Time-Resolved Dynamic Optical Coherence Tomography for Retinal Blood Flow Analysis.

Purpose: Optical coherence tomography (OCT) representations in clinical practice are static and do not allow for a dynamic visualization and quantification of blood flow. This study aims to present a method to analyze retinal blood flow dynamics using time-resolved structural OCT. Methods: We developed novel imaging protocols to acquire video-rate time-resolved OCT B-scans (1024 × 496 pixels, 10 degrees field of view) at four different sensor integration times (integration time of 44.8 µs at a nominal A-scan rate of 20 kHz, 22.4 µs at 40 kHz, 11.2 µs at 85 kHz, and 7.24 µs at 125 kHz). The vessel centers were manually annotated for each B-scan and surrounding subvolumes were extracted. We used a velocity model based on signal-to-noise ratio (SNR) drops due to fringe washout to calculate blood flow velocity profiles in vessels within five optic disc diameters of the optic disc rim. Results: Time-resolved dynamic structural OCT revealed pulsatile SNR changes in the analyzed vessels and allowed the calculation of potential blood flow velocities at all integration times. Fringe washout was stronger in acquisitions with longer integration times; however, the ratio of the average SNR to the peak SNR inside the vessel was similar across all integration times. Conclusions: We demonstrated the feasibility of estimating blood flow profiles based on fringe washout analysis, showing pulsatile dynamics in vessels close to the optic nerve head using structural OCT. Time-resolved dynamic OCT has the potential to uncover valuable blood flow information in clinical settings.

Human selection bias drives the linear nature of the more ground truth effect in explainable deep learning optical coherence tomography image segmentation.

Supervised deep learning (DL) algorithms are highly dependent on training data for which human graders are assigned, for example, for optical coherence tomography (OCT) image annotation. Despite the tremendous success of DL, due to human judgment, these ground truth labels can be inaccurate and/or ambiguous and cause a human selection bias. We therefore investigated the impact of the size of the ground truth and variable numbers of graders on the predictive performance of the same DL architecture and repeated each experiment three times. The largest training dataset delivered a prediction performance close to that of human experts. All DL systems utilized were highly consistent. Nevertheless, the DL under-performers could not achieve any further autonomous improvement even after repeated training. Furthermore, a quantifiable linear relationship between ground truth ambiguity and the beneficial effect of having a larger amount of ground truth data was detected and marked as the more-ground-truth effect.

The Optical Coherence Tomography and Microperimetry Biomarker Evaluation in Patients with Geographic Atrophy (OMEGA) Study: Design and Baseline Characteristics - OMEGA Report 1.

INTRODUCTION: The aim of this study was to describe the design and the participants' baseline characteristics of a prospective natural history study of geographic atrophy (GA) secondary to age-related macular degeneration. METHODS: The optical coherence tomography (OCT) and microperimetry biomarker evaluation in patients with GA (OMEGA) study was conducted at a tertiary referral center (ClinicalTrials.gov identifier: NCT05963646). Participants were followed for 12 months during 4 visits (baseline and follow-up exams at weeks 12, 24, and 48) with best-corrected Early Treatment of Diabetic Retinopathy Study visual acuity, low-luminance visual acuity (LLVA), and quick contrast sensitivity function testing. Further, participants underwent spectral-domain OCT, OCT angiography, fundus autofluorescence imaging, and mesopic microperimetry testing. RESULTS: Thirty participants (median [IQR] age of 79 [77, 84] years) and 37 study eyes were included with a (median [IQR]) GA area of 1.40 mm2 (0.49, 5.24) at baseline. Out of 37 study eyes, six developed macular neovascularizations (16%). The study-eye best-corrected visual acuity was (median [IQR]) 0.18 logarithm of the minimum angle of resolution (logMAR) (0.06, 0.26), LLVA 0.66 logMAR (0.36, 0.88), and the microperimetry mean sensitivity 18.4 dB (9.21, 20.9). The highest correlation between square root GA area and a visual function test was evident for LLVA (R2 of 0.578), followed by area under the log contrast sensitivity function curve (0.519) and microperimetral retinal sensitivity (0.487). CONCLUSION: This report lays out the design and baseline characteristics of the OMEGA study, which aims to contribute to the understanding of the natural history of GA. The OMEGA study will provide estimates of the ability to detect change and retest reliability for a panel of structure and functional assessments.

Validation of collaborative cyberspace virtual reality oculometry enhanced with near real-time spatial audio.

Currently, most medical image data, such as optical coherence tomography (OCT) images, are displayed in two dimensions on a computer screen. Advances in computer information technology have contributed to the growing storage of these data in electronic form. However, the data are usually processed only locally on site. To overcome such hurdles, a cyberspace virtual reality (csVR) application was validated, in which interactive OCT data were presented simultaneously to geographically distant sites (Lucerne, London, and Barcelona) where three graders independently measured the ocular csVR OCT diameters. A total of 109 objects were measured, each three times, resulting in a total of 327 csVR measurements. A minor mean absolute difference of 5.3 µm was found among the 3 measurements of an object (standard deviation 4.2 µm, coefficient of variation 0.3% with respect to the mean object size). Despite the 5 h of online work, csVR was well tolerated and safe. Digital high-resolution OCT data can be remotely and collaboratively processed in csVR. With csVR, measurements and actions enhanced with spatial audio communication can be made consistently in near real time, even if the users are situated geographically far apart. The proposed visuo-auditory framework has the potential to further boost the convenience of digital medicine toward csVR precision and collaborative medicine.

Cynomolgus monkey's retina volume reference database based on hybrid deep learning optical coherence tomography segmentation.

Cynomolgus monkeys (Macaca fascicularis) are commonly used in pre-clinical ocular studies. However, studies that report the morphological features of the macaque retina are based only on minimal sample sizes; therefore, little is known about the normal distribution and background variation. This study was conducted using optical coherence tomography (OCT) imaging to investigate the variations in retinal volumes of healthy cynomolgus monkeys and the effects of sex, origin, and eye side on the retinal volumes to establish a comprehensive reference database. A machine-learning algorithm was employed to segment the retina within the OCT data (i.e., generated pixel-wise labels). Furthermore, a classical computer vision algorithm has identified the deepest point in a foveolar depression. The retinal volumes were determined and analyzed based on this reference point and segmented retinal compartments. Notably, the overall foveolar mean volume in zone 1, which is the region of the sharpest vision, was 0.205 mm3 (range 0.154-0.268 mm3), with a relatively low coefficient of variation of 7.9%. Generally, retinal volumes exhibit a relatively low degree of variation. However, significant differences in the retinal volumes due to the monkey's origin were identified. Additionally, sex had a significant impact on the paracentral retinal volume. Therefore, the origin and sex of cynomolgus monkeys should be considered when evaluating the macaque retinal volumes based on this dataset.

Iris Color Matters-A Contractility Analysis With Dynamic Volume-Rendered Optical Coherence Tomography Pupillometry.

Purpose: To analyze natural variability in pupillary contractility with dynamic volume-rendered optical coherence tomography (OCT) pupillometry regarding iris color, age, and sex in healthy Caucasian participants. Methods: The intrapupillary spaces (IPSs) derived from anterior segment swept-source OCT of 71 healthy eyes were retrospectively analyzed. Baseline scotopic and photopic volumes and the functional parameters of pupillary ejection fraction (PEF), three-dimensional (3D) contractility, and relative light response (RLR) were measured on the swept-source OCT volumes. The effect on these parameters of iris color (brown, green, and blue), age, and sex was assessed. Results: More pigmented irises were more contractile than less pigmented irises. Iris color significantly affected scotopic baseline IPSs (brown, 10.39 ± 4.86 mm3; green, 9.68 ± 3.31 mm3; blue, 6.75 ± 4.27 mm3; P = 0.018), PEF (brown, 90.8% ± 2.7%; green, 89.1% ± 2.5%; blue, 85.0% ± 9.3%; P = 0.010), 3D contractility (brown, 9.52 ± 4.59 mm3; green, 8.66 ± 3.07 mm3; blue, 6.44 ± 4.87 mm3; P = 0.016), and RLR (brown, 11.90 ± 4.03; green, 9.75 ± 2.73; blue, 8.52 ± 3.88; P = 0.026). Absolute scotopic volume (P = 0.022) and 3D contractility (P = 0.024) decreased with age. Sex showed no correlations. Conclusions: The natural variability of pupillary contractility can be analyzed with dynamic OCT pupillometry. Iris color and age can impact pupillary response with this method. Translational Relevance: Iris contractility parameters can be measured using a commercially available OCT system, allowing for quantification of the aqueous humor volume inside the pupil.

Feasibility of Automated Segmentation of Pigmented Choroidal Lesions in OCT Data With Deep Learning.

Purpose: To evaluate the feasibility of automated segmentation of pigmented choroidal lesions (PCLs) in optical coherence tomography (OCT) data and compare the performance of different deep neural networks. Methods: Swept-source OCT image volumes were annotated pixel-wise for PCLs and background. Three deep neural network architectures were applied to the data: the multi-dimensional gated recurrent units (MD-GRU), the V-Net, and the nnU-Net. The nnU-Net was used to compare the performance of two-dimensional (2D) versus three-dimensional (3D) predictions. Results: A total of 121 OCT volumes were analyzed (100 normal and 21 PCLs). Automated PCL segmentations were successful with all neural networks. The 3D nnU-Net predictions showed the highest recall with a mean of 0.77 ± 0.22 (MD-GRU, 0.60 ± 0.31; V-Net, 0.61 ± 0.25). The 3D nnU-Net predicted PCLs with a Dice coefficient of 0.78 ± 0.13, outperforming MD-GRU (0.62 ± 0.23) and V-Net (0.59 ± 0.24). The smallest distance to the manual annotation was found using 3D nnU-Net with a mean maximum Hausdorff distance of 315 ± 172 µm (MD-GRU, 1542 ± 1169 µm; V-Net, 2408 ± 1060 µm). The 3D nnU-Net showed a superior performance compared with stacked 2D predictions. Conclusions: The feasibility of automated deep learning segmentation of PCLs was demonstrated in OCT data. The neural network architecture had a relevant impact on PCL predictions. Translational Relevance: This work serves as proof of concept for segmentations of choroidal pathologies in volumetric OCT data; improvements are conceivable to meet clinical demands for the diagnosis, monitoring, and treatment evaluation of PCLs.

Volumetric subfield analysis of cynomolgus monkey's choroid derived from hybrid machine learning optical coherence tomography segmentation.

This study aimed to provide volumetric choroidal readings regarding sex, origin, and eye side from healthy cynomolgus monkey eyes as a reference database using optical coherence tomography (OCT) imaging. A machine learning (ML) algorithm was used to extract the choroid from the volumetric OCT data. Classical computer vision methods were then applied to automatically identify the deepest location in the foveolar depression. The choroidal thickness was determined from this reference point. A total of 374 eyes of 203 cynomolgus macaques from Asian and Mauritius origin were included in the analysis. The overall subfoveolar mean choroidal volume in zone 1, in the region of the central bouquet, was 0.156 mm3 (range, 0.131-0.193 mm3). For the central choroid volume, the coefficient of variation (CV) was found of 6.3%, indicating relatively little variation. Our results show, based on analyses of variance, that monkey origin (Asian or Mauritius) does not influence choroid volumes. Sex had a significant influence on choroidal volumes in the superior-inferior axis (p ≤ 0.01), but not in the fovea centralis. A homogeneous foveolar choroidal architecture was also observed.

Cynomolgus monkey's choroid reference database derived from hybrid deep learning optical coherence tomography segmentation.

Cynomolgus monkeys exhibit human-like features, such as a fovea, so they are often used in non-clinical research. Nevertheless, little is known about the natural variation of the choroidal thickness in relation to origin and sex. A combination of deep learning and a deterministic computer vision algorithm was applied for automatic segmentation of foveolar optical coherence tomography images in cynomolgus monkeys. The main evaluation parameters were choroidal thickness and surface area directed from the deepest point on OCT images within the fovea, marked as the nulla with regard to sex and origin. Reference choroid landmarks were set underneath the nulla and at 500 µm intervals laterally up to a distance of 2000 µm nasally and temporally, complemented by a sub-analysis of the central bouquet of cones. 203 animals contributed 374 eyes for a reference choroid database. The overall average central choroidal thickness was 193 µm with a coefficient of variation of 7.8%, and the overall mean surface area of the central bouquet temporally was 19,335 µm2 and nasally was 19,283 µm2. The choroidal thickness of the fovea appears relatively homogeneous between the sexes and the studied origins. However, considerable natural variation has been observed, which needs to be appreciated.

IMAGING THE VITREOUS WITH A NOVEL BOOSTED OPTICAL COHERENCE TOMOGRAPHY TECHNIQUE: Posterior Vitreous Detachment.

PURPOSE: To evaluate the anatomic changes in the vitreous associated with evolving posterior vitreous detachment over the macula. METHODS: A novel scanning method by which four A-scans at each position were averaged before the Fourier transform that boosted the image quality sufficiently such that frame averaging could occur. B-scans and volume rendered images of eyes with evidence of any partial separation of the vitreous in the macular regions were evaluated. RESULTS: There were 43 eyes of 23 subjects with particular attention paid to the findings of seven eyes with various stages of posterior vitreous detachment occurring over the macula. In eyes from young subjects with no vitreous degeneration, the outer vitreous showed a diffuse, poorly defined increase in reflectivity in the region where the vitreous cortex was expected to be. In eyes with vitreous degeneration, there was a hyperreflective zone, called the cortical vitreous condensation, that coursed parallel to the curvature of the retina. The posterior vitreous face elevated from the retina with either a well-defined, smooth outer surface, consistent with the posterior vitreous membrane, or a poorly defined flocculent outer border. The cortical vitreous near the fovea was thin and in eyes in the process of posterior vitreous detachment had visible tears. In more advanced eyes, a circular dehiscence of the cortical vitreous in the central macula occurred with herniation of the vitreous gel through the hole. CONCLUSION: The methodology produced images of unprecedented clarity that highlighted several newly described details concerning the vitreous changes associated with posterior vitreous detachment over the macula.

Reference database of total retinal vessel surface area derived from volume-rendered optical coherence tomography angiography.

Optical coherence tomography angiography (OCTA) enables three-dimensional, high-resolution, depth-resolved flow to be distinguished from non-vessel tissue signals in the retina. Thus, it enables the quantification of the 3D surface area of the retinal vessel signal. Despite the widespread use of OCTA, no representative spatially rendered reference vessel surface area data are published. In this study, the OCTA vessel surface areas in 203 eyes of 107 healthy participants were measured in the 3D domain. A Generalized Linear Model (GLM) model analysis was performed to investigate the effects of sex, age, spherical equivalent, axial length, and visual acuity on the OCTA vessel surface area. The mean overall vessel surface area was 54.53 mm2 (range from 27.03 to 88.7 mm2). OCTA vessel surface area was slightly negatively correlated with age. However, the GLM model analysis identified axial length as having the strongest effect on OCTA vessel surface area. No significant correlations were found for sex or between left and right eyes. This is the first study to characterize three-dimensional vascular parameters in a population based on OCTA with respect to the vessel surface area.

IMAGING THE VITREOUS WITH A NOVEL BOOSTED OPTICAL COHERENCE TOMOGRAPHY TECHNIQUE: Vitreous Degeneration and Cisterns.

PURPOSE: To evaluate the degenerative findings including cistern formation in the premacular vitreous using optical coherence tomography. METHODS: A novel enhanced vitreous imaging method by which four A-scans at each position were averaged before the Fourier transform increased the image quality per frame so that subsequent image registration for averaging could occur. Analysis of B-scans and volume-rendered images of eyes in subjects of various ages was performed. RESULTS: There were 43 eyes of 23 subjects ranging in age from 23 to 68 years. The texture in the vitreous images suggests specific orientations of the vitreous fibers in the macular region; there were fibers circumferential to the retina immediately anterior to the premacular bursa. The pattern of the vitreous fibers seemed less well-defined internal to the zone of circumferential fibers. In younger eyes, there were striations oriented in a roughly inferior to superior direction in this zone. In older eyes, there were striations in the same orientation but actually were alternating zones of vitreous synchysis and syneresis. In these same eyes, numerous cisterns appeared at various levels in the vitreous gel. With extensive vitreous condensation and synchysis, definition of the premacular bursa was lost. CONCLUSION: With this novel method of enhanced vitreous imaging, the vitreous seemed to have stereotypic patterns of degeneration. The formation of vitreous syneresis and synchysis may be related to organization architecture of the vitreous, including the pattern of vitreous collagen deposition, and the effects of eye motion through decades of time.

State of the art spatial visualization of the response of neovascularisation to anti-vascular endothelial growth factor therapy.

PURPOSE: To visualize the mode of action of anti-vascular endothelial growth factor (anti-VEGFs) therapy on retinal neovascularization (RNV) in a patient with macular telangiectasia (MacTel) type 2 using a detailed three-dimensional data environment. OBSERVATION: A 60-year-old man presented with visual acuity loss and was diagnosed with MacTel type 2. Fluorescein angiography was not possible for safety reasons because of a history of severe reaction to fluorescein dye at his referring hospital. Optical coherence tomography angiography (OCTA) imaging revealed new retinal neovascular membranes (RNV) in the macula of both eyes. A marked reduction in the size of the RNV in both eyes was evident on volume-rendered three-dimensional OCTA retinal imaging after the first anti-VEGF injection. CONCLUSION AND IMPORTANCE: The ability to directly observe the effect of anti-VEGF injections on a RNV using three-dimensional OCTA was successfully demonstrated. This can be useful in patients with previous allergic and potentially lethal complications to fluorescein. In addition, enhanced three-dimensional spatial display of RNV leads to a greater understanding of the perfusion profile and the anatomical changes that occur in ocular neovascularization relative to surrounding tissue. This has the potential to provide insight into the pathobiology of angiogenesis.

Dynamic volume-rendered optical coherence tomography pupillometry.

PURPOSE: To assess intrapupillary space (IPS) changes in healthy subjects with regard to decreased iris motility in patients with pseudoexfoliation glaucoma (PEXG) or non-arteritic anterior ischaemic optic neuropathy (NAION) in a feasibility study in a clinical environment. METHODS: Scotopic and photopic IPS measurements using three-dimensionally rendered swept-source optical coherence tomography (SS-OCT) data were obtained and compared for all subjects. Intrapupillary space (IPS) parameters were evaluated such as absolute volumetric differences, relative light response for volumetric ratios and pupillary ejection fraction (PEF) for functional contraction measurements. RESULTS: From a total of 122 IPS from 66 subjects, 106 IPS were eligible for comparison providing values for 72 normal, 30 PEXG and 4 NAION eyes. In healthy, PEXG and NAION subjects, scotopic overall mean IPS was 8.90, 3.45 and 4.16 mm3 , and photopic overall mean IPS was 0.87, 0.74 and 1.13 mm3 , respectively. Three-dimensional contractility showed a mean absolute difference of 8.03 mm3 for normals (defined as 100% contractility), 2.72 mm3 for PEXG (33.88% of normal) and 3.03 mm3 for NAION (38.50% of normal) with a relative light response ratio between scotopic and photopic volumes of 10.26 (100%), 4.69 (45.70%) and 3.67 (35.78%), respectively. Pupillary ejection fraction (PEF) showed a contractile pupillary emptying of 88.11% for normals, 76.92% for PEXG and 70.91% for NAION patients. CONCLUSION: This 3D pupillometry OCT assessment allows for quantitative measurements of pupil function, contractility and response to light. More specifically, PEF is presented as a potential (neuro)-pupillary outcome measure that could be useful in the monitoring of ophthalmic disorders that affect pupillary function.

Uncovering of intraspecies macular heterogeneity in cynomolgus monkeys using hybrid machine learning optical coherence tomography image segmentation.

The fovea is a depression in the center of the macula and is the site of the highest visual acuity. Optical coherence tomography (OCT) has contributed considerably in elucidating the pathologic changes in the fovea and is now being considered as an accompanying imaging method in drug development, such as antivascular endothelial growth factor and its safety profiling. Because animal numbers are limited in preclinical studies and automatized image evaluation tools have not yet been routinely employed, essential reference data describing the morphologic variations in macular thickness in laboratory cynomolgus monkeys are sparse to nonexistent. A hybrid machine learning algorithm was applied for automated OCT image processing and measurements of central retina thickness and surface area values. Morphological variations and the effects of sex and geographical origin were determined. Based on our findings, the fovea parameters are specific to the geographic origin. Despite morphological similarities among cynomolgus monkeys, considerable variations in the foveolar contour, even within the same species but from different geographic origins, were found. The results of the reference database show that not only the entire retinal thickness, but also the macular subfields, should be considered when designing preclinical studies and in the interpretation of foveal data.

Hypertension treatment with Combretum micranthum or Hibiscus sabdariffa, as decoction or tablet: a randomized clinical trial.

Hibiscus sabdariffa L. (local names: bissap, karkade) and Combretum micranthum (kinkeliba) are widely known in traditional medicines and popular beliefs for their antihypertensive effect. This study assessed the clinical effectiveness of these two plants in the galenic forms of tablet and brew (decoction) in noncomplicated hypertensive patients. In total, 219 hypertensive patients with systolic blood pressure (SBP) between 140 and 180 mmHg and/or diastolic blood pressure (DBP) between 90 and 110 mmHg, without cardiovascular or renal complications, were involved in a multicentric randomized clinical trial in Senegal comparing five treatment regimens: bissap tablets (2 × 375 mg/day), bissap brew (10 g of calyx/day), kinkeliba tablets (2 × 200 mg/day), kinkeliba brew (10 g of leaves/day), and captopril (2 × 50 mg/day) as control. During the 6 months' follow-up, a significant and equivalent decrease of SBP was observed with the herbal drug approach (-19.5 ± 16.1 mmHg, p < 0.001) and control group (-19.7 ± 16.7, p < 0.001). Regarding the galenic forms, the brews tended to be slightly more effective than tablets (reduction of SBP: -20.7 ± 15.1 mmHg vs -18.7 ± 16.7). The rates of clinically significant effectiveness (decrease in SBP ≥ 10 mmHg) were 75%, 67%, and 65% with bissap, kinkeliba, and captopril, respectively. After 6 months, target blood pressure of <140/90 mmHg was attained by 49% of patients with bissap, 51% with kinkeliba and 40% with captopril. Bissap and kinkeliba appeared, at doses utilized, to be as effective as captopril over the 6 months' follow-up. In subsequent studies, brews might be started with a lower dosage.