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1
Big Trends in the History of
OCT – Inventor’s Perspective
David Huang, MD, PhD
Weeks Professor of Ophthalmic Research
Prof. of Ophthalmology & Biomedical Engineering
Casey Eye Institute,
Oregon Health & Science University
Portland, Oregon
Financial Interests: Optovue, Inc.: stock options, patent royalty, grants, speaker honorarium & travel support
Carl Zeiss Meditec, Inc.: patent royalty
Ophthalmic Photographers’ Society Meeting
Orlando, Florida, 23 October 2011
I have the following financial interests or relationships to disclose:
Dr. D. Huang has a significiant financial interest in Optovue, a company that may have a commercial interest in the results of this research and technology. This potential individual conflict of interest has been reviewed and managed by OHSU.
Financial Disclosure
2
Prof. James G. Fujimoto
MIT Ultrafast Optics Group
Low-Coherence Interferometry
Coherent Light Low Coherence Light
Axial resolution
Beamsplitter
Light
source
Reference mirror
Detector
Reflected measurement beam
Courtesy of Michael Hee, MD, PhD
3
Huang D, Wang J, Lin CP, Puliafito CA, Fujimoto
JG. Micron-resolution ranging of cornea and
anterior chamber by optical reflectometry.
Lasers Surg Med 1991;11:419-25
4
OCT Scanning
Axial Scan Transverse Scan
CorneaCornea
AqueousAqueous
LensLens
IrisIris
ScleraSclera
Log Reflection Log Reflection 4 mm4 mm
Prof. James Fujimoto
MIT
OCT started
with retinal
imaging
•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; 254:1178
•Fercher AF, Hitzenberger CK, Drexler W, Kamp G, and
Sattmann H, In Vivo Optical Coherence Tomography. Am J
Ophthalmol 1993; 116:113.
•Swanson EA., Izatt JA, Hee MR, Huang D Lin CP, Schuman
JS, Puliafito CA, Fujimoto JG. In vivo retinal imaging by
optical coherence tomography. Optics Letters 1993; 18:1864.
5
OCT and the Eye:
A Perfect Match
OCT
High resolution
Shallow penetration
Thin layers (retina, cornea)
Clear media
Eye
The ‘501 OCT Patent
Eric Swanson, MS
(MIT Lincoln Laboratory,
Sycamore Networks,
Lightlab)
E.A. Swanson, D. Huang, J.G. Fujimoto, C.A. Puliafito, C.P. Lin, J.S. Schuman.
“Methods and Apparatus for Optical Imaging with means for controlling the
longitudinal range of the sample.” U.S. patent No. 5,321,501, issued June 14, 1994.
6
CorneaCornea
AqueousAqueous
LensLens
IrisIris
ScleraSclera
Log Reflection Log Reflection 4 mm4 mm
Izatt JA, Hee MR, Swanson EA, Lin CP, Huang D, Schuman JS, Puliafito CA,
Fujimoto JG. Micrometer-scale resolution imaging of the anterior eye in vivo with
optical coherence tomography. Archives of Ophthalmology 1994;11:1584-9.
The First Corneal OCT
Joseph Izatt, PhD
(MIT, Case Western Reserve U, Duke)
Hee MR, Izatt JA, Swanson EA, Huang D, Schuman JS, Lin CP, Puliafito CA,
Fujimoto JG. Optical coherence tomography of the human retina. Archive of
Ophthalmology 1995;113:325-32
The First Clinical Retinal OCT
Michael Hee, MD, PhD
(Harvard-MIT, UC San Francisco)
Carmen Puliafito, MD, MBA
(Harvard, Tufts, U Miami, USC)
7
JS Schuman et al. Arch Ophthalmol, 113:586 (1995).
The First Glaucoma OCT
Joel Schuman, MD
(Harvard, Tufts, U Pittsburgh)
OCT prototype -1994
45 A-scans / sec, 16µm resolution
Jay Wei, OCT project leader, Humphrey Instruments, 1994
CEO, Optovue, Inc. 2006-present
8
2006: A Generational Leap
A jump of 65x speed & 2x resolution
Zeiss
OCT1/2
1996
Zeiss Stratus
2002
2006
26,000
400
100
16 10 5
Speed
(A-scans
/sec)
Resolution (mm)
Fourier domain
Time domain
David Huang, MD, PhD www.COOLLab.net
Commercial Ophthalmic OCT Evolution
Zeiss
OCT1/2
1996
Zeiss
OCT3
2002
Optovue
RTVue
2006
100Hz
16 µm
400Hz
10µm
26,000Hz
5µm
9
Frame registration and averaging
further enhances image quality
Tracked and registered 100-frame average, Optovue 2011
Fourier-Domain Technology Lead to An
Explosion of New OCT Products
Zeiss Cirrus Optovue RTVue Heidelberg Spectralis
Bioptigen Topcon 3D-OCT Optopol Copernicus OTI OCT SLO
Tomey SS-1000
Michael Hee & David Huang
10
CNV 1 month after
Ranibizumab (Lucentis)
subretinal fluid decreased
Choroidal neovascularization (CNV)
David Huang, MD, PhD
www.COOLLab.net
#1 Application of OCT: Monitoring Treatment of Wet Age-
Related Macular Degeneration with Anti-VEGF agent
OCT procedures surpassed the sum of
other ophthalmic imaging procedures
0
1,000,000
2,000,000
3,000,000
4,000,000
5,000,000
6,000,000
7,000,000
8,000,000
9,000,000
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
Nu
mb
er o
f A
llow
ed S
ervi
ces
Year
Allowed CPT 92135 Medicare Services vs Year
92235
92250
92135
Fluorescein angiography
Fundus photography
OCT*
*OCT represents 92% of CPT 92235 procedures according to statistics from 3 eye centers
Swanson EA, Huang D. Ophthalmic OCT reaches $1 billion per year. Retina Physician, 2011.
11
OCT now paid less per procedure than
other ophthalmic imaging modalities
Fluorescein angiography
Fundus photography
$0
$20
$40
$60
$80
$100
$120
$140
$160
$180
1999 2000 2001 2002 2003 2004 2005 2006 2007 2008 2009 2010
Co
st/S
eriv
e
Year
Medicare CPT 92135 Cost/Service vs Year
92235
92250
92135
OCT*
*OCT represents 92% of CPT 92235 procedures according to statistics from 3 eye centers
Swanson EA, Huang D. Ophthalmic OCT reaches $1 billion per year. Retina Physician, 2011.
OCT-related research funding 2000-2011
estimated $500M from governments worldwide
Swanson EA, One decade and $500M: The impact of federal funding on OCT. BioOptics
World, 2011.
12
OCT charges likely surpassed $1 Billion worldwide in 2010
• Estimated 9,000,000 Medicare CPT 92135 procedures
• Estimated 8,289,000 Medicare OCT procedures (92% of CPT 92135)
• Estimated 16,257,000 U.S. OCT procedures (Medicare = 51% of total in 3 surveyed centers)
• Average reimbursement $48 per procedure
• Estimated $780M OCT charges in U.S.A.
• Worldwide utilization likely surpass $1B
Swanson EA, Huang D. Ophthalmic OCT reaches $1 billion per year. Retina Physician, 2011.
OCT is also taking off in cardiovascular
diseases and other fields
13
More Speed &
Penetration
The next generation of
ophthalmic OCT systems
may use different
technologies
Longer wavelength (1050 nm)
penetrates deeper into lamina
cribrosa
Ultrahigh-speed OCT provides full-sampled
3-dimensional volumetric scans
Optic nerve head
3D
En face
C-scans
Ultrahigh-Speed 1050 nm Swept-Source OCT, James G. Fujimoto, MIT Optics & Quantum Electronics Group & New England Eye Center
Present by Yueli Chen et al., SPIE Photonics West BIOS 2009
14
Outer Choroid Inner Choroid
Photoreceptors &
Retinal Pigment Epithelium
Ultrahigh-Speed 1050 nm Swept-Source OCT, James G. Fujimoto, MIT Optics & Quantum Electronics Group & New England Eye Center
Present by Yueli Chen et al., SPIE Photonics West BIOS 2009
Ganglion Cell Layer
Outer Plexiform &
Outer Nuclear Layers
Inner plexiform &
Inner Nuclear Layers Retinal Nerve Fiber Layer
Ultrahigh-speed OCT provides detailed
layer-by-layer view of the retina and choroid
Macula C-scans
High-speed and special registration algorithm makes
possible wide-field motion artifact-free 3D OCT cube scans
En face view of
3D OCT cube
SS-OCT System: Ben Potsaid,
James G. Fujimoto, et al. MIT
3D registration algorithm: Martin Kraus,
Hoachim Hornegger, U. Erlangen
Images: Ou Tan, David Huang www.COOLLab.net
15
Retinal Angiography &
Blood Flow Measurement
OCT is going beyond structure
Double
circular scan
transects all
retinal branch
vessels 6
times per
second
Inner Circle
Outer Circle
David Huang, MD, PhD www.AIGStudy.net
Wang Y, Lu A, Gil-Flamer J, Tan O, Izatt JA, Huang D, Measurement of
total blood flow in the normal human retina using Doppler Fourier-domain
optical coherence tomography. Br J Ophthalmol 2009;93:634-637
16
Semi-automated grading software was
developed for Doppler OCT reading center
Probe beam
Doppler angle
En face view of
3D OCT scan
Vessel-normal
vector
Vessel cross-sections from
double circular scans
Doppler OCT of Retinal Circulation (DOCTORC) software uses both double-circular
and 3D volumetric scans
Flow vector
Ou Tan, PhD & David Huang, MD, PhD www.COOLLab.net
Glaucoma, PDR and NAION Show Different
Patterns of Retinal Blood Flow Change
Group
(# of eyes)
Blood Flow
(μl/min)
Venous Area*
(mm2)
Venous
Velocity
(mm/s)
Arterial
Area*
(mm2)
Arterial
Velocity
(mm/s)
Normal
(20) 47.6 ± 5.4 0.046 ± 0.008 17.7 ± 3.1 0.033 ± 0.005 24.6 ± 4.0
Glaucoma
(16)
34.1 ± 4.9
(p<0.001)
0.046 ± 0.008
(p=0.977)
12.7 ± 1.7
(p<0.001)
0.034 ± 0.008
(p=0.454)
17.1 ± 3.6
(p<0.001)
NAION
(7)
28.2 ± 8.2
(p<0.001)
0.030 ± 0.007
(p<0.001)
15.4 ± 3.2
(p=0.109)
0.025 ± 0.006
(p=0.002)
19.0 ± 3.4
(p=0.003)
PDR
(5)
15.8 ± 10.1
(p<0.001)
0.024 ± 0.007
(p<0.001)
10.4 ± 3.6
(p=0.001)
0.018 ± 0.011
(p<0.001)
16.0 ± 5.0
(p=0.001)
Wang Y, Fawzi AA, Varma R, Sadun AA, Zhang X, Tan O, Izatt JA, Huang D. Pilot Study of Optical Coherence
Tomography Measurement of Retinal Blood Flow in Retinal and Optic Nerve Diseases. IOVS 2010
17
Visual field was independently correlated
with both blood flow and neural tissue loss
Model Blood Flow OCT NFL R2
BF 1.91 (<0.001) 0.29
NFL 3.29(0.01) 0.13
BF + NFL 1.62 (0.001) 2.56 (0.03) 0.33
Regression coefficients (p-value) in the perimetric glaucoma group
BF = blood flow; NFL = nerve fiber layer thickness
All values in dB scale normalized against 27 normal eyes.
Models for visual field mean deviation in 47 eyes with perimetric glaucoma
David Huang, MD, PhD www.AIGStudy.net
Both NFL and Doppler scans were performed on the
Optovue RTVue FD-OCT system
RTVue is FDA-approved for ocular imaging
Experimental Doppler software not yet FDA-approved
Blood flow has a direct effect on visual function
independent of neural structural loss
Elevated IOP
Loss of retinal
ganglion cells &
nerve fibers
Loss of visual
field
Decreased
blood flow
David Huang, MD, PhD www.AIGStudy.net
18
OCT Amplitude Decorrelation Angiography
of The Macula
500 µm
0.1
0.2
0.3
3
4
5
3.0
5.0
log
in
ten
sit
y (
a.u
.)
0.1
0.3
Deco
rr. In
dex (
a.u
.)
Retinal Choroidal
500µm
Angiography algorithm: Yali Jia, David Huang, OHSU www.AIGStudy.net
SS-OCT System: Ben Potsaid, James G. Fujimoto, et al. MIT
OCT Amplitude Decorrelation Angiography
of The Optic Nerve Head
0.1
0.2
0.3
3
4
5
3.0
5.0
log
in
ten
sit
y (
a.u
.)
0.1
0.3
Deco
rr. In
dex (
a.u
.)
Structure Flow
Angiography algorithm: Yali Jia, David Huang, OHSU www.AIGStudy.net
3D registration algorithm: Martin Kraus, Hoachim Hornegger, U. Erlangen
19
OCT Amplitude Decorrelation Angiography
of The Optic Nerve Head – Layer by Layer
Angiography algorithm: Yali Jia, David Huang, MD, OHSU www.AIGStudy.net
SS-OCT System: Ben Potsaid, James G. Fujimoto, et al. MIT
3D registration algorithm: Martin Kraus, Hoachim Hornegger, U. Erlangen
David Huang,
MD, PhD
Maolong Tang,
PhD
Yan Li,
PhD
Ou Tan,
PhD
Yimin Wang,
PhD
Xinbo Zhang,
PhD
www.COOLLab.net
Jason Tokayer,
MS
Janice Van
Norman, COT Matthew Bald
Michelle
Montalto
Yali Jia,
PhD
Kathleen S.
Torok, MA
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