16 chen different oct systems - ucsf cme...chauhan et al. ophthalmology 2013. tsikata et al. iovs...

Comparison of Different OCT Systems

Teresa C. Chen, MDAssociate Professor of Ophthalmology, Harvard Medical School

Glaucoma Service, Massachusetts Eye and Ear Infirmary

• I have the following financial interests or relationships to disclose:

– Department of Defense: Grant Support

– Harvard Foundation Grant (Fidelity Charitable Fund): Grant Support

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Review the literature on the use of SD‐OCT to help diagnose glaucoma 2006 to 2018

All commercially available SD‐OCT machines RNFL, optic nerve, macula

not lamina no OCTA

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PubMed and Cochrane Library Databases February 2006 to April 2018

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Lin SC, Singh K, Jampel HD, Hodapp EA, Smith SD, Francis BA, Dueker DK, FechtnerRD, Samples JS, Schuman JS, Minckler DS. Optic Nerve Head and RNFL Analysis. Ophthalmology 2007;114:1937‐1949.

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Lin SC, Singh K, Jampel HD, Hodapp EA, Smith SD, Francis BA, Dueker DK, FechtnerRD, Samples JS, Schuman JS, Minckler DS. Optic Nerve Head and RNFL Analysis. Ophthalmology 2007;114:1937‐1949.

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Chen TC, Hoguet A, Junk A, Nouri‐Mahdavi K, Radhakrishnan S, Takusagawa H, Chen PP. Spectral Domain OCT: Helping the Clinician Diagnose Glaucoma. Ophthalmology 2018;125:1817‐1827.

SLD Light Source

Reference Mirror

Photo Detector A-line

Beam Splitter

How Time Domain OCT Works

Huang D, Swanson EA, Lin CP, Schuman JS, Stinson WG, Chang W, Hee MR, Flotte T, Gregory K, Puliafito CA, Fujimoto JG. Optical Coherence Tomography. Science, 1991.

SLD Light Source

Reference Mirror

Spectrometer

Beam Splitter

Fourier transform

How Spectral Domain OCT Works

American Glaucoma Society

Sarasota, Florida, 2004

“Ultra High Speed Optical Coherence Tomography” Video-Rate SD-OCT

White BR, Pierce MC, Nassif N, Cense B, Park BH, Chen TC, de Boer JF…Imaging Using Ultra-High-Speed Spectral Domain Optical Doppler Tomography. Optics Express 2003; 11 (25): 3490-7.

Johannes de Boer PhD (MGH)

White BR, Pierce MC, Nassif N, Cense B, Park BH, Chen TC, de Boer JF…Imaging Using Ultra-High-Speed Spectral Domain Optical Doppler Tomography. Optics Express 2003; 11 (25): 3490-7.

Nassif N, Cense B, Park BH, Yun SH, Chen TC, Bouma BE, Tearney GJ, de Boer JF. In vivo Human Retinal Imaging by Ultrahigh-Speed Spectral Domain OCT. Opt Lett 2004;29(5):480-482.

Nassif N, Cense B, Park BH, Pierce M, Yun SH, Bouma BE, Tearney GJ, Chen TC, de Boer JF. In vivo High-resolution Video-Rate Spectral Domain OCT of the Human Retina and Optic Nerve. Opt Express 2004;12(3):367-376.

Cense B, Nassif N, Chen TC, Pierce MC, Yun SH, Park BH, Bouma BE, Tearney GJ, de Boer JF. Ultrahigh-resolution High-speed Retinal Imaging Using Spectral Domain OCT. Opt Express 2004;12(11):2435-2447.

3D Spectral Domain OCT - 2003 imaging the eye

for the first time in 3D (video-rate)

in real time

SDOCT (3D = Video-Rate)

wide field!

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708 articlesInclusion criteria:- SD-OCT was the technology - RNFL, optic nerve, macula- original research- SD-OCT & glaucoma diagnosis- adult subjects- at least 125 patientsExclusion criteria:- reproducibility- progression- level III evidence


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708 articlesInclusion criteria:- original research- SD-OCT was the technology - RNFL, optic nerve, macula- SD-OCT & glaucoma diagnosis- adult subjects- at least 125 patientsExclusion criteria:- reproducibility- progression- level III evidence


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Inclusion & exclusion criteria yielded:- 2 level I articles- 57 level II articles



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Many different SD‐OCT machines

Spectralis

Spectral OCT SLO

SOCT Copernicus

Bioptigen

RTVue

Cirrus

Topcon3D OCT

time domain

OCT

• Cirrus HD-OCT (Carl Zeiss Meditec, Inc, Dublin, California)

• RTVue (Optovue, Inc, Fremont, California)

• Spectralis SD-OCT (Heidelberg Engineering GmbH, Heidelberg, Germany)

• 3D-OCT (Topcon Medical Systems, Inc, Paramus, New Jersey)

• Bioptigen Envisu SD-OCT (Bioptigen, Inc, Research Triangle Park, North Carolina)

• SOCT Copernicus HR (Optopol Technology, SA, Zawiercie, Poland)

Many SD-OCT machines

Spectralis

Spectral OCT SLO

SOCT Copernicus

Bioptigen

RTVue

Cirrus

Topcon3D OCT






time domain

OCT

Spectralis

Spectral OCT SLO

SOCT Copernicus

Bioptigen

RTVue

Cirrus

Topcon3D OCT

SDOCT machines appear to have similar clinical diagnostic abilities1-4

1. Akashi et al. IOVS 2013;54(7):4478-4484.2. Akashi et al. IOVS 2013;54(9):6025-6032.3. Leite et al. Ophthalmology

2011:118(7):1334-1339.4. Lee, et al. Optom Vis Sci 2011:88(6):751-

758.






time domain

OCT

Spectralis

Spectral OCT SLO

SOCT Copernicus

Bioptigen

RTVue

Cirrus

Topcon3D OCT

RNFL thickness values between machines are not interchangeable1

1. Lee, et al. Optom Vis Sci 2011;88(6):751-758.

2. Seibold, et al. Am J Ophthalmol2010;150(6):807-814.






time domain

OCT

Stratus Cirrus Spectralis

Artifacts in OCT Imaging

110.1 ± 12.8 98.7 ± 10.9 106.6 ± 12.8

RTVue

112.8± 13.2

Comparison of RNFL Thickness in Normal Eyes Using TDOCT and SDOCT. Leonard Seibold, Naresh Mandava, Malik Kahook. Am J Ophthalmol 2010.

40 normals

RNFL values are not interchangeable for different SDOCT machines…


RNFL “thinning” due to different SDOCT machines…

Stratus Cirrus Spectralis

2009 2013 2014

∼ 104 microns ∼ 97 microns ∼ 105 microns


different signal strength range

SDOCT Machine Scan Quality Index

Cirrus HD-OCT Signal Strength > 6 (max. 10)

RTVue Signal Strength Index (SSI) ≥ 30 (max. 100)

3D-OCT Image quality > 45 (max. 160)

Spectralis SD-OCT Quality (Q) > 15 (max. 40)


Effect of Corneal Drying on Optical Coherence Tomography. Daniel Stein, Gadi Wollstein, Hiroshi Ishikawa, Ellen Hertzmark, Robert Noecker, Joel Schuman. Ophthalmology 2006; 113: 985-991.

Artifacts in OCT ImagingMany SD-OCT machinesdifferent normative databases

Outline

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Similar diagnostic data

Different machines…

RNFL values not interchangeablesignal strength rangesnormative databasessoftware


RNFL optic nerve macula

SD-OCT Software Differences


most commonly used

Table 1.3.4mm to 3.46 mm diameter scan circle



most commonly used

Table 1.3.4mm to 3.46 mm diameter scan circle


● Spectralis Glaucoma Module Premium Edition (GMPE)FDA approved in 2016

● RNFL scan protocol:● 12°/14°/16° arc● centered over BMO● 3.5 mm, 4.1 mm, and 4.65 mm*

* Gmeiner et al. IOVS 2016;57(9):575‐584.



● Spectralis Glaucoma Module Premium Edition (GMPE)FDA approved in 2016

● RNFL scan protocol:● 12°/14°/16° arc● centered over BMO● 3.5 mm, 4.1 mm, and 4.65 mm*





Table 1.reference plane vs. reference plane independent


● reference plane independent parameters○ Spectralis – BMO‐MRW

old way new way

AGS 2004

Software 2D 3D

● reference plane dependent parameterso Cirrus ‐ 200 microns above RPE

o RTVue – 150 microns above RPE

o 3D OCT – 120 microns above RPE

SD-OCT Software Differencesoptic nerve

● reference plane independent parameters

Chen TC, Zeng A, Sun W, Mujat M, de Boer JF. Spectral Domain Optical Coherence Tomography in Glaucoma. International Ophthalmology Clinics 2008 Fall; 48 (4): 29‐45.

Chen TC. Trans Am Oph Soc 2009;107:254‐81.

old way new way● reference plane dependent parameterso Cirrus ‐ 200 microns above RPE




● reference plane independent parameters

…better than reference plane parametersChauhan et al. Ophthalmology 2013.Tsikata et al. IOVS 2016.

old way new way● reference plane dependent parameterso Cirrus ‐ 200 microns above RPE




minimum distance band (MDB)

BMO‐MRW

minimum circumpapillary band (MCB)

MDB (16 eyes)area and thicknessRPE/BM complex (193 raster lines)(Chen, Int Oph Clinics 2008Chen, Trans Am Oph Soc 2009)

MCB (3 eyes)areaElschnig’s ring (60 raster lines)(Povazay, JBO 2007)

BMO‐MRW (155 patients)area and widthBMO (24 radial lines)(Chauhan, Ophthalmol 2013)

REFERENCE PLANE INDEPENDENT PARAMETERS

reference plane independent neuroretinal rim parameter

RNFL

Spectral Domain OCToptic nerve macula

RNFL


3D OCTGCCGCIPLNFLSpectralisTotal retina thickness

NFL: Nerve fiber layer (ganglion cells axons)GCL: Ganglion Cell Layer (ganglion cells bodies)IPL: Inner Plexiform Layer (ganglion cells dendrites)Retina: total retinal thickness

RTVueGCC: Ganglion Cell Complex = NFL + GCL + IPL

Cirrus GCA: Ganglion Cell AnalysisGCC = NFL + GCL + IPLGCIPL = GCL + IPL


diagram from Akashi et al. IOVS 2013

Spectralis Glaucoma Module Premium Edition (GMPE)GMPE FDA approved in 2016

Posterior Pole Asymmetry Analysis (PPAA)● 8 X 8 array or superpixel 3°X3°● 30°X25° volume scan● 61 horizontal Bscans (120 microns apart)

Miraftabi et al TVST 2016

ganglion cell thickness maps

Miraftabi, Amini, Morales, Henry, Yu, Afifi, Coleman, Caprioli, Nouri‐Mahdavi. IOVS 2016.

“Measuring GCL does not provide any advantage for detection of progression with current SD‐OCT technology”

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Similar diagnostic data

Different machines…

RNFL values not interchangeablesignal strength rangesnormative databasessoftware


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similar across machines

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similar across machines location severe disease signal strength

Cirrus

RTVueSpectralis3D OCT

Outline

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Conclusions Accuracy of a test is quantified by AUROC:

AUROC = 1 is a perfect testAUROC = 0.5 uninformative test

Excellent test (AUROC 0.90 – 1.0)Good test (AUROC 0.80 – 0.90)Fair test (AUROC 0.70 – 0.80)Poor test (AUROC 0.60 – 0.70)

similar across machines

Cirrus

RTVueSpectralis3D OCT

Cirrus and Glaucoma


Cirrus

global or average RNFL can distinguish normal from glaucoma patientsAUROC 0.677 – 0.969 (poor to excellent)

inferior and superior quadrants bestinferior quadrant AUROC 0.686 – 0.963 (poor to excellent)superior quadrant AUROC 0.601 – 0.944 (poor to excellent)

better diagnostic ability for worse disease severitypre‐perimetric glaucoma AUROC 0.752 – 0.860 (fair to good)advanced glaucoma AUROC 0.936 – 0.981 (excellent)

26 articles studied Cirrus RNFL thickness:


Cirrus

Cirrus SD‐OCT same or better AUROC curves Cirrus SD‐OCT had better resolution (i.e. 5 versus 10 microns)Cirrus SD‐OCT had faster acquisition speedsCirrus SD‐OCT had better signal strength

poor signal strength (1.0% of Cirrus versus 23% of Stratus scans)Cirrus SD‐OCT had less measurement variability

COV (< 6.4% for Cirrus and < 12.8% for Stratus)Cirrus has added advantage of RNFL thickness deviation maps

size, shape, depth, location, disc margin distance

Studies comparing Cirrus SD‐OCT versus Stratus TD‐OCT RNFL thickness:


Cirrus

8 articles studied Cirrus disc parameters:

Rim areaDisc areaAverage cup‐to‐disc ratioVertical cup‐to‐disc ratio Cup volume


Cirrus


Rim area AUROC 0.655 – 0.960 (poor to excellent)Disc areaAverage cup‐to‐disc ratioVertical cup‐to‐disc ratio AUROC 0.400 – 0.962 (uninformative to excellent)Cup volume


Cirrus


Rim area AUROC 0.655 – 0.960 (poor to excellent)Disc areaAverage cup‐to‐disc ratioVertical cup‐to‐disc ratio AUROC 0.400 – 0.962 (uninformative to excellent)Cup volume

better diagnostic ability for worse disease severityadvanced glaucoma ‐ rim area AUROC 0.937 (excellent)advanced glaucoma – vertical cup‐to‐disc ratio AUROC 0.911‐0.941 (excellent)


Cirrus

14 articles studied Cirrus macular parameters best parameters were…

Minimum GCIPL AUROC 0.702 – 0.980 (fair to excellent)Inferior temporal GCIPL AUROC 0.752 – 0.970 (fair to excellent)Average GCIPL AUROC 0.703 – 0.960 (fair to excellent)Inferior GCIPL thickness AUROC 0.702 – 0.950 (fair to excellent)Superior temporal GCIPL thickness AUROC 0.652 – 0.932 (poor to excellent)Average GCC AUROC 0.901 – 0.945 (excellent)Inferior temporal GCC AUROC 0.922 (excellent)Superior temporal GCC AUROC 0.910 (excellent)Inferior GCC AUROC 0.904 – 0.908 (excellent)

macula

Cirrus

13 articles studied Cirrus combined parameters:

Most studies suggest that best macular, RNFL, and disc parameters are similar

One study suggested that macular inferior temporal GCIPL was better than inferior RNFL for discriminating myopic glaucoma from myopia alone

(0.752 vs. 0.686 p = 0.036)

optic nerveRNFL

RTVue and Glaucoma


RTVue

19 articles studied RTVue RNFL thickness:

average RNFL best for distinguishing normal from glaucoma patientsAUROC 0.828 – 0.977 (good to excellent)

inferior and superior quadrants next bestinferior quadrant AUROC 0.823 – 0.982 (good to excellent)superior quadrant AUROC 0.805 – 0.944 (good to excellent)


RTVue

19 articles studied RTVue RNFL thickness:

better diagnostic ability for worse disease severitypre‐perimetric glaucoma AUROC 0.720 – 0.820 (fair to good)advanced glaucoma AUROC 0.936 – 0.977 (excellent)

better diagnostic data with improved signal strength index (SSI)SSI ≥ 30 AUROC 0.678 – 0.890 (fair to good)SSI ≥ 70 AUROC 0.962 – 0.994 (excellent)


RTVue

Cup area Disc areaRim areaRim volumeNerve head volumeCup volumeCup disc area ratioHorizontal cup‐to‐disc ratioVertical cup‐to‐disc ratio

8 articles studied RTVue disc parameters:


RTVue

Cup area Disc areaRim area AUROC 0.720 – 0.960 (fair to excellent)Rim volumeNerve head volumeCup volumeCup disc area ratioHorizontal cup‐to‐disc ratioVertical cup‐to‐disc ratio AUROC 0.621 – 0.970 (poor to excellent)


Inferior


RTVue

Cup area Disc areaRim area AUROC 0.720 – 0.960 (fair to excellent)Rim volumeNerve head volumeCup volumeCup disc area ratioHorizontal cup‐to‐disc ratioVertical cup‐to‐disc ratio AUROC 0.621 – 0.970 (poor to excellent)


Inferior


RTVue

articles studied RTVue disc parameters:

rim area diagnostic data increased as disease severity increased

rim area has better diagnostic data for perimetric glaucoma with improved SSIrim area (SSI ≥ 30) AUROC 0.651 – 0.747 (poor to fair)rim area (SSI ≥ 70) AUROC 0.873 – 0.922 (good to excellent)


RTVue

19 articles studied RTVue macular parameters:

average GCC thickness best for distinguishing normal from glaucoma patientsAUROC 0.642 – 0.957 (poor to excellent)

inferior GCC thickness next bestAUROC 0.743 – 0.949 (fair to excellent)


RTVue


GCC thickness with better diagnostic ability for worse disease severitypre‐perimetric glaucoma AUROC 0.720 – 0.780 (fair)advanced glaucoma AUROC 0.916 (excellent)

better diagnostic data for perimetric glaucoma with improved SSIaverage GCC thickness (SSI ≤ 30) AUROC 0.726 – 0.873 (fair to good)average GCC thickness (SSI ≤ 70) AUROC 0.886 – 0.959 (good to excellent)


RTVue


Suggested that macular parameters provide better diagnostic data vs. RNFL thicknessi.e. AUROC does not decrease with high myopiaRNFL thickness AUROC 0.939 vs. 0.827 (excellent versus good)GCC thickness AUROC 0.933 vs. 0.935 (excellent)

macula

8 articles studies compared RNFL vs. disc vs. macular parameters:

Most studies (6 of 8) suggest that best RNFL, disc, and macular parameters are similar

optic nerveRNFL

RTVue

Spectralis and Glaucoma


Spectralis

● RNFL thickness scan● most common scan● 12° arc● 3.45 mm circle for typical axial length● with tracking

● GMPE scan protocol:● 12°/14°/16° arc● centered over BMO● 3.5 mm, 4.1 mm, and 4.65 mm*



Spectralis

Global RNFL thickness AUROC 0.880 – 0.978 (good to excellent)Inferior RNFL thickness AUROC 0.850 – 0.958 (good to excellent)Superior RNFL thickness AUROC 0.880 – 0.936 (good to excellent)Temporal‐inferior RNFL thickness AUROC 0.855 – 0.959 (good to excellent)Temporal‐superior RNFL thickness AUROC 0.803 – 0.951 (good to excellent)

12 articles studied Spectralis RNFL parameters best parameters were…


Spectralis

BMO‐MRW (24 radial line scan) AUROC 0.929 – 0.960 (excellent)

Unclear if BMO‐MRW better than RNFL thickness


Spectralis

MDB (high‐density 193 raster scan)

MDB better than RNFL thickness, especially…nasal regiontemporal regioninferonasal regionsuperonasal region

2 studies suggest that BMO‐MRW and MDB thicknessbetter than rim area and thickness


Spectralis

inferior macular retina thickness bestAUROC 0.858 (good)

Topcon 3D OCT and Glaucoma

RNFL macula

3D OCT-1000 or 3D OCT-2000optic nerve

4 articles studied 3D OCT‐1000 or 3D OCT‐2000 parameters:

Best RNFL thickness parameters for distinguishing normal from glaucoma patientsaverage or global RNFL AUROC 0.890 – 0.974 (good to excellent)inferior RNFL AUROC 0.909 – 0.964 (excellent)superior RNFL AUROC 0.826 – 0.909 (good to excellent)

Best macular parametersaverage GC/IPL AUROC 0.830 – 0.954 (good to excellent)average GCC AUROC 0.872 – 0.968 (good to excellent)inferior GC/IPL AUROC 0.856 – 0.954 (good to excellent)inferior GCC AUROC 0.888 – 0.969 (good to excellent)

Outline

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Conclusions

SD‐OCT important tool for glaucoma SD‐OCT > TD‐OCT

resolution acquisition speed scan quality (signal strength) inter‐test variability RNFL thickness maps

Different SD‐OCT machines have similar abilities to distinguish between normal & glaucoma patients

Values between machines are not interchangeable

Outline

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Better AUROC values for… greater disease severity better signal strength

Diagnosis(RNFL ~ macula ~ disc) maybe macula for myopes

Combining parameters improves diagnostic performance

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Conclusions

Most important parameters …1) RNFL thickness2) Macula

• GCC • GC/IPL

3) Disc• rim area• vertical cup‐disc ratio

Most important regions … average inferior & superior inferior temporal & superior temporal

OCT Diseasesthat should always be correlated with clinical dataSDOCT has a lot of great information…

Harvard Foundation Grant (Fidelity Charitable Fund)National Institutes of Health - RO1 EY14975-01

Harvard CatalystAmerican Glaucoma Society Mid-Career AwardMassachusetts Lions Eye Research Fund, Inc.

Department of Defense SBIR

Massachusetts General Hospital

and VU University• Johannes de Boer, PhD

• B. Hyle Park, PhD

• Mircea Mujat, PhD

• Vivek Srinivasan, PhD

• Barry Cense, PhD

• Gary Tearney, PhD

• Brett Bouma, PhD

• Mark Pierce, PhD

• Wei Sun, BS

• Vivek Srinivasan, PhD

• Ben Vakoc, PhD

Massachusetts Eye and Ear Infirmary• Kayoung Yi, MD, PhD• Edem Tsikata, PhD• Alice Vercellin Verticchio, MD• John B. Miller, MD• Iryna Falkenstein, MD• Linda Yi-Chieh Poon, MD• Stacey Brauner, MD• Ziad Khoueir, MD• Derrick T. Lin, MD• Daniel Deschler, MD• Peter A.D. Rubin, MD• Mark Latina, MD• Joan W. Miller, MD

THANKS

Outline

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Methods

Results

Conclusions

Pictures from Carl Zeiss Meditec, Inc

Limitations of Time Domain OCT

Video Rate Spectral Domain OCT

2D 3Dpictures courtesy Mary Beth Cunnane, MD

OCT Terminology

(A-line) (frame)C-mode

Video Rate Spectral Domain OCT

B-scan

2D 3D1DA-scan

● Shieh et al. AJO 2016.● Tsikata et al. IOVS 2016.● Fan et al. Journal of Glaucoma 2017.

2D 3Dbest disc parameters:global rim areainferior rim areavertical cup-to-disc ratio

best disc parameters:MDB

Software 2D 3D


best disc parameters:MDB


Software 2D 3D


best disc parameters:MDBBMO-MRW


Software 2D 3D


best disc parameters:MDBBMO-MRWrim volume


Software 2D 3D


rim width ‐ RW




RW (9 monkeys)area and widthBMO (80 radial lines)(Strouthidis, IOVS 2011)



rim width ‐ RW







rim width ‐ RW







rim width ‐ RW






disc photos

HVF


rim width ‐ RW






16 chen different oct systems - ucsf cme...chauhan et al. ophthalmology 2013. tsikata et al. iovs...

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