Glaucoma Diagnosis & Tracking with Optical Coherence Tomography

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Glaucoma Diagnosis &. Tracking with Optical. Coherence Tomography. David Huang, MD, PhD. Charles C. Manger III, MD Chair of Corneal Laser Surgery.

Glaucoma Diagnosis & Tracking with Optical Coherence Tomography David Huang, MD, PhD Charles 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, grant Carl Zeiss Meditec, Inc.: patent royalty

R01 EY013516 www.AIGStudy.net

Consortium PI: David Huang MD, PhD

Brian Francis, Site PI: Rohit Varma, MD, MPH MD

Vikas Chopra, MD

Ou Tan, PhD

Site PI: David Greenfield, MD

Mitra Sehi, PhD

Carolyn Quinn, MD

Krisha S. Kishor, MD

Site PI: Joel S. Schuman, MD

Robert Noecker, MD

Gadi Wollstein, MD

Hiroshi Ishikawa, Larry Kagemann, MD MS

Yimin Wang, PhD

Robert DiLaura

Xinbo Zhang, PhD

Sharon Bi, MCIS

Site PI: James G. Fujimoto, PhD

The Rationale for Quantitative Imaging in Glaucoma Diagnosis

David Huang, MD, PhD www.COOLLab.net

Visual field has poor repeatability

OHTS: 85.9% of abnormal and “reliable” fields were not confirmed on retest!

David Huang, MD, PhD www.AIGStudy.net

3 consecutive fields are required to reliably confirm glaucoma! “The proportion of VF test results that were normal subsequent to a VF POAG end point in eyes whose abnormality was confirmed by 2 consecutive, abnormal, reliable test results was significantly higher (73 [66%] of 110) compared with eyes whose abnormality was confirmed by 3 consecutive, abnormal, reliable test results. (46 [12%] of 381) (P=.01).” z

Keltner et al. for the Ocular Hypertension Treatment Study Group, Arch Ophthalmol 123:1201 (2005).

David Huang, MD, PhD www.AIGStudy.net

Structural loss precedes functional loss

Disc change precedes VF loss in most cases

David Huang, MD, PhD www.COOLLab.net

Quantitative Imaging may detect glaucoma at an earlier stage N

T

MD -1.2 dB PSD 1.75 dB

N

T

N

T

MD -1.73 dB PSD 1.62 dB

MD -1.77 dB PSD 1.71 dB VF Normal

David Huang, MD, PhD www.COOLLab.net

OCT Abn.

GDX Abn.

HRT Abn

Why use OCT? (rather than other imaging modalities)

David Huang, MD, PhD www.COOLLab.net

Let’s compare diagnostic accuracy

Stratus TD-OCT

GDx-ECC

HRT2

Scanning Laser Polarimetry Scanning Laser Tomography David Huang, MD, PhD www.COOLLab.net

Stratus OCT had significantly better diagnostic accuracy (best combination of continuous variables) Continuous scale Stratus: overall, Inferior or superior quadrant RNFL GDx-ECC NFI HRT2 C/D area ratio

AROC

P. v. OCT

0.92 0.87

0.006

0.83

0.0008

Lu ATH, Wang M, Varma R, Schuman JS, Greenfield DS, Smith SD, Huang D; Advanced Imaging for Glaucoma Study Group. Combining nerve fiber layer parameters to optimize glaucoma diagnosis with optical coherence tomography. Ophthalmology 2008;115:1352-7

David Huang, MD, PhD www.COOLLab.net

Previous literature comparisons Paper Pueyo et al.

AROC Stratus

GDx-VCC

HRT2

N

G

Overall RNFL

NFI 0.88*

MRA 0.90

66

73

NFI 0.88

Mikelberg 0.90

66

74

NFI 0.91

LDF 0.86

66

75

LDF 0.84

MHC N/I 0.86

50

41

J. Glaucoma 2007

0.91

Pueyo et al.

Overall RNFL

ARCH SOC ESP OFTALMOL 2006

0.93

Medeiros et al.

Arch Ophthalmol. 2004

Inferior RNFL

0.92

Zangwill et al. 5 o’clock RNLF 0.87

Arch Ophthalmol. 2001

# Subjects

NFI = nerve fiber index; MRA = Moorefields regression analysis; LDF = linear discriminant function; MHC = mean height contour, N/I = nasal/inferior

More accuarate NFL mapping with FD-OCT

David Huang, MD, PhD www.COOLLab.net

TD-OCT susceptible to eye movements •768 pixels (A‐ scans) captured  in 1.92 seconds is  slower than eye  movements •Stabilizing the  retina reveals  true scan path  (white circles)1

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

Scan location and eye movements affect results

Properly centered

T

S

N

I

Poorly centered: too inferior Poorly centered: too superior

T

Normal Double Hump

T

S

N

I

T

Inferior RNFL “Loss”

T

S

N

I

T

Superior RNFL “Loss”

FD-OCT can scan more points in less time – sampling greater area with less motion error RTVue FD-OCT Optic Nerve Head Map (ONH) 9510 a-scans 0.39 sec David Huang, MD, PhD www.COOLLab.net

New advances from the Advanced Imaging for Glaucoma Study: Mapping the Ganglion Cell Complex to Further Improve Glaucoma Diagnosis and Tracking

David Huang, MD, PhD www.COOLLab.net

Glaucoma affects 3 areas in the posterior segment of the eye

Cupping Nerve fiber thinning

Ganglion cell loss David Huang, MD, PhD www.COOLLab.net

Glaucoma preferentially thins the Ganglion Cell Complex (GCC) which includes the axons, cell bodies, and dendrites of retinal ganglion cells GCC

Normal NFL GCL IPL

}GCC

Glaucoma with thinner GCC

Ishikawa H , et al., IOVS 2005 Tan O, et al., Ophthalmology, 2008;115:949-56. David Huang, MD, PhD www.AIGStudy.net

GCC

Glaucoma: Macular Ganglion Cell Mapping RTVue FDFD-OCT, 26,000 A-scan perper-second 5 micron axial resolution

David Huang, MD, PhD www.AIGStudy.net

NFL GCL IPL

}GCC

Ganglion Cell Complex (GCC) 7 mm scan area 14,944 a-scans, 0.58 sec

}

Retina

GCC = Ganglion Cell Complex

mGCC thickness map

micron

GCC Deviation Map

% loss = actual scan value – normal value normal value

color coded map z

Percent loss value at each pixel location relative to normal based on age-adjusted normative database of over 300 healthy eyes z

Blue = thinning 20-30% relative to normal

z

Black = 50% loss or greater David Huang, MD, PhD www.AIGStudy.net

GCC Significance Map

color coded map shows regions where the change from normal reaches statistical significance z

Green = values within normal range (p-value 5% to 95%)

z

Yellow = borderline results (p-value < 5%)

z

Red = outside normal limits (p-value

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