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8/18/2019 Glaucoma Diagnosis Amp Tracking With Optical
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Glaucoma Diagnosis &Tracking with Optical
Coherence Tomography
David Huang, MD, PhDCharles C. Manger III, MD Chair of Corneal Laser Surgery Assoc. Prof. of Ophthalmology & Biomedical Engineering
Doheny Eye Institute,University of Southern California
Financial Interests:Optovue, Inc.: stock options, patent royalty, travel, grantCarl Zeiss Meditec, Inc.: patent royalty
R01 EY013516 www.AIGStudy.net
Site PI: James G.Fujimoto, PhD
Consortium PI:David Huang
MD, PhD
Site PI: Joel S.Schuman, MD
Site PI: David
Greenfield, MD
Site PI: RohitVarma, MD, MPH
Yimin Wang,PhD
Ou Tan,PhD
Vikas Chopra,MD
Xinbo Zhang,PhD
Brian Francis,MD
Carolyn Quinn,MD
Krisha S. Kishor,MD
Mitra Sehi,
PhD
RobertNoecker, MD
Gadi Wollstein,MD
Hiroshi Ishikawa,MD
Larry Kagemann,MS
Robert DiLaura Sharon Bi, MCIS
8/18/2019 Glaucoma Diagnosis Amp Tracking With Optical
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The Rationale for Quanti tativeImaging in Glaucoma Diagnosis
David Huang, MD, PhD www.COOLLab.net
Visual field has poor repeatability
OHTS: 85.9% of abnormal and “reliable” fieldswere not confirmed on retest!
David Huang, MD, PhD www.AIGStudy.net
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3 consecutive fields are required toreliably confirm glaucoma!
“The proportion of VF test results that were normalsubsequent to a VF POAG end point in eyes whoseabnormality was confirmed by 2 consecutive, abnormal,reliable test results was significantly higher (73 [66%] of110) compared with eyes whose abnormality wasconfirmed by 3 consecutive, abnormal, reliable testresults. (46 [12%] of 381) (P=.01).”
Keltner et al. for the Ocular Hypertension Treatment StudyGroup, Arch Ophthalmol 123:1201 (2005).
David Huang, MD, PhD www.AIGStudy.net
Structural loss precedes functionalloss
Disc change precedes VF loss in mostcases
David Huang, MD, PhD www.COOLLab.net
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VF Normal OCT Abn. GDX Abn. HRT Abn
N T
N T
N T
MD -1.2 dBPSD 1.75 dB
MD -1.73 dBPSD 1.62 dB
MD -1.77 dBPSD 1.71 dB
Quantitative Imaging may detect glaucoma atan earlier stage
David Huang, MD, PhD www.COOLLab.net
Why use OCT?(rather than other imagingmodalities)
David Huang, MD, PhD www.COOLLab.net
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StratusTD-OCT
GDx-ECCScanning Laser Polarimetry
HRT2Scanning Laser Tomography
Let’s compare diagnostic accuracy
David Huang, MD, PhD www.COOLLab.net
Stratus OCT had significantly betterdiagnostic accuracy(best combination of continuous variables)
Continuous scale AROC P. v. OCTStratus: overall,Inferior o r superiorquadrant RNFL
0.92
GDx-ECC NFI 0.87 0.006HRT2C/D area ratio
0.83 0.0008
Lu ATH, Wang M, Varma R, Schuman JS, Greenfield DS, Smith SD, Huang D; Advanced Imaging forGlaucoma Study Group. Combining nerve fiber layer parameters t o optimize glaucoma diagnosis with opticalcoherence tomography. Ophthalmology 2008;115:1352-7
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Paper AROC # SubjectsStratus GDx-VCC HRT2 N G
Pueyo et al.J. Glaucoma 2007
Overall RNFL0.91
NFI0.88 *
MRA0.90
66 73
Pueyo et al. ARCH SOC ESPOFTALMOL 2006
Overall RNFL0.93
NFI0.88
Mikelberg0.90
66 74
Medeiros etal. ArchOphthalmol. 2004
Inferior RNFL0.92
NFI0.91
LDF0.86
66 75
Zangwill et al. Arch Ophthalmol.2001
5 o’clock RNLF0.87
LDF0.84
MHC N/I0.86 50 41
NFI = nerve fiber index; MRA = Moorefields regression analysis;LDF = linear discriminant function; MHC = mean height contour, N/I = nasal/inferior
Previous literature comparisonsDavid Huang, MD, PhD www.COOLLab.net
More accuarate NFL mapping withFD-OCT
David Huang, MD, PhD www.COOLLab.net
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TD-OCT susceptible to eye movements
1. Koozekanani, Boyer and Roberts. “Tracking the Optic Nervehead in OCT Video Using Dual Eigenspaces and an Adaptive Vascular Distribution Model”; IEEE Transactions on Medical Imaging, Vol. 22, No. 12, 2003
•768 pixels (A‐scans) captured
in 1.92 seconds is slower than eye
movements
•Stabilizing the retina reveals true scan path
(white circles)
1
Scan location and eye movementsaffect results
T S N I T T S N I T T S N I T
Properly centered
Normal Double Hump
Poorly centered: too inferior Poorly centered: too superior
Inferior RNFL “Loss” Superior RNFL “Loss”
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RTVueFD-OCT
OpticNerveHeadMap
(ONH)
9510a-scans
0.39 sec
FD-OCT can scan more points in less time – sampling greater area with less motion error
David Huang, MD, PhD www.COOLLab.net
New advances from the AdvancedImaging for Glaucoma Study:
Mapping the Ganglion Cell Complex toFurther Improve Glaucoma Diagnosis
and Tracking
David Huang, MD, PhD www.COOLLab.net
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Glaucoma affects 3 areas in the
posterior segment of the eye
Cupping
Nerve fiber thinning
Ganglion cell lossDavid Huang, MD, PhD www.COOLLab.net
Glaucoma preferentially thins the Ganglion Cell
Complex (GCC) which includes the axons, cellbodies, and dendrites of retinal ganglion cells
Normal
Glaucoma with thinner GCC
GCC
GCC
NFLGCL
IPL}GCC
Ishikawa H , et al., IOVS 2005Tan O, et al., Ophthalmology , 2008;115:949-56.
David Huang, MD, PhD www.AIGStudy.net
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Ganglion Cell Complex (GCC)7 mm scan area
14,944 a-scans, 0.58 sec
GCC = Ganglion Cell Complex
Glaucoma: Macular Ganglion Cell Mapping
RTVue FDRTVue FD --OCT,OCT,26,00026,000 A A--scanscanper per --secondsecond55 micron axialmicron axialresolutionresolution
mGCC thickness map
NFLGCL
IPL
}GCC
}Retina
micron
David Huang, MD, PhD www.AIGStudy.net
GCC Deviation Map
color coded map
Percent loss value at each pixel location relative tonormal based on age-adjus ted normative database ofover 300 healthy eyes
Blue = thinning 20-30% relative to normal
Black = 50% loss or g reater
% loss =
actual scan value – normal valuenormal value
David Huang, MD, PhD www.AIGStudy.net
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GCC Significance Map
color coded map shows regions where the change fromnormal reaches statistical signi ficance
Green = values withi n nor mal range (p-value 5% to 95%)
Yellow = borderl ine result s (p-value < 5%)
Red = outside normal limits (p-value
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Combining measurements f rom all 3 anatomicregions with machine learning classifiersfurther boos ted diagnostic accuracy
DiagnosticParameter
AROC Sensitivity(at 5 percentile cutoff)
Support VectorMachine (SVM)
0.963P < 0.02
86%P < 0.01
Best NFL 0.924 67%
Best GCC 0.920 68%
Best Disc 0.886 56%
85 normal eyes, 72 perimetric glaucoma eyesDavid Huang, MD, PhD www.AIGStudy.net
High-speed FD-OCT allows correlation of glaucoma
disease patterns – Pre-Perimetric Glaucoma
T N
PatternDeviation
Peripapillary NFL loss Macular GCC loss (FLV p
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FD-OCT improved the repeatability of macular ganglioncell complex compared to TD-OCT circumpapillarynerve fiber layer measurements, thus improving the
potential to track glaucoma over timeOCT system Thickness Parameter CV (%)
Group N PPG PG
RTVueFD-OCT
mGCC-avg 1.09 1.23 1.25
StratusTD-OCT
cpNFL-avg 1.72 1.75 2.86
David Huang, MD, PhD www.AIGStudy.net
2x
Rule of thumb for progressionanalysis
Stratus NFL overall average: 10% losssignificant, if confirmed on repeat visitRTVue GCC overall average: 5% losssignificant, if confirmed on repeat visitIf IOP more than 2 mm Hg different, the
comparison may not be reliable
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GCC Progression Analysis (visit every 6 months)
David Huang, MD, PhD www.AIGStudy.net
5% lossconfirmed
RTVue™
OCT angle imaging is also useful forthe glaucoma specialist
Yan Li, PhD Bing Qin, MD
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Schlemm’scanal
Trabecular meshwork
Scleral spur
Cornealendothelium
Schwalbe’s line
External limbus
OCT provides near-
histological details ofangle structures
AOD_SL
David Huang, MD, PhD www.COOLLab.net
Narrow Angle
RTVue™
Open AngleSchwalbe’sline
External limbus
Scleral Spur
Trabecular meshwork
Schlemm’scanal
AOD_SL= 473 µ m
David Huang, MD, PhD www.COOLLab.net
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Neovascular Glaucoma withSynechial Angle Closure
Schwalbe’sline
PASIrisvessel
Scleralvessel
Courtesy of Brian Francis, MD; Doheny Eye Institute
EL
SLTMR
TC IR
SS
Iris
After Trabectome Surgery
Courtesy of Brian Francis, MD; Doheny Eye Institute
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FD-OCT provides more information thanother advanced imaging technologies
FD-OCT SLT (HRT) SLP (GDx)
ppNFLthickness + +
MacularGCC +
Disc & Cup + +
Total retinalblood flow *
Angle +Cornea +
*Under development, not yet released commercially David Huang, MD, PhD
FD-OCT may have a growing role inglaucoma diagnosis
David Huang, MD, PhD www.COOLLab.net
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Glaucoma Diagnosis Case Examples
Subject 005 OS
42 year oldIOP 11C/D 0.1
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Stratus TD-OCT
Superonasal NFL thinner than normal
Inferotemporal NFL thicker than normal
RTVueFD-OCTGCC
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RTVueFD-OCTNFL
VF
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Subject 005 OS
Normal eyeStratus TD-OCT NFL abnormal due tosuperonasal scan decentrationRTVue FD-OCT within normal for bothNFL and GCC
Subject 046 OS
62 year oldIOP 17.5 withmedicationC/D 0.4
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Stratus
temporal NFL borderline thin
Nasal NFL thicker than normal
RTVueGCC
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RTVueNFL
VF
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Subject 046 OS
Perimetric glaucomaNFL by Stratus TD-OCT decentered – probably normalNFL normal by RTVue FD-OCTMacular GCC is abnormal in agreementwith VF: central loss more severe in thesuperior macula / inferior field
Glaucoma Tracking Case Example
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Subject 108 Perimetr ic Glaucoma OS
Baseline 1 year 2 year 3 year
Hemorrhage Rim thinning Rim thinning Rim thinning
Stratus Advanced Serial Analysis
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RTVue GCC Glaucoma Progression Report
Time Baseline 1 year 2 year 3 year
IOP (mm Hg) 12.5 12.5 10.0 13.0
RTVue NFL Glaucoma Progression Report
Time Baseline 1 year 2 year 3 year
IOP (mm Hg) 12.5 12.5 10.0 13.0
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Humphrey Glaucoma Progression Analysis
Subject 108 OS
Perimetric glaucomaProgression detected by GCC and discphotographyProgression not detected by NFL or VFDrop in IOP on year 2 visit caused
artifactual improvement on NFL & GCC
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David Huang,MD, PhD
Maolong Tang,PhD
Yan Li, PhD
Ou Tan, PhD
Sylvia Ramos,COA
Yimin Wang,PhD
Xinbo Zhang,PhD
Timothy Hsia,MS
Doheny Eye Institute
www.COOLLab.net
Jason Tokayer,MS
Bing Qin, MD Wei Wu, MSNehal Samy,MD
Habeeb Ahmad,MD
CatherineCleary, MD