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