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54. Sensory loss—vision

Author

Foster, Paul J, additional, Khawaja, Anthony, additional, Balk, Lisanne J, additional, Muthy, Zaynah, additional, and Petzold, Axel, additional

Published
2020
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57. Exploring Vitreous Haze as a Potential Biomarker for Accelerated Glymphatic Outflow and Neurodegeneration in Multiple Sclerosis: A Cross-Sectional Study.

Author

Kaçar, Sezgi, Coric, Danko, Ometto, Giovanni, Montesano, Giovanni, Denniston, Alastair K., Keane, Pearse A., Uitdehaag, Bernard M. J., Crabb, David P., Schoonheim, Menno M., Petzold, Axel, and Strijbis, Eva M. M.

Subjects
MULTIPLE sclerosis, OPTICAL coherence tomography, NEURODEGENERATION, GENERALIZED estimating equations, HAZE, OPTIC neuritis
Abstract

Background: The glymphatic system removes neurodegenerative debris. The ocular glymphatic outflow is from the eye to the proximal optic nerve. In multiple sclerosis (MS), atrophy of the optic nerve increases the glymphatic outflow space. Here, we tested whether vitreous haze (VH) can provide novel insights into the relationship between neurodegeneration and the ocular glymphatic system in MS. Methods: This cross-sectional study comprised 315 persons with MS and 87 healthy controls (HCs). VH was quantified from optical coherence tomography (OCT) volume scans. Neurodegeneration was determined on three-dimensional T1 (3DT1) MRI, lesion detection on fluid-attenuated inversion (FLAIR), and layer thickness on OCT. Generalized estimating equations, corrected for age, were used to analyze associations between VH and metrics for neurodegeneration, demographics, and clinical scales. Group differences were determined between mild, moderate, and severe disability. Results: On the group level, VH scores were comparable between MS and control (p = 0.629). In MS, VH scores declined with disease duration (β = −0.009, p = 0.004) and age (β = −0.007, p = 0.001). There was no relation between VH scores and higher age in HCs. In MS patients, VH was related to normalized gray (NGMV, β = 0.001, p = 0.011) and white matter volume (NWMV, β = 0.001, p = 0.003), macular ganglion cell–inner plexiform layer thickness (mGCIPL, β = 0.006, p < 0.001), and peripapillary retinal nerve fiber layer thickness (pRNFL, β = 0.004, p = 0.008). VH was significantly lower in severe compared to mild disability (mean difference −28.86%, p = 0.058). Conclusions: There is a correlation between VH on OCT and disease duration, more severe disability and lower brain volumes in MS. Biologically, these relationships suggest accelerated glymphatic clearance with disease-related atrophy. [ABSTRACT FROM AUTHOR]

Published
2024
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58. Peripheral Neuropathy in Virologically Suppressed People Living with HIV: Evidence from the PIVOT Trial.

Author

Schuldt, Anna L., Bern, Henry, Hart, Melanie, Gompels, Mark, Winston, Alan, Clarke, Amanda, Chen, Fabian, Stöhr, Wolfgang, Heslegrave, Amanda, Paton, Nicholas I., Petzold, Axel, and Arenas-Pinto, Alejandro

Subjects
PERIPHERAL neuropathy, HIV-positive persons, CD4 lymphocyte count, HIV infections, BLOOD sugar
Abstract

The aim of this study is to identify the factors associated with peripheral neuropathy and to explore neurofilament light chain (NfL) as a biomarker for peripheral neuropathy (PN) in effectively virologically suppressed adults living with HIV. All protease inhibitor monotherapy versus ongoing triple therapy in the long-term management of HIV infection (PIVOT) trial participants with data on PN at baseline were included in the study. NfL plasma levels (pNfL) were measured in a sub-set of participants. Multivariable logistic regression was used to examine the associations of PN with potential risk factors (including age, sex, nadir CD4 cell count, history of dideoxynucleoside (d-drugs) exposure, and blood glucose levels) and NfL levels. Of the 585 participants included, 131 (22.4%) reported PN during the study period (median of 44 months). The participants were predominantly male (76.6%), White (68.2%), and virologically suppressed for a median period of 37 months (range of 20–63) before recruitment. The age at baseline was 44.3 years (standard deviation (SD) of 9.2). PN was independently associated with age (adjusted odds ratio (aOR) = 1.35, 95% CI of 1.20–1.52; additional 5 years), history of d-drugs (aOR 1.88, 95% CI of 1.12–3.16), height (aOR 1.19, 95% CI of 1.05–1.35; additional 5 cm), nadir CD4 cell count (aOR 1.10 CI of 1.00–1.20; 50 cells fewer), and metabolic syndrome (aOR 2.31, 95% CI of 1.27 4.20), but not pNfL. The excess risk for PN associated with d-drug use remains after the exposure has stopped for years, suggesting non-reversible toxicity. In people with HIV, metabolic syndrome is independently associated with PN. There was no additional value for pNfL as a screening test for peripheral neuropathy in effectively virologically suppressed adults living with HIV. [ABSTRACT FROM AUTHOR]

Published
2024
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59. Peripherin is a biomarker of axonal damage in peripheral nervous system disease.

Author

Keddie, Stephen, Smyth, Duncan, Keh, Ryan Y S, Chou, Michael K L, Grant, Donna, Surana, Sunaina, Heslegrave, Amanda, Zetterberg, Henrik, Wieske, Luuk, Michael, Milou, Eftimov, Filip, Bellanti, Roberto, Rinaldi, Simon, Hart, Melanie S, Petzold, Axel, and Lunn, Michael P

Subjects
PERIPHERAL neuropathy, MOTOR neurons, CHRONIC inflammatory demyelinating polyradiculoneuropathy, PERIPHERAL nervous system, INTERMEDIATE filament proteins, POLYNEUROPATHIES
Abstract

Valid, responsive blood biomarkers specific to peripheral nerve damage would improve management of peripheral nervous system (PNS) diseases. Neurofilament light chain (NfL) is sensitive for detecting axonal pathology but is not specific to PNS damage, as it is expressed throughout the PNS and CNS. Peripherin, another intermediate filament protein, is almost exclusively expressed in peripheral nerve axons. We postulated that peripherin would be a promising blood biomarker of PNS axonal damage. We demonstrated that peripherin is distributed in sciatic nerve, and to a lesser extent spinal cord tissue lysates, but not in brain or extra-neural tissues. In the spinal cord, anti-peripherin antibody bound only to the primary cells of the periphery (anterior horn cells, motor axons and primary afferent sensory axons). In vitro models of antibody-mediated axonal and demyelinating nerve injury showed marked elevation of peripherin levels only in axonal damage and only a minimal rise in demyelination. We developed an immunoassay using single molecule array technology for the detection of serum peripherin as a biomarker for PNS axonal damage. We examined longitudinal serum peripherin and NfL concentrations in individuals with Guillain-Barré syndrome (GBS, n = 45, 179 time points), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP, n = 35, 70 time points), multiple sclerosis (n = 30), dementia (as non-inflammatory CNS controls, n = 30) and healthy individuals (n = 24). Peak peripherin levels were higher in GBS than all other groups (median 18.75 pg/ml versus < 6.98 pg/ml, P < 0.0001). Peak NfL was highest in GBS (median 220.8 pg/ml) and lowest in healthy controls (median 5.6 pg/ml), but NfL did not distinguish between CIDP (17.3 pg/ml), multiple sclerosis (21.5 pg/ml) and dementia (29.9 pg/ml). While peak NfL levels were higher with older age (rho = +0.39, P < 0.0001), peak peripherin levels did not vary with age. In GBS, local regression analysis of serial peripherin in the majority of individuals with three or more time points of data (16/25) displayed a rise-and-fall pattern with the highest value within the first week of initial assessment. Similar analysis of serial NfL concentrations showed a later peak at 16 days. Group analysis of serum peripherin and NfL levels in GBS and CIDP patients were not significantly associated with clinical data, but in some individuals with GBS, peripherin levels appeared to better reflect clinical outcome measure improvement. Serum peripherin is a promising new, dynamic and specific biomarker of acute PNS axonal damage. [ABSTRACT FROM AUTHOR]

Published
2023
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64. Application of diagnostic criteria for optic neuritis – Authors' reply

Author

Petzold, Axel, primary, Liu, Yaou, additional, Fraser, Clare, additional, Abegg, Mathias, additional, Alroughani, Raed, additional, Alshowaeir, Daniah, additional, Alvarenga, Regina, additional, Andris, Cécile, additional, Asgari, Nasrin, additional, Barnett, Yael, additional, Battistella, Roberto, additional, Behbehani, Raed, additional, Berger, Thomas, additional, Bikbov, Mukharram M., additional, Biotti, Damien, additional, Biousse, Valerie, additional, Boschi, Antonella, additional, Brazdil, Milan, additional, Brezhnev, Andrei, additional, Calabresi, Peter, additional, Cordonnier, Monique, additional, Costello, Fiona, additional, Cruz, Franz Marie, additional, Cunha, Leonardo Provetti, additional, Daoudi, Smail, additional, Deschamps, Romain, additional, DeSeze, Jerome, additional, Diem, Ricarda, additional, Etemadifar, Masoud, additional, Flores-Rivera, Jose, additional, Fonseca, Pedro, additional, Frederiksen, Jette, additional, Frohman, Elliot, additional, Frohman, Teresa, additional, FromentTilikete, Caroline, additional, Fujihara, Kazuo, additional, Gálvez, Alberto, additional, Gouider, Riadh, additional, Gracia, Fernando, additional, Grigoriadis, Nikolaos, additional, Guajardo, José Manuel, additional, Habek, Mario, additional, Hawlina, Marko, additional, Hernández-Martínez de Lapiscina, Elena, additional, Hooker, Juzar, additional, Hor, Jyh Yung, additional, Howlett, William, additional, Huang-Link, Yumin, additional, Idrissova, Zhannat, additional, Illes, Zsolt, additional, Jancic, Jasna, additional, Jindahra, Panitha, additional, Karussis, Dimitrios, additional, Kerty, Emilia, additional, Kim, Ho Jin, additional, Lagrèze, Wolf, additional, Leocani, Letizia, additional, Levin, Netta, additional, Liskova, Petra, additional, Maiga, Youssoufa, additional, Marignier, Romain, additional, McGuigan, Chris, additional, Meira, Dália, additional, Merle, Harold, additional, Monteiro, Mário L.R., additional, Moodley, Anand, additional, Moura, Frederico, additional, Muñoz, Silvia, additional, Mustafa, Sharik, additional, Nakashima, Ichiro, additional, Noval, Susana, additional, Oehninger, Carlos, additional, Ogun, Olufunmilola, additional, Omoti, Afekhide, additional, Pandit, Lekha, additional, Paul, Friedemann, additional, Rebolleda, Gema, additional, Reddel, Stephen, additional, Rejdak, Konrad, additional, Rejdak, Robert, additional, Rodriguez-Morales, Alfonso, additional, Rougier, Marie-Bénédicte, additional, Sa, Maria Jose, additional, Sanchez-Dalmau, Bernardo, additional, Saylor, Deanna, additional, Shatriah, Ismail, additional, Siva, Aksel, additional, Stiebel-Kalish, Hadas, additional, Szatmary, Gabriella, additional, Ta, Linh, additional, Tenembaum, Sylvia, additional, Tran, Huy, additional, Trufanov, Yevgen, additional, VanPesch, Vincent, additional, Wang, An-Guor, additional, Wattjes, Mike P., additional, Willoughby, Ernie, additional, Zakaria, Magd, additional, Zvornicanin, Jasmin, additional, Balcer, Laura, additional, and Plant, Gordon T., additional

Published
2023
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66. Identification and treatment of the visual processing asymmetry in MS patients with optic neuritis: The Pulfrich phenomenon

Author

Sobhanian, Millad J., Agarwal, Rohit, Meltzer, Ethan, Kildebeck, Eric, Frohman, Benjamin S., Frohman, Ashley N., Galetta, Steven L., Saidha, Shiv, White, Owen, Villoslada, Pablo, Paul, Friedemann, Petzold, Axel, Rennaker, Robert L., Martinez-Lapiscina, Elena H., Balcer, Laura J., Kardon, Randy, Frohman, Elliot M., and Frohman, Teresa C.

Published
2018
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69. Cohort profile:rationale and methods of UK Biobank repeat imaging study eye measures to study dementia

Author

Foster, Paul J., Atan, Denize, Khawaja, Anthony, Lotery, Andrew, MacGillivray, Tom, Owen, Christopher G., Patel, Praveen J., Petzold, Axel, Rudnicka, Alicja, Sun, Zihan, Sheard, Simon, and Allen, Naomi

Abstract

PURPOSE: The retina provides biomarkers of neuronal and vascular health that offer promising insights into cognitive ageing, mild cognitive impairment and dementia. This article described the rationale and methodology of eye and vision assessments with the aim of supporting the study of dementia in the UK Biobank Repeat Imaging study. PARTICIPANTS: UK Biobank is a large-scale, multicentre, prospective cohort containing in-depth genetic, lifestyle, environmental and health information from half a million participants aged 40-69 enrolled in 2006-2010 across the UK. A subset (up to 60 000 participants) of the cohort will be invited to the UK Biobank Repeat Imaging Study to collect repeated brain, cardiac and abdominal MRI scans, whole-body dual-energy X-ray absorptiometry, carotid ultrasound, as well as retinal optical coherence tomography (OCT) and colour fundus photographs. FINDINGS TO DATE: UK Biobank has helped make significant advances in understanding risk factors for many common diseases, including for dementia and cognitive decline. Ophthalmic genetic and epidemiology studies have also benefited from the unparalleled combination of very large numbers of participants, deep phenotyping and longitudinal follow-up of the cohort, with comprehensive health data linkage to disease outcomes. In addition, we have used UK Biobank data to describe the relationship between retinal structures, cognitive function and brain MRI-derived phenotypes. FUTURE PLANS: The collection of eye-related data (eg, OCT), as part of the UK Biobank Repeat Imaging study, will take place in 2022-2028. The depth and breadth and longitudinal nature of this dataset, coupled with its open-access policy, will create a major new resource for dementia diagnostic discovery and to better understand its association with comorbid diseases. In addition, the broad and diverse data available in this study will support research into ophthalmic diseases and various other health outcomes beyond dementia.

Published
2023

71. Neurofilaments as biomarkers in neurological disorders

Author

Khalil, Michael, Teunissen, Charlotte E., Otto, Markus, Piehl, Fredrik, Sormani, Maria Pia, Gattringer, Thomas, Barro, Christian, Kappos, Ludwig, Comabella, Manuel, Fazekas, Franz, Petzold, Axel, Blennow, Kaj, Zetterberg, Henrik, and Kuhle, Jens

Published
2018
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73. 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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74. Association Between Retinal Features From Multimodal Imaging and Schizophrenia

Author

Wagner, Siegfried K., primary, Cortina-Borja, Mario, additional, Silverstein, Steven M., additional, Zhou, Yukun, additional, Romero-Bascones, David, additional, Struyven, Robbert R., additional, Trucco, Emanuele, additional, Mookiah, Muthu R. K., additional, MacGillivray, Tom, additional, Hogg, Stephen, additional, Liu, Timing, additional, Williamson, Dominic J., additional, Pontikos, Nikolas, additional, Patel, Praveen J., additional, Balaskas, Konstantinos, additional, Alexander, Daniel C., additional, Stuart, Kelsey V., additional, Khawaja, Anthony P., additional, Denniston, Alastair K., additional, Rahi, Jugnoo S., additional, Petzold, Axel, additional, and Keane, Pearse A., additional

Published
2023
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80. 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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84. novel eye-movement impairment in multiple sclerosis indicating widespread cortical damage.

Author

Bijvank, Jenny A Nij, Hof, Sam N, Prouskas, Stefanos E, Schoonheim, Menno M, Uitdehaag, Bernard M J, Rijn, Laurentius J van, and Petzold, Axel

Subjects
MULTIPLE sclerosis, SACCADIC eye movements, VISUAL evoked potentials, VISION, OPTIC neuritis, NEUROPROSTHESES
Abstract

In multiple sclerosis, remyelination trials have yet to deliver success like that achieved for relapse rates with disease course modifying treatment trials. The challenge is to have a clinical, functional outcome measure. Currently, there are none that have been validated, other than visual evoked potentials in optic neuritis. Like vision, quick eye movements (saccades) are heavily dependent on myelination. We proposed that it is possible to extrapolate from demyelination of the medial longitudinal fasciculus in the brainstem to quantitative assessment of cortical networks governing saccadic eye movements in multiple sclerosis. We have developed and validated a double-step saccadic test, which consists of a pair of eye movements towards two stimuli presented in quick succession (the demonstrate eye movement networks with saccades protocol). In this single-centre, cross-sectional cohort study we interrogated the structural and functional relationships of double-step saccades in multiple sclerosis. Data were collected for double-step saccades, cognitive function (extended Rao's Brief Repeatable Battery), disability (Expanded Disability Status Scale) and visual functioning in daily life (National Eye Institute Visual Function Questionnaire). MRI was used to quantify grey matter atrophy and multiple sclerosis lesion load. Multivariable linear regression models were used for analysis of the relationships between double-step saccades and clinical and MRI metrics. We included 209 individuals with multiple sclerosis (mean age 54.3 ± 10.5 years, 58% female, 63% relapsing-remitting multiple sclerosis) and 60 healthy control subjects (mean age 52.1 ± 9.2 years, 53% female). The proportion of correct double-step saccades was significantly reduced in multiple sclerosis (mean 0.29 ± 0.22) compared to controls (0.45 ± 0.22, P < 0.001). Consistent with this, there was a significantly larger double-step dysmetric saccadic error in multiple sclerosis (mean vertical error −1.18 ± 1.20°) compared to controls (−0.54 ± 0.86°, P < 0.001). Impaired double-step saccadic metrics were consistently associated with more severe global and local grey matter atrophy (correct responses—cortical grey matter: β = 0.42, P < 0.001), lesion load (vertical error: β = −0.28, P < 0.001), progressive phenotypes, more severe physical and cognitive impairment (correct responses—information processing: β = 0.46, P < 0.001) and visual functioning. In conclusion, double-step saccades represent a robust metric that revealed a novel eye-movement impairment in individuals with multiple sclerosis. Double-step saccades outperformed other saccadic tasks in their statistical relationship with clinical, cognitive and visual functioning, as well as global and local grey matter atrophy. Double-step saccades should be evaluated longitudinally and tested as a potential novel outcome measure for remyelination trials in multiple sclerosis. [ABSTRACT FROM AUTHOR]

Published
2023
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91. The Role of Optical Coherence Tomography Criteria and Machine Learning in Multiple Sclerosis and Optic Neuritis Diagnosis

Author

Kenney, Rachel C., primary, Liu, Mengling, additional, Hasanaj, Lisena, additional, Joseph, Binu, additional, Abu Al-Hassan, Abdullah, additional, Balk, Lisanne J., additional, Behbehani, Raed, additional, Brandt, Alexander, additional, Calabresi, Peter A., additional, Frohman, Elliot, additional, Frohman, Teresa C., additional, Havla, Joachim, additional, Hemmer, Bernhard, additional, Jiang, Hong, additional, Knier, Benjamin, additional, Korn, Thomas, additional, Leocani, Letizia, additional, Martinez-Lapiscina, Elena Hernandez, additional, Papadopoulou, Athina, additional, Paul, Friedemann, additional, Petzold, Axel, additional, Pisa, Marco, additional, Villoslada, Pablo, additional, Zimmermann, Hanna, additional, Thorpe, Lorna E., additional, Ishikawa, Hiroshi, additional, Schuman, Joel S., additional, Wollstein, Gadi, additional, Chen, Yu, additional, Saidha, Shiv, additional, Galetta, Steven, additional, and Balcer, Laura J., additional

Published
2022
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93. 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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98. N

Author

Cohen, Daniel A., Hornung, David E., Mays, Lawrence, Douglas, Rodney, Kennedy, Henry, Knoblauch, Kenneth, Martin, Kevan, Abramov, Valery V., Gontova, Irina A., Abramova, Tatjana Ya., Kozlov, Vladimir A., Kusnecov, Alexander, Benchenane, Karim, Zugaro, Michaël, Wiener, Sidney, Witt, Martin, Moschovakis, Adonis, Braun, Anna Katharina, Kuratani, Shigeru, Murakami, Fujio, Starkweather, Angela, Dalezios, Yannis, Aihara, Kazuyuki, Okada, Masato, Adachi, Masaharu, Watanabe, Masataka, Rokni, Uri, Smith, Peter G., Richter, Diethelm W., Müller, Michael, Griffiths, M., Neal, J. W, Gasque, P., Bernhardi, Rommy von, Guillemin, Gilles J., Buijs, Ruud M., Kalsbeek, Andries, Darlington, Cynthia L., Swaab, Dick F., Lucassen, Paul J., Huitinga, Inge, Bao, Ai-Min, Ladwig, Bernd, Ohl, Frank W., Schnitzler, Hans-Ulrich, Denzinger, Annette, Takahashi, Terry, Warzecha, Anne-Kathrin, Kern, Roland, Oishi, Koji, Nakajima, Kazunori, Bernardino, Liliana, Agasse, Fabienne, Malva, João O., Bird, Thomas D., Alonso, Mariana, Dubayle, David, Menetrey, D., Haddad, John J., Lobell, Anna, Stahel, Philip F., Felderhoff-Mueser, Ursula, Barnum, Scott R., Jafarian-Tehrani, Mehrnaz, Mizuno, Tetsuya, Dietrich, W. Dalton, Keane, Robert W., Han, Jung-Soo, Dhaini, Hassan R., Spain, William J., Mandairon, Nathalie, Didier, Anne, Rich, Mark M., Kudo, Yoshihisa, Ruangkittisakul, Araya, Ballanyi, Klaus, Syed, Naweed I., Petzold, Axel, Rumbaugh, Jeffrey A., Nath, Avindra, Aldskogius, Håkan, Delgado-García, José M., Kengaku, Mineko, Kim, Joanne SM, Zhen, Mei, Mathie, Alistair, Veale, Emma L., Stengel, Maike, Baron, Ralf, Samson, Willis K., Chee, Melissa J. S., Colmers, William F., Smith, Paul F., Pauen, Michael, Elliott, Stacy L., Northoff, Georg, Jorna, René J., Inoue, Kazuhide, Kawabe, Hiroshi, Varoqueaux, Frederique, Brose, Nils, Tanaka, Kohichi, Whelan, Patrick J., Petralia, Ronald S., Wenthold, Robert J., Ramer, Matt S., McPhail, Lowell T., Mullaney, Ian, Widera, Darius, Kaltschmidt, Christian, Kaltschmidt, Barbara, Pennypacker, Keith R., Pollock, Glen, Saporta, Samuel, Koerber, H. Richard, Handwerker, Herrmann O., Smale, Laura, Nunez, Antonio A., Shimkin, Nahum, Tse, Frederick W., Wang, Nan, Yan, Lei, Tse, Amy, Covey, Ellen, Travagli, R. Alberto, Binder, Marc D., editor, Hirokawa, Nobutaka, editor, and Windhorst, Uwe, editor

Published
2009
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99. Automated detection of hyperreflective foci in the outer nuclear layer of the retina.

Author

Schmidt, Mathias Falck, Christensen, Jakob Lønborg, Dahl, Vedrana Andersen, Toosy, Ahmed, Petzold, Axel, Hanson, James V. M., Schippling, Sven, Frederiksen, Jette Lautrup, and Larsen, Michael

Subjects
RETINA, CONVOLUTIONAL neural networks, OPTICAL coherence tomography, IMAGE analysis, DIABETIC retinopathy
Abstract

Purpose: Hyperreflective foci are poorly understood transient elements seen on optical coherence tomography (OCT) of the retina in both healthy and diseased eyes. Systematic studies may benefit from the development of automated tools that can map and track such foci. The outer nuclear layer (ONL) of the retina is an attractive layer in which to study hyperreflective foci as it has no fixed hyperreflective elements in healthy eyes. In this study, we intended to evaluate whether automated image analysis can identify, quantify and visualize hyperreflective foci in the ONL of the retina. Methods: This longitudinal exploratory study investigated 14 eyes of seven patients including six patients with optic neuropathy and one with mild non‐proliferative diabetic retinopathy. In total, 2596 OCT B‐scan were obtained. An image analysis blob detector algorithm was used to detect candidate foci, and a convolutional neural network (CNN) trained on a manually labelled subset of data was then used to select those candidate foci in the ONL that fitted the characteristics of the reference foci best. Results: In the manually labelled data set, the blob detector found 2548 candidate foci, correctly detecting 350 (89%) out of 391 manually labelled reference foci. The accuracy of CNN classifier was assessed by manually splitting the 2548 candidate foci into a training and validation set. On the validation set, the classifier obtained an accuracy of 96.3%, a sensitivity of 88.4% and a specificity of 97.5% (AUC 0.989). Conclusion: This study demonstrated that automated image analysis and machine learning methods can be used to successfully identify, quantify and visualize hyperreflective foci in the ONL of the retina on OCT scans. [ABSTRACT FROM AUTHOR]

Published
2023
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100. Clinical review of retinotopy.

Author

Nij Bijvank, Jenny, de Buy Wenniger, Lucas Maillette, de Graaf, Pim, and Petzold, Axel

Abstract

Two observations made 29 years apart are the cornerstones of this review on the contributions of Dr Gordon T. Plant to understanding pathology affecting the optic nerve. The first observation laid the anatomical basis in 1990 for the interpretation of optical coherence tomography (OCT) findings in 2009. Retinal OCT offers clinicians detailed in vivo structural imaging of individual retinal layers. This has led to novel observations which were impossible to make using ophthalmoscopy. The technique also helps to re-introduce the anatomically grounded concept of retinotopy to clinical practise. This review employs illustrations of the anatomical basis for retinotopy through detailed translational histological studies and multimodal brain-eye imaging studies. The paths of the prelaminar and postlaminar axons forming the optic nerve and their postsynaptic path from the dorsal lateral geniculate nucleus to the primary visual cortex in humans are described. With the mapped neuroanatomy in mind we use OCT-MRI pairings to discuss the patterns of neurodegeneration in eye and brain that are a consequence of the hard wired retinotopy: anterograde and retrograde axonal degeneration which can, within the visual system, propagate trans-synaptically. The technical advances of OCT and MRI for the first time enable us to trace axonal degeneration through the entire visual system at spectacular resolution. In conclusion, the neuroanatomical insights provided by the combination of OCT and MRI allows us to separate incidental findings from sinister pathology and provides new opportunities to tailor and monitor novel neuroprotective strategies. [ABSTRACT FROM AUTHOR]

Published
2023
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