glaucoma diagnosis amp tracking with optical

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


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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).


Structural loss precedes functionalloss

Disc change precedes VF loss in mostcases



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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



Quantitative Imaging may detect glaucoma atan earlier stage


Why use OCT?(rather than other imagingmodalities)



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StratusTD-OCT

GDx-ECCScanning Laser Polarimetry

HRT2Scanning Laser Tomography

Let’s compare diagnostic accuracy


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



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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


New advances from the AdvancedImaging for Glaucoma Study:

Mapping the Ganglion Cell Complex toFurther Improve Glaucoma Diagnosis

and Tracking



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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.



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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


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



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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


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)


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


Narrow Angle

RTVue™

Open AngleSchwalbe’sline

External limbus

Scleral Spur

Trabecular meshwork

Schlemm’scanal

AOD_SL= 473 µ m



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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



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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

glaucoma diagnosis amp tracking with optical

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