Fourier Domain OCT: The RTVue Michael J. Sinai, PhD Director of Clinical Affairs Optovue, Inc.

Rise of Structural Assessment with Scanning Lasers Scanning lasers provide objective and quantitative information for numerous ocular pathologies First appeared over 20 years ago as a research tool Today, structural assessment with retinal imaging devices has become an indispensable tool for clinicians

Role of imaging in clinical practice AAO preferred practice patterns recommends using scanning laser imaging in routine clinical exams In glaucoma, studies show imaging results can be as good as expert grading of high quality stereo-photographs1 Pre-perimetric glaucoma is now commonly accepted In OHTS, most converted based on structural assessment only (not fields) 2 OHTS has shown that imaging results have a high positive and negative predictive power for detecting glaucoma 3 Wollstein et al. Ophthalmology 2000 Kass et al. Arch Ophthalmol 2001 Zangwill LM, Weinreb RN, et al. Archives of Ophthalmol. 2005.

Birefringent structure 3 Imaging technologies have been shown to be effective in detecting and managing ocular pathologies Scanning Laser Polarimetry (SLP) Confocal Scanning Laser Ophthalmoscopy (CSLO) Optical Coherence Tomography (OCT) Retardation Light Polarizer Two polarized components Birefringent structure (RNFL)

SLP – GDx VCC Strengths Weaknesses Provides RNFL thickness Large database Easy to use/interpret (deviation map/automated classifier) Progression Weaknesses Atypical Pattern Birefringence (RNFL artifact)1 Converts retardation to thickness assuming uniform birefringence (not true) 2 Only RNFL information (No Optic Disc info and no Retina info) Data not backwards compatible Normal Glaucoma Atypical 1. Bagga, Greenfield, Feuer. AJO, 2005: 139: 437. 2. Huang, Bagga, Greenfield, Knighton IOVS, 2004: 45: 3037.

CSLO – HRT 3 Strengths Weaknesses Provides Optic Disc morphology Sophisticated Progression Analysis Large ethnic Specific Database comparisons Automated classifier Data backwards compatible Some retinal capabilities Cornea microscope attachment Weaknesses Only Optic Disc assessment (poor RNFL) Manual Contour Line drawing Reference plane based on surface height (can change) Retina analysis confined to edema detection and sensitive to image quality Cornea scans very difficult and impractical

OCT – Time Domain (Stratus from CZM and SLO/OCT from OTI) Strengths Provides Cross Sectional images Useful to calculate RNFL thickness Cross section scans useful for retinal pathologies Database comparisons Weaknesses Slow scan speed (400 A scans / second) Limited data for glaucoma, 768 pixel (A-scan) ring for RNFL Limited data for retina, 6 radial lines with 128 A scans (pixels) each Macula maps 97% interpolated No progression analysis Location of scan ring affects RNFL results Prone to motion artifacts because of slow scan speed Poor optic disc measurements

Time Domain 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 affects results Properly centered Poorly centered: too inferior Poorly centered: too superior T S N I T T S N I T T S N I T Normal Double Hump Inferior RNFL “Loss” Superior RNFL “Loss”

Time Domain OCT artifacts can be common Sadda, Wu, et al. Ophthalmology 2006;113:285-293 Ray, Stinnett, Jaffe . Am J Ophth 2005; 139:18-29 Bartsch, Gong, et al. Proc. of SPIE Vol. 5370; 2140-2151

The Future of OCT RTVue Fourier Domain OCT overcomes limitations of Time Domain OCT Devices Better resolution (5 micron VS 10 micron) Faster scan speeds (26,000 A scans / sec VS 400) 3-D data sets (won’t miss pathology) Large data maps (less interpolation) Progression capabilities Layer by layer assessment Versatility (Anterior Chamber Imaging) Retina Glaucoma Anterior Chamber

The Evolution of OCT Technology 40,000 RTVue 2006 26,000 20,000 Speed (A-scans per sec) Time domain OCT Fourier domain OCT ~ 65 x faster ~ 2 x resolution Zeiss OCT 1 and 2, 1996 Zeiss OCT1 debuted at 100 axial scans per second. The Stratus quadrupled the speed in 2002. 400 axial scans per second was sufficient to make OCT a standard for the diagnosis of many retinal diseases and glaucoma. By using the new Fourier-domain technology, OptoVue is introducing the RTVue OCT system at an amazing 26,000 axial scans per second, a whopping 65-fold advance over the Stratus. This generational leap in speed is greater than the difference between a 1920 biplane and the latest Boeing jet airliner. The RTVue also offer a 2-fold advance in resolution to 5 micron, close to the “ultrahigh-resolution” level. 400 Zeiss Stratus 2002 100 16 10 7 5 Depth Resolution (mm)

Comparison of OCT Images (Time Domain) 1996 Stratus OCT (Time Domain) 2002 RTVue (Fourier Domain) 2006

Drusen not visible in Stratus Time Domain OCT Case 1: AMD Stratus (Time Domain) RTVue (Fourier Domain) Drusen not visible in Stratus Time Domain OCT

Case 2: DME Stratus (Time Domain) RTVue (Fourier Domain)

Same eye, PED missed by Stratus Case 3: PED Stratus (Time Domain) RTVue (Fourier Domain) Same eye, PED missed by Stratus

Case 4: Macula Hole Stratus (Time Domain) RTVue (Fourier Domain)

Time Domain OCT vs Fourier Domain OCT A-scan generated sequentially one pixel at a time in depth Moving reference mirror 400 A scans per second 10 micron depth resolution B scan (512 A scans) in 1.28 sec Slower than eye movements Fourier Domain Entire A scan generated at once based on Fourier transform of spectrometer analysis Stationary reference mirror 26,000 A scans per second 5 micron depth resolution B scan (1024 A-scans) in 0.04 sec Faster than eye movements FD OCT can capture 2000 pixels simultaneously, while TD OCT captures one pixel at a time. So in the time it take TD OCT to form one single axial scan, FD OCT can capture an entire image. The higher speed and resolution of FD-OCT allows higher definition, or more pixels per image. As anyone familiar with high definition TV know, this makes the picture much sharper. Details such as small blood vessels and the photoreceptore inner and outer segment boundary become clearly visible. Because the FD OCT picture is captured in a small fraction of a second, there is no motion artifact that is commonly seen in conventional OCT images. Finally, because of the efficiency of simultaneous signal acquisition, FD OCT actually has higher signal, or appear brighter and cleaner, than TD OCT. Even deep choroidal vessels can be visible in normal eyes.

Summary of Fourier Domain OCT Advantages High speed reduces eye motion artifacts present in time domain OCT High resolution provides precise detail, allows more structures to visualized Layer by layer assessment Larger scanning areas allow data rich maps & accurate registration for change analysis 3-D scanning improves clinical utility

RTVue Clinical Applications Anterior Chamber Retina Glaucoma

Retina Analysis with the RTVue: Line Scans Cross Line Scan Provides vertical and horizontal high resolution B scan Image averaging increases S/N Data Captured: 1024 A scans (pixels) Time: 39 msec Area covered: 6 mm line (adjustable 2-12 mm) Data Captured: 2048 A scans (pixels) Time: 78 msec Area covered: 2 x 6 mm lines (adjustable 2-12 mm) Provides High resolution B scan Image averaging increases S/N

Line Scan: Cystoid Macula Edema Courtesy: Michael Turano, CRA Columbia University. Courtesy: Michael Turano, CRA Columbia University.

Retina Analysis with the RTVue: 3-D Scans Provides 3 D map Comprehensive assessment Fly through review C scan view SLO OCT image simultaneously captured Data Captured: 51,712 A scans (pixels) Time: 2 seconds Area covered: 4 x 4 X 2 mm (adjustable) 101 B scans each 512 A scans

3-D view reveals extent of damage over large area Top Image: En face view of retinal surface from 3-D scan Bottom Image: B scan from corresponding location (green line)

Full retinal thickness Retina Analysis with the RTVue: Macula Maps (MM5) Layer specific thickness maps Detailed B scans ETDRS thickness grid Data Captured: 19,496 A scans (pixels) Time: 750 msec Area covered: 5 mm x 5 mm (grid pattern) Provides: Full retinal thickness Inner retinal thickness Outer retinal thickness RPE/Choroid Elevation Surface Topography ILM to RPE ILM to IPL IPL to RPE RPE height ILM height

Glaucoma Analysis with the RTVue: Nerve Head Map 16 sector analysis compares sector values to normative database and color codes result based on probability values (p values) Provides Cup Area Rim Area RNFL Map Color shaded regions represent normative database ranges based on p-values TSNIT graph

Glaucoma Analysis with the RTVue: Nerve Head Map Parameters RNFL Parameters Optic Disc Parameters All parameters color-coded based on comparison to normative database

Glaucoma Analysis with the RTVue: Nerve Head Map Nerve Head Map (NHM) Ganglion Cell Map (MM7) 3-D Optic Disc Data Captured: 9,510 A scans (pixels) Time: 370 msec Area covered: 4 mm diameter circle Data Captured: 51,712 A scans (pixels) Time: 2 seconds Area covered: 4 x 4 X 2 mm Data Captured: 14,810 A scans (pixels) Time: 570 msec Area covered: 7 x 7 mm Provides Cup Area Rim Area RNFL Map Provides Ganglion cell complex assessment in macula Inner retina thickness is: NFL Ganglion cell body Dendrites Provides 3 D map Comprehensive assessment TSNIT graph

The ganglion cell complex (ILM – IPL) Inner retinal layers provide complete Ganglion cell assessment: Nerve fiber layer (g-cell axons) Ganglion cell layer (g-cell body) Inner plexiform layer (g-cell dendrites) The speed and resolution of the RTVue is also very useful in glaucoma diagnosis. In the Advanced Imaging for Glaucoma study, we use the RTVue to measure the ganglion cells over a wide macular area. Images courtesy of Dr. Ou Tan, USC

Normal vs Glaucoma Normal Glaucoma Cup Rim NHM4 RNFL Ganglion cell assessment with inner retinal layer map GCC Normal Glaucoma

Glaucoma Cases Optovue, RTVue

Glaucoma Patient Case BK 64 year old white male Normal 24-2 white on white visual field Nerve Head Map on RTVue

Glaucoma Patient Case BK Macula Inner Retina Map on RTVue Normal 10-2 white on white visual field

RTVue Normative Database Age Adjusted comparisons for more accurate comparisons Age and Optic Disc adjusted comparisons for Nerve Head Map scans Over 300 eyes, ethnically mixed, collected at 8 clinical sites worldwide IRB approved study from independent agency

Nerve Head Map (NHM4) with Database comparisons Patient Information RNFL Thickness Map RNFL Sector Analysis Optic Disc Analysis Parameter Tables TSNIT graph Asymmetry Analysis

Ganglion Cell Complex (GCC) with Database comparisons Patient Information GCC Thickness Map Deviation Map Parameter Table Significance Map

Early Glaucoma Borderline Sector results in Superior-temporal region Abnormal parameters OS Normal TSNIT dips below normal TSNIT shows significant Asymmetry

GCC Analysis may detect damage before RNFL GCC and RNFL analysis will be correlated, however GCC analysis may be more sensitive for detecting early damage

Glaucoma Progression Analysis (Nerve Head Map of stable eye) Thickness Maps Change in optic disc parameters TSNIT graph comparisons Change in RNFL parameters RNFL trend analysis

Glaucoma Progression Analysis (GCC of stable glaucomatous eye) Thickness Maps Deviation Maps Significance Maps GCC parameter change analysis

Versatility: Scanning the Anterior Chamber with the same device Cornea Adapter Module (CAM)

Higher resolution allows better visualization of LASIK flap 2 years after LASIK with mechanical microkeratome Image enhanced by frame averaging

Post-LASIK interface fluid & epithelial ingrowth 056-CP Post-LASIK interface fluid & epithelial ingrowth Epithelial ingrowth Fluid Fibrosis

Higher resolution helps visualize pathogens Acanthamoeba in 0.25% agar

Pachymetry Maps Inferotemporal thinning Normal Keratoconus

Angle Measurements Normal Narrow

Narrow angle after peripheral iridotomy LD044, OS Narrow angle after peripheral iridotomy Limbus Angle Opening Distance 500 mm anterior to scleral spur (AOD 500) Scleral spur 47

Normal Angle MaTa, OD Limbus Trabecular meshwork-Iris Space 750 mm anterior to scleral spur (TISA750) Scleral spur 48

Advantages of the RTVue 5 micron resolution allows more structures and detail to be visualized High speed allows larger areas to be scanned Layer by layer assessment Data-rich maps Volumetric analysis Comprehensive glaucoma assessment (Cup, Rim, RNFL, ganglion cell complex) Normative Database Progression Analysis Anterior Chamber imaging

Thank You!