Imaging limbal and scleral vasculature using Swept Source Optical Coherence Tomography

We demonstrate application of high-speed swept source optical coherence tomography for vessel visualization in the anterior segment of the human eye. The human corneo-scleral junction and sclera was imaged in vivo. Imaging was performed using a swept source OCT system operating at 1050nm wavelength range and 100kHz A-scan rate. The high imaging speed enables generation of 3D depth-resolved vasculature maps. The vessel visualization method revealed the rich vascular system in the conjunctiva and episclera.National Institutes of Health (U.S.) (NIH grant R01-EY011289-25)National Institutes of Health (U.S.) (NIH grant R01-EY013178-11)National Institutes of Health (U.S.) (NIH grant R01-EY01356-06)National Institutes of Health (U.S.) (NIH grant R01 CA075289-15)United States. Air Force Office of Scientific Research (FA9550-10-1-0551)United States. Air Force Office of Scientific Research (FA9550-10-1-0063)Foundation for Polish Science (KOLUMB Programme; KOL/3/2010I

Documentation of Intraretinal Retinal Pigment Epithelium Migration via High-Speed Ultrahigh-Resolution Optical Coherence Tomography

Purpose To describe the features of intraretinal retinal pigment epithelium (RPE) migration documented on a prototype spectral-domain, high-speed, ultrahigh-resolution optical coherence tomography (OCT) device in a group of patients with early to intermediate dry age-related macular degeneration (AMD) and to correlate intraretinal RPE migration on OCT to RPE pigment clumping on fundus photographs. Design Retrospective, noncomparative, noninterventional case series. Participants Fifty-five eyes of 44 patients seen at the New England Eye Center between December 2007 and June 2008 with early to intermediate dry AMD. Methods Three-dimensional OCT scan sets from all patients were analyzed for the presence of intraretinal RPE migration, defined as small discreet hyperreflective and highly backscattering lesions within the neurosensory retina. Fundus photographs also were analyzed to determine the presence of RPE pigment clumping, defined as black, often spiculated, areas of pigment clumping within the macula. The en face OCT images were correlated with fundus photographs to demonstrate correspondence of intraretinal RPE migration on OCT and RPE clumping on fundus photography. Main Outcome Measures Drusen, dry AMD, intraretinal RPE migration, and RPE pigment clumping. Results On OCT scans, 54.5% of eyes (61.4% of patients) demonstrated intraretinal RPE migration. Of the fundus photographs, 56.4% demonstrated RPE pigment clumping. All eyes with intraretinal RPE migration on OCT had corresponding RPE pigment clumping on fundus photographs. The RPE pigment migrated most frequently into the outer nuclear layer (66.7% of eyes) and less frequently into more anterior retinal layers. Intraretinal RPE migration mainly occurred above areas of drusen (73.3% of eyes). Conclusions The appearance of intraretinal RPE migration on OCT is a common occurrence in early to intermediate dry AMD, occurring in 54.5% of eyes, or 61.4% of patients. The area of intraretinal RPE migration on OCT always correlated to areas of pigment clumping on fundus photography. Conversely, all but 1 eye with RPE pigment clumping on fundus photography also had areas of intraretinal RPE migration on OCT. The high incidence of intraretinal RPE migration observed above areas of drusen suggests that drusen may play physical and catalytic roles in facilitating intraretinal RPE migration in dry AMD patients.National Institutes of Health (U.S.) (Contract RO1-EY11289-23)National Institutes of Health (U.S.) (Contract R01-EY13178-07)National Institutes of Health (U.S.) (Contract R01-EY013516-07)United States. Air Force Office of Scientific Research (FA9550-07-1-0101)United States. Air Force Office of Scientific Research (FA9550-07-1-0014

Parafoveal Retinal Vascular Response to Pattern Visual Stimulation Assessed with OCT Angiography

We used optical coherence tomography (OCT) angiography with a high-speed swept-source OCT system to investigate retinal blood flow changes induced by visual stimulation with a reversing checkerboard pattern. The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm was used to quantify blood flow as measured with parafoveal flow index (PFI), which is proportional to the density of blood vessels and the velocity of blood flow in the parafoveal region of the macula. PFI measurements were taken in 15 second intervals during a 4 minute period consisting of 1 minute of baseline, 2 minutes with an 8 Hz reversing checkerboard pattern stimulation, and 1 minute without stimulation. PFI measurements increased 6.1±4.7% (p = .001) during the first minute of stimulation, with the most significant increase in PFI occurring 30 seconds into stimulation (p<0.001). These results suggest that pattern stimulation induces a change to retinal blood flow that can be reliably measured with OCT angiography.National Institutes of Health (U.S.) (Grant R01 EY013516)National Institutes of Health (U.S.) (Grant Rosenbaum's P30EY010572)Research to Prevent Blindness, Inc. (United States) (Grant R01-Ey11289-26)United States. Air Force Office of Scientific Research (FA9550-10-1-0551

Speckle reduction in swept source optical coherence tomography images with slow-axis averaging

The effectiveness of speckle reduction using traditional frame averaging technique was limited in ultrahigh speed optical coherence tomography (OCT). As the motion between repeated frames was very small, the speckle pattern of the frames might be identical. This problem could be solved by averaging frames acquired at slightly different locations. The optimized scan range depended on the spot size of the laser beam, the smoothness of the boundary, and the homogeneity of the tissue. In this study we presented a method to average frames obtained within a narrow range along the slow-axis. A swept-source OCT with 100,000 Hz axial scan rate was used to scan the retina in vivo. A series of narrow raster scans (0-50 micron along the slow axis) were evaluated. Each scan contained 20 image frames evenly distributed in the scan range. The imaging frame rate was 417 HZ. Only frames with high correlation after rigid registration were used in averaging. The result showed that the contrast-to-noise ratio (CNR) increased with the scan range. But the best edge reservation was obtained with 15 micron scan range. Thus, for ultrahigh speed OCT systems, averaging frames from a narrow band along the slow-axis could achieve better speckle reduction than traditional frame averaging techniques

Assessment of Artifacts and Reproducibility across Spectral- and Time-Domain Optical Coherence Tomography Devices

Purpose To report the frequency of optical coherence tomography (OCT) scan artifacts and to compare macular thickness measurements, interscan reproducibility, and interdevice agreeability across 3 spectral-domain (SD) OCT (also known as Fourier domain; Cirrus HD-OCT, RTVue-100, and Topcon 3D-OCT 1000) devices and 1 time-domain (TD) OCT (Stratus OCT) device. Design Prospective, noncomparative, noninterventional case series. Participants Fifty-two patients seen at the New England Eye Center, Tufts Medical Center Retina Service, between February and August 2008. Methods Two scans were performed for each of the SD OCT protocols: Cirrus macular cube 512×128 (software version 3.0; Carl Zeiss Meditec, Inc., Dublin, CA), RTVue (E)MM5 and MM6 (software version 3.5; Optovue, Inc., Fremont, CA), Topcon 3D Macular and Radial (software version 2.12; Topcon, Inc., Paramus, NJ), in addition to 1 TD OCT scan via Stratus macular thickness protocol (software version 4.0; Carl Zeiss Meditec, Inc.). Scans were inspected for 6 types of OCT scan artifacts and were analyzed. Interscan reproducibility and interdevice agreeability were assessed by intraclass correlation coefficients (ICCs) and Bland-Altman plots, respectively. Main Outcome Measures Optical coherence tomography image artifacts, macular thickness, reproducibility, and agreeability. Results Time-domain OCT scans contained a significantly higher percentage of clinically significant improper central foveal thickness (IFT) after manual correction (11-μm change or more) compared with SD OCT scans. Cirrus HD-OCT had a significantly lower percentage of clinically significant IFT (11.1%) compared with the other SD OCT devices (Topcon 3D, 20.4%; Topcon Radial, 29.6%; RTVue (E)MM5, 42.6%; RTVue MM6, 24.1%; P = 0.001). All 3 SD OCT devices had central foveal subfield thicknesses that were significantly more than that of TD OCT after manual correction (P<0.0001). All 3 SD OCT devices demonstrated a high degree of reproducibility in the central foveal region (ICCs, 0.92–0.97). Bland-Altman plots showed low agreeability between TD and SD OCT scans. Conclusions Out of all OCT devices analyzed, cirrus HD-OCT scans exhibited the lowest occurrence of any artifacts (68.5%), IFT (40.7%), and clinically significant IFT (11.1%), whereas Stratus OCT scans exhibited the highest occurrence of clinically significant IFT. Further work on improving segmentation algorithm to decrease artifacts is warranted.Research to Prevent Blindness, Inc. (United States) (Challenge Grant)National Institutes of Health (U.S.) (Grant R01-EY11289-23)National Institutes of Health (U.S.) (Grant R01-EY13178-07)National Institutes of Health (U.S.) (Grant P30-EY008098)United States. Air Force Office of Scientific Research (Grant FA9550-07-1-0101)United States. Air Force Office of Scientific Research (Grant FA9550-07-1-0014

Reproducibility of a Long-Range Swept-Source Optical Coherence Tomography Ocular Biometry System and Comparison with Clinical Biometers

Objective To demonstrate a novel swept source optical coherence tomography (SS-OCT) imaging device using a vertical cavity surface-emitting laser (VCSEL) capable of imaging the full eye length and to introduce a method using this device for noncontact ocular biometry. To compare the measurements of intraocular distances using this SS-OCT instrument with commercially available optical and ultrasound biometers. To evaluate the intersession reproducibility of measurements of intraocular distances using SS-OCT. Design Evaluation of technology. Participants Twenty eyes of 10 healthy subjects imaged at the New England Eye Center at Tufts Medical Center and Massachusetts Institute of Technology between May and September 2012. Methods Averaged central depth profiles were extracted from volumetric SS-OCT datasets. The intraocular distances, such as central corneal thickness (CCT), aqueous depth (AD), anterior chamber depth (ACD), crystalline lens thickness (LT), vitreous depth (VD), and axial length (AL), were measured and compared with a partial coherence interferometry device (IOLMaster; Carl Zeiss Meditec, Inc., Dublin, CA) and an immersion ultrasound (IUS) A-scan biometer (Axis-II PR; Quantel Medical, Inc., Cournon d'Auvergne Cedex, France). Main Outcome Measures Reproducibility of the measurements of intraocular distances, correlation coefficients, and intraclass correlation coefficients. Results The standard deviations of the repeated measurements of intraocular distances using SS-OCT were 6 μm (CCT), 16 μm (ACD), 14 μm (AD), 13 μm (LT), 14 μm (VD), and 16 μm (AL). Strong correlations among all 3 biometric instruments were found for AL (r > 0.98). The AL measurement using SS-OCT correlates better with the IOLMaster (r=0.998) than with IUS (r=0.984). The SS-OCT and IOLMaster measured higher AL values than ultrasound (175 and 139 μm, respectively). No statistically significant difference in ACD between the optical (SS-OCT or IOLMaster) and ultrasound methods was detected. High intersession reproducibility of SS-OCT measurements of all intraocular distances was observed with intraclass correlation coefficients >0.99. Conclusions The SS-OCT using VCSEL technology enables full eye length imaging and high-precision, noncontact ocular biometry. The measurements with the prototype SS-OCT instrument correlate well with commercial biometers. The SS-OCT biometry has the potential to provide clinically useful comprehensive biometric parameters for pre- and postoperative eye evaluation.National Institutes of Health (U.S.) (Grant R01-EY011289-27)National Institutes of Health (U.S.) (Grant R01-EY013178-12)National Institutes of Health (U.S.) (Grant R01-EY013516-09)National Institutes of Health (U.S.) (Grant R01-EY019029-04)National Institutes of Health (U.S.) (Grant R44EY022864-01)National Institutes of Health (U.S.) (Grant R01-CA075289-16)National Institutes of Health (U.S.) (Grant R01-NS057476-05)National Institutes of Health (U.S.) (Grant R44CA101067-05)United States. Air Force Office of Scientific Research (Grant FA9550-10-1-0551)United States. Air Force Office of Scientific Research (Grant FA9550-10-1-0063)Thorlabs, Inc

Optical coherence tomography angiography of optic nerve head and parafovea in multiple sclerosis

Aims To investigate swept-source optical coherence tomography (OCT) angiography in the optic nerve head (ONH) and parafoveal regions in patients with multiple sclerosis (MS). Methods Fifty-two MS eyes and 21 healthy control (HC) eyes were included. There were two MS subgroups: 38 MS eyes without an optic neuritis (ON) history (MS −ON), and 14 MS eyes with an ON history (MS +ON). The OCT images were captured by high-speed 1050 nm swept-source OCT. The ONH flow index (FI) and parafoveal FI were quantified from OCT angiograms. Results The mean ONH FI was 0.160±0.010 for the HC group, 0.156±0.017 for the MS−ON group, and 0.140±0.020 for the MS+ON group. The ONH FI of the MS+ON group was reduced by 12.5% compared to HC eyes (p=0.004). A higher percentage of MS+ON eyes had abnormal ONH FI compared to HC patients (43% vs 5%, p=0.01). Mean parafoveal FIs were 0.126±0.007, 0.127±0.010, and 0.129±0.005 for the HC, MS−ON, and MS +ON groups, respectively, and did not differ significantly among them. The coefficient of variation (CV) of intravisit repeatability and intervisit reproducibility were 1.03% and 4.53% for ONH FI, and 1.65% and 3.55% for parafoveal FI. Conclusions Based on OCT angiography, the FI measurement is feasible, highly repeatable and reproducible, and it is suitable for clinical measurement of ONH and parafoveal perfusion. The ONH FI may be useful in detecting damage from ON and quantifying its severity.National Institutes of Health (U.S.) (Clinical and Translational Science Award Grant UL1TR000128)National Institutes of Health (U.S.) (Grant R01 EY023285)National Institutes of Health (U.S.) (Grant R01 EY013516)National Institutes of Health (U.S.) (Grant R01-EY11289)National Institutes of Health (U.S.) (Grant P30EY010572)United States. Air Force Office of Scientific Research (FA9550-10-1-0551)United States. Air Force Office of Scientific Research (FA9550-12-1-0499)German Research Foundation (DFG-HO-1791/11-1)Research to Prevent Blindness, Inc. (United States

En Face Enhanced-Depth Swept-Source Optical Coherence Tomography Features of Chronic Central Serous Chorioretinopathy

Objective To characterize en face features of the retinal pigment epithelium (RPE) and choroid in eyes with chronic central serous chorioretinopathy (CSCR) using a high-speed, enhanced-depth swept-source optical coherence tomography (SS-OCT) prototype. Design Consecutive patients with chronic CSCR were prospectively examined with SS-OCT. Participants Fifteen eyes of 13 patients. Methods Three-dimensional 6×6 mm macular cube raster scans were obtained with SS-OCT operating at 1050 nm wavelength and 100 000 A-lines/sec with 6 μm axial resolution. Segmentation of the RPE generated a reference surface; en face SS-OCT images of the RPE and choroid were extracted at varying depths every 3.5 μm (1 pixel). Abnormal features were characterized by systematic analysis of multimodal fundus imaging, including color photographs, fundus autofluorescence, fluorescein angiography, and indocyanine-green angiography (ICGA). Main Outcome Measures En face SS-OCT morphology of the RPE and individual choroidal layers. Results En face SS-OCT imaging at the RPE level revealed absence of signal corresponding to RPE detachment or RPE loss in 15 of 15 (100%) eyes. En face SS-OCT imaging at the choriocapillaris level showed focally enlarged vessels in 8 of 15 eyes (53%). At the level of Sattler's layer, en face SS-OCT documented focal choroidal dilation in 8 of 15 eyes (53%) and diffuse choroidal dilation in 7 of 15 eyes (47%). At the level of Haller's layer, these same features were observed in 3 of 15 eyes (20%) and 12 of 15 eyes (80%), respectively. In all affected eyes, these choroidal vascular abnormalities were seen just below areas of RPE abnormalities. In 2 eyes with secondary choroidal neovascularization (CNV), distinct en face SS-OCT features corresponded to the neovascular lesions. Conclusions High-speed, enhanced-depth SS-OCT at 1050 nm wavelength enables the visualization of pathologic features of the RPE and choroid in eyes with chronic CSCR not usually appreciated with standard spectral domain (SD) OCT. En face SS-OCT imaging seems to be a useful tool in the identification of CNV without the use of angiography. This in vivo documentation of the RPE and choroidal vasculature at variable depths may help elucidate the pathophysiology of disease and can contribute to the diagnosis and management of chronic CSCR.National Institutes of Health (U.S.) (R01-EY011289-27)National Institutes of Health (U.S.) (R01-EY013178-12)National Institutes of Health (U.S.) (R01-EY018184-05)National Institutes of Health (U.S.) (R44EY022864-01)National Institutes of Health (U.S.) (GR01-CA075289-16)National Institutes of Health (U.S.) (R01-NS057476-05)National Institutes of Health (U.S.) (R44-EY022864-01)United States. Air Force Office of Scientific Research (FA9550-10-1-0551)United States. Air Force Office of Scientific Research (FA9550-10-1-0063)Research to Prevent Blindness, Inc. (United States)Massachusetts Lions ClubGerman Science Foundation (DFG-GSC80-SAOT

Enhanced Vitreous Imaging in Healthy Eyes Using Swept Source Optical Coherence Tomography

Purpose To describe enhanced vitreous imaging for visualization of anatomic features and microstructures within the posterior vitreous and vitreoretinal interface in healthy eyes using swept-source optical coherence tomography (SS-OCT). The study hypothesis was that long-wavelength, high-speed, volumetric SS-OCT with software registration motion correction and vitreous window display or high-dynamic-range (HDR) display improves detection sensitivity of posterior vitreous and vitreoretinal features compared to standard OCT logarithmic scale display. Design Observational prospective cross-sectional study. Methods Multiple wide-field three-dimensional SS-OCT scans (500×500A-scans over 12×12 mm2) were obtained using a prototype instrument in 22 eyes of 22 healthy volunteers. A registration motion-correction algorithm was applied to compensate motion and generate a single volumetric dataset. Each volumetric dataset was displayed in three forms: (1) standard logarithmic scale display, enhanced vitreous imaging using (2) vitreous window display and (3) HDR display. Each dataset was reviewed independently by three readers to identify features of the posterior vitreous and vitreoretinal interface. Detection sensitivities for these features were measured for each display method. Results Features observed included the bursa premacularis (BPM), area of Martegiani, Cloquet's/BPM septum, Bergmeister papilla, posterior cortical vitreous (hyaloid) detachment, papillomacular hyaloid detachment, hyaloid attachment to retinal vessel(s), and granular opacities within vitreous cortex, Cloquet's canal, and BPM. The detection sensitivity for these features was 75.0% (95%CI: 67.8%–81.1%) using standard logarithmic scale display, 80.6% (95%CI: 73.8%–86.0%) using HDR display, and 91.9% (95%CI: 86.6%–95.2%) using vitreous window display. Conclusions SS-OCT provides non-invasive, volumetric and measurable in vivo visualization of the anatomic microstructural features of the posterior vitreous and vitreoretinal interface. The vitreous window display provides the highest sensitivity for posterior vitreous and vitreoretinal interface analysis when compared to HDR and standard OCT logarithmic scale display. Enhanced vitreous imaging with SS-OCT may help assess the natural history and treatment response in vitreoretinal interface diseases.Massachusetts Lions Eye Research Fund, Inc.Research to Prevent Blindness, Inc. (United States)United States. Air Force Office of Scientific Research (grant FA9550-1010551)United States. Air Force Office of Scientific Research (grant FA9550-12-1-0499)German Research Foundation (DFG-HO-1791/11-1)German Research Foundation (DFGGSC80-SAOT)German Research Foundation (DFG Research Training Group 1773)Champalimaud Foundation (Champalimaud Vision Award Fund)National Institutes of Health (U.S.) (R01- EY11289-28)National Institutes of Health (U.S.) (R01-CA075289-16)National Institutes of Health (U.S.) (R44-EY022864-01

Quantitative Optical Coherence Tomography Angiography of Choroidal Neovascularization in Age-Related Macular Degeneration

Purpose To detect and quantify choroidal neovascularization (CNV) in patients with age-related macular degeneration (AMD) using optical coherence tomography (OCT) angiography. Design Observational, cross-sectional study. Participants A total of 5 normal subjects and 5 subjects with neovascular AMD were included. Methods A total of 5 eyes with neovascular AMD and 5 normal age-matched controls were scanned by a high-speed (100 000 A-scans/seconds) 1050-nm wavelength swept-source OCT. The macular angiography scan covered a 3×3-mm area and comprised 200×200×8 A-scans acquired in 3.5 seconds. Flow was detected using the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm. Motion artifacts were removed by 3-dimensional (3D) orthogonal registration and merging of 4 scans. The 3D angiography was segmented into 3 layers: inner retina (to show retinal vasculature), outer retina (to identify CNV), and choroid. En face maximum projection was used to obtain 2-dimensional angiograms from the 3 layers. The CNV area and flow index were computed from the en face OCT angiogram of the outer retinal layer. Flow (decorrelation) and structural data were combined in composite color angiograms for both en face and cross-sectional views. Main Outcome Measures The CNV angiogram, CNV area, and CNV flow index. Results En face OCT angiograms of CNV showed sizes and locations that were confirmed by fluorescein angiography (FA). Optical coherence tomography angiography provided more distinct vascular network patterns that were less obscured by subretinal hemorrhage. The en face angiograms also showed areas of reduced choroidal flow adjacent to the CNV in all cases and significantly reduced retinal flow in 1 case. Cross-sectional angiograms were used to visualize CNV location relative to the retinal pigment epithelium and Bruch's layer and classify type I and type II CNV. A feeder vessel could be identified in 1 case. Higher flow indexes were associated with larger CNV and type II CNV. Conclusions Optical coherence tomography angiography provides depth-resolved information and detailed images of CNV in neovascular AMD. Quantitative information regarding CNV flow and area can be obtained. Further studies are needed to assess the role of quantitative OCT angiography in the evaluation and treatment of neovascular AMD.National Institutes of Health (U.S.) (Grant 1R01 EY023285-01)National Institutes of Health (U.S.) (Grant R01 EY013516)Rosenbaum's P30EY010572National Institutes of Health (U.S.) (Clinical and Translational Science Award Grant UL1TR000128)Research to Prevent Blindness, Inc. (United States) (Grant R01-EY11289-26)United States. Air Force Office of Scientific Research (FA9550-10-1-0551)German Research Foundation (DFG-HO-1791/11-1)German Research Foundation (DFG-GSC80-SAOT