OCT angiography of ONH blood flow in glaucoma
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1 Hawaiian Eye Meeting January 2013 OCT angiography of ONH blood flow in glaucoma David Huang, MD, Weeks Professor of Ophthalmic Research Professor of Ophthalmology & Biomedical Engineering Casey Eye Institute, Oregon Health & Science University Portland, Oregon Financial Interests: 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. Optovue, Inc.: stock options, patent royalty, grants, speaker honorarium & travel support Carl Zeiss Meditec, Inc.: patent royalty OCT captures tissue function as well as structure Signal Information En Face Cross Section Reflectance Anatomy Structural OCT Doppler shift (between consecutive A-scans) Decorrelation (between consecutive B-scans) Total retinal blood flow (global circulation) Angiography (local circulation) Functional OCT David Huang, MD, 1
2 Intensity Ultrahigh-Speed Swept-Source OCT Developed by MIT Optic & Quantum Electronic Group (Fujimoto) and OHSU Center for Ophthalmic Optics and Lasers (Huang) Performance features: 100,000 axial scans/sec 1050 nm tunable laser (deep penetration) 5.3 µm axial resolution in tissue Experimental System - Not FDA-approved Potsaid B, et al., Optics Express 2010; 18:20029 OCT amplitude-decorrelation angiography uses intrinsic contrast no dye injection! D1 D2 D3 D4 D5 D6 D7 flow 1 N 1 N 1 n 1 D n static 8 consecutive OCT scans at each position (M-B-scan Mode, N=8) Frame # An x, z An 1 x, z D xz, 1 n [ An x, z An 1 x, z ] 2 2 ( n 1 N 1) static tissue Problem: 8 frames at one position do not provide sufficient angiography quality Flow image Decorrelation blood flow 2
3 Decorrelation (a.u.) Solution: Split-Spectrum Amplitude Decorrelation (SSADA) Algorithm 32 low resolution OCT amplitude frame 28 decorrelation frame 8 high resolution OCT amplitude frame M-B frames (N=8) Split spectrum (M=4) averaged decorrelation 8 frames at one position now provides good angiography quality SSADA improves signal to noise ratio of flow detection Full Spectrum Less Background Noise FAZ Split Spectrum Clear Vessels Jia Y, Tan O, Tokayer J, Potsaid B, Wang Y, Liu JJ, Kraus MF, Subhash H, Fujimoto JG, Hornegger J, Huang D. Split-spectrum amplitude-decorrelation angiography with optical coherence tomography. Optics Express 2012; 20:4710 3
4 Decorrelation (a.u.) Comparison of Angiography Algorithms More continuous microvascular network Less Noise >2x SNR Full-Spectrum Amplitude Decorrelation Split-Spectrum Amplitude Decorrelation Jia Y, Tan O, Tokayer J, Potsaid B, Wang Y, Liu JJ, Kraus MF, Subhash H, Fujimoto JG, Hornegger J, Huang D. Split-spectrum amplitude-decorrelation angiography with optical coherence tomography. Optics Express 2012; 20:4710 Motion error can be removed with 3D registration of x-fast and y-fast scans X-Fast A 2X+2Y Registered B Kraus et al. Biomedical Optics Express 2012; 3:1182 Yali Jia,, David Huang, MD, 4
5 Decorr. Index (a.u.) log intensity (a.u.) 3D OCT angiography of optic nerve head SSADA algorithm used 500µm 3x3x3 mm OCT 3D angiography acquired in a 3-second scan Reflectance (Structure) Decorrelation (Flow) Jia Y, Tan O, Tokayer J, Potsaid B, Wang Y, Liu JJ, Kraus MF, Subhash H, Fujimoto JG, Hornegger J, Huang D. Split-spectrum amplitude-decorrelation angiography with optical coherence tomography. Optics Express 2012; 20:4710 OCT Angiography of the Optic Nerve Head Layer by Layer SSADA algorithm used 3x3x3 mm OCT 3D angiography acquired in a 3-second scan Jia Y, Tan O, Tokayer J, Potsaid B, Wang Y, Liu JJ, Kraus MF, Subhash H, Fujimoto JG, Hornegger J, Huang D. Split-spectrum amplitude-decorrelation angiography with optical coherence tomography. Optics Express 2012; 20:4710 5
6 Pilot Study Subject Characteristics Normal 20 eyes of 20 subjects Age: 50 ± 9 years (mean ± SD) Glaucoma 10 eyes of 10 subjects 6 perimetric glaucoma, 3 pre-perimetric glaucoma, 1 suspect (ocular hypertension) Age: 66 ±10 years David Huang, MD,, John Morrison, MD, Yali Jia, Variability of Disc Flow Index (2x 2y registered OCT angiogram) Normal Subjects Intra-Visit Repeatability (n = 3) Inter-Subject Variability (n = 20) 1.1% 4.8% Less variable than OCT NFL measurement! David Huang, MD,, John Morrison, MD, Yali Jia, 6
7 500µm Glaucoma reduced ONH flow index Visual field Structure (cslo) Blood flow Parameter Normal Glaucoma P Value* Mean deviation (db) Pattern standard deviation (db) Numbers displayed are mean ± population standard deviation; cslo, scanning laser ophthalmoscopy * Wilxson rank sum 0.05 ± ± ± ± 2.31 < Rim area (mm 2 ) 1.61 ± ± Cup/Disc area ratio 0.10 ± ± Disc flow index ± ± < Glaucoma caused a -19% drop of blood flow in optic disc David Huang, MD,, John Morrison, MD, Yali Jia, OCT Angiography Showing Reduced ONH Blood Flow in Pre-Perimetric Glaucoma Normal A (OS) ONH flow index = Normal Preperimetric Glaucoma (OS) PPG Disc Photo 500µm OCT Angiography ONH flow index = David Huang, MD,, John Morrison, MD, Yali Jia, 7
8 Whole Disc Flow Index Whole Disc Flow Index Whole Disc Flow Index Whole Disc Flow Index (db) ONH flow index vs. visual field 1 0 R = Glaucoma Suspect Visual Field PSD (db) David Huang, MD,, John Morrison, MD, Yali Jia, Difference between normal and glaucoma not due to age, cup/disc ratio or rim area Normal 0.07 Glaucoma Suspect Age (yr) Normal 0.07 Glaucoma Suspect C/D Area Ratio Normal 0.07 Glaucoma Suspect cslo Rim Area (mm 2 ) David Huang, MD,, John Morrison, MD, Yali Jia, 8
9 Summary & Conclusions ONH microcirculation is reduced in glaucoma Pre-perimetric changes can be detected by quantitative OCT angiography ONH flow index can be measured with high repeatability: 1.1 % CV Variability is small among normals: 4.8% CV OCT angiography with the SSADA algorithm may be a useful new tool in the evaluation of glaucoma David Huang, MD,, OCT Angiography (SSADA) v. Fluorescein/ICG Angiography OCT Advantages 3 dimensional Easily separates disc, retinal, and choroidal circulations Sections & projections along any plane Quantitative Flow index No injection No vomiting or anaphylactic reaction OCT Disadvantages Small field (3 mm) Field will increase with higher speed No visualization of leakage and stain But can visualize fluid space and thickening David Huang, MD, 9
10 R01 EY Consortium PI: David Huang MD, Ou Tan, Yimin Wang, Xinbo Zhang, Site PI: Rohit Brian Francis, Varma, MD, MPH MD Vikas Chopra, MD Site PI: David Greenfield, MD Mitra Sehi, Carolyn Quinn, MD Krisha S. Kishor, MD Robert DiLaura Sharon Bi, MCIS Site PI: Joel S. Schuman, MD Robert Noecker, MD Gadi Wollstein, MD Hiroshi Ishikawa, MD Larry Kagemann, MS Site PI: James G. Fujimoto, Acknowledgement of other supports Unrestricted grant from Research to Prevent Blindness 10
11 David Huang, MD, Ou Tan, Maolong Tang, Yan Li, Xinbo Zhang, Yali Jia, Janice Van Norman, COT Jason Tokayer, MS Kathleen S. Torok, MA 11
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