaja, Anthony P, additional, and Channa, Roomasa, additional

Published
2021
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37. Association of Smoking, Alcohol Consumption, Blood Pressure, Body Mass Index, and Glycemic Risk Factors With Age-Related Macular Degeneration: A Mendelian Randomization Study

Author

Kuan, Valerie, Warwick, Alasdair, Hingorani, Aroon, Tufail, Adnan, Cipriani, Valentina, Burgess, Stephen, Sofat, Reecha, International AMD Genomics Consortium (IAMDGC), Burgess, Stephen [0000-0001-5365-8760], and Apollo - University of Cambridge Repository

Subjects
Vascular Endothelial Growth Factor A, genetic structures, Alcohol Drinking, Smoking, Visual Acuity, Angiogenesis Inhibitors, Blood Pressure, Mendelian Randomization Analysis, Blindness, eye diseases, Body Mass Index, Diabetes Mellitus, Type 2, Risk Factors, Wet Macular Degeneration, Humans, sense organs, Genome-Wide Association Study
Abstract

IMPORTANCE: Advanced age-related macular degeneration (AMD) is a leading cause of blindness in Western countries. Causal, modifiable risk factors need to be identified to develop preventive measures for advanced AMD. OBJECTIVE: To assess whether smoking, alcohol consumption, blood pressure, body mass index, and glycemic traits are associated with increased risk of advanced AMD. DESIGN, SETTING, PARTICIPANTS: This study used 2-sample mendelian randomization. Genetic instruments composed of variants associated with risk factors at genome-wide significance (P < 5 × 10-8) were obtained from published genome-wide association studies. Summary-level statistics for these instruments were obtained for advanced AMD from the International AMD Genomics Consortium 2016 data set, which consisted of 16 144 individuals with AMD and 17 832 control individuals. Data were analyzed from July 2020 to September 2021. EXPOSURES: Smoking initiation, smoking cessation, lifetime smoking, age at smoking initiation, alcoholic drinks per week, body mass index, systolic and diastolic blood pressure, type 2 diabetes, glycated hemoglobin, fasting glucose, and fasting insulin. MAIN OUTCOMES AND MEASURES: Advanced AMD and its subtypes, geographic atrophy (GA), and neovascular AMD. RESULTS: A 1-SD increase in logodds of genetically predicted smoking initiation was associated with higher risk of advanced AMD (odds ratio [OR], 1.26; 95% CI, 1.13-1.40; P < .001), while a 1-SD increase in logodds of genetically predicted smoking cessation (former vs current smoking) was associated with lower risk of advanced AMD (OR, 0.66; 95% CI, 0.50-0.87; P = .003). Genetically predicted increased lifetime smoking was associated with increased risk of advanced AMD (OR per 1-SD increase in lifetime smoking behavior, 1.32; 95% CI, 1.09-1.59; P = .004). Genetically predicted alcohol consumption was associated with higher risk of GA (OR per 1-SD increase of log-transformed alcoholic drinks per week, 2.70; 95% CI, 1.48-4.94; P = .001). There was insufficient evidence to suggest that genetically predicted blood pressure, body mass index, and glycemic traits were associated with advanced AMD. CONCLUSIONS AND RELEVANCE: This study provides genetic evidence that increased alcohol intake may be a causal risk factor for GA. As there are currently no known treatments for GA, this finding has important public health implications. These results also support previous observational studies associating smoking behavior with risk of advanced AMD, thus reinforcing existing public health messages regarding the risk of blindness associated with smoking.

Published
2021
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38. Evolving Treatment Patterns and Outcomes of Neovascular Age-Related Macular Degeneration Over a Decade

Author

Schwartz, Roy, primary, Warwick, Alasdair, additional, Olvera-Barrios, Abraham, additional, Pikoula, Maria, additional, Lee, Aaron Y., additional, Denaxas, Spiros, additional, Taylor, Paul, additional, Egan, Catherine, additional, Chakravarthy, Usha, additional, Lip, Peck Lin, additional, Tufail, Adnan, additional, Akerele, T., additional, Antcliff, R., additional, Bailey, C., additional, Brand, C., additional, Chakravarthy, U., additional, Davis, A., additional, Dhingra, N., additional, Downey, L., additional, Eleftheriadis, H., additional, George, S., additional, Ghanchi, F., additional, Jones, C., additional, Khan, R., additional, Kumar, V., additional, Lip, P., additional, Lobo, A., additional, Lotery, A., additional, Mahmood, S., additional, Menon, G., additional, Mukherjee, R., additional, Natha, S., additional, Palmer, H., additional, Patra, S., additional, Patwardhan, A., additional, Paul, B., additional, Talks, J., additional, and Wilkinson, E., additional

Published
2021
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39. Alcohol Consumption and Incident Cataract Surgery in Two Large UK Cohorts

Author

Chua, Sharon Y.L., primary, Luben, Robert N., additional, Hayat, Shabina, additional, Broadway, David C., additional, Khaw, Kay-Tee, additional, Warwick, Alasdair, additional, Britten, Abigail, additional, Day, Alexander C., additional, Strouthidis, Nicholas, additional, Patel, Praveen J., additional, Khaw, Peng T., additional, Foster, Paul J., additional, and Khawaja, Anthony P., additional

Published
2021
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40. Quantification of Key Retinal Features in Early and Late Age-Related Macular Degeneration Using Deep Learning

Author

Liefers, Bart, primary, Taylor, Paul, additional, Alsaedi, Abdulrahman, additional, Bailey, Clare, additional, Balaskas, Konstantinos, additional, Dhingra, Narendra, additional, Egan, Catherine A., additional, Rodrigues, Filipa Gomes, additional, Gonzalo, Cristina González, additional, Heeren, Tjebo F.C., additional, Lotery, Andrew, additional, Müller, Philipp L., additional, Olvera-Barrios, Abraham, additional, Paul, Bobby, additional, Schwartz, Roy, additional, Thomas, Darren S., additional, Warwick, Alasdair N., additional, Tufail, Adnan, additional, and Sánchez, Clara I., additional

Published
2021
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42. Association of ambient air pollution with age-related macular degeneration and retinal thickness in UK Biobank

Author

Chua, Sharon Y L, primary, Warwick, Alasdair, additional, Peto, Tunde, additional, Balaskas, Konstantinos, additional, Moore, Anthony T, additional, Reisman, Charles, additional, Desai, Parul, additional, Lotery, Andrew J, additional, Dhillon, Baljean, additional, Khaw, Peng T, additional, Owen, Christopher G, additional, Khawaja, Anthony P, additional, Foster, Paul J, additional, and Patel, Praveen J, additional

Published
2021
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43. Association of ambient air pollution with age-related macular degeneration and retinal thickness in UK Biobank.

Author

Chua, Sharon Y. L., Warwick, Alasdair, Peto, Tunde, Balaskas, Konstantinos, Moore, Anthony T., Reisman, Charles, Desai, Parul, Lotery, Andrew J., Dhillon, Baljean, Khaw, Peng T., Owen, Christopher G., Khawaja, Anthony P., Foster, Paul J., and Patel, Praveen J.

Abstract

Aim To examine the associations of air pollution with both self-reported age-related macular degeneration (AMD), and in vivo measures of retinal sublayer thicknesses. Methods We included 115 954 UK Biobank participants aged 40-69 years old in this cross-sectional study. Ambient air pollution measures included particulate matter, nitrogen dioxide (NO2) and nitrogen oxides (NOx). Participants with self-reported ocular conditions, high refractive error (< -6 or > +6 diopters) and poor spectral-domain optical coherence tomography (SD-OCT) image were excluded. Self-reported AMD was used to identify overt disease. SD-OCT imaging derived photoreceptor sublayer thickness and retinal pigment epithelium (RPE) layer thickness were used as structural biomarkers of AMD for 52 602 participants. We examined the associations of ambient air pollution with self-reported AMD and both photoreceptor sublayers and RPE layer thicknesses. Results After adjusting for covariates, people who were exposed to higher fine ambient particulate matter with an aerodynamic diameter <2.5 μm (PM2.5, per IQR increase) had higher odds of self-reported AMD (OR=1.08, p=0.036), thinner photoreceptor synaptic region (β=-0.16 μm, p=2.0 × 10-5), thicker photoreceptor inner segment layer (β=0.04 μm, p=0.001) and thinner RPE (β=-0.13 μm, p=0.002). Higher levels of PM2.5 absorbance and NO2 were associated with thicker photoreceptor inner and outer segment layers, and a thinner RPE layer. Higher levels of PM10 (PM with an aerodynamic diameter <10 μm) was associated with thicker photoreceptor outer segment and thinner RPE, while higher exposure to NOx was associated with thinner photoreceptor synaptic region. Conclusion Greater exposure to PM2.5 was associated with self-reported AMD, while PM2.5, PM2.5 absorbance, PM10, NO2 and NOx were all associated with differences in retinal layer thickness. [ABSTRACT FROM AUTHOR]

Published
2022
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44. Contextualising Single-Arm Ophthalmology Trials With Real-World Data: An Emulated Target Trial Comparing The Efficacy of Interventions For Neovascular Age-Related Macular Degeneration

Author

Thomas, Darren S., primary, Lee, Aaron Y., additional, Müller, Philipp L., additional, Schwartz, Roy, additional, Olvera-Barrios, Abraham, additional, Warwick, Alasdair N., additional, Patel, Praveen J., additional, Heeren, Tjebo F.C., additional, Egan, Catherine, additional, Taylor, Paul, additional, and Tufail, Adnan, additional

Published
2020
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46. Contextualizing single‐arm trials with real‐world data: An emulated target trial comparing therapies for neovascular age‐related macular degeneration.

Author

Thomas, Darren S., Lee, Aaron Y., Müller, Philipp L., Schwartz, Roy, Olvera‐Barrios, Abraham, Warwick, Alasdair N., Patel, Praven J., Heeren, Tjebo F.C., Egan, Catherine, Taylor, Paul, and Tufail, Adnan

Subjects
RETINAL degeneration, BEVACIZUMAB, ELECTRONIC health records, VISUAL acuity, PROPENSITY score matching, DIABETIC retinopathy
Abstract

One‐in‐four ophthalmology trials are single‐armed, which poses challenges to their interpretation. We demonstrate how real‐world cohorts used as external/synthetic control arms can contextualize such trials. We herein emulated a target trial on the intention‐to‐treat efficacy of off‐label bevacizumab (q6w) pro re nata relative to fixed‐interval aflibercept (q8w) for improving week 54 visual acuity of eyes affected by neovascular age‐related macular degeneration. The bevacizumab arm (n = 65) was taken from the ABC randomized controlled trial. A total of 4,471 aflibercept‐treated eyes aligning with the ABC trial eligibility were identified from electronic health records and synthetic control arms were created by emulating randomization conditional on age, sex, and baseline visual read via exact matching and propensity score methods. We undertook an inferiority analysis on mean difference at 54 weeks; outcomes regression on achieving a change in visual acuity of greater than or equal to 15, greater than or equal to 10, and less than or equal to −15 Early Treatment Diabetic Retinopathy (ETDRS) letters at week 54; and a time‐to‐event analysis on achieving a change in visual acuity of greater than or equal to 15, greater than or equal to 10, and less than or equal to −15 ETDRS letters by week 54. The findings suggest off‐label bevacizumab to be neither inferior nor superior to licensed aflibercept. Our study highlights how real‐world cohorts representing the counterfactual intervention could aid the interpretation of single‐armed trials when analyzed in accord to the target trial framework. Study HighlightsWHAT IS THE CURRENT KNOWLEDGE ON THE TOPIC?One‐in‐four randomized controlled trials in ophthalmology are single‐armed, which poses challenges for interpreting their efficacy relative to standard of care. Recent conceptual advances in the methods of causal inference and in the emulation of target trials suggests that the standard‐of‐care arms representing the counterfactual intervention can be approximated with observational data. WHAT QUESTION DID THIS STUDY ADDRESS?How real‐world cohorts representing the counterfactual intervention can aid the interpretation of single‐armed ophthalmological trials. WHAT DOES THIS STUDY ADD TO OUR KNOWLEDGE?Our study highlights how real‐world cohorts representing the counterfactual intervention could aid the interpretation of single‐armed ophthalmological trials when undertaken in accord with the target trial framework. HOW MIGHT THIS CHANGE CLINICAL PHARMACOLOGY OR TRANSLATIONAL SCIENCE?External counterfactual arms could reduce the time and cost to reach potential regulatory approval. [ABSTRACT FROM AUTHOR]

Published
2021
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47. Fixed bimonthly aflibercept in naïve and switched neovascular age related macular degeneration patients: 1 year outcomes

Author

Warwick, Alasdair, Leaver, Hannah, Lotery, Andrew, and Goverdhan, Srini

Subjects
genetic structures, sense organs, eye diseases
Abstract

Aim: To determine real life clinical outcomes in poorly responsive and treatment-naïve neovascular age related macular degeneration (nvAMD) patients using bi-monthly fixed dosing aflibercept regimen.Methods: This was a retrospective study of 165 eyes with nvAMD started on aflibercept at Southampton Eye Unit between June 2013 and June 2014. Patients were either switched from pro re nata (PRN) ranibizumab/bevacizumab due to poor response (107 eyes), or treatment-naïve (58 eyes). Patients received 3 initial monthly intravitreal aflibercept injections followed by 2-monthly fixed doses. Clinic visits were scheduled at months 0, 4, 10 and 12. Mean change in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) from baseline were assessed using the Wilcoxon signed-rank test. The proportion of patients maintaining BCVA (Results: Mean BCVA change at month 12 was +3.29 and +4.67 letters in the switched and naïve aflibercept groups respectively (pConclusion: Fixed bimonthly aflibercept is effective in both treatment-naïve and poorly responsive nvAMD patients. Adopting a fixed dosing regimen can reduce patient burden without compromising on outcomes.

Published
2016

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