title: Optical coherence tomography reflects brain atrophy in multiple sclerosis: A four-year study.
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.
  
  
  CONCLUSIONS
  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.affiliation: Department of Neurology, Johns Hopkins University, Baltimore, MD.
authors.forename: Shiv
authors.initials: S
authors.lastname: Saidha
authors.affiliation: Department of Neurology, Johns Hopkins University, Baltimore, MD.
authors.forename: Omar
authors.initials: O
authors.lastname: Al-Louzi
authors.affiliation: Department of Neurology, Johns Hopkins University, Baltimore, MD.
authors.forename: John N
authors.initials: JN
authors.lastname: Ratchford
authors.affiliation: Department of Neurology, Johns Hopkins University, Baltimore, MD.
authors.forename: Pavan
authors.initials: P
authors.lastname: Bhargava
authors.affiliation: Department of Neurology, Johns Hopkins University, Baltimore, MD.
authors.forename: Jiwon
authors.initials: J
authors.lastname: Oh
authors.affiliation: Department of Neurology, Johns Hopkins University, Baltimore, MD.
authors.forename: Scott D
authors.initials: SD
authors.lastname: Newsome
authors.affiliation: Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD.|Department of Computer Science, Johns Hopkins University, Baltimore, MD.|Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD.
authors.forename: Jerry L
authors.initials: JL
authors.lastname: Prince
authors.affiliation: Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD.|Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD.|Center for Neuroscience and Regenerative Medicine, The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD.
authors.forename: Dzung
authors.initials: D
authors.lastname: Pham
authors.affiliation: Department of Electrical and Computer Engineering, Johns Hopkins University, Baltimore, MD.|Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD.|Center for Neuroscience and Regenerative Medicine, The Henry M. Jackson Foundation for the Advancement of Military Medicine, Bethesda, MD.
authors.forename: Snehashis
authors.initials: S
authors.lastname: Roy
authors.affiliation: Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD.
authors.forename: Peter
authors.initials: P
authors.lastname: van Zijl
authors.affiliation: Department of Neurology, New York University Langone Medical Center, New York, NY.
authors.forename: Laura J
authors.initials: LJ
authors.lastname: Balcer
authors.affiliation: Department of Neurology and Ophthalmology, University of Texas Southwestern, Dallas, TX.
authors.forename: Elliot M
authors.initials: EM
authors.lastname: Frohman
authors.affiliation: Department of Neurology, Johns Hopkins University, Baltimore, MD.|Department of Radiology and Radiological Science, Johns Hopkins University, Baltimore, MD.|Department of Biostatistics, Johns Hopkins University, Baltimore, MD.|Translational Neuroradiology Unit, National Institute of Neurological Disorders and Stroke, Bethesda, MD.
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Reich
authors.affiliation: Department of Biostatistics, Johns Hopkins University, Baltimore, MD.
authors.forename: Ciprian
authors.initials: C
authors.lastname: Crainiceanu
authors.affiliation: Department of Neurology, Johns Hopkins University, Baltimore, MD.
authors.forename: Peter A
authors.initials: PA
authors.lastname: Calabresi
mesh_terms: D000328:Adult; D000368:Aged; D001284:Atrophy; D001921:Brain / Q000473:pathology*; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000473:pathology*; D009902:Optic Neuritis / Q000473:pathology; D012160:Retina / Q000473:pathology*; D012165:Retinal Ganglion Cells / Q000473:pathology; D013788:Thalamus / Q000473:pathology; D041623:Tomography, Optical Coherence / Q000379:methods*