Optical coherence tomography reflects brain atrophy in multiple sclerosis: A four-year study

Shiv Saidha, Omar Al-Louzi, John N. Ratchford, Pavan Bhargava, Jiwon Oh, Scott Newsome, Jerry Ladd Prince, Dzung Pham, Snehashis Roy, Peter C Van Zijl, Laura J. Balcer, Elliot M. Frohman, Daniel S. Reich, Ciprian M Crainiceanu, Peter Calabresi

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)801-813
Number of pages13
JournalAnnals of Neurology
Volume78
Issue number5
DOIs
StatePublished - Nov 1 2015

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Optical Coherence Tomography
Multiple Sclerosis
Atrophy
Ganglia
Brain
Optic Neuritis
Relapsing-Remitting Multiple Sclerosis
Disease Progression
Linear Models
Magnetic Resonance Imaging
Phenotype

ASJC Scopus subject areas

  • Neurology
  • Clinical Neurology

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Optical coherence tomography reflects brain atrophy in multiple sclerosis : A four-year study. / Saidha, Shiv; Al-Louzi, Omar; Ratchford, John N.; Bhargava, Pavan; Oh, Jiwon; Newsome, Scott; Prince, Jerry Ladd; Pham, Dzung; Roy, Snehashis; Van Zijl, Peter C; Balcer, Laura J.; Frohman, Elliot M.; Reich, Daniel S.; Crainiceanu, Ciprian M; Calabresi, Peter.

In: Annals of Neurology, Vol. 78, No. 5, 01.11.2015, p. 801-813.

Research output: Contribution to journalArticle

Saidha, Shiv ; Al-Louzi, Omar ; Ratchford, John N. ; Bhargava, Pavan ; Oh, Jiwon ; Newsome, Scott ; Prince, Jerry Ladd ; Pham, Dzung ; Roy, Snehashis ; Van Zijl, Peter C ; Balcer, Laura J. ; Frohman, Elliot M. ; Reich, Daniel S. ; Crainiceanu, Ciprian M ; Calabresi, Peter. / Optical coherence tomography reflects brain atrophy in multiple sclerosis : A four-year study. In: Annals of Neurology. 2015 ; Vol. 78, No. 5. pp. 801-813.
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AU - Al-Louzi, Omar

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AU - Bhargava, Pavan

AU - Oh, Jiwon

AU - Newsome, Scott

AU - Prince, Jerry Ladd

AU - Pham, Dzung

AU - Roy, Snehashis

AU - Van Zijl, Peter C

AU - Balcer, Laura J.

AU - Frohman, Elliot M.

AU - Reich, Daniel S.

AU - Crainiceanu, Ciprian M

AU - Calabresi, Peter

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N2 - 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.

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