Shiv Saidha1, Omar Al-Louzi1, John N Ratchford1, Pavan Bhargava1, Jiwon Oh1, Scott D Newsome1, Jerry L Prince2,3,4, Dzung Pham2,4,5, Snehashis Roy2,4,5, Peter van Zijl4, Laura J Balcer6, Elliot M Frohman7, Daniel S Reich1,4,8,9, Ciprian Crainiceanu8, Peter A Calabresi1. 1. Department of Neurology, Johns Hopkins University, Baltimore, MD. 2. Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD. 3. Department of Computer Science, Johns Hopkins University, Baltimore, MD. 4. Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD. 5. Center for Neuroscience and Regenerative Medicine, The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD. 6. Department of Neurology, New York University Langone Medical Center, New York, NY. 7. Department of Neurology and Ophthalmology, University of Texas Southwestern, Dallas, TX. 8. Department of Biostatistics, Johns Hopkins University, Baltimore, MD. 9. Translational Neuroradiology Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD.
Abstract
OBJECTIVE: The aim of this work was to determine whether atrophy of specific retinal layers and brain substructures are associated over time, in order to further validate the utility of optical coherence tomography (OCT) as an indicator of neuronal tissue damage in patients with multiple sclerosis (MS). METHODS: Cirrus high-definition OCT (including automated macular segmentation) was performed in 107 MS patients biannually (median follow-up: 46 months). Three-Tesla magnetic resonance imaging brain scans (including brain-substructure volumetrics) were performed annually. Individual-specific rates of change in retinal and brain measures (estimated with linear regression) were correlated, adjusting for age, sex, disease duration, and optic neuritis (ON) history. RESULTS: Rates of ganglion cell + inner plexiform layer (GCIP) and whole-brain (r = 0.45; p < 0.001), gray matter (GM; r = 0.37; p < 0.001), white matter (WM; r = 0.28; p = 0.007), and thalamic (r = 0.38; p < 0.001) atrophy were associated. GCIP and whole-brain (as well as GM and WM) atrophy rates were more strongly associated in progressive MS (r = 0.67; p < 0.001) than relapsing-remitting MS (RRMS; r = 0.33; p = 0.007). However, correlation between rates of GCIP and whole-brain (and additionally GM and WM) atrophy in RRMS increased incrementally with step-wise refinement to exclude ON effects; excluding eyes and then patients (to account for a phenotype effect), the correlation increased to 0.45 and 0.60, respectively, consistent with effect modification. In RRMS, lesion accumulation rate was associated with GCIP (r = -0.30; p = 0.02) and inner nuclear layer (r = -0.25; p = 0.04) atrophy rates. INTERPRETATION: Over time GCIP atrophy appears to mirror whole-brain, and particularly GM, atrophy, especially in progressive MS, thereby reflecting underlying disease progression. Our findings support OCT for clinical monitoring and as an outcome in investigative trials.
OBJECTIVE: The aim of this work was to determine whether atrophy of specific retinal layers and brain substructures are associated over time, in order to further validate the utility of optical coherence tomography (OCT) as an indicator of neuronal tissue damage in patients with multiple sclerosis (MS). METHODS: Cirrus high-definition OCT (including automated macular segmentation) was performed in 107 MS patients biannually (median follow-up: 46 months). Three-Tesla magnetic resonance imaging brain scans (including brain-substructure volumetrics) were performed annually. Individual-specific rates of change in retinal and brain measures (estimated with linear regression) were correlated, adjusting for age, sex, disease duration, and optic neuritis (ON) history. RESULTS: Rates of ganglion cell + inner plexiform layer (GCIP) and whole-brain (r = 0.45; p < 0.001), gray matter (GM; r = 0.37; p < 0.001), white matter (WM; r = 0.28; p = 0.007), and thalamic (r = 0.38; p < 0.001) atrophy were associated. GCIP and whole-brain (as well as GM and WM) atrophy rates were more strongly associated in progressive MS (r = 0.67; p < 0.001) than relapsing-remitting MS (RRMS; r = 0.33; p = 0.007). However, correlation between rates of GCIP and whole-brain (and additionally GM and WM) atrophy in RRMS increased incrementally with step-wise refinement to exclude ON effects; excluding eyes and then patients (to account for a phenotype effect), the correlation increased to 0.45 and 0.60, respectively, consistent with effect modification. In RRMS, lesion accumulation rate was associated with GCIP (r = -0.30; p = 0.02) and inner nuclear layer (r = -0.25; p = 0.04) atrophy rates. INTERPRETATION: Over time GCIP atrophy appears to mirror whole-brain, and particularly GM, atrophy, especially in progressive MS, thereby reflecting underlying disease progression. Our findings support OCT for clinical monitoring and as an outcome in investigative trials.
Authors: Iñigo Gabilondo; Elena H Martínez-Lapiscina; Eloy Martínez-Heras; Elena Fraga-Pumar; Sara Llufriu; Santiago Ortiz; Santiago Bullich; Maria Sepulveda; Carles Falcon; Joan Berenguer; Albert Saiz; Bernardo Sanchez-Dalmau; Pablo Villoslada Journal: Ann Neurol Date: 2014-01-02 Impact factor: 10.422
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Authors: J H van Waesberghe; W Kamphorst; C J De Groot; M A van Walderveen; J A Castelijns; R Ravid; G J Lycklama à Nijeholt; P van der Valk; C H Polman; A J Thompson; F Barkhof Journal: Ann Neurol Date: 1999-11 Impact factor: 10.422
Authors: Anna M Pietroboni; Tiziana Carandini; Laura Dell'Arti; Francesca Bovis; Annalisa Colombi; Milena A De Riz; Elena Casazza; Elisa Scola; Chiara Fenoglio; Andrea Arighi; Giorgio G Fumagalli; Fabio Triulzi; Daniela Galimberti; Francesco Viola; Elio Scarpini Journal: Neurol Sci Date: 2020-04-30 Impact factor: 3.307
Authors: Julia Button; Omar Al-Louzi; Andrew Lang; Pavan Bhargava; Scott D Newsome; Teresa Frohman; Laura J Balcer; Elliot M Frohman; Jerry Prince; Peter A Calabresi; Shiv Saidha Journal: Neurology Date: 2017-01-11 Impact factor: 9.910
Authors: Angeliki G Filippatou; Jeffrey Lambe; Elias S Sotirchos; Kathryn C Fitzgerald; Andrew Aston; Olwen C Murphy; Nicole Pellegrini; Nicholas Fioravante; Hunter Risher; Esther Ogbuokiri; Ohemaa Kwakyi; Brandon Toliver; Simidele Davis; Nicholas Luciano; Ciprian Crainiceanu; Jerry L Prince; Ellen M Mowry; Peter A Calabresi; Shiv Saidha Journal: Mult Scler Date: 2020-04-16 Impact factor: 6.312