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

Abstract

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.

Keywords

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

Abbreviations

OCT

Optical coherence tomography

TD-OCT

Time domain OCT

SD-OCT

Spectral domain OCT

MS

Multiple sclerosis

RRMS

Relapsing remitting MS

SPMS

Secondary progressive MS

PPMS

Primary progressive MS

CNS

Central nervous system

ON

Optic neuritis

AMT

Average macular thickness

RNFL

Retinal nerve fiber layer

pRNFL

Peripapillary RNFL

mRNFL

Macular RNFL

GCL

Ganglion cell layer

FAS

Fully automated segmentation

FMS

Fully manual segmentation

CAMS

Computer-aided manual segmentation

HC

Healthy control

ART

Automatic real time

ILM

Inner limiting membrane

IPL

Inner plexiform layer

INL

Inner nuclear layer

OPL

Outer plexiform layer

ELM

External limiting membrane

IS/OS

Inner and outer photoreceptor segment junction

IS

Inner photoreceptor segments

BM

Bruch’s membrane

GCIP

Ganglion cell layer + inner plexiform layer

ONL

Outer nuclear layer

ONL + PR

Outer nuclear layer + photoreceptor segments

RPE+

Retinal pigment epithelium

ETDRS

Early Treatment Diabetic Retinopathy Study

ICC

Intraclass correlation coefficient

LOA

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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