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1. 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

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

Published
2023
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2. 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

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

Published
2023
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3. 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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4. Investigation of associations between retinal microvascular parameters and albuminuria in UK Biobank: a cross-sectional case-control study

Author

Paterson, Euan N., Cardwell, Chris, MacGillivray, Thomas J., Trucco, Emanuele, Doney, Alexander S., Foster, Paul, Maxwell, Alexander P., McKay, Gareth, Aslam, Tariq, Barman, Sarah, Barrett, Jenny, Bishop, Paul, Blows, Peter, Bunce, Catey, Carare, Roxana, Chakravarthy, Usha, Chan, Michelle, Chianca, Antonietta, Cipriani, Valentina, Crabb, David, Cumberland, Philippa, Day, Alexander, Desai, Parul, Dhillon, Bal, Dick, Andrew, Egan, Cathy, Ennis, Sarah, Fruttiger, Marcus, Gallacher, John, Garway-Heath, David (Ted), Gibson, Jane, Gore, Dan, Guggenheim, Jeremy, Hammond, Chris, Hardcastle, Alison, Harding, Simon, Hogg, Ruth, Hysi, Pirro, Keane, Pearse A., Khaw, Sir Peng Tee, Khawaja, Anthony, Lascaratos, Gerassimos, Lotery, Andrew, Luthert, Phil, MacGillivray, Tom, Mackie, Sarah, Martin, Keith, Morgan, James, Self, Jay, Stratton, Irene, Ophthalmology, APH - Mental Health, APH - Methodology, Amsterdam Neuroscience - Neuroinfection & -inflammation, McKay, Gareth J [0000-0001-8197-6280], and Apollo - University of Cambridge Repository

Subjects
Male, medicine.medical_specialty, 030204 cardiovascular system & hematology, Fundus (eye), lcsh:RC870-923, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Internal medicine, Medicine, Albuminuria, Humans, Renal Insufficiency, Chronic, Aged, Biological Specimen Banks, business.industry, Case-control study, Retinal Vessels, Retinal, Odds ratio, Diabetic retinopathy, Organ Size, Middle Aged, medicine.disease, lcsh:Diseases of the genitourinary system. Urology, United Kingdom, Blood pressure, Cross-Sectional Studies, chemistry, Nephrology, Case-Control Studies, Microvessels, 030221 ophthalmology & optometry, Cardiology, Female, RE, medicine.symptom, business, Kidney disease, Research Article, RC
Abstract

Background Associations between microvascular variation and chronic kidney disease (CKD) have been reported previously. Non-invasive retinal fundus imaging enables evaluation of the microvascular network and may offer insight to systemic risk associated with CKD. Methods Retinal microvascular parameters (fractal dimension [FD] – a measure of the complexity of the vascular network, tortuosity, and retinal arteriolar and venular calibre) were quantified from macula-centred fundus images using the Vessel Assessment and Measurement Platform for Images of the REtina (VAMPIRE) version 3.1 (VAMPIRE group, Universities of Dundee and Edinburgh, Scotland) and assessed for associations with renal damage in a case-control study nested within the multi-centre UK Biobank cohort study. Participants were designated cases or controls based on urinary albumin to creatinine ratio (ACR) thresholds. Participants with ACR ≥ 3 mg/mmol (ACR stages A2-A3) were characterised as cases, and those with an ACR Results Lower FD (less extensive microvascular branching) was associated with a small increase in odds of albuminuria independent of blood pressure, diabetes and other potential confounding variables (odds ratio [OR] 1.18, 95% confidence interval [CI] 1.03–1.34 for arterioles and OR 1.24, CI 1.05–1.47 for venules). Measures of tortuosity or retinal arteriolar and venular calibre were not significantly associated with ACR. Conclusions This study supports previously reported associations between retinal microvascular FD and other metabolic disturbances affecting the systemic vasculature. The association between retinal microvascular FD and albuminuria, independent of diabetes and blood pressure, may represent a useful indicator of systemic vascular damage associated with albuminuria.

Published
2021

5. Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error

Author

Fan, Qiao, Pozarickij, Alfred, Tan, Nicholas Y. Q., Guo, Xiaobo, Verhoeven, Virginie J. M., Vitart, Veronique, Guggenheim, Jeremy A., Miyake, Masahiro, Tideman, J. Willem L., Khawaja, Anthony P., Zhang, Liang, MacGregor, Stuart, Höhn, René, Chen, Peng, Biino, Ginevra, Wedenoja, Juho, Saffari, Seyed Ehsan, Tedja, Milly S., Xie, Jing, Lanca, Carla, Wang, Ya Xing, Sahebjada, Srujana, Mazur, Johanna, Mirshahi, Alireza, Martin, Nicholas G., Yazar, Seyhan, Pennell, Craig E., Yap, Maurice, Haarman, Annechien E. G., Enthoven, Clair A., Polling, JanRoelof, Hewitt, Alex W., Jaddoe, Vincent W. V., Van Duijn, Cornelia M., Hayward, Caroline, Polasek, Ozren, Tai, E-Shyong, Yoshikatsu, Hosoda, Hysi, Pirro G., Young, Terri L., Tsujikawa, Akitaka, Wang, Jie Jing, Mitchell, Paul, Pfeiffer, Norbert, Pärssinen, Olavi, Foster, Paul J., Fossarello, Maurizio, Yip, Shea Ping, Williams, Cathy, Hammond, Christopher J., Jonas, Jost B., He, Mingguang, Mackey, David A., Wong, Tien-Yin, Klaver, Caroline C. W., Saw, Seang-Mei, Baird, Paul N., Cheng, Ching-Yu, Bailey-Wilson, Joan E., Veluchamy, Amutha Barathi, Burdon, Kathryn P., Campbell, Harry, Chen, Li Jia, Chew, Emily Y., Craig, Jamie E., Cumberland, Phillippa M., Deangelis, Margaret M., Delcourt, Cécile, Ding, Xiaohu, Evans, David M., Gharahkhani, Puya, Iglesias, Adriana I., Haller, Toomas, Han, Xikun, Hoang, Quan, Igo, Robert P., Iyengar, Sudha K., Kähönen, Mika, Kaprio, Jaakko, Klein, Barbara E., Klein, Ronald, Lass, Jonathan H., Lee, Kris, Lehtimäki, Terho, Lewis, Deyana D., Li, Qing, Li, Shi-Ming, Lyytikäinen, Leo-Pekka, Meguro, Akira, Metspalu, Andres, Middlebrooks, Candace D., Mizuki, Nobuhisa, Musolf, Anthony M., Nickels, Stefan, Oexle, Konrad, Pang, Chi Pui, Paterson, Andrew D., Rahi, Jugnoo S., Raitakari, Olli, Rudan, Igor, Stambolian, Dwight, Simpson, Claire L., Wang, Ningli, Bin Wei, Wen, Williams, Katie M., Wilson, James F., Wojciechowski, Robert, Yamashiro, Kenji, Yam, Jason C. S., Zhou, Xiangtian, Aslam, Tariq, Barman, Sarah A., Barrett, Jenny H., Bishop, Paul, Blows, Peter, Bunce, Catey, Carare, Roxana O., Chakravarthy, Usha, Chan, Michelle, Chua, Sharon Y. L., Crabb, David P., Cumberland, Philippa M., Day, Alexander, Desai, Parul, Dhillon, Bal, Dick, Andrew D., Egan, Cathy, Ennis, Sarah, Fruttiger, Marcus, Gallacher, John E. J., Garway-Heath, David F., Gibson, Jane, Gore, Dan, Hardcastle, Alison, Harding, Simon P., Hogg, Ruth E., Keane, Pearse A., Khaw, Sir Peng T., Lascaratos, Gerassimos, Lotery, Andrew J., Macgillivray, Tom, Mackie, Sarah, Martin, Keith, McGaughey, Michelle, McGuinness, Bernadette, McKay, Gareth J., McKibbin, Martin, Mitry, Danny, Moore, Tony, Morgan, James E., Muthy, Zaynah A., O’Sullivan, Eoin, Owen, Chris G., Patel, Praveen, Paterson, Euan, Peto, Tunde, Petzold, Axel, Rudnikca, Alicja R., Self, Jay, Sivaprasad, Sobha, Steel, David, Stratton, Irene, Strouthidis, Nicholas, Sudlow, Cathie, Thomas, Dhanes, Trucco, Emanuele, Tufail, Adnan, Vernon, Stephen A., Viswanathan, Ananth C., Williams, Katie, Woodside, Jayne V., Yates, Max M., Yip, Jennifer, Zheng, Yalin, Verhoeven, Virginie J. M. [0000-0001-7359-7862], Vitart, Veronique [0000-0002-4991-3797], Guggenheim, Jeremy A. [0000-0001-5164-340X], Khawaja, Anthony P. [0000-0001-6802-8585], Zhang, Liang [0000-0001-9264-170X], MacGregor, Stuart [0000-0001-6731-8142], Wedenoja, Juho [0000-0002-6155-0378], Saffari, Seyed Ehsan [0000-0002-6473-4375], Tedja, Milly S. [0000-0003-0356-9684], Lanca, Carla [0000-0001-9918-787X], Wang, Ya Xing [0000-0003-2749-7793], Martin, Nicholas G. [0000-0003-4069-8020], Yap, Maurice [0000-0003-4687-4101], Hewitt, Alex W. [0000-0002-5123-5999], Jaddoe, Vincent W. V. [0000-0003-2939-0041], Hayward, Caroline [0000-0002-9405-9550], Hysi, Pirro G. [0000-0001-5752-2510], Young, Terri L. [0000-0001-6994-9941], Wang, Jie Jing [0000-0001-9491-4898], Pfeiffer, Norbert [0000-0002-5766-2617], Foster, Paul J. [0000-0002-4755-177X], Hammond, Christopher J. [0000-0002-3227-2620], Jonas, Jost B. [0000-0003-2972-5227], Klaver, Caroline C. W. [0000-0002-2355-5258], Baird, Paul N. [0000-0002-1305-3502], and Apollo - University of Cambridge Repository

Subjects
genetic structures, 45, 692/699/3161/3163, 631/208/727/2000, 631/208/205/2138, 45/43, article, sense organs, eye diseases
Abstract

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia.

Published
2021
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6. Retinal asymmetry in multiple sclerosis

Author

Petzold, Axel, Chua, Sharon Y. L., Khawaja, Anthony P., Keane, Pearse A., Khaw, Peng T., Reisman, Charles, Dhillon, Baljean, Strouthidis, Nicholas G., Foster, Paul J., Patel, Praveen J., Atan, Denize, Aslam, Tariq, Barman, Sarah A., Barrett, Jenny H., Bishop, Paul, Bunce, Catey, Carare, Roxana O., Chakravarthy, Usha, Chan, Michelle, Crabb, David P., Day, Alexander, Desai, Parul, Dhillon, Bal, Dick, Andrew D., Egan, Cathy, Ennis, Sarah, Fruttiger, Marcus, Gallacher, John E. J., Garway-Heath, David F., Gibson, Jane, Gore, Dan, Guggenheim, Jeremy A., Hammond, Chris J., Hardcastle, Alison, Harding, Simon P., Hogg, Ruth E., Hysi, Pirro, Khaw, Sir Peng T., Lascaratos, Gerassimos, Lotery, Andrew J., MacGillivray, Tom, MacKie, Sarah, McGaughey, Michelle, McGuinness, Bernadette, McKay, Gareth J., McKibbin, Martin, Moore, Tony, Morgan, James E., Muthy, Zaynah A., O'Sullivan, Eoin, Owen, Chris G., Patel, Praveen, Paterson, Euan, Peto, Tunde, Rahi, Jugnoo S., Rudnikca, Alicja R., Self, Jay, Sivaprasad, Sobha, Steel, David, Stratton, Irene, Strouthidis, Nicholas, Sudlow, Cathie, Thomas, Dhanes, Trucco, Emanuele, Tufail, Adnan, Vitart, Veronique, Vernon, Stephen A., Viswanathan, Ananth C., Williams, Cathy, Williams, Katie, Woodside, Jayne V., Yates, Max M., Zheng, Yalin, Consortium, UK Biobank Eye and Vision, Gallacher, JE, Neurology, Ophthalmology, APH - Mental Health, APH - Methodology, and Amsterdam Neuroscience - Neuroinfection & -inflammation

Subjects
Male, genetic structures, Youden's J statistic, Optic neuritis, Imaging, chemistry.chemical_compound, 0302 clinical medicine, medicine.diagnostic_test, AcademicSubjects/SCI01870, imaging, Middle Aged, Biobank, Female, demyelination, Demyelination, Tomography, Optical Coherence, medicine.medical_specialty, Multiple Sclerosis, Clinical Neurology, Sensitivity and Specificity, Retina, Multiple sclerosis, 03 medical and health sciences, Optical coherence tomography, SDG 3 - Good Health and Well-being, Ophthalmology, medicine, Humans, optic neuritis, Research ethics, Community level, Neuromyelitis optica, Receiver operating characteristic, business.industry, biomarkers, Retinal, Original Articles, medicine.disease, Confidence interval, eye diseases, chemistry, North west, 030221 ophthalmology & optometry, Optometry, AcademicSubjects/MED00310, RE, Neurology (clinical), sense organs, business, 030217 neurology & neurosurgery, Biomarkers, RC
Abstract

In a large community-based study, Petzold et al. show that optical coherence tomography measures of retinal asymmetry have high diagnostic sensitivity for multiple sclerosis, particularly in younger individuals without relevant comorbidities. The technique should be considered in future revisions of diagnostic criteria., The diagnosis of multiple sclerosis is based on a combination of clinical and paraclinical tests. The potential contribution of retinal optical coherence tomography (OCT) has been recognized. We tested the feasibility of OCT measures of retinal asymmetry as a diagnostic test for multiple sclerosis at the community level. In this community-based study of 72 120 subjects, we examined the diagnostic potential of the inter-eye difference of inner retinal OCT data for multiple sclerosis using the UK Biobank data collected at 22 sites between 2007 and 2010. OCT reporting and quality control guidelines were followed. The inter-eye percentage difference (IEPD) and inter-eye absolute difference (IEAD) were calculated for the macular retinal nerve fibre layer (RNFL), ganglion cell inner plexiform layer (GCIPL) complex and ganglion cell complex. Area under the receiver operating characteristic curve (AUROC) comparisons were followed by univariate and multivariable comparisons accounting for a large range of diseases and co-morbidities. Cut-off levels were optimized by ROC and the Youden index. The prevalence of multiple sclerosis was 0.0023 [95% confidence interval (CI) 0.00229–0.00231]. Overall the discriminatory power of diagnosing multiple sclerosis with the IEPD AUROC curve (0.71, 95% CI 0.67–0.76) and IEAD (0.71, 95% CI 0.67–0.75) for the macular GCIPL complex were significantly higher if compared to the macular ganglion cell complex IEPD AUROC curve (0.64, 95% CI 0.59–0.69, P = 0.0017); IEAD AUROC curve (0.63, 95% CI 0.58–0.68, P 0.14) with narrow confidence intervals. In conclusion, the OCT macular GCIPL complex IEPD and IEAD may be considered as supportive measurements for multiple sclerosis diagnostic criteria in a young patient without relevant co-morbidity. The metric does not allow separation of multiple sclerosis from neuromyelitis optica. Retinal OCT imaging is accurate, rapid, non-invasive, widely available and may therefore help to reduce need for invasive and more costly procedures. To be viable, higher sensitivity and specificity levels are needed.

Published
2021

7. Ambient Air Pollution Associations with Retinal Morphology in the UK Biobank

Author

Chua, Sharon Y.L., Khawaja, Anthony P., Dick, Andrew D., Morgan, James, Dhillon, Baljean, Lotery, Andrew J., Strouthidis, Nicholas G., Reisman, Charles, Peto, Tunde, Khaw, Peng T., Foster, Paul J., Patel, Praveen J., Littlejohns, Thomas, Allen, Naomi, Beli, Eleni, Atan, Denize, Aslam, Tariq, Barman, Sarah A., Barrett, Jenny H., Bishop, Paul, Bunce, Catey, Carare, Roxana O., Chakravarthy, Usha, Chan, Michelle, Crabb, David P., Day, Alexander, Desai, Parul, Dhillon, Bal, Egan, Cathy, Ennis, Sarah, Fruttiger, Marcus, Gallacher, John E.J., Garway-Heath, David F., Gibson, Jane, Gore, Dan, Guggenheim, Jeremy A., Hammond, Chris J., Hardcastle, Alison, Harding, Simon P., Hogg, Ruth E., Hysi, Pirro, Keane, Pearse A., Lascaratos, Gerassimos, Macgillivray, Tom, Mackie, Sarah, McGaughey, Michelle, McGuinness, Bernadette, McKay, Gareth J., McKibbin, Martin, Moore, Tony, Morgan, James E., Muthy, Zaynah A., O’Sullivan, Eoin, Owen, Chris G., Paterson, Euan, Petzold, Axel, Rahi, Jugnoo S., Rudnikca, Alicja R., Self, Jay, Sivaprasad, Sobha, Steel, David, Stratton, Irene, Strouthidis, Nicholas, Sudlow, Cathie, Thomas, Dhanes, Trucco, Emanuele, Tufail, Adnan, Vitart, Veronique, Vernon, Stephen A., Viswanathan, Ananth C., Williams, Cathy, Williams, Katie, Woodside, Jayne V., Yates, Max M., and Zheng, Yalin

Subjects
Adult, Male, Retinal Ganglion Cells, medicine.medical_specialty, Retinal layers, air pollution, Air pollution, Nerve fiber layer, Glaucoma, Outer plexiform layer, Retinal Pigment Epithelium, Absorbance, 03 medical and health sciences, chemistry.chemical_compound, 0302 clinical medicine, Nerve Fibers, Retinal Diseases, Ophthalmology, Surveys and Questionnaires, medicine, Humans, Outer nuclear layer, Aged, Biological Specimen Banks, Chemistry, Clinical and Epidemiologic Research, Retinal, retinal layers, Middle Aged, medicine.disease, GF, SDG 11 - Sustainable Cities and Communities, United Kingdom, medicine.anatomical_structure, Cross-Sectional Studies, OCT, Inner nuclear layer, 030221 ophthalmology & optometry, Female, Nitrogen Oxides, Particulate Matter, RE, sense organs, Layer (electronics), 030217 neurology & neurosurgery, Tomography, Optical Coherence, Photoreceptor Cells, Vertebrate
Abstract

PURPOSE. Because air pollution has been linked to glaucoma and AMD, we characterized the relationship between pollution and retinal structure. METHODS. We examined data from 51,710 UK Biobank participants aged 40 to 69 years old. Ambient air pollution measures included particulates and nitrogen oxides. SD-OCT imaging measured seven retinal layers: retinal nerve fiber layer, ganglion cell–inner plexiform layer, inner nuclear layer, outer plexiform layer + outer nuclear layer, photoreceptor inner segments, photoreceptor outer segments, and RPE. Multivariable regression was used to evaluate associations between pollutants (per interquartile range increase) and retinal thickness, adjusting for age, sex, race, Townsend deprivation index, body mass index, smoking status, and refractive error. RESULTS. Participants exposed to greater particulate matter with an aerodynamic diameter of CONCLUSIONS. Greater exposure to PM2.5, PM2.5 absorbance, and nitrogen oxides were all associated with apparently adverse retinal structural features.

Published
2020

8. Genome-wide association meta-analysis of corneal curvature identifies novel loci and shared genetic influences across axial length and refractive error

Author

Fan, Qiao, Pozarickij, Alfred, Tan, Nicholas Y. Q., Guo, Xiaobo, Verhoeven, Virginie J. M., Vitart, Veronique, Guggenheim, Jeremy A., Miyake, Masahiro, Tideman, J. Willem L., Khawaja, Anthony P., Zhang, Liang, MacGregor, Stuart, Höhn, René, Chen, Peng, Biino, Ginevra, Wedenoja, Juho, Saffari, Seyed Ehsan, Tedja, Milly S., Xie, Jing, Lanca, Carla, Wang, Ya Xing, Sahebjada, Srujana, Mazur, Johanna, Mirshahi, Alireza, Martin, Nicholas G., Yazar, Seyhan, Pennell, Craig E., Yap, Maurice, Haarman, Annechien E. G., Enthoven, Clair A., Polling, JanRoelof, Bailey-Wilson, Joan E., Veluchamy, Amutha Barathi, Burdon, Kathryn P., Campbell, Harry, Chen, Li Jia, Chew, Emily Y., Craig, Jamie E., Cumberland, Phillippa M., Deangelis, Margaret M., Delcourt, Cécile, Ding, Xiaohu, Evans, David M., Gharahkhani, Puya, Iglesias, Adriana I., Haller, Toomas, Han, Xikun, Hoang, Quan, Igo, Robert P., Iyengar, Sudha K., Kähönen, Mika, Kaprio, Jaakko, Klein, Barbara E., Klein, Ronald, Lass, Jonathan H., Lee, Kris, Lehtimäki, Terho, Lewis, Deyana D., Li, Qing, Li, Shi-Ming, Lyytikäinen, Leo-Pekka, Meguro, Akira, Metspalu, Andres, Middlebrooks, Candace D., Mizuki, Nobuhisa, Musolf, Anthony M., Nickels, Stefan, Oexle, Konrad, Pang, Chi Pui, Paterson, Andrew D., Rahi, Jugnoo S., Raitakari, Olli, Rudan, Igor, Stambolian, Dwight, Simpson, Claire L., Wang, Ningli, Bin Wei, Wen, Williams, Katie M., Wilson, James F., Wojciechowski, Robert, Yamashiro, Kenji, Yam, Jason C. S., Zhou, Xiangtian, Aslam, Tariq, Barman, Sarah A., Barrett, Jenny H., Bishop, Paul, Blows, Peter, Bunce, Catey, Carare, Roxana O., Chakravarthy, Usha, Chan, Michelle, Chua, Sharon Y. L., Crabb, David P., Cumberland, Philippa M., Day, Alexander, Desai, Parul, Dhillon, Bal, Dick, Andrew D., Egan, Cathy, Ennis, Sarah, Fruttiger, Marcus, Gallacher, John E. J., Garway-Heath, David F., Gibson, Jane, Gore, Dan, Hardcastle, Alison, Harding, Simon P., Hogg, Ruth E., Keane, Pearse A., Khaw, Sir Peng T., Lascaratos, Gerassimos, Lotery, Andrew J., Macgillivray, Tom, Mackie, Sarah, Martin, Keith, McGaughey, Michelle, McGuinness, Bernadette, McKay, Gareth J., McKibbin, Martin, Mitry, Danny, Moore, Tony, Morgan, James E., Muthy, Zaynah A., O’Sullivan, Eoin, Owen, Chris G., Patel, Praveen, Paterson, Euan, Peto, Tunde, Petzold, Axel, Rudnikca, Alicja R., Self, Jay, Sivaprasad, Sobha, Steel, David, Stratton, Irene, Strouthidis, Nicholas, Sudlow, Cathie, Thomas, Dhanes, Trucco, Emanuele, Tufail, Adnan, Vernon, Stephen A., Viswanathan, Ananth C., Williams, Katie, Woodside, Jayne V., Yates, Max M., Yip, Jennifer, Zheng, Yalin, Hewitt, Alex W., Jaddoe, Vincent W. V., van Duijn, Cornelia M., Hayward, Caroline, Polasek, Ozren, Tai, E-Shyong, Yoshikatsu, Hosoda, Hysi, Pirro G., Young, Terri L., Tsujikawa, Akitaka, Wang, Jie Jing, Mitchell, Paul, Pfeiffer, Norbert, Pärssinen, Olavi, Foster, Paul J., Fossarello, Maurizio, Yip, Shea Ping, Williams, Cathy, Hammond, Christopher J., Jonas, Jost B., He, Mingguang, Mackey, David A., Wong, Tien-Yin, Klaver, Caroline C. W., Saw, Seang-Mei, Baird, Paul N., and Cheng, Ching-Yu

Subjects
genetic structures, likinäköisyys, sense organs, geneettiset tekijät, eye diseases
Abstract

Corneal curvature, a highly heritable trait, is a key clinical endophenotype for myopia - a major cause of visual impairment and blindness in the world. Here we present a trans-ethnic meta-analysis of corneal curvature GWAS in 44,042 individuals of Caucasian and Asian with replication in 88,218 UK Biobank data. We identified 47 loci (of which 26 are novel), with population-specific signals as well as shared signals across ethnicities. Some identified variants showed precise scaling in corneal curvature and eye elongation (i.e. axial length) to maintain eyes in emmetropia (i.e. HDAC11/FBLN2 rs2630445, RBP3 rs11204213); others exhibited association with myopia with little pleiotropic effects on eye elongation. Implicated genes are involved in extracellular matrix organization, developmental process for body and eye, connective tissue cartilage and glycosylation protein activities. Our study provides insights into population-specific novel genes for corneal curvature, and their pleiotropic effect in regulating eye size or conferring susceptibility to myopia. peerReviewed

Published
2020

9. Associations with photoreceptor thickness measures in the UK Biobank

Author

Chua, Sharon YL, Dhillon, Baljean, Aslam, Tariq, Balaskas, Konstantinos, Yang, Qi, Keane, Pearse A, Tufail, Adnan, Reisman, Charles, Foster, Paul J, Patel, Praveen J, Bishop, Paul, Barman, Sarah A, Barrett, Jenny H, Blows, Peter, Bunce, Catey, Carare, Roxana O, Chakravarthy, Usha, Chan, Michelle, Crabb, David P, Cumberland, Philippa M, Day, Alexander, Desai, Parul, Sudlow, Cathie, Dick, Andrew D, Egan, Cathy, Ennis, Sarah, Fruttiger, Marcus, Gallacher, John EJ, Garway-Heath, David F, Gibson, Jane, Gore, Dan, Guggenheim, Jeremy A, Hammond, Chris J, Hardcastle, Alison, Harding, Simon P, Hogg, Ruth E, Hysi, Pirro, Khaw, Sir Peng T, Khawaja, Anthony P, Lascaratos, Gerassimos, Lotery, Andrew J, Macgillivray, Tom, Mackie, Sarah, Martin, Keith, Mcgaughey, Michelle, Mcguinness, Bernadette, Mckay, Gareth J, Mckibbin, Martin, Mitry, Danny, Moore, Tony, Morgan, James E, Muthy, Zaynah A, O'Sullivan, Eoin, Owen, Chris G, Paterson, Euan, Peto, Tunde, Petzold, Axel, Rahi, Jugnoo S, Rudnicka, Alicja R, Self, Jay, Sivaprasad, Sobha, Steel, David, Stratton, Irene, Strouthidis, Nicholas, Thaung, Caroline, Thomas, Dhanes, Trucco, Emanuele, Vitart, Veronique, Vernon, Stephen A, Viswanathan, Ananth C, Williams, Cathy, Williams, Katie, Woodside, Jayne V, Yates, Max M, Yip, Jennifer, Zheng, Yalin, Tapp, Robyn, Consortium, UK Biobank Eye Vision, Dhillon, Baljean [0000-0001-5993-0278], Foster, Paul J [0000-0002-4755-177X], Patel, Praveen J [0000-0001-8682-4067], and Apollo - University of Cambridge Repository

Subjects
0301 basic medicine, Male, Refractive error, Intraocular pressure, Visual acuity, genetic structures, Epidemiology, Visual Acuity, lcsh:Medicine, Retinal Pigment Epithelium, Cornea, chemistry.chemical_compound, 0302 clinical medicine, lcsh:Science, Biological Specimen Banks, Multidisciplinary, medicine.diagnostic_test, Age Factors, Middle Aged, medicine.anatomical_structure, Eye examination, Female, medicine.symptom, Tomography, Optical Coherence, Photoreceptor Cells, Vertebrate, Adult, medicine.medical_specialty, Article, 03 medical and health sciences, Sex Factors, Ophthalmology, medicine, Humans, General, Intraocular Pressure, Aged, Retinal pigment epithelium, business.industry, lcsh:R, Retinal, medicine.disease, United Kingdom, eye diseases, 030104 developmental biology, Blood pressure, chemistry, Risk factors, 030221 ophthalmology & optometry, RE, lcsh:Q, sense organs, business
Abstract

Funder: DH | NIHR | Health Services Research Programme (NIHR Health Services Research Programme); doi: https://doi.org/10.13039/501100001923, Spectral-domain OCT (SD-OCT) provides high resolution images enabling identification of individual retinal layers. We included 32,923 participants aged 40-69 years old from UK Biobank. Questionnaires, physical examination, and eye examination including SD-OCT imaging were performed. SD OCT measured photoreceptor layer thickness includes photoreceptor layer thickness: inner nuclear layer-retinal pigment epithelium (INL-RPE) and the specific sublayers of the photoreceptor: inner nuclear layer-external limiting membrane (INL-ELM); external limiting membrane-inner segment outer segment (ELM-ISOS); and inner segment outer segment-retinal pigment epithelium (ISOS-RPE). In multivariate regression models, the total average INL-RPE was observed to be thinner in older aged, females, Black ethnicity, smokers, participants with higher systolic blood pressure, more negative refractive error, lower IOPcc and lower corneal hysteresis. The overall INL-ELM, ELM-ISOS and ISOS-RPE thickness was significantly associated with sex and race. Total average of INL-ELM thickness was additionally associated with age and refractive error, while ELM-ISOS was additionally associated with age, smoking status, SBP and refractive error; and ISOS-RPE was additionally associated with smoking status, IOPcc and corneal hysteresis. Hence, we found novel associations of ethnicity, smoking, systolic blood pressure, refraction, IOPcc and corneal hysteresis with photoreceptor thickness.

Published
2019

10. Quantile regression analysis reveals widespread evidence for gene-environment or gene-gene interactions in myopia development

Author

Pozarickij, Alfred, Williams, Cathy, Hysi, Pirro G., Guggenheim, Jeremy A., Aslam, Tariq, Barman, Sarah A., Barrett, Jenny H., Bishop, Paul, Blows, Peter, Bunce, Catey, Carare, Roxana O., Chakravarthy, Usha, Chan, Michelle, Chua, Sharon Y.L., Crabb, David P., Cumberland, Philippa M., Day, Alexander, Desai, Parul, Dhillon, Bal, Dick, Andrew D., Egan, Cathy, Ennis, Sarah, Foster, Paul, Fruttiger, Marcus, Gallacher, John E.J., Garway-Heath, David F., Gibson, Jane, Gore, Dan, Hammond, Chris J., Hardcastle, Alison, Harding, Simon P., Hogg, Ruth E., Keane, Pearse A., Khaw, Sir Peng T., Khawaja, Anthony P., Lascaratos, Gerassimos, Lotery, Andrew J., Mac Gillivray, Tom, Mackie, Sarah, Martin, Keith, McGaughey, Michelle, McGuinness, Bernadette, McKay, Gareth J., McKibbin, Martin, Mitry, Danny, Moore, Tony, Morgan, James E., Muthy, Zaynah A., O’Sullivan, Eoin, and Self, Jay

Abstract

A genetic contribution to refractive error has been confirmed by the discovery of more than 150 associated variants in genome-wide association studies (GWAS). Environmental factors such as education and time outdoors also demonstrate strong associations. Currently however, the extent of gene-environment or gene-gene interactions in myopia is unknown. We tested the hypothesis that refractive error-associated variants exhibit effect size heterogeneity, a hallmark feature of genetic interactions. Of 146 variants tested, evidence of non-uniform, non-linear effects were observed for 66 (45%) at Bonferroni-corrected significance (P < 1.1 × 10 −4) and 128 (88%) at nominal significance (P < 0.05). LAMA2 variant rs12193446, for example, had an effect size varying from −0.20 diopters (95% CI −0.18 to −0.23) to −0.89 diopters (95% CI −0.71 to −1.07) in different individuals. SNP effects were strongest at the phenotype extremes and weaker in emmetropes. A parsimonious explanation for these findings is that gene-environment or gene-gene interactions in myopia are pervasive.

Published
2019

11. Comparison of Associations with Different Macular Inner Retinal Thickness Parameters in a Large Cohort

Author

Khawaja, Anthony P., primary, Chua, Sharon, additional, Hysi, Pirro G., additional, Georgoulas, Stelios, additional, Currant, Hannah, additional, Fitzgerald, Tomas W., additional, Birney, Ewan, additional, Ko, Fang, additional, Yang, Qi, additional, Reisman, Charles, additional, Garway-Heath, David F., additional, Hammond, Chris J., additional, Khaw, Peng T., additional, Foster, Paul J., additional, Patel, Praveen J., additional, Strouthidis, Nicholas, 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, Chua, Sharon Y.L., 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, Gibson, Jane, additional, Gore, Dan, additional, Guggenheim, Jeremy A., additional, Hardcastle, Alison, additional, Harding, Simon P., additional, Hogg, Ruth E., additional, Hysi, Pirro, additional, Keane, Pearse A., additional, Khaw, Sir Peng T., additional, Khawaja, Anthony P., 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, 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, Max M., additional, Yip, Jennifer, additional, and Zheng, Yalin, additional

Published
2020
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12. Multi-trait genome-wide association study identifies new loci associated with optic disc parameters

Author

Bonnemaijer, Pieter WM, van Leeuwen, Elisabeth M, Iglesias, Adriana I, Gharahkhani, Puya, Vitart, Veronique, Khawaja, Anthony P, Simcoe, Mark, Hoehn, Rene, Cree, Angela J, Igo, Rob P, Burdon, Kathryn P, Craig, Jamie E, Hewitt, Alex W, Jonas, Jost, Khor, Chiea-Cheun, Pasutto, Francesca, Mackey, David A, Mitchell, Paul, Mishra, Aniket, Pang, Calvin, Pasquale, Louis R, Springelkamp, Henriette, Thorleifsson, Gudmar, Thorsteinsdottir, Unnur, Viswanathan, Ananth C, Wojciechowski, Robert, Wong, Tien, Young, Terrri L, Zeller, Tanja, Atan, Denize, Aslam, Tariq, Barman, Sarah A, Barrett, Jenny H, Bishop, Paul, Blows, Peter, Bunce, Catey, Carare, Roxana O, Chakravarthy, Usha, Chan, Michelle, Chua, Sharon YL, Crabb, David P, Cumberland, Philippa M, Day, Alexander, Desai, Parul, Dhillon, Bal, Dick, Andrew D, Egan, Cathy, Ennis, Sarah, Foster, Paul, Fruttiger, Marcus, Gallacher, John EJ, Garway, David F, Gibson, Jane, Gore, Dan, Guggenheim, Jeremy A, Hardcastle, Alison, Harding, Simon P, Hogg, Ruth E, Keane, Pearse A, Khaw, Peng T, Lascaratos, Gerassimos, Macgillivray, Tom, Mackie, Sarah, Martin, Keith, McGaughey, Michelle, McGuinness, Bernadette, Mckay, Gareth J, McKibbin, Martin, Mitry, Danny, Moore, Tony, Morgan, James E, Muthy, Zaynah A, O'Sullivan, Eoin, Owen, Chris G, Patel, Praveen, Paterson, Euan, Peto, Tunde, Petzold, Axel, Rahi, Jugnoo S, Rudnikca, Alicja R, Self, Jay, Sivaprasad, Sobha, Steel, David, Stratton, Irene, Strouthidis, Nicholas, Sudlow, Cathie, Thomas, Dhanes, Trucco, Emanuele, Tufail, Adnan, Vernon, Stephen A, Williams, Cathy, Williams, Katie, Woodside, Jayne V, Yates, Max M, Yip, Jennifer, Zheng, Yalin, Allingham, Rand, Budenz, Don, Bailey, Jessica Cooke, Fingert, John, Gaasterland, Douglas, Gaasterland, Teresa, Haines, Jonathan L, Hark, Lisa, Hauser, Michael, Kang, Jae Hee, Kraft, Peter, Lee, Richard, Lichter, Paul, Liu, Yutao, Moroi, Syoko, Pericak, Margaret, Realini, Anthony, Rhee, Doug, Richards, Julia R, Ritch, Robert, Scott, William K, Singh, Kuldev, Sit, Arthur, Vollrath, Douglas, Weinreb, Robert, Wollstein, Gadi, Wilmer, Don Zack, Gerhold-Ay, Aslihan, Nickels, Stefan, Wilson, James F, Hayward, Caroline, Boutin, Thibaud S, Polasek, Ozren, Aung, Tin, Khor, Chiea Chuen, Amin, Najaf, Lotery, Andrew J, Wiggs, Janey L, Cheng, Ching-Yu, Hysi, Pirro G, Hammond, Christopher J, Thiadens, Alberta AHJ, MacGregor, Stuart, Klaver, Caroline CW, van Duijn, Cornelia M, Consortium, Int Glaucoma Genetics, Consortium, Uk Biobank Eye Vision, Consortium, NEIGHBORHOOD, Epidemiology, Ophthalmology, Clinical Genetics, Bonnemaijer, Pieter WM [0000-0001-5154-6765], Iglesias, Adriana I [0000-0001-5532-764X], Gharahkhani, Puya [0000-0002-4203-5952], Vitart, Veronique [0000-0002-4991-3797], Khawaja, Anthony P [0000-0001-6802-8585], Simcoe, Mark [0000-0003-2432-0810], Nickels, Stefan [0000-0003-0415-2354], Wilson, James F [0000-0001-5751-9178], Hayward, Caroline [0000-0002-9405-9550], Boutin, Thibaud S [0000-0003-4754-1675], Khor, Chiea Chuen [0000-0002-1128-4729], Lotery, Andrew J [0000-0001-5541-4305], Wiggs, Janey L [0000-0003-1890-3278], Cheng, Ching-Yu [0000-0003-0655-885X], Hysi, Pirro G [0000-0001-5752-2510], Hammond, Christopher J [0000-0002-3227-2620], MacGregor, Stuart [0000-0001-6731-8142], Klaver, Caroline CW [0000-0002-2355-5258], and Apollo - University of Cambridge Repository

Subjects
genetic structures, Optic disk, Medicine (miscellaneous), Genome-wide association study, Neurodegenerative, Genome-wide association studies, Sensory disorders Donders Center for Medical Neuroscience [Radboudumc 12], 0302 clinical medicine, Optic Nerve Diseases, 2.1 Biological and endogenous factors, Aetiology, 610 Medicine & health, lcsh:QH301-705.5, 0303 health sciences, Agricultural and Biological Sciences(all), Single Nucleotide, medicine.anatomical_structure, NEIGHBORHOOD consortium, General Agricultural and Biological Sciences, Optic disc, Signal Transduction, Optic Disk, Quantitative Trait Loci, International Glaucoma Genetics Consortium, Quantitative trait locus, Biology, Genetic correlation, Polymorphism, Single Nucleotide, General Biochemistry, Genetics and Molecular Biology, Article, UK Biobank Eye and Vision Consortium, 03 medical and health sciences, Quantitative Trait, Quantitative Trait, Heritable, medicine, Genetics, Humans, Genetic Predisposition to Disease, 1000 Genomes Project, Polymorphism, Heritable, Eye Disease and Disorders of Vision, Genetic Association Studies, 030304 developmental biology, Genetic association, CENTRAL CORNEAL THICKNESS, METAANALYSIS, GLAUCOMA, EXPRESSION, HERITABILITY, PREVALENCE, STATISTICS, PANEL, Biochemistry, Genetics and Molecular Biology(all), Gene Expression Profiling, Haplotype, Human Genome, Computational Biology, Glaucoma, Molecular Sequence Annotation, eye diseases, lcsh:Biology (General), Evolutionary biology, Case-Control Studies, RE, sense organs, 030217 neurology & neurosurgery, Genome-Wide Association Study
Abstract

A new avenue of mining published genome-wide association studies includes the joint analysis of related traits. The power of this approach depends on the genetic correlation of traits, which reflects the number of pleiotropic loci, i.e. genetic loci influencing multiple traits. Here, we applied new meta-analyses of optic nerve head (ONH) related traits implicated in primary open-angle glaucoma (POAG); intraocular pressure and central corneal thickness using Haplotype reference consortium imputations. We performed a multi-trait analysis of ONH parameters cup area, disc area and vertical cup-disc ratio. We uncover new variants; rs11158547 in PPP1R36-PLEKHG3 and rs1028727 near SERPINE3 at genome-wide significance that replicate in independent Asian cohorts imputed to 1000 Genomes. At this point, validation of these variants in POAG cohorts is hampered by the high degree of heterogeneity. Our results show that multi-trait analysis is a valid approach to identify novel pleiotropic variants for ONH., The International Glaucoma Genetics Consortium reports a genome-wide association study meta-analysis of optic disc parameters relevant to primary open-angle glaucoma. They identify two novel variants in PPP1R36-PLEKHG3 and SERPINE3 by multi-trait analysis in European-ancestry cohorts that were replicated in independent Asian cohorts.

Published
2019

13. Association Between Polygenic Risk Score and Risk of Myopia

Author

Mojarrad, Neema Ghorbani, Plotnikov, Denis, Williams, Cathy, Guggenheim, Jeremy A, Aslam, Tariq, Barman, Sarah A, Barrett, Jenny H, Bishop, Paul, Blows, Peter, Bunce, Catey, Carare, Roxana O, Chakravarthy, Usha, Chan, Michelle, Chua, Sharon YL, Crabb, David P, Cumberland, Philippa M, Day, Alexander, Desai, Parul, Dhillon, Bal, Dick, Andrew D, Egan, Cathy, Ennis, Sarah, Foster, Paul, Fruttiger, Marcus, Gallacher, John EJ, Garway-Heath, David F, Gibson, Jane, Gore, Dan, Hammond, Chris J, Hardcastle, Alison, Harding, Simon P, Hogg, Ruth E, Hysi, Pirro, Keane, Pearse A, Khaw, Sir Peng T, Khawaja, Anthony P, Lascaratos, Gerassimos, Lotery, Andrew J, Macgillivray, Tom, Mackie, Sarah, Martin, Keith, McGaughey, Michelle, McGuinness, Bernadette, Mckay, Gareth J, McKibbin, Martin, Mitry, Danny, Moore, Tony, Morgan, James E, Muthy, Zaynah A, O'Sullivan, Eoin, Owen, Chris G, Patel, Praveen, Paterson, Euan, Peto, Tunde, Petzold, Axel, Rahi, Jugnoo S, Rudnikca, Alicja R, Self, Jay, Sivaprasad, Sobha, Steel, David, Stratton, Irene, Strouthidis, Nicholas, Sudlow, Cathie, Thomas, Dhanes, Trucco, Emanuele, Tufail, Adnan, Vitart, Veronique, Vernon, Stephen A, Viswanathan, Ananth C, Williams, Katie, Woodside, Jayne V, Yates, Max M, Yip, Jennifer, Zheng, Yalin, Consortium, Uk Biobank Eye Vision, and Gallacher, JEJ

Subjects
Adult, Male, Longitudinal study, Pediatrics, medicine.medical_specialty, genetic structures, Population, 01 natural sciences, Risk Assessment, law.invention, 03 medical and health sciences, 0302 clinical medicine, Polygenic risk score, Randomized controlled trial, law, medicine, Genetic predisposition, Myopia, Humans, Genetic Predisposition to Disease, Genetic Testing, 0101 mathematics, education, Child, Aged, education.field_of_study, business.industry, 010102 general mathematics, Infant, Newborn, Infant, ALSPAC, Middle Aged, Personalized medicine, Educational attainment, United Kingdom, Genetic prediction, Ophthalmology, ROC Curve, Area Under Curve, Child, Preschool, Cohort, 030221 ophthalmology & optometry, Female, Age of onset, business, Cohort study, Genome-Wide Association Study
Abstract

Importance Myopia is a leading cause of untreatable visual impairment and is increasing in prevalence worldwide. Interventions for slowing childhood myopia progression have shown success in randomized clinical trials; hence, there is a need to identify which children would benefit most from treatment intervention. Objectives To examine whether genetic information alone can identify children at risk of myopia development and whether including a child’s genetic predisposition to educational attainment is associated with improved genetic prediction of the risk of myopia. Design, Setting, and Participants Meta-analysis of 3 genome-wide association studies (GWAS) including a total of 711 984 individuals. These were a published GWAS for educational attainment and 2 GWAS for refractive error in the UK Biobank, which is a multisite cohort study that recruited participants between January 2006 and October 2010. A polygenic risk score was applied in a population-based validation sample examined between September 1998 and September 2000 (Avon Longitudinal Study of Parents and Children [ALSPAC] mothers). Data analysis was performed from February 2018 to May 2019. Main Outcomes and Measures The primary outcome was the area under the receiver operating characteristic curve (AUROC) in analyses for predicting myopia, using noncycloplegic autorefraction measurements for myopia severity levels of less than or equal to −0.75 diopter (D) (any), less than or equal to −3.00 D (moderate), or less than or equal to −5.00 D (high). The predictor variable was a polygenic risk score (PRS) derived from genome-wide association study data for refractive error (n = 95 619), age of onset of spectacle wear (n = 287 448), and educational attainment (n = 328 917). Results A total of 383 067 adults aged 40 to 69 years from the UK Biobank were included in the new GWAS analyses. The PRS was evaluated in 1516 adults aged 24 to 51 years from the ALSPAC mothers cohort. The PRS had an AUROC of 0.67 (95% CI, 0.65-0.70) for myopia, 0.75 (95% CI, 0.70-0.79) for moderate myopia, and 0.73 (95% CI, 0.66-0.80) for high myopia. Inclusion in the PRS of information associated with genetic predisposition to educational attainment marginally improved the AUROC for myopia (AUROC, 0.674 vs 0.668; P = .02), but not those for moderate and high myopia. Individuals with a PRS in the top 10% were at 6.1-fold higher risk (95% CI, 3.4–10.9) of high myopia. Conclusions and Relevance A personalized medicine approach may be feasible for detecting very young children at risk of myopia. However, accuracy must improve further to merit uptake in clinical practice; currently, cycloplegic autorefraction remains a better indicator of myopia risk (AUROC, 0.87).

Published
2019

14. The Relationship Between Ambient Atmospheric Fine Particulate Matter (PM2.5) and Glaucoma in a Large Community Cohort

Author

Chua, Sharon YL, Khawaja, Anthony P, Morgan, James, Strouthidis, Nicholas, Reisman, Charles, Dick, Andrew D, Khaw, Peng T, Patel, Praveen J, Foster, Paul J, Atan, Denize, Aslam, Tariq, Barman, Sarah A, Barrett, Jenny H, Bishop, Paul, Bunce, Catey, Carare, Roxana O, Chakravarthy, Usha, Chan, Michelle, Crabb, David P, Day, Alexander, Desai, Parul, Dhillon, Bal, Egan, Cathy, Ennis, Sarah, Fruttiger, Marcus, Gallacher, John EJ, Garway-Heath, David F, Gibson, Jane, Gore, Dan, Guggenheim, Jeremy A, Hammond, Chris J, Hardcastle, Alison, Harding, Simon P, Hogg, Ruth E, Hysi, Pirro, Keane, Pearse A, Lascaratos, Gerassimos, Lotery, Andrew J, Macgillivray, Tom, Mackie, Sarah, McGaughey, Michelle, McGuinness, Bernadette, McKay, Gareth J, McKibbin, Martin, Moore, Tony, Muthy, Zaynah A, O'Sullivan, Eoin, Owen, Chris G, Paterson, Euan, Peto, Tunde, Petzold, Axel, Rahi, Jugnoo S, Rudnikca, Alicja R, Self, Jay, Sivaprasad, Sobha, Steel, David, Stratton, Irene, Sudlow, Cathie, Thomas, Dhanes, Trucco, Emanuele, Tufail, Adnan, Vitart, Veronique, Vernon, Stephen A, Viswanathan, Ananth C, Williams, Cathy, Williams, Katie, Woodside, Jayne V, Yates, Max M, Zheng, Yalin, and Consortium, UK Biobank Eye Vision

Subjects
Adult, Male, Retinal Ganglion Cells, Intraocular pressure, medicine.medical_specialty, optical coherence, genetic structures, Population, Glaucoma, tomography, Tonometry, Ocular, Nerve Fibers, Interquartile range, Air Pollution, Surveys and Questionnaires, Ophthalmology, Humans, Medicine, education, Intraocular Pressure, Aged, Air Pollutants, education.field_of_study, business.industry, Odds ratio, Diabetic retinopathy, Middle Aged, medicine.disease, Confidence interval, eye diseases, glaucoma, fine particulate matter, Cohort, GCIPL, Female, Particulate Matter, Self Report, sense organs, Visual Fields, business, Tomography, Optical Coherence, intraocular pressure
Abstract

PURPOSE: Glaucoma is more common in urban populations than in others. Ninety percent of the world's population are exposed to air pollution above World Health Organization (WHO) recommended limits. Few studies have examined the association between air pollution and glaucoma. METHODS: Questionnaire data, ophthalmic measures, and ambient residential area air quality data for 111,370 UK Biobank participants were analyzed. Particulate matter with an aerodynamic diameter < 2.5 μm (PM2.5) was selected as the air quality exposure of interest. Eye measures included self-reported glaucoma, intraocular pressure (IOP), and average thickness of macular ganglion cell-inner plexiform layer (GCIPL) across nine Early Treatment Diabetic Retinopathy Study (ETDRS) retinal subfields as obtained from spectral-domain optical coherence tomography. We examined the associations of PM2.5 concentration with self-reported glaucoma, IOP, and GCIPL. RESULTS: Participants resident in areas with higher PM2.5 concentration were more likely to report a diagnosis of glaucoma (odds ratio = 1.06, 95% confidence interval [CI] = 1.01-1.12, per interquartile range [IQR] increase P = 0.02). Higher PM2.5 concentration was also associated with thinner GCIPL (β = -0.56 μm, 95% CI = -0.63 to -0.49, per IQR increase, P = 1.2 × 10-53). A dose-response relationship was observed between higher levels of PM2.5 and thinner GCIPL (P < 0.001). There was no clinically relevant relationship between PM2.5 concentration and IOP. CONCLUSIONS: Greater exposure to PM2.5 is associated with both self-reported glaucoma and adverse structural characteristics of the disease. The absence of an association between PM2.5 and IOP suggests the relationship may occur through a non-pressure-dependent mechanism, possibly neurotoxic and/or vascular effects.

Published
2019

15. Associations with Corneal Hysteresis in a Population Cohort Results from 96 010 UK Biobank Participants

Author

Zhang, Bing, Shweikh, Yusrah, Khawaja, Anthony P, Gallacher, John, Bauermeister, Sarah, Foster, Paul J, Aslam, Tariq, Barman, Sarah A, Barrett, Jenny H, Bishop, Paul, Blows, Peter, Bunce, Catey, Carare, Roxana O, Chakravarthy, Usha, Chan, Michelle, Chua, Sharon YL, Crabb, David P, Cumberland, Philippa M, Day, Alexander, Desai, Parul, Dhillon, Bal, Dick, Andrew D, Egan, Cathy, Ennis, Sarah, Foster, Paul, Fruttiger, Marcus, Gallacher, John EJ, Garway-Heath, David F, Gibson, Jane, Gore, Dan, Guggenheim, Jeremy A, Hammond, Chris J, Hardcastle, Alison, Harding, Simon P, Hogg, Ruth E, Hysi, Pirro, Keane, Pearse A, Khaw, Sir Peng T, dos Lascaratos, Gerassim, Lotery, Andrew J, Macgillivray, Tom, Mackie, Sarah, Martin, Keith, McGaughey, Michelle, McGuinness, Bernadette, McKay, Gareth J, McKibbin, Martin, Mitry, Danny, Moore, Tony, Morgan, James E, Muthy, Zaynah A, O'Sullivan, Eoin, Owen, Chris G, Patel, Praveen, Paterson, Euan, Peto, Tunde, Petzold, Axel, Rahi, Jugnoo S, Rudnikca, Alicja R, Self, Jay, Sivaprasad, Sobha, Steel, David, Stratton, Irene, Strouthidis, Nicholas, Sudlow, Cathie, Thomas, Dhanes, Trucco, Emanuele, Tufail, Adnan, Vitart, Veronique, Vernon, Stephen A, Viswanathan, Ananth C, Williams, Cathy, Williams, Katie, Woodside, Jayne V, Yates, Max M, Yip, Jennifer, Zheng, Yalin, and Consortium, UKBiobank Eye Vision

Published
2019

16. Cohort profile: Design and methods in the eye and vision consortium of UK Biobank

Author

Chua, Sharon Yu Lin, Thomas, Dhanes, Allen, Naomi, Lotery, Andrew, Desai, Parul, Patel, Praveen, Muthy, Zaynah, Sudlow, Cathie, Peto, Tunde, Khaw, Peng Tee, Foster, Paul J., Zheng, Yalin, Aslam, Tariq, Barman, Sarah A., Barrett, Jenny H., Bishop, Paul, Blows, Peter, Bunce, Catey, Carare, Roxana O., Chakravarthy, Usha, Chan, Michelle, Crabb, David P., Cumberland, Philippa M., Day, Alexander, Dhillon, Bal, Dick, Andrew D., Egan, Cathy, Ennis, Sarah, Fruttiger, Marcus, Gallacher, John E.J., Garway-Heath, David F., Gibson, Jane, Gore, Dan, Guggenheim, Jeremy A., Hammond, Chris J., Hardcastle, Alison, Harding, Simon P., Hogg, Ruth E., Hysi, Pirro, Keane, Pearse A., Khawaja, Anthony P., Lascaratos, Gerassimos, MacGillivray, Tom, Mackie, Sarah, Martin, Keith, McGaughey, Michelle, McGuinness, Bernadette, McKay, Gareth J., Morgan, James E., and Self, Jay

Subjects
genetic structures, sense organs, eye diseases
Abstract

Purpose To describe the rationale, methods and research potential of eye and vision measures available in UK Biobank. Participants UK Biobank is a large, multisite, prospective cohort study. Extensive lifestyle and health questionnaires, a range of physical measures and collection of biological specimens are collected. The scope of UK Biobank was extended midway through data collection to include assessments of other measures of health, including eyes and vision. The eye assessment at baseline included questionnaires detailing past ophthalmic and family history, measurement of visual acuity, refractive error and keratometry, intraocular pressure (IOP), corneal biomechanics, spectral domain optical coherence tomography (OCT) of the macula and a disc-macula fundus photograph. Since recruitment, UK Biobank has collected accelerometer data and begun multimodal imaging data (including brain, heart and abdominal MRI) in 100 000 participants. Dense genotypic data and a panel of 20 biochemistry measures are available, and linkage to medical health records for the full cohort has begun. Findings to date A total of 502 665 people aged between 40 and 69 were recruited to participate in UK Biobank. Of these, 117 175 took part in baseline assessment of vision, IOP, refraction and keratometry. A subgroup of 67 321 underwent OCT and retinal photography. The introduction of eye and vision measures in UK Biobank was accompanied by intensive training, support and a data monitoring quality control process. Future plans UK Biobank is one of the largest prospective cohorts worldwide with extensive data on ophthalmic diseases and conditions. Data collection is an ongoing process and a repeat of the baseline assessment including the questionnaires, measurements and sample collection will be performed in subsets of 25 000 participants every 2-3 years. The depth and breadth of this dataset, coupled with its open-access policy, will create a powerful resource for all researchers to investigate the eye diseases in later life.

Published
2019

17. Associations with Corneal Hysteresis in a Population Cohort

Author

Zhang, Bing, primary, Shweikh, Yusrah, additional, Khawaja, Anthony P., additional, Gallacher, John, additional, Bauermeister, Sarah, additional, Foster, Paul J., 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, Chua, Sharon Y.L., 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, Gerassim dos, 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, FRCOphth, 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, Max M., additional, Yip, Jennifer, additional, and Zheng, Yalin, additional

Published
2019
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19. Optimization of Oxygen Dynamics, UV-A Delivery, and Drug Formulation for Accelerated Epi-On Corneal Crosslinking.

Author

Hill, Jason, Liu, Cailing, Deardorff, Phillip, Tavakol, Behrouz, Eddington, William, Thompson, Vance, Gore, Dan, Raizman, Michael, and Adler, Desmond C.

Subjects
OXYGEN, SODIUM iodide, BENZALKONIUM chloride, ELASTIC modulus, VITAMIN B2
Abstract

Purpose: Corneal collagen crosslinking (CXL) through an intact epithelium (epi-on) at high irradiance could potentially improve patient comfort, visual recovery, and clinical workflow compared to conventional epi-off CXL. However, intact epithelium limits stromal delivery of the oxygen, photosensitizer, and ultraviolet-A (UV-A) radiation needed to drive CXL. This ex vivo study evaluated three different epi-on CXL protocols compared to positive and negative controls, specifically focusing on the impact of supplemental oxygen. Endpoints included stromal oxygen levels, stiffness of crosslinked tissue, and acute flattening of whole eyes. Materials & Methods: Ex vivo porcine eyes were held in a custom environmental chamber. Intrastromal oxygen levels were continuously measured before, during, and after UV illumination by a fiberoptic probe inserted into a laser-cut flap. Accelerated, high irradiance, epi-on CXL protocols using riboflavin formulated with benzalkonium chloride (BAC) were studied, with and without supplemental oxygen. These were compared to an alternate, low irradiance, epi-on protocol using riboflavin formulated with sodium iodide. Both negative (no CXL) and positive (epi-off modified Dresden protocol) controls were performed. Post-CXL elastic modulus was measured using extensiometry and anterior tangential curvature was measured using a Scheimpflug tomographer. Results: Protocols including supplemental oxygen resulted in an approximately 5-fold increase in stromal oxygen levels prior to CXL. During epi-on, high-irradiance UV-A delivery under hyperoxic conditions, an aerobic state was maintained. Conversely, under normoxic conditions, stromal oxygen rapidly depleted to 0-5% for all other protocols. The combination of supplemental oxygen, BAC formulation, and high-irradiance UV-A resulted in the largest biomechanical changes and most pronounced flattening effects of the three epi-on protocols. Conclusions: Ex vivo analysis of stromal oxygen levels, corneal stiffness, and acute anterior curvature change indicates that simultaneous optimization of the oxygen environment, riboflavin formulation, and UV-A protocol can significantly increase the effects of corneal collagen crosslinking. [ABSTRACT FROM AUTHOR]

Published
2020
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