adaptive optics and octa€¦ · octa is becoming a staple of retinal clinical practice in the...
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Judy E. Kim, MDProfessor of Ophthalmology
Medical College of Wisconsin
Adaptive Optics and OCTA:Update on Retinal Imaging
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Financial Disclosure
▪ Advisory Board▪ Alimera Science, Allergan, Bayer, Novartis
▪ Research Equipment▪ Optos, Notal Vision
▪ None related to this presentation
▪ Device for research use only and not yet FDA approved
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What is OCT Angiography?
▪A non invasive way of performing
retinal angiography without the use
of extraneous dyes
▪Done using newer generation OCT
machines
▪ Takes 3-4 secs per eye
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OCTA: How is it done?
• Speed
• Resolution
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Depth Resolved Microvasculature
3x3mm
Total Superficial
Intermediate Deep
Choriocapillaris
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Pressing Questions
▪ Where is OCTA clinically useful? What does it do better than what we have now?
▪ Does it add to information from standard imaging modalities
▪ Does it allow for better follow up
▪ Does it drive better treatment options
▪ Does it improve prognosis
▪ What are the cost and time implications
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Disease Modalities
▪ Diabetic retinopathy
▪ Choroidal neovascularization
▪ Exudative AMD
▪ Non-exudative AMD
▪ Other retinal vascular disease
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OCTA in Diabetic Retinopathy
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OCTA in Diabetic Retinopathy
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Vessel Density
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Vision Limiting Macular Ischemia
2.8.161.4.16 8.8.16 10.31.16
VA 20/200 VA 20/70 VA 20/50 VA 20/40
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OCTA in PDR
▪ Identify NV
▪ Follow NV for regression
▪ Follow NV for re-growth
NVD
Well delineated abnormal vessels
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Disease Modalities
▪Diabetic retinopathy
▪Choroidal neovascularization
▪Other retinal vascular disease
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OCTA of CNV: Type 1
Flow underPED
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Kuehlewein L, Dansingani KK, de Carlo TE, Bonini Filho MA, Iafe NA, Lenis TL, Freund KB, Waheed NK, Duker JS, Sadda SR, Sarraf D. OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF TYPE 3 NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION. Retina. 2015;35:2229-35.
Type 3 CNV
OCTA of CNV: Type 3
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OCTA: Sensitivity and Specificity• Investigated CNV qualities on OCTA
• Sensitivity and specificity of CNV detection by OCTA using
FA as the gold standard:• Sensitivity = 4/8 (50%)
• Specificity = 20/22 (91%)
• Sensitivity 70-100% in type 1 CNV
CNV on FA
No CNV on FA
CNV on OCTA
4 2 6
No CNV on OCTA
4 20 24
8 22 30
• de Carlo TE, Bonini Filho MA, Chin AT, Adhi M, Ferrara D, Baumal CR, Witkin AJ, Reichel E, Duker JS, Waheed NK. Ophthalmology. 2015 Jun;122(6):1228-38.
• Bonini Filho MA, de Carlo TE, Ferrara D, Adhi M, Baumal CR, Witkin AJ, Reichel E, Duker JS, Waheed NK.. JAMAOphthalmol. 2015 Aug;133(8):899-906.
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CNV 1 Week Post-
InjectionCNV 3 Weeks
Post-Injection
OCTA: Size of Lesion
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CNV Treatment Effect: Size of lesion
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Case # 1
▪ 58-year-old Asian man followed for dry AMDOD 20/50 OS 20/70+2
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OD Depth-encoded OCTA
Neovascular ‘Dry’ AMD
OS
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Disease Modalities
▪Choroidal neovascularization
▪Diabetic retinopathy
▪Other retinal vascular disease
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BRVO on OCTA
FA OCTA Wide-Field Montage
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Clinical Utility of OCTA
▪ Multidimensional imaging modality▪ OCTA provides all the information that you would get in a regular OCT, AND provides
cross-registered vascular information
▪ Depth Resolved▪ Can separate out the superficial from the deep layers of vasculature
▪ Non-Invasive and Fast▪ Repeat at multiple visits and to closely monitor patients
▪ Acquisition times are 3-4s per eye.
▪ Total time in room is 10 mins
▪ OCTA is becoming a staple of retinal clinical practice in the diagnosis and management of AMD, DR and Retinal Vascular Disease
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Adaptive Optics
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Joseph Carroll, PhD
Robert Cooper, PhD
Alfredo Dubra, PhD
Mara Goldberg
Brian Higgins
Chris Langlo
Drew Scoles, PhD
Yusufu Sulai, PhD
Phyllis Summerfelt
Melissa Wilk
Tom Connor, Jr, MD
Dennis Han, MD
Judy Kim, MD
David Weinberg, MD
William Wirostko, MD
Shawn Batson
Shawn Hanson
Drew Davis, MD
Peter Karth, MD
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?
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Adaptive Optics
▪ Technology used to improve the
performance of optical systems by
reducing the effect of wave front
distortions
▪Corrects aberrations in lens and cornea
that distort wavefront
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Components of Adaptive Optics
WavefrontSensor
WavefrontCorrector
Lenslet array CCD array
Δxi
Controller
S V
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Components of Adaptive Optics
WavefrontSensor
WavefrontCorrector
Lenslet array CCD array
Δxi
Controller
S V
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How does it work?
flatmirror
deformablemirror
Courtesy of Geunyoung Yoon
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3
3.5
Retinal Images
No AO correction AO correction
50 mm
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Resolutions of Adaptive Optics
Retinal Cameras
AO-fundus camera
AO-confocal SLO
AO-SD OCT
Lateral Axial
2 mm
2 mm
2 mm
60 mm
20 mm
3 mm
Resolution
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Resolutions of Adaptive Optics
Retinal Cameras
AO-fundus camera
AO-confocal SLO
AO-SD OCT
Lateral Axial
2 mm
2 mm
2 mm
60 mm
20 mm
3 mm
Resolution
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50 um
A
B
Courtesy: Mina Chung, MD
AOSLO montage overlaid
on fundus photo
Cone mosaic 10 from foveal
center
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Create a montage from
many locations
Cone Density Profile
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Cone-rod dystrophy
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AOSLO montage overlaid on fundus photograph
of a patient with MacTel : 10o from fovea
Courtesy: Hongxin Song, MD PhD and Mina Chung MD
AB
50 um
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Rod Image @ 10 degreeHistology In vivo Image
A. Dubra, Y. Sulai, J.L. Norris, et al. Biomed. Opt. Express 2011; 2 (7): 1864-1876
rods
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Foveal Cones
Scale bar: 10μm
A. Dubra, Y. Sulai, J.L. Norris, et al. Biomed. Opt. Express 2011; 2 (7): 1864-1876
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Cone Reflectance Variation Over Time
R.F. Cooper, A.M. Dubis, A. Pavaskar, J. Rha, A. Dubra , J. Carroll
Biomed. Opt. Express 2011; 2(9): 2577-2589
“Twinkle Twinkle Little Cones”
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Rod Reflectance Variation Over Time
R.F. Cooper, A.M. Dubis, A. Pavaskar, J. Rha, A. Dubra and J. Carroll
Biomed. Opt. Express 2011;2(9): 2577-2589
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J.I. W. Morgan, A. Dubra, R. Wolfe, W.H. Merigan and D.R. Williams. IOVS 2009;50:1350-1359
Retinal Pigment Epithelial Cell Mosaic
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Nerve Fiber Layer
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Glaucoma
62 y.o. female
D.H. Scoles, Y.N. Sulai, A.D. Manguikian, S. Shareef and A. Dubra. 2012 ARVO Meeting Abstract 53:6957
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500 μm
Glaucoma
D.H. Scoles, Y.N. Sulai, A.D. Manguikian,
S. Shareef and A. Dubra
2012 ARVO Abstract 53:6957
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1°
Optic Nerve Imaging: Lamina Cribrosa
Courtesy: Imagine Eyes
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Vascular Imaging and Perfusion Maps:
50 µm
Standard deviation
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Scale bar: 100 µm
Foveal Perfusion Map: Normal Subject
Without Fluorescein Dye
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▪Despite macular hole (MH) closure
following pars plana vitrectomy (PPV)
surgery, vision loss or metamorphopsia
may persist
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▪Despite macular hole (MH) closure
following pars plana vitrectomy (PPV)
surgery, vision loss or metamorphopsia
may persist
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▪SD-OCT studies have shown that mild
outer segment changes are common in
the early post-operative course
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Macular Hole Closure
▪What is going on at the
photoreceptor layer at the
fovea following surgery?
▪Why are there differences in
VA even when MH is closed?
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100µm 100µm
Case 1: 3 months post-op VA 20/50 -
2Case 1: 3 months post-op VA 20/50 -2
Case 1: 3 months post-op VA 20/50 -2Case 1: 3 months post-op
VA 20/50-2
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100µm 100µm
Case 1: 3 months post-op VA
20/50-2
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100µm 100µm
Case 1: 3 months post-op VA
20/50-2
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100µm 100µ
Case 1: 3 months post-op VA
20/50-2
17 months post-op
VA 20/30-2
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100µm 100µm
Case 1: 3 months post-op VA
20/50-217 months post-op
VA 20/30-2
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12 months post-op
VA 20/30
100 mm
100 mm
Case 2: 3 months post-op
VA 20/80
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Case 2: 3 months post-op
VA 20/8012 months post-op
VA 20/30
100 mm
100 mm
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Case 2: 3 months post-op
VA 20/80
12 months post-op
VA 20/30
100 mm 100 mm
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▪Significant photoreceptor disruption
appears to exist following MH closure
▪Remodeling of the foveal cone mosaic
can continue following surgery, perhaps
accounting for the delayed post-
operative VA improvements
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Cones present
but not wave-guiding
“Dark Cones”
Cones are absent
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AO SLO Imaging of Photoreceptors
Visualization of cone structure with confocal
AOSLO relies on IS/OS alignment and intact outer
segment structure
Scoles D, et al., In vivo imaging of human cone photoreceptor inner segments, IOVS 2014:6;55(7):4244-51
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AO SLO Imaging of Photoreceptors
Visualization of cone structure with confocal
AOSLO relies on IS/OS alignment and intact outer
segment structure
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Split Detector AOSLO
• Captures the non-confocal light and divides it spatially
• Creates good contrast for structures that scatter light
• Blood vessels
• Rounded pole of photoreceptor inner segments
Scoles D, et al., In vivo
imaging of human cone
photoreceptor inner
segments, IOVS
2014:6;55(7):4244-51
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Scoles D, et al., In vivo imaging of human cone
photoreceptor inner segments, IOVS 2014:6;55(7):4244-51
Co
nfo
cal
AO
SLO
Split
Dete
cto
r
AO
SLO
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Scoles et al. (submitted)
Confocal AO Split detector AO
100 mm
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Variable Foveal Cone Structure in Achromatopsia
300 mm
CNGB3
c.1148 delC: p.Thr383fs
c.983T>A: p.Met328Lys
CNGB3
c.1148 delC: p.Thr383fs
c.1255G>T: p.Glu419stop
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Achromatopsia (ACHM)
• Autosomal recessive; ≈1 in 33,000 incidence
• Caused by defects in CNGA3, CNGB3, GNAT2,
PDE6C, PDE6H, or ATF6
• Affected individuals are thought to have no cone
function (though see Nishiguchi, et al., 2005)
• Photophobia, reduced acuity, nystagmus
• Histological data concerning remnant cone structure
is variable, ranging from normal numbers in the fovea
(Falls et al., 1965) to reduced numbers throughout
(Larsen, 1921)
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Variable Foveal Cone Structure in Achromatopsia
100 mm
300 mm
CNGB3
c.1148 delC: p.Thr383fs
c.983T>A: p.Met328Lys
CNGB3
c.1148 delC: p.Thr383fs
c.1255G>T: p.Glu419stop
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▪ Recent success in retinal gene therapy
▪ May be possible to restore cone function in
some retinal disorders
“…identifying and then targeting retinal
locations with retained photoreceptors will be
a prerequisite for successful gene therapy in
humans…” Jacobson et al. (2005)
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Why is AO needed?
▪ Necessary to detect photoreceptor loss early
▪ Assist in selection of candidates for therapies
▪ Earlier detection of treatment effect
20/20 20/20
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▪ Assist in better understanding of
photoreceptor structure and vessels
▪ Allow assessment of the therapeutic
potential and outcomes in patients with retinal disorders
AO Imaging