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