Optical coherence tomography angiography of optic disc perfusion in glaucoma.

PURPOSE: To compare optic disc perfusion between normal subjects and subjects with glaucoma using optical coherence tomography (OCT) angiography and to detect optic disc perfusion changes in glaucoma. DESIGN: Observational, cross-sectional study. PARTICIPANTS: Twenty-four normal subjects and 11 patients with glaucoma were included. METHODS: One eye of each subject was scanned by a high-speed 1050-nm-wavelength swept-source OCT instrument. The split-spectrum amplitude-decorrelation angiography (SSADA) algorithm was used to compute 3-dimensional optic disc angiography. A disc flow index was computed from 4 registered scans. Confocal scanning laser ophthalmoscopy (cSLO) was used to measure disc rim area, and stereo photography was used to evaluate cup/disc (C/D) ratios. Wide-field OCT scans over the discs were used to measure retinal nerve fiber layer (NFL) thickness. MAIN OUTCOME MEASURES: Variability was assessed by coefficient of variation (CV). Diagnostic accuracy was assessed by sensitivity and specificity. Comparisons between glaucoma and normal groups were analyzed by Wilcoxon rank-sum test. Correlations among disc flow index, structural assessments, and visual field (VF) parameters were assessed by linear regression. RESULTS: In normal discs, a dense microvascular network was visible on OCT angiography. This network was visibly attenuated in subjects with glaucoma. The intra-visit repeatability, inter-visit reproducibility, and normal population variability of the optic disc flow index were 1.2%, 4.2%, and 5.0% CV, respectively. The disc flow index was reduced by 25% in the glaucoma group (P = 0.003). Sensitivity and specificity were both 100% using an optimized cutoff. The flow index was highly correlated with VF pattern standard deviation (R(2) = 0.752, P = 0.001). These correlations were significant even after accounting for age, C/D area ratio, NFL, and rim area. CONCLUSIONS: Optical coherence tomography angiography, generated by the new SSADA, repeatably measures optic disc perfusion and may be useful in the evaluation of glaucoma and glaucoma progression.

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.

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 100000 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.

Swept source optical coherence microscopy using a 1310 nm VCSEL light source.

We demonstrate high speed, swept source optical coherence microscopy (OCM) using a MEMS tunable vertical cavity surface-emitting laser (VCSEL) light source. The light source had a sweep rate of 280 kHz, providing a bidirectional axial scan rate of 560 kHz. The sweep bandwidth was 117 nm centered at 1310 nm, corresponding to an axial resolution of 13.1 µm in air, corresponding to 8.1 µm (9.6 µm spectrally shaped) in tissue. Dispersion mismatch from different objectives was compensated numerically, enabling magnification and field of view to be easily changed. OCM images were acquired with transverse resolutions between 0.86 µm - 3.42 µm using interchangeable 40X, 20X and 10X objectives with ~600 µm x 600 µm, ~1 mm x 1 mm and ~2 mm x 2 mm field-of-view (FOV), respectively. Parasitic variations in path length with beam scanning were corrected numerically. These features enable swept source OCM to be integrated with a wide range of existing scanning microscopes. Large FOV mosaics were generated by serially acquiring adjacent overlapping microscopic fields and combining them in post-processing. Fresh human colon, thyroid and kidney specimens were imaged ex vivo and compared to matching histology sections, demonstrating the ability of OCM to image tissue specimens.

Split-spectrum amplitude-decorrelation angiography with optical coherence tomography.

Amplitude decorrelation measurement is sensitive to transverse flow and immune to phase noise in comparison to Doppler and other phase-based approaches. However, the high axial resolution of OCT makes it very sensitive to the pulsatile bulk motion noise in the axial direction. To overcome this limitation, we developed split-spectrum amplitude-decorrelation angiography (SSADA) to improve the signal-to-noise ratio (SNR) of flow detection. The full OCT spectrum was split into several narrower bands. Inter-B-scan decorrelation was computed using the spectral bands separately and then averaged. The SSADA algorithm was tested on in vivo images of the human macula and optic nerve head. It significantly improved both SNR for flow detection and connectivity of microvascular network when compared to other amplitude-decorrelation algorithms.

Efficient and high accuracy 3-D OCT angiography motion correction in pathology.

We describe a novel method for non-rigid 3-D motion correction of orthogonally raster-scanned optical coherence tomography angiography volumes. This is the first approach that aligns predominantly axial structural features such as retinal layers as well as transverse angiographic vascular features in a joint optimization. Combined with orthogonal scanning and favorization of kinematically more plausible displacements, subpixel alignment and micrometer-scale distortion correction is achieved in all 3 dimensions. As no specific structures are segmented, the method is by design robust to pathologic changes. Furthermore, the method is designed for highly parallel implementation and short runtime, allowing its integration into clinical workflow even for high density or wide-field scans. We evaluated the algorithm with metrics related to clinically relevant features in an extensive quantitative evaluation based on 204 volumetric scans of 17 subjects, including patients with diverse pathologies and healthy controls. Using this method, we achieve state-of-the-art axial motion correction and show significant advances in both transverse co-alignment and distortion correction, especially in the subgroup with pathology.

Three-Dimensional Enhanced Imaging of Vitreoretinal Interface in Diabetic Retinopathy Using Swept-Source Optical Coherence Tomography.

PURPOSE: To analyze the vitreoretinal interface in diabetic eyes using 3-dimensional wide-field volumes acquired using high-speed, long-wavelength swept-source optical coherence tomography (SSOCT). DESIGN: Prospective cross-sectional study. METHODS: Fifty-six diabetic patients (88 eyes) and 11 healthy nondiabetic controls (22 eyes) were recruited. Up to 8 SSOCT volumes were acquired for each eye. A registration algorithm removed motion artifacts and merged multiple SSOCT volumes to improve signal. Vitreous visualization was enhanced using vitreous windowing method. RESULTS: Of 88 diabetic eyes, 20 eyes had no retinopathy, 21 eyes had nonproliferative diabetic retinopathy (NPDR) without macular edema, 20 eyes had proliferative diabetic retinopathy (PDR) without macular edema, and 27 eyes had diabetic macular edema (DME) with either NPDR or PDR. Thick posterior hyaloid relative to healthy nondiabetic controls was observed in 0 of 20 (0%) diabetic eyes without retinopathy, 4 of 21 (19%) eyes with NPDR, 11 of 20 (55%) eyes with PDR, and 11 of 27 (41%) eyes with DME (P = .0001). Vitreoschisis was observed in 6 of 22 (27%) healthy nondiabetic eyes, 9 of 20 (45%) diabetic eyes without retinopathy, 10 of 21 (48%) eyes with NPDR, 13 of 20 (65%) eyes with PDR, and 17 of 27 (63%) eyes with DME (P = .007). While no healthy nondiabetic controls and diabetic eyes without retinopathy had adhesions/pegs between detached posterior hyaloid and retina, 1 of 21 (4%), 11 of 20 (55%), and 11 of 27 (41%) eyes with NPDR, PDR, and DME, respectively, demonstrated this feature (P = .0001). CONCLUSION: SSOCT with motion-correction and vitreous windowing provides wide-field 3-dimensional information of vitreoretinal interface in diabetic eyes. This may be useful in assessing progression of retinopathy, planning diabetic vitreous surgery, and predicting treatment outcomes.

Characterization of Choroidal Layers in Normal Aging Eyes Using Enface Swept-Source Optical Coherence Tomography.

PURPOSE: To characterize qualitative and quantitative features of the choroid in normal eyes using enface swept-source optical coherence tomography (SS-OCT). METHODS: Fifty-two eyes of 26 consecutive normal subjects were prospectively recruited to obtain multiple three-dimensional 12 x 12 mm volumetric scans using a long-wavelength high-speed SS-OCT prototype. A motion-correction algorithm merged multiple SS-OCT volumes to improve signal. Retinal pigment epithelium (RPE) was segmented as the reference and enface images were extracted at varying depths every 4.13 µm intervals. Systematic analysis of the choroid at different depths was performed to qualitatively assess the morphology of the choroid and quantify the absolute thicknesses as well as the relative thicknesses of the choroidal vascular layers including the choroidal microvasculature (choriocapillaris, terminal arterioles and venules; CC) and choroidal vessels (CV) with respect to the subfoveal total choroidal thickness (TC). Subjects were divided into two age groups: younger (<40 years) and older (≥ 40 years). RESULTS: Mean age of subjects was 41.92 (24-66) years. Enface images at the level of the RPE, CC, CV, and choroidal-scleral interface were used to assess specific qualitative features. In the younger age group, the mean absolute thicknesses were: TC 379.4 µm (SD ± 75.7 µm), CC 81.3 µm (SD ± 21.2 µm) and CV 298.1 µm (SD ± 63.7 µm). In the older group, the mean absolute thicknesses were: TC 305.0 µm (SD ± 50.9 µm), CC 56.4µm (SD ± 12.1 µm) and CV 248.6µm (SD ± 49.7 µm). In the younger group, the relative thicknesses of the individual choroidal layers were: CC 21.5% (SD ± 4.0%) and CV 78.4% (SD ± 4.0%). In the older group, the relative thicknesses were: CC 18.9% (SD ± 4.5%) and CV 81.1% (SD ± 4.5%). The absolute thicknesses were smaller in the older age group for all choroidal layers (TC p=0.006, CC p=0.0003, CV p=0.03) while the relative thickness was smaller only for the CC (p=0.04). CONCLUSIONS: Enface SS-OCT at 1050 nm enables a precise qualitative and quantitative characterization of the individual choroidal layers in normal eyes. Only the CC is relatively thinner in the older eyes. In-vivo evaluation of the choroid at variable depths may be potentially valuable in understanding the natural history of age-related posterior segment disease.

En face imaging of the choroid in polypoidal choroidal vasculopathy using swept-source optical coherence tomography.

OBJECTIVE: To define morphologic features of polypoidal choroidal vasculopathy (PCV) using en face images from swept-source optical coherence tomography (SS OCT). DESIGN: Prospective cross-sectional study. METHODS: The study included 10 eyes from 6 patients with PCV and 10 eyes from 5 age-matched normal subjects. All subjects were prospectively scanned with a prototype SS OCT system. A motion correction algorithm was applied to correct and merge scans into a single volumetric dataset. En face images were generated at intervals of 4.13 µm (1 pixel) relative to the Bruch membrane. RESULTS: Age ± standard deviation for the normal group was 62.4 (±12.1) years and for the PCV group was 68.3 (±5.2) years. En face SS OCT imaging of PCV eyes demonstrated the relationship between larger pigment epithelial detachments (PEDs) and small adjoining PEDs that correlated with the polypoidal lesions seen on indocyanine green angiography in all PCV eyes. En face SS OCT demonstrated choroidal vascular abnormalities in 7 out of 7 eyes with PCV, and in 2 out of 3 enrolled fellow eyes in patients with unilateral PCV. Out of 7 PCV eyes, focal choroidal vascular dilation was noted in 3 eyes and diffuse choroidal vascular dilation was noted in 1 eye. In addition, a branching vascular network was noted above the Bruch membrane in 1 eye, below the Bruch membrane within the choriocapillaris in 1 eye, and in the larger choroidal vascular layer in 1 eye. CONCLUSIONS: En face SS OCT provides an in vivo tool to visualize the pathologic features and the choroidal vasculature in PCV.

Choroid, Haller's, and Sattler's layer thickness in intermediate age-related macular degeneration with and without fellow neovascular eyes.

PURPOSE: To analyze choroidal, Sattler's, and Haller's layer thickness maps in age-related macular degeneration (AMD) patients having eyes with bilateral large drusen and pigment changes (intermediate AMD), in patients having intermediate AMD eyes with neovascular fellow eyes (nAMD), and in healthy subjects using three-dimensional (3D) 1060-nm optical coherence tomography (OCT). METHODS: Automatically generated choroidal thickness (ChT), retinal thickness, and Sattler's and Haller's layer thickness maps were statistically analyzed in 67 subjects consisting of intermediate AMD (n = 21), intermediate AMD (n = 22) with fellow nAMD eyes (n = 22), and healthy eyes (n = 24) with no age and axial eye length difference between groups of eyes (P > 0.05, ANOVA). Eyes were imaged by a prototype high-speed (60,000 A-scans/s) spectral-domain 3D 1060-nm OCT over a 36° × 36° field of view. RESULTS: The mean ± SD (µm) subfoveal ChT for healthy subjects and for bilateral intermediate AMD, unilateral intermediate AMD, and their nAMD fellow eyes was 259 ± 95 and 222 ± 98, 149 ± 60, and 171 ± 78, respectively. Choroidal thickness maps demonstrated significant submacular thinning in unilateral intermediate AMD in comparison to healthy and bilateral intermediate AMD eyes (P < 0.001, ANOVA, post hoc P < 0.001 and P < 0.05, respectively). Sattler's and Haller's layers were thinnest in intermediate AMDs that presented with nAMD fellow eyes (Kruskal-Wallis test P < 0.01). For the choroid and its sublayers, there was no difference between the intermediate AMD eyes and their fellow nAMD eyes (paired testing, P < 0.05). CONCLUSIONS: The 3D 1060-nm OCT choroidal imaging visualized significant changes in choroidal, Sattler's, and Haller's layer thickness in relation to the progression of AMD. This may be important for understanding the choroidopathy in the pathophysiology of AMD.

Depth-encoded all-fiber swept source polarization sensitive OCT.

Polarization sensitive optical coherence tomography (PS-OCT) is a functional extension of conventional OCT and can assess depth-resolved tissue birefringence in addition to intensity. Most existing PS-OCT systems are relatively complex and their clinical translation remains difficult. We present a simple and robust all-fiber PS-OCT system based on swept source technology and polarization depth-encoding. Polarization multiplexing was achieved using a polarization maintaining fiber. Polarization sensitive signals were detected using fiber based polarization beam splitters and polarization controllers were used to remove the polarization ambiguity. A simplified post-processing algorithm was proposed for speckle noise reduction relaxing the demand for phase stability. We demonstrated systems design for both ophthalmic and catheter-based PS-OCT. For ophthalmic imaging, we used an optical clock frequency doubling method to extend the imaging range of a commercially available short cavity light source to improve polarization depth-encoding. For catheter based imaging, we demonstrated 200 kHz PS-OCT imaging using a MEMS-tunable vertical cavity surface emitting laser (VCSEL) and a high speed micromotor imaging catheter. The system was demonstrated in human retina, finger and lip imaging, as well as ex vivo swine esophagus and cardiovascular imaging. The all-fiber PS-OCT is easier to implement and maintain compared to previous PS-OCT systems and can be more easily translated to clinical applications due to its robust design.

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.

Quantitative 3D-OCT motion correction with tilt and illumination correction, robust similarity measure and regularization.

Variability in illumination, signal quality, tilt and the amount of motion pose challenges for post-processing based 3D-OCT motion correction algorithms. We present an advanced 3D-OCT motion correction algorithm using image registration and orthogonal raster scan patterns aimed at addressing these challenges. An intensity similarity measure using the pseudo Huber norm and a regularization scheme based on a pseudo L0.5 norm are introduced. A two-stage registration approach was developed. In the first stage, only axial motion and axial tilt are coarsely corrected. This result is then used as the starting point for a second stage full optimization. In preprocessing, a bias field estimation based approach to correct illumination differences in the input volumes is employed. Quantitative evaluation was performed using a large set of data acquired from 73 healthy and glaucomatous eyes using SD-OCT systems. OCT volumes of both the optic nerve head and the macula region acquired with three independent orthogonal volume pairs for each location were used to assess reproducibility. The advanced motion correction algorithm using the techniques presented in this paper was compared to a basic algorithm corresponding to an earlier version and to performing no motion correction. Errors in segmentation-based measures such as layer positions, retinal and nerve fiber thickness, as well as the blood vessel pattern were evaluated. The quantitative results consistently show that reproducibility is improved considerably by using the advanced algorithm, which also significantly outperforms the basic algorithm. The mean of the mean absolute retinal thickness difference over all data was 9.9 um without motion correction, 7.1 um using the basic algorithm and 5.0 um using the advanced algorithm. Similarly, the blood vessel likelihood map error is reduced to 69% of the uncorrected error for the basic and to 47% of the uncorrected error for the advanced algorithm. These results demonstrate that our advanced motion correction algorithm has the potential to improve the reliability of quantitative measurements derived from 3D-OCT data substantially.

Choroidal Haller's and Sattler's layer thickness measurement using 3-dimensional 1060-nm optical coherence tomography.

OBJECTIVES: To examine the feasibility of automatically segmented choroidal vessels in three-dimensional (3D) 1060-nmOCT by testing repeatability in healthy and AMD eyes and by mapping Haller's and Sattler's layer thickness in healthy eyes. METHODS: Fifty-five eyes (from 45 healthy subjects and 10 with non-neovascular age-related macular degeneration (AMD) subjects) were imaged by 3D-1060-nmOCT over a 36°x36° field of view. Haller's and Sattler's layer were automatically segmented, mapped and averaged across the Early Treatment Diabetic Retinopathy Study grid. For ten AMD eyes and ten healthy eyes, imaging was repeated within the same session and on another day. Outcomes were the repeatability agreement of Haller's and Sattler's layer thicknesses in healthy and AMD eyes, the validation with ICGA and the statistical analysis of the effect of age and axial eye length (AL) on both healthy choroidal sublayers. RESULTS: The coefficients of repeatability for Sattler's and Haller's layers were 35% and 21% in healthy eyes and 44% and 31% in AMD eyes, respectively. The mean±SD healthy central submacular field thickness for Sattler's and Haller's was 87±56 µm and 141±50 µm, respectively, with a significant relationship for AL (P<.001). CONCLUSIONS: Automated Sattler's and Haller's thickness segmentation generates rapid 3D measurements with a repeatability corresponding to reported manual segmentation. Sublayers in healthy eyes thinned significantly with increasing AL. In the presence of the thinned Sattler's layer in AMD, careful measurement interpretation is needed. Automatic choroidal vascular layer mapping may help to explain if pathological choroidal thinning affects medium and large choroidal vasculature in addition to choriocapillaris loss.

Choroidal analysis in healthy eyes using swept-source optical coherence tomography compared to spectral domain optical coherence tomography.

PURPOSE: To compare analyses of choroidal thickness and volume in healthy eyes measured concurrently with prototype long-wavelength swept-source optical coherence tomography (OCT) and commercially available spectral-domain optical coherence tomography (OCT) with and without enhanced depth imaging (EDI). DESIGN: Prospective cross sectional study. METHODS: The study included 19 healthy subjects (19 eyes), who were prospectively recruited to undergo 2 consecutive imaging sessions on the same randomly selected eye using spectral domain OCT and a prototype long-wavelength swept-source OCT. On spectral domain OCT, 2 line scans, 1 with and 1 without EDI, and 1 volumetric scan were obtained. On swept-source OCT, 1 line scan and 1 volumetric scan were obtained. Scan patterns on swept-source OCT were created to simulate those available on Cirrus HD-OCT to keep the time of image acquisition constant. Swept-source OCT volumetric scans were motion corrected using a novel registration algorithm. Choroidal thickness and volume were analyzed. RESULTS: The choroidoscleral interface was clearly visualized in 19/19 (100%) of eyes imaged by swept-source OCT, compared to 14/19 (73.6%) and 13/19 (68.4%) eyes imaged by spectral domain OCT, with and without EDI, respectively. There was no significant difference in choroidal thickness measurements on the line scans obtained on either system (P = 0.10). Choroidal volume could not be assessed on volumetric scans from spectral domain OCT. Mean choroidal volume from swept-source OCT volumetric scans was 11.77 ± 3.13 mm(3) (6.43 mm(3)-17.15 mm(3)). CONCLUSION: This is the first study that compares simultaneously a prototype long-wavelength swept-source OCT to a commercially available spectral domain OCT for a detailed analysis of choroid in healthy eyes. Swept-source OCT shows potential for better choroidal analysis. Studies using swept-source OCT in diseased eyes will further define this new technology's utility in chorioretinal diseases.

In vivo imaging of the rodent eye with swept source/Fourier domain OCT.

Swept source/Fourier domain OCT is demonstrated for in vivo imaging of the rodent eye. Using commercial swept laser technology, we developed a prototype OCT imaging system for small animal ocular imaging operating in the 1050 nm wavelength range at an axial scan rate of 100 kHz with ~6 µm axial resolution. The high imaging speed enables volumetric imaging with high axial scan densities, measuring high flow velocities in vessels, and repeated volumetric imaging over time. The 1050 nm wavelength light provides increased penetration into tissue compared to standard commercial OCT systems at 850 nm. The long imaging range enables multiple operating modes for imaging the retina, posterior eye, as well as anterior eye and full eye length. A registration algorithm using orthogonally scanned OCT volumetric data sets which can correct motion on a per A-scan basis is applied to compensate motion and merge motion corrected volumetric data for enhanced OCT image quality. Ultrahigh speed swept source OCT is a promising technique for imaging the rodent eye, proving comprehensive information on the cornea, anterior segment, lens, vitreous, posterior segment, retina and choroid.

Automated three-dimensional choroidal vessel segmentation of 3D 1060 nm OCT retinal data.

A fully automated, robust vessel segmentation algorithm has been developed for choroidal OCT, employing multiscale 3D edge filtering and projection of "probability cones" to determine the vessel "core", even in the tomograms with low signal-to-noise ratio (SNR). Based on the ideal vessel response after registration and multiscale filtering, with computed depth related SNR, the vessel core estimate is dilated to quantify the full vessel diameter. As a consequence, various statistics can be computed using the 3D choroidal vessel information, such as ratios of inner (smaller) to outer (larger) choroidal vessels or the absolute/relative volume of choroid vessels. Choroidal vessel quantification can be displayed in various forms, focused and averaged within a special region of interest, or analyzed as the function of image depth. In this way, the proposed algorithm enables unique visualization of choroidal watershed zones, as well as the vessel size reduction when investigating the choroid from the sclera towards the retinal pigment epithelium (RPE). To the best of our knowledge, this is the first time that an automatic choroidal vessel segmentation algorithm is successfully applied to 1060 nm 3D OCT of healthy and diseased eyes.

Handheld ultrahigh speed swept source optical coherence tomography instrument using a MEMS scanning mirror.

We developed an ultrahigh speed, handheld swept source optical coherence tomography (SS-OCT) ophthalmic instrument using a 2D MEMS mirror. A vertical cavity surface-emitting laser (VCSEL) operating at 1060 nm center wavelength yielded a 350 kHz axial scan rate and 10 µm axial resolution in tissue. The long coherence length of the VCSEL enabled a 3.08 mm imaging range with minimal sensitivity roll-off in tissue. Two different designs with identical optical components were tested to evaluate handheld OCT ergonomics. An iris camera aided in alignment of the OCT beam through the pupil and a manual fixation light selected the imaging region on the retina. Volumetric and high definition scans were obtained from 5 undilated normal subjects. Volumetric OCT data was acquired by scanning the 2.4 mm diameter 2D MEMS mirror sinusoidally in the fast direction and linearly in the orthogonal slow direction. A second volumetric sinusoidal scan was obtained in the orthogonal direction and the two volumes were processed with a software algorithm to generate a merged motion-corrected volume. Motion-corrected standard 6 x 6 mm(2) and wide field 10 x 10 mm(2) volumetric OCT data were generated using two volumetric scans, each obtained in 1.4 seconds. High definition 10 mm and 6 mm B-scans were obtained by averaging and registering 25 B-scans obtained over the same position in 0.57 seconds. One of the advantages of volumetric OCT data is the generation of en face OCT images with arbitrary cross sectional B-scans registered to fundus features. This technology should enable screening applications to identify early retinal disease, before irreversible vision impairment or loss occurs. Handheld OCT technology also promises to enable applications in a wide range of settings outside of the traditional ophthalmology or optometry clinics including pediatrics, intraoperative, primary care, developing countries, and military medicine.

Ultrahigh speed endoscopic optical coherence tomography using micromotor imaging catheter and VCSEL technology.

We developed a micromotor based miniature catheter with an outer diameter of 3.2 mm for ultrahigh speed endoscopic swept source optical coherence tomography (OCT) using a vertical cavity surface-emitting laser (VCSEL) at a 1 MHz axial scan rate. The micromotor can rotate a micro-prism at several hundred frames per second with less than 5 V drive voltage to provide fast and stable scanning, which is not sensitive to the bending of the catheter. The side-viewing probe can be pulled back to acquire a three-dimensional (3D) data set covering a large area on the specimen. The VCSEL provides a high axial scan rate to support dense sampling under high frame rate operation. Using a high speed data acquisition system, in vivo 3D-OCT imaging in the rabbit GI tract and ex vivo imaging of a human colon specimen with 8 µm axial resolution, 8 µm lateral resolution and 1.2 mm depth range in tissue at a frame rate of 400 fps was demonstrated.

Automated lamina cribrosa microstructural segmentation in optical coherence tomography scans of healthy and glaucomatous eyes.

We demonstrate an automated segmentation method for in-vivo 3D optical coherence tomography (OCT) imaging of the lamina cribrosa (LC). Manual segmentations of coronal slices of the LC were used as a gold standard in parameter selection and evaluation of the automated technique. The method was validated using two prototype OCT devices; each had a subject cohort including both healthy and glaucomatous eyes. Automated segmentation of in-vivo 3D LC OCT microstructure performed comparably to manual segmentation and is useful for investigative research and in clinical quantification of the LC.