Retinal layer segmentation in multiple sclerosis: a systematic review and meta-analysis
Axel Petzold, Laura J Balcer, Peter A Calabresi, Fiona Costello, Teresa C Frohman, Elliot M Frohman, Elena H Martinez-Lapiscina, Ari J Green, Randy Kardon, Olivier Outteryck, Friedemann Paul, Sven Schippling, Patrik Vermersch, Pablo Villoslada, Lisanne J Balk, ERN-EYE IMSVISUAL, Orhan Aktas, Philipp Albrecht, Jane Ashworth, Nasrin Asgari, Laura Balcer, Lisanne Balk, Graeme Black, Daniel Boehringer, Raed Behbehani, Leslie Benson, Robert Bermel, Jacqueline Bernard, Alexander Brandt, Jodie Burton, Peter Calabresi, Jonathan Calkwood, Christian Cordano, Fiona Costello, Ardith Courtney, Andrés Cruz-Herranz, Ricarda Diem, Avril Daly, Helene Dollfus, Christina Fasser, Carsten Finke, Jette Frederiksen, Elliot Frohman, Teresa Frohman, Elenaw Garcia-Martin, Inés González Suárez, Gorm Pihl-Jensen, Jennifer Graves, Ari Green, Joachim Havla, Bernhard Hemmer, Su-Chun Huang, Jaime Imitola, Hong Jiang, David Keegan, Eric Kildebeck, Alexander Klistorner, Benjamin Knier, Scott Kolbe, Thomas Korn, Bart LeRoy, Letizia Leocani, Dorothee Leroux, Netta Levin, Petra Liskova, Birgit Lorenz, Jana Lizrova Preiningerova, Elena Hernández Martínez-Lapiscina, Janine Mikolajczak, Xavier Montalban, Mark Morrow, Rachel Nolan, Timm Oberwahrenbrock, Frederike Cosima Oertel, Celia Oreja-Guevara, Benjamin Osborne, Olivier Outteryck, Athina Papadopoulou, Friedemann Paul, Axel Petzold, Marius Ringelstein, Shiv Saidha, Bernardo Sanchez-Dalmau, Jaume Sastre-Garriga, Sven Schippling, Robert Shin, Neil Shuey, Kerstin Soelberg, Ahmed Toosy, Rubén Torres, Angela Vidal-Jordana, Pablo Villoslada, Amy Waldman, Owen White, Ann Yeh, Sui Wong, Hanna Zimmermann, Axel Petzold, Laura J Balcer, Peter A Calabresi, Fiona Costello, Teresa C Frohman, Elliot M Frohman, Elena H Martinez-Lapiscina, Ari J Green, Randy Kardon, Olivier Outteryck, Friedemann Paul, Sven Schippling, Patrik Vermersch, Pablo Villoslada, Lisanne J Balk, ERN-EYE IMSVISUAL, Orhan Aktas, Philipp Albrecht, Jane Ashworth, Nasrin Asgari, Laura Balcer, Lisanne Balk, Graeme Black, Daniel Boehringer, Raed Behbehani, Leslie Benson, Robert Bermel, Jacqueline Bernard, Alexander Brandt, Jodie Burton, Peter Calabresi, Jonathan Calkwood, Christian Cordano, Fiona Costello, Ardith Courtney, Andrés Cruz-Herranz, Ricarda Diem, Avril Daly, Helene Dollfus, Christina Fasser, Carsten Finke, Jette Frederiksen, Elliot Frohman, Teresa Frohman, Elenaw Garcia-Martin, Inés González Suárez, Gorm Pihl-Jensen, Jennifer Graves, Ari Green, Joachim Havla, Bernhard Hemmer, Su-Chun Huang, Jaime Imitola, Hong Jiang, David Keegan, Eric Kildebeck, Alexander Klistorner, Benjamin Knier, Scott Kolbe, Thomas Korn, Bart LeRoy, Letizia Leocani, Dorothee Leroux, Netta Levin, Petra Liskova, Birgit Lorenz, Jana Lizrova Preiningerova, Elena Hernández Martínez-Lapiscina, Janine Mikolajczak, Xavier Montalban, Mark Morrow, Rachel Nolan, Timm Oberwahrenbrock, Frederike Cosima Oertel, Celia Oreja-Guevara, Benjamin Osborne, Olivier Outteryck, Athina Papadopoulou, Friedemann Paul, Axel Petzold, Marius Ringelstein, Shiv Saidha, Bernardo Sanchez-Dalmau, Jaume Sastre-Garriga, Sven Schippling, Robert Shin, Neil Shuey, Kerstin Soelberg, Ahmed Toosy, Rubén Torres, Angela Vidal-Jordana, Pablo Villoslada, Amy Waldman, Owen White, Ann Yeh, Sui Wong, Hanna Zimmermann
Abstract
Background: Structural retinal imaging biomarkers are important for early recognition and monitoring of inflammation and neurodegeneration in multiple sclerosis. With the introduction of spectral domain optical coherence tomography (SD-OCT), supervised automated segmentation of individual retinal layers is possible. We aimed to investigate which retinal layers show atrophy associated with neurodegeneration in multiple sclerosis when measured with SD-OCT.
Methods: In this systematic review and meta-analysis, we searched for studies in which SD-OCT was used to look at the retina in people with multiple sclerosis with or without optic neuritis in PubMed, Web of Science, and Google Scholar between Nov 22, 1991, and April 19, 2016. Data were taken from cross-sectional cohorts and from one timepoint from longitudinal studies (at least 3 months after onset in studies of optic neuritis). We classified data on eyes into healthy controls, multiple-sclerosis-associated optic neuritis (MSON), and multiple sclerosis without optic neuritis (MSNON). We assessed thickness of the retinal layers and we rated individual layer segmentation performance by random effects meta-analysis for MSON eyes versus control eyes, MSNON eyes versus control eyes, and MSNON eyes versus MSON eyes. We excluded relevant sources of bias by funnel plots.
Findings: Of 25 497 records identified, 110 articles were eligible and 40 reported data (in total 5776 eyes from patients with multiple sclerosis [1667 MSON eyes and 4109 MSNON eyes] and 1697 eyes from healthy controls) that met published OCT quality control criteria and were suitable for meta-analysis. Compared with control eyes, the peripapillary retinal nerve fibre layer (RNFL) showed thinning in MSON eyes (mean difference -20·10 μm, 95% CI -22·76 to -17·44; p<0·0001) and in MSNON eyes (-7·41 μm, -8·98 to -5·83; p<0·0001). The macula showed RNFL thinning of -6·18 μm (-8·07 to -4·28; p<0·0001) in MSON eyes and -2·15 μm (-3·15 to -1·15; p<0·0001) in MSNON eyes compared with control eyes. Atrophy of the macular ganglion cell layer and inner plexiform layer (GCIPL) was -16·42 μm (-19·23 to -13·60; p<0·0001) for MSON eyes and -6·31 μm (-7·75 to -4·87; p<0·0001) for MSNON eyes compared with control eyes. A small degree of inner nuclear layer (INL) thickening occurred in MSON eyes compared with control eyes (0·77 μm, 0·25 to 1·28; p=0·003). We found no statistical difference in the thickness of the combined outer nuclear layer and outer plexiform layer when we compared MSNON or MSON eyes with control eyes, but we found a small degree of thickening of the combined layer when we compared MSON eyes with MSNON eyes (1·21 μm, 0·24 to 2·19; p=0·01).
Interpretation: The largest and most robust differences between the eyes of people with multiple sclerosis and control eyes were found in the peripapillary RNFL and macular GCIPL. Inflammatory disease activity might be captured by the INL. Because of the consistency, robustness, and large effect size, we recommend inclusion of the peripapillary RNFL and macular GCIPL for diagnosis, monitoring, and research.
Funding: None.
Copyright © 2017 Elsevier Ltd. All rights reserved.
Source: PubMed