NEGATIVE VESSEL REMODELING IN STARGARDT DISEASE QUANTIFIED WITH VOLUME-RENDERED OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To quantify retinal vasculature changes in Stargardt disease1 (STGD1) with volume-rendered optical coherence tomography angiography. METHODS: Optical coherence tomography angiography volumes from healthy subjects and two subgroups of patients with STGD1 with the presence/absence of definitely decreased autofluorescence areas were compared. Optical coherence tomography angiography vessel surface area and vessel volume were measured in central zones (Z) of 1-, 2-, and 3-mm diameter. RESULTS: Twenty nine eyes of 15 patients with STGD1 (20/9 eyes with/without definitely decreased autofluorescence) and 30 eyes of 15 controls contributed data. An enlarged foveal avascular zone was found in patients with STGD1 without and even more with definitely decreased autofluorescence associated with a vessel rarefication in central and also paracentral zones with unnoticeable autofluorescence. Vessel surface area and vessel volume were reduced in both STGD1 subgroups for all zones (P < 0.0001). Stargardt disease 1 eyes when compared to without definitely decreased autofluorescence showed reduced vessel surface area and vessel volume in Z2+3 (both P < 0.05). CONCLUSION: Volume rendering of optical coherence tomography angiography in STGD1 shows a reduced retinal flow in the central macula. This is most likely secondary to loss of neurosensory tissue with disease progression and therefore not likely be favorably influenced by gene transfer and retinal pigment epithelial transplantation. Retinal blood flow assessed by 3D volume-rendered optical coherence tomography angiography could serve as surrogate marker for vascular changes of the central retina.

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.

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.

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.

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.

Volume-rendered optical coherence tomography angiography during ocular interventions: Advocating for noninvasive intraoperative retinal perfusion monitoring.

We aimed to test for feasibility of volume-rendered optical coherence tomography angiography (OCTA) as a novel method for assessing/quantifying retinal vasculature during ocular procedures and to explore the potential for intraoperative use. Thirty patients undergoing periocular anaesthesia were enrolled, since published evidence suggests a reduction in ocular blood flow. Retinal perfusion was monitored based on planar OCTA image-derived data provided by a standard quantification algorithm and postprocessed/volume-rendered OCTA data using a custom software script. Overall, imaging procedures were successful, yet imaging artifacts occurred frequently. In interventional eyes, perfusion parameters decreased during anaesthesia. Planar image-derived and volume rendering-derived parameters were correlated. No correlation was found between perfusion parameters and a motion artifact score developed for this study, yet all perfusion parameters correlated with signal strength as displayed by the device. Concluding, volume-rendered OCTA allows for noninvasive three-dimensional retinal vasculature assessment/quantification in challenging surgical settings and appears generally feasible for intraoperative use.

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.

Feasibility and tolerability of ophthalmic virtual reality as a medical communication tool in children and young people.

PURPOSE: Virtual reality (VR) can be useful in explaining diseases and complications that affect children in order to improve medical communications with this vulnerable patient group. So far, children and young people's responses to high-end medical VR environments have never been assessed. METHODS: An unprecedented number of 320 children and young people were given the opportunity to interact with a VR application displaying original ophthalmic volume data via a commercially available tethered head-mounted display (HMD). Participants completed three surveys: demographics and experience with VR, usability and perceived utility of this technology and the Simulator Sickness Questionnaire. The second survey also probed participants for suggestions on improvements and whether this system could be useful for increasing engagement in science. RESULTS: A total of 206 sets of surveys were received. 165 children and young people (84 female) aged 12-18 years (mean, 15 years) completed surveys that could be used for analysis. 69 participants (47.59%) were VR-naïve, and 76 (52.41%) reported that they had previous VR experience. Results show that VR facilitated understanding of ophthalmological complications and was reasonably tolerated. Lastly, exposure to VR raised children and young people's awareness and interest in science. CONCLUSIONS: The VR platform used was successfully utilized and was well accepted in children to display and interact with volume-rendered 3D ophthalmological data. Virtual reality (VR) is suitable as a novel image display platform in ophthalmology to engage children and young people.

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.