Journal of Neurology

, Volume 259, Issue 10, pp 2119–2130

In vivo assessment of retinal neuronal layers in multiple sclerosis with manual and automated optical coherence tomography segmentation techniques

  • Michaela A. Seigo
  • Elias S. Sotirchos
  • Scott Newsome
  • Aleksandra Babiarz
  • Christopher Eckstein
  • E’Tona Ford
  • Jonathan D. Oakley
  • Stephanie B. Syc
  • Teresa C. Frohman
  • John N. Ratchford
  • Laura J. Balcer
  • Elliot M. Frohman
  • Peter A. Calabresi
  • Shiv Saidha
Original Communication


Macular optical coherence tomography (OCT) segmentation, enabling quantification of retinal axonal and neuronal subpopulations, may help elucidate the neuroretinal pathobiology of multiple sclerosis (MS). This study aimed to determine the agreement, reproducibility, and visual correlations of retinal layer thicknesses measured by different OCT segmentation techniques, on two spectral-domain OCT devices. Macular scans of 52 MS patients and 30 healthy controls from Spectralis OCT and Cirrus HD-OCT were segmented using fully manual (Spectralis), computer-aided manual (Spectralis and Cirrus), and fully automated (Cirrus) segmentation techniques. Letter acuity was recorded. Bland-Altman analyses revealed low mean differences across OCT segmentation techniques on both devices for ganglion cell + inner plexiform layers (GCIP; 0.76–2.43 μm), inner nuclear + outer plexiform layers (INL + OPL; 0.36–1.04 μm), and outer nuclear layers including photoreceptor segment (ONL + PR; 1.29–3.52 μm) thicknesses. Limits of agreement for GCIP and ONL + PR thicknesses were narrow. Results of fully manual and computer-aided manual segmentation were comparable to those of fully automated segmentation. MS patients demonstrated macular RNFL, GCIP, and ONL + PR thinning compared to healthy controls across OCT segmentation techniques, irrespective of device (p < 0.03 for all). Low-contrast letter acuity in MS correlated significantly and more strongly with GCIP than peripapillary RNFL thicknesses, regardless of the segmentation method or device. GCIP and ONL + PR thicknesses, measured by different OCT devices and segmentation techniques, are reproducible and agree at the individual and cohort levels. GCIP thinning in MS correlates with visual dysfunction. Significant ONL + PR thinning, detectable across OCT segmentation techniques and devices, strongly supports ONL pathology in MS. Fully automated, fully manual and computer-assisted manual OCT segmentation techniques compare closely, highlighting the utility of accurate and time-efficient automated segmentation outcomes in MS clinical trials.


Ganglion cell layer Multiple sclerosis Optical coherence tomography Retinal pathology Retinal segmentation Visual function 



Optical coherence tomography


Time domain OCT


Spectral domain OCT


Multiple sclerosis


Relapsing remitting MS


Secondary progressive MS


Primary progressive MS


Central nervous system


Optic neuritis


Average macular thickness


Retinal nerve fiber layer


Peripapillary RNFL


Macular RNFL


Ganglion cell layer


Fully automated segmentation


Fully manual segmentation


Computer-aided manual segmentation


Healthy control


Automatic real time


Inner limiting membrane


Inner plexiform layer


Inner nuclear layer


Outer plexiform layer


External limiting membrane


Inner and outer photoreceptor segment junction


Inner photoreceptor segments


Bruch’s membrane


Ganglion cell layer + inner plexiform layer


Outer nuclear layer


Outer nuclear layer + photoreceptor segments


Retinal pigment epithelium


Early Treatment Diabetic Retinopathy Study


Intraclass correlation coefficient


Limits of agreement

Supplementary material

415_2012_6466_MOESM1_ESM.doc (36 kb)
Supplementary material 1 (DOC 35 kb)
415_2012_6466_MOESM2_ESM.doc (56 kb)
Supplementary material 2 (DOC 56 kb)
415_2012_6466_MOESM3_ESM.doc (37 kb)
Supplementary material 3 (DOC 37 kb)
415_2012_6466_MOESM4_ESM.doc (38 kb)
Supplementary material 4 (DOC 38 kb)


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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Michaela A. Seigo
    • 1
  • Elias S. Sotirchos
    • 1
  • Scott Newsome
    • 1
  • Aleksandra Babiarz
    • 1
  • Christopher Eckstein
    • 2
  • E’Tona Ford
    • 1
  • Jonathan D. Oakley
    • 3
  • Stephanie B. Syc
    • 1
  • Teresa C. Frohman
    • 4
  • John N. Ratchford
    • 1
  • Laura J. Balcer
    • 5
  • Elliot M. Frohman
    • 4
  • Peter A. Calabresi
    • 1
  • Shiv Saidha
    • 1
  1. 1.Department of NeurologyJohns Hopkins University School of MedicineBaltimoreUSA
  2. 2.Department of NeurologyUniversity of South Alabama College of MedicineMobileUSA
  3. 3.Voxeleron LLCPleasantonUSA
  4. 4.Departments of Neurology and OphthalmologyUniversity of Texas Southwestern Medical CenterDallasUSA
  5. 5.Departments of Neurology and OphthalmologyUniversity of Pennsylvania School of MedicinePhiladelphiaUSA

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