Alex D. Pechauer

Optical Coherence Tomography Angiography of the Peripapillary Retina in Glaucoma

IMPORTANCE Vascular factors may have important roles in the pathophysiology of glaucoma. A practical method for the clinical evaluation of ocular perfusion is needed to improve glaucoma management. OBJECTIVE To detect peripapillary retinal perfusion in glaucomatous eyes compared with normal eyes using optical coherence tomography (OCT) angiography. DESIGN, SETTING, AND PARTICIPANTS Prospective observational study performed from July 24, 2013, to April 17, 2014. Participants were recruited and tested at Casey Eye Institute, Oregon Health & Science University. In total, 12 glaucomatous eyes and 12 age-matched normal eyes were analyzed. The optic disc region was imaged twice using a 3 × 3-mm scan by a 70-kHz, 840-nm-wavelength spectral OCT system. The split-spectrum amplitude-decorrelation angiography algorithm was used. Peripapillary flow index was calculated as the mean decorrelation value in the peripapillary region, defined as a 700-µm-wide elliptical annulus around the disc. Peripapillary vessel density was the percentage area occupied by vessels. The data statistical analysis was performed from October 30, 2013, to May 30, 2014. MAIN OUTCOMES AND MEASURES Variability was assessed by the coefficient of variation. The Mann-Whitney test was used to compare the 2 groups of eyes. Correlations between vascular and visual field variables were assessed by linear regression analysis. RESULTS In 12 normal eyes, a dense microvascular network around the disc was visible on OCT angiography. In 12 glaucomatous eyes, this network was visibly attenuated globally and focally. In normal eyes, between-visit reproducibilities of peripapillary flow index and peripapillary vessel density were 4.3% and 2.7% of the coefficient of variation, respectively, while the population variabilities of peripapillary flow index and peripapillary vessel density were 8.2% and 3.0% of the coefficient of variation, respectively. Peripapillary flow index and peripapillary vessel density in glaucomatous eyes were lower than those in normal eyes (P < .001 for both). Peripapillary flow index (Pearson r = -0.808) and peripapillary vessel density (Pearson r = -0.835) were highly correlated with visual field pattern standard deviation in glaucomatous eyes (P = .001 for both). The areas under the receiver operating characteristic curve for normal vs glaucomatous eyes were 0.892 for peripapillary flow index and 0.938 for peripapillary vessel density. CONCLUSIONS AND RELEVANCE Using OCT angiography, reduced peripapillary retinal perfusion in glaucomatous eyes can be visualized as focal defects and quantified as peripapillary flow index and peripapillary vessel density, with high repeatability and reproducibility. Quantitative OCT angiography may have value in future studies to determine its potential usefulness in glaucoma evaluation.

Optical coherence tomography angiography of peripapillary retinal blood flow response to hyperoxia

PURPOSE To measure the change in peripapillary retinal blood flow in response to hyperoxia by using optical coherence tomography (OCT) angiography. METHODS One eye of each healthy human participants (six) was scanned with a commercial high-speed (70 kHz) spectral OCT. Scans were captured twice after 10-minute exposures to normal breathing (baseline) and hyperoxia. Blood flow was detected by the split-spectrum amplitude-decorrelation angiography (SSADA) algorithm. Peripapillary retinal blood flow index and vessel density were calculated from en face maximum projections of the retinal layers. The experiment was performed on 2 separate days for each participant. Coefficient of variation (CV) was used to measure within-day repeatability and between-day reproducibility. Paired t-tests were used to compare means of baseline and hyperoxic peripapillary retinal blood flow. RESULTS A decrease of 8.87% ± 3.09% (mean ± standard deviation) in flow index and 2.61% ± 1.50% in vessel density was observed under hyperoxia. The within-day repeatability CV of baseline measurements was 5.75% for flow index and 1.67% for vessel density. The between-day reproducibility CV for baseline flow index and vessel density was 11.1% and 1.14%, respectively. The between-day reproducibility of the hyperoxic response was 3.71% and 1.67% for flow index and vessel density, respectively. CONCLUSIONS Optical coherence tomography angiography with SSADA was able to detect a decrease in peripapillary retinal blood flow in response to hyperoxia. The response was larger than the variability of baseline measurements. The magnitude of an individuals hyperoxic response was highly variable between days. Thus, reliable assessment may require averaging multiple measurements.

Advanced image processing for optical coherence tomographic angiography of macular diseases.

This article provides an overview of advanced image processing for three dimensional (3D) optical coherence tomographic (OCT) angiography of macular diseases, including age-related macular degeneration (AMD) and diabetic retinopathy (DR). A fast automated retinal layers segmentation algorithm using directional graph search was introduced to separates 3D flow data into different layers in the presence of pathologies. Intelligent manual correction methods are also systematically addressed which can be done rapidly on a single frame and then automatically propagated to full 3D volume with accuracy better than 1 pixel. Methods to visualize and analyze the abnormalities including retinal and choroidal neovascularization, retinal ischemia, and macular edema were presented to facilitate the clinical use of OCT angiography.

The reliability of parafoveal cone density measurements

Background Adaptive optics scanning light ophthalmoscopy (AOSLO) enables direct visualisation of the cone mosaic, with metrics such as cone density and cell spacing used to assess the integrity or health of the mosaic. Here we examined the interobserver and inter-instrument reliability of cone density measurements. Methods For the interobserver reliability study, 30 subjects with no vision-limiting pathology were imaged. Three image sequences were acquired at a single parafoveal location and aligned to ensure that the three images were from the same retinal location. Ten observers used a semiautomated algorithm to identify the cones in each image, and this was repeated three times for each image. To assess inter-instrument reliability, 20 subjects were imaged at eight parafoveal locations on one AOSLO, followed by the same set of locations on the second AOSLO. A single observer manually aligned the pairs of images and used the semiautomated algorithm to identify the cones in each image. Results Based on a factorial study design model and a variance components model, the interobserver studys largest contribution to variability was the subject (95.72%) while the observers contribution was only 1.03%. For the inter-instrument study, an average cone density intraclass correlation coefficient (ICC) of between 0.931 and 0.975 was calculated. Conclusions With the AOSLOs used here, reliable cone density measurements can be obtained between observers and between instruments. Additional work is needed to determine how these results vary with differences in image quality.

Automated motion correction using parallel-strip registration for wide-field en face OCT angiogram.

We propose an innovative registration method to correct motion artifacts for wide-field optical coherence tomography angiography (OCTA) acquired by ultrahigh-speed swept-source OCT (>200 kHz A-scan rate). Considering that the number of A-scans along the fast axis is much higher than the number of positions along slow axis in the wide-field OCTA scan, a non-orthogonal scheme is introduced. Two en face angiograms in the vertical priority (2 y-fast) are divided into microsaccade-free parallel strips. A gross registration based on large vessels and a fine registration based on small vessels are sequentially applied to register parallel strips into a composite image. This technique is extended to automatically montage individual registered, motion-free angiograms into an ultrawide-field view.

Automated volumetric segmentation of retinal fluid on optical coherence tomography.

We propose a novel automated volumetric segmentation method to detect and quantify retinal fluid on optical coherence tomography (OCT). The fuzzy level set method was introduced for identifying the boundaries of fluid filled regions on B-scans (x and y-axes) and C-scans (z-axis). The boundaries identified from three types of scans were combined to generate a comprehensive volumetric segmentation of retinal fluid. Then, artefactual fluid regions were removed using morphological characteristics and by identifying vascular shadowing with OCT angiography obtained from the same scan. The accuracy of retinal fluid detection and quantification was evaluated on 10 eyes with diabetic macular edema. Automated segmentation had good agreement with manual segmentation qualitatively and quantitatively. The fluid map can be integrated with OCT angiogram for intuitive clinical evaluation.

En face Doppler total retinal blood flow measurement with 70 kHz spectral optical coherence tomography.

Abstract. An automated algorithm was developed for total retinal blood flow (TRBF) using 70-kHz spectral optical coherence tomography (OCT). The OCT was calibrated for the transformation from Doppler shift to speed based on a flow phantom. The TRBF scan pattern contained five repeated volume scans (2×2  mm) obtained in 3 s and centered on central retinal vessels in the optic disc. The TRBF was calculated using an en face Doppler technique. For each retinal vein, blood flow was measured at an optimal plane where the calculated flow was maximized. The TRBF was calculated by summing flow in all veins. The algorithm tracked vascular branching so that either root or branch veins are summed, but never both. The TRBF in five repeated volumes were averaged to reduce variation due to cardiac cycle pulsation. Finally, the TRBF was corrected for eye length variation. Twelve healthy eyes and 12 glaucomatous eyes were enrolled to test the algorithm. The TRBF was 45.4±6.7  μl/min for healthy control and 34.7±7.6  μl/min for glaucomatous participants (p-value=0.01). The intravisit repeatability was 8.6% for healthy controls and 8.4% for glaucoma participants. The proposed automated method provided repeatable TRBF measurement.

Postprocessing algorithms to minimize fixed-pattern artifact and reduce trigger jitter in swept source optical coherence tomography.

We propose methods to align interferograms affected by trigger jitter to a reference interferogram based on the information (amplitude/phase) at a fixed-pattern noise location to reduce residual fixed-pattern noise and improve the phase stability of swept source optical coherence tomography (SS-OCT) systems. One proposed method achieved this by introducing a wavenumber shift (k-shift) in the interferograms of interest and searching for the k-shift that minimized the fixed-pattern noise amplitude. The other method calculated the relative k-shift using the phase information at the residual fixed-pattern noise location. Repeating this wavenumber alignment procedure for all A-lines of interest produced fixed-pattern noise free and phase stable OCT images. A system incorporating these correction routines was used for human retina OCT and Doppler OCT imaging. The results from the two methods were compared, and it was found that the intensity-based method provided better results.

Detecting Blood Flow Response to Stimulation of the Human Eye

Retinal blood supply is tightly regulated under a variety of hemodynamic considerations in order to satisfy a high metabolic need and maintain both vessel structure and function. Simulation of the human eye can induce hemodynamics alterations, and attempt to assess the vascular reactivity response has been well documented in the scientific literature. Advancements in noninvasive imaging technologies have led to the characterization of magnitude and time course in retinal blood flow response to stimuli. This allowed for a better understanding of the mechanism in which blood flow is regulated, as well as identifying functional impairments in the diseased eye. Clinically, the ability to detect retinal blood flow reactivity during stimulation of the eye offers potential for the detection, differentiation, and diagnosis of diseases.

Calibration of optical coherence tomography angiography with a microfluidic chip

Abstract. A microfluidic chip with microchannels ranging from 8 to 96  μm was used to mimic blood vessels down to the capillary level. Blood flow within the microfluidic channels was analyzed with split-spectrum amplitude-decorrelation angiography (SSADA)-based optical coherence tomography (OCT) angiography. It was found that the SSADA decorrelation value was related to both blood flow speed and channel width. SSADA could differentiate nonflowing blood inside the microfluidic channels from static paper. The SSADA decorrelation value was approximately linear with blood flow velocity up to a threshold Vsat of 5.83±1.33  mm/s (mean±standard deviation over the range of channel widths). Beyond this threshold, it approached a saturation value Dsat. Dsat was higher for wider channels, and approached a maximum value Dsm as the channel width became much larger than the beam focal spot diameter. These results indicate that decorrelation values (flow signal) in capillary networks would be proportional to both flow velocity and vessel caliber but would be capped at a saturation value in larger blood vessels. These findings are useful for interpretation and quantification of clinical OCT angiography results.