Wide-Field Three-Dimensional Depth-Invariant Cellular-Resolution Imaging of the Human Retina.

Three-dimensional (3D) cellular-resolution imaging of the living human retina over a large field of view will bring a great impact in clinical ophthalmology, potentially finding new biomarkers for early diagnosis and improving the pathophysiological understanding of ocular diseases. While hardware-based and computational adaptive optics (AO) optical coherence tomography (OCT) have been developed to achieve cellular-resolution retinal imaging, these approaches support limited 3D imaging fields, and their high cost and intrinsic hardware complexity limit their practical utility. Here, this work demonstrates 3D depth-invariant cellular-resolution imaging of the living human retina over a 3 × 3 mm field of view using the first intrinsically phase-stable multi-MHz retinal swept-source OCT and novel computational defocus and aberration correction methods. Single-acquisition imaging of photoreceptor cells, retinal nerve fiber layer, and retinal capillaries is presented across unprecedented imaging fields. By providing wide-field 3D cellular-resolution imaging in the human retina using a standard point-scan architecture routinely used in the clinic, this platform proposes a strategy for expanded utilization of high-resolution retinal imaging in both research and clinical settings.

QUANTIFICATION OF RETINAL CAPILLARY NONPERFUSION IN DIABETICS USING WIDE-FIELD OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To combine advances in high-speed, wide-field optical coherence tomography angiography (OCTA) with image processing methods for semiautomatic quantitative analysis of capillary nonperfusion in patients with diabetic retinopathy (DR). METHODS: Sixty-eight diabetic patients (73 eyes), either without retinopathy or with different degrees of retinopathy, were prospectively recruited for volumetric swept-source OCTA imaging using 12 mm × 12 mm fields centered at the fovea. A custom, semiautomatic software algorithm was used to quantify areas of capillary nonperfusion. RESULTS: The mean percentage of nonperfused area was 0.1% (95% confidence interval: 0.0-0.4) in the eyes without DR; 2.1% (95% confidence interval: 1.2-3.7) in the nonproliferative DR eyes (mild, moderate, and severe), and 8.5% (95% confidence interval: 5.0-14.3) in the proliferative DR eyes. The percentage of nonperfused area increased in a statistically significant manner from eyes without DR, to eyes with nonproliferative DR, to eyes with proliferative DR. CONCLUSION: Capillary nonperfusion area in the posterior retina increases with increasing DR severity as measured by swept-source OCTA. Quantitative analysis of retinal nonperfusion on wide-field OCTA may be useful for early detection and monitoring of disease in patients with diabetes and DR.

SPATIAL DISTRIBUTION OF CHORIOCAPILLARIS IMPAIRMENT IN EYES WITH CHOROIDAL NEOVASCULARIZATION SECONDARY TO AGE-RELATED MACULAR DEGENERATION: A Quantitative OCT Angiography Study.

PURPOSE: To develop an optical coherence tomography angiography (OCTA)-based framework for quantitatively analyzing the spatial distribution of choriocapillaris (CC) impairment around choroidal neovascularization (CNV) secondary to age-related macular degeneration. METHODS: In a retrospective, cross-sectional study, 400-kHz swept-source OCTA images from 7 eyes of 6 patients with CNV secondary to age-related macular degeneration were quantitatively analyzed using custom software. A lesion-centered zonal OCTA analysis technique-which portioned the field-of-view into zones relative to CNV boundaries-was developed to quantify the spatial dependence of CC flow deficits. RESULTS: Quantitative, lesion-centered zonal analysis of CC OCTA images revealed highest flow-deficit percentages near CNV boundaries, decreasing in zones farther from the boundaries. Optical coherence tomography angiography using shorter (1.5 ms) interscan times revealed more severe flow deficits than OCTA using longer (3.0 ms) interscan times; however, spatial trends were similar for both interscan times. A detailed description of the OCTA processing steps and parameters was provided so as to elucidate their influence on quantitative measurements. CONCLUSION: Impairment of the CC, assessed by flow-deficit percentages, was most prominent closest to CNV boundaries. The lesion-centered zonal analysis technique enabled quantitative CC measurements relative to focal lesions. Understanding how processing steps, imaging/processing parameters, and artifacts can affect quantitative CC measurements is important for longitudinal, OCTA-based studies of disease progression, and treatment response.

Optical Coherence Tomography Angiography Characteristics of Iris Melanocytic Tumors.

PURPOSE: To evaluate tumor vasculature with optical coherence tomography angiography (OCTA) in malignant iris melanomas and benign iris lesions. DESIGN: Cross-sectional observational clinical study. PARTICIPANTS: Patients with iris lesions and healthy volunteers. METHODS: Eyes were imaged using OCTA systems operating at 1050- and 840-nm wavelengths. Three-dimensional OCTA scans were acquired. Iris melanoma patients treated with radiation therapy were imaged again after I-125 plaque brachytherapy at 6 and 18 months. MAIN OUTCOME MEASURES: OCT and OCTA images, qualitative evaluation of iris and tumor vasculature, and quantitative vessel density. RESULTS: One eye each of 8 normal volunteers and 9 patients with iris melanomas or benign iris lesions, including freckles, nevi, and an iris pigment epithelial (IPE) cyst, were imaged. The normal iris has radially oriented vessels within the stroma on OCTA. Penetration of flow signal in normal iris depended on iris color, with best penetration seen in light to moderately pigmented irides. Iris melanomas demonstrated tortuous and disorganized intratumoral vasculature. In 2 eyes with nevi there was no increased vascularity; in another, fine vascular loops were noted near an area of ectropion uveae. Iris freckles and the IPE cyst did not have intrinsic vascularity. The vessel density was significantly higher within iris melanomas (34.5%±9.8%, P < 0.05) than in benign iris nevi (8.0%±1.4%) or normal irides (8.0%±1.2%). Tumor regression after radiation therapy for melanomas was associated with decreased vessel density. OCTA at 1050 nm provided better visualization of tumor vasculature and penetration through thicker tumors than at 840 nm. But in very thick tumors and highly pigmented lesions even 1050-nm OCTA could not visualize their full thickness. Interpretable OCTA images were obtained in 82% of participants in whom imaging was attempted. CONCLUSIONS: This is the first demonstration of OCTA in iris tumors. OCTA may provide a dye-free, no-injection, cost-effective method for monitoring a variety of tumors, including iris melanocytic lesions, for growth and vascularity. This could be helpful in evaluating tumors for malignant transformation and response to treatment. Penetration of the OCT beam remains a limitation for highly pigmented tumors, as does the inability to image the entire iris in a single field.

ULTRAHIGH SPEED SWEPT SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY OF RETINAL AND CHORIOCAPILLARIS ALTERATIONS IN DIABETIC PATIENTS WITH AND WITHOUT RETINOPATHY.

PURPOSE: To investigate the utility of ultrahigh speed, swept source optical coherence tomography angiography in visualizing retinal microvascular and choriocapillaris (CC) changes in diabetic patients. METHODS: The study was prospective and cross-sectional. A 1,050 nm wavelength, 400 kHz A-scan rate swept source optical coherence tomography prototype was used to perform volumetric optical coherence tomography angiography of the retinal and CC vasculatures in diabetic patients and normal subjects. Sixty-three eyes from 32 normal subjects, 9 eyes from 7 patients with proliferative diabetic retinopathy, 29 eyes from 16 patients with nonproliferative diabetic retinopathy, and 51 eyes from 28 diabetic patients without retinopathy were imaged. RESULTS: Retinal and CC microvascular abnormalities were observed in all stages of diabetic retinopathy. In nonproliferative diabetic retinopathy and proliferative diabetic retinopathy, optical coherence tomography angiography visualized a variety of vascular abnormalities, including clustered capillaries, dilated capillary segments, tortuous capillaries, regions of capillary dropout, reduced capillary density, abnormal capillary loops, and foveal avascular zone enlargement. In proliferative diabetic retinopathy, retinal neovascularization above the inner limiting membrane was visualized. Regions of CC flow impairment in patients with proliferative diabetic retinopathy and nonproliferative diabetic retinopathy were also observed. In 18 of the 51 of eyes from diabetic patients without retinopathy, retinal mircrovascular abnormalities were observed and CC flow impairment was found in 24 of the 51 diabetic eyes without retinopathy. CONCLUSION: The ability of optical coherence tomography angiography to visualize retinal and CC microvascular abnormalities suggests it may be a useful tool for understanding pathogenesis, evaluating treatment response, and earlier detection of vascular abnormalities in patients with diabetes.

SWEPT-SOURCE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY REVEALS CHORIOCAPILLARIS ALTERATIONS IN EYES WITH NASCENT GEOGRAPHIC ATROPHY AND DRUSEN-ASSOCIATED GEOGRAPHIC ATROPHY.

PURPOSE: To investigate choriocapillaris (CC) alteration in patients with nascent geographic atrophy (nGA) and/or drusen-associated geographic atrophy (DAGA) using swept-source optical coherence tomography angiography (OCTA). METHODS: A 1,050-nm wavelength, 400 kHz A-scan rate swept-source optical coherence tomography prototype was used to perform volumetric swept-source optical coherence tomography angiography over 6 mm × 6 mm fields of view in patients with nGA and/or DAGA. The resulting optical coherence tomography (OCT) and OCTA data were analyzed using a combination of en face and cross-sectional techniques. Variable interscan time analysis (VISTA) was used to differentiate CC flow impairment from complete CC atrophy. RESULTS: A total of 7 eyes from 6 patients (mean age: 73.8 ± 5.7 years) were scanned. Seven areas of nGA and three areas of DAGA were identified. Analysis of cross-sectional OCT and OCTA images identified focal alterations of the CC underlying all seven areas of nGA and all three areas of DAGA. En face OCTA analysis of the CC revealed diffuse CC alterations in all eyes. Variable interscan time analysis processing suggested that the observed CC flow alterations predominantly corresponded to flow impairment rather than complete CC atrophy. CONCLUSION: The OCTA imaging of the CC revealed focal CC flow impairment associated with areas of nGA and DAGA, as well as diffuse CC flow impairment throughout the imaged field. En face OCT analysis should prove useful for understanding the pathogenesis of nGA and DAGA and for identifying the formation of nGA and DAGA as endpoints in therapeutic trials.

AN AUTOMATIC, INTERCAPILLARY AREA-BASED ALGORITHM FOR QUANTIFYING DIABETES-RELATED CAPILLARY DROPOUT USING OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY.

PURPOSE: To develop a robust, sensitive, and fully automatic algorithm to quantify diabetes-related capillary dropout using optical coherence tomography (OCT) angiography (OCTA). METHODS: A 1,050-nm wavelength, 400 kHz A-scan rate swept-source optical coherence tomography prototype was used to perform volumetric optical coherence tomography angiography imaging over 3 mm × 3 mm fields in normal controls (n = 5), patients with diabetes without diabetic retinopathy (DR) (n = 7), patients with nonproliferative diabetic retinopathy (NPDR) (n = 9), and patients with proliferative diabetic retinopathy (PDR) (n = 5); for each patient, one eye was imaged. A fully automatic algorithm to quantify intercapillary areas was developed. RESULTS: Of the 26 evaluated eyes, the segmentation was successful in 22 eyes (85%). The mean values of the 10 and 20 largest intercapillary areas, either including or excluding the foveal avascular zone, showed a consistent trend of increasing size from normal control eyes, to eyes with diabetic retinopathy but without diabetic retinopathy, to nonproliferative diabetic retinopathy eyes, and finally to PDR eyes. CONCLUSION: Optical coherence tomography angiography-based screening and monitoring of patients with diabetic retinopathy is critically dependent on automated vessel analysis. The algorithm presented was able to automatically extract an intercapillary area-based metric in patients having various stages of diabetic retinopathy. Intercapillary area-based approaches are likely more sensitive to early stage capillary dropout than vascular density-based methods.

TOWARD QUANTITATIVE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY: Visualizing Blood Flow Speeds in Ocular Pathology Using Variable Interscan Time Analysis.

PURPOSE: Currently available optical coherence tomography angiography systems provide information about blood flux but only limited information about blood flow speed. The authors develop a method for mapping the previously proposed variable interscan time analysis (VISTA) algorithm into a color display that encodes relative blood flow speed. METHODS: Optical coherence tomography angiography was performed with a 1,050 nm, 400 kHz A-scan rate, swept source optical coherence tomography system using a 5 repeated B-scan protocol. Variable interscan time analysis was used to compute the optical coherence tomography angiography signal from B-scan pairs having 1.5 millisecond and 3.0 milliseconds interscan times. The resulting VISTA data were then mapped to a color space for display. RESULTS: The authors evaluated the VISTA visualization algorithm in normal eyes (n = 2), nonproliferative diabetic retinopathy eyes (n = 6), proliferative diabetic retinopathy eyes (n = 3), geographic atrophy eyes (n = 4), and exudative age-related macular degeneration eyes (n = 2). All eyes showed blood flow speed variations, and all eyes with pathology showed abnormal blood flow speeds compared with controls. CONCLUSION: The authors developed a novel method for mapping VISTA into a color display, allowing visualization of relative blood flow speeds. The method was found useful, in a small case series, for visualizing blood flow speeds in a variety of ocular diseases and serves as a step toward quantitative optical coherence tomography angiography.

Ultrahigh-Speed, Swept-Source Optical Coherence Tomography Angiography in Nonexudative Age-Related Macular Degeneration with Geographic Atrophy.

PURPOSE: To investigate ultrahigh-speed, swept-source optical coherence tomography (SSOCT) angiography for visualizing vascular changes in eyes with nonexudative age-related macular degeneration (AMD) with geographic atrophy (GA). DESIGN: Observational, prospective, cross-sectional study. PARTICIPANTS: A total of 63 eyes from 32 normal subjects and 12 eyes from 7 patients with nonexudative AMD with GA. METHODS: A 1050-nm, 400-kHz A-scan rate SSOCT system was used to perform volumetric optical coherence tomography angiography (OCTA) of the retinal and choriocapillaris (CC) vasculatures in normal subjects and patients with nonexudative AMD with GA. Optical coherence tomography angiography using variable interscan time analysis (VISTA) was performed to assess CC alteration and differentiate varying degrees of CC flow impairment. MAIN OUTCOME MEASURES: Qualitative comparison of retinal and CC vasculatures in normal subjects versus those in patients with a clinical diagnosis of nonexudative AMD with GA. RESULTS: In all 12 eyes with GA, OCTA showed pronounced CC flow impairment within the region of GA. In 10 of the 12 eyes with GA, OCTA with VISTA showed milder CC flow impairment extending beyond the margin of GA. Of the 5 eyes exhibiting foveal-sparing GA, OCTA showed CC flow within the region of foveal sparing in 4 of the eyes. CONCLUSIONS: The ability of ultrahigh-speed, swept-source OCTA to noninvasively visualize alterations in the retinal and CC vasculatures makes it a promising tool for assessing nonexudative AMD with GA. Optical coherence tomography angiography using VISTA can distinguish varying degrees of CC alteration and flow impairment and may be useful for elucidating disease pathogenesis, progression, and response to therapy.

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.

In vivo imaging of renal microvasculature in a murine ischemia-reperfusion injury model using optical coherence tomography angiography.

Optical coherence tomography angiography (OCTA) provides three-dimensional structural and semiquantitative imaging of microvasculature in vivo. We developed an OCTA imaging protocol for a murine kidney ischemia-reperfusion injury (IRI) model to investigate the correlation between renal microvascular changes and ischemic damage. Mice were divided into mild and moderate IRI groups according to the duration of ischemia (10 and 35 mins, respectively). Each animal was imaged at baseline; during ischemia; and at 1, 15, 30, 45, and 60 mins after ischemia. Amplitude decorrelation OCTA images were constructed with 1.5-, 3.0-, and 5.8-ms interscan times, to calculate the semiquantitative flow index in the superficial (50-70 µm) and the deep (220-340 µm) capillaries of the renal cortex. The mild IRI group showed no significant flow index change in both the superfial and the deep layers. The moderate IRI group showed a significantly decreased flow index from 15 and 45 mins in the superficial and deep layers, respectively. Seven weeks after IRI induction, the moderate IRI group showed lower kidney function and higher collagen deposition than the mild IRI group. OCTA imaging of the murine IRI model revealed changes in superficial blood flow after ischemic injury. A more pronounced decrease in superficial blood flow than in deep blood flow was associated with sustained dysfunction after IRI. Further investigation on post-IRI renal microvascular response using OCTA may improve our understanding of the relationship between the degree of ischemic insult and kidney function.

Microfluidics-based assessment of cell deformability.

Mechanical properties of cells have been shown to have a significant role in disease, as in many instances cell stiffness changes when a cell is no longer healthy. We present a high-throughput microfluidics-based approach that exploits the connection between travel time of a cell through a narrow passage and cell stiffness. The system resolves both cell travel time and relative cell diameter while retaining information on the cell level. We show that stiffer cells have longer transit times than less stiff ones and that cell size significantly influences travel times. Experiments with untreated HeLa cells and cells made compliant with latrunculin A and cytochalasin B further demonstrate that travel time is influenced by cell stiffness, with the compliant cells having faster transit time.

Analysis of Fall Events, Physical Fitness, and Gait Speed According to Fall Risk in Older Korean Women.

The present study aimed to investigate the associations between fall risk and previous fall events, physical fitness, and gait speeds on flat ground and during obstacle avoidance in older adult women in Korea. Data were analyzed for 148 women over 65 years of age, divided into low (n = 52) and high Berg Balance Scale (BBS) score groups (n = 96). Physical fitness was assessed using arm curl, chair stand, 2 min step, chair sit-and-reach, timed up-and-go, and single-leg stance tests. Gait speed was measured on flat ground and during obstacle avoidance (5 cm, 10% of height, 30 cm). The incidence of falls was 18.2% lower among participants with BBS scores above the mean than in those with scores below the mean (p < 0.05). Furthermore, the two groups exhibited significant differences in the chair stand, chair sit-and-reach, timed up-and-go, and single-leg stance test results. The upper BBS group appeared faster at all four gait speeds, and participants in the upper BBS group were less likely to exhibit lower physical fitness in each test, with odds ratios (ORs) ranging from 0.227 to 0.447. The upper BBS group was also less likely to exhibit lower gait speed in most conditions, with ORs ranging from 0.327 to 0.516. Further studies should consider exercise programs that promote balance, muscular strength, and proprioception to lower the risk of falling in older adults.

Visualization of three-dimensional microcirculation of rodents' retina and choroid for studies of critical illness using optical coherence tomography angiography.

We developed a method to measure the relative blood flow speed using optical coherence tomography angiography (OCTA) in retina and choroid, and investigated the feasibility of this method for assessing microcirculatory function in rat models of sepsis and hemorrhagic shock. Two sepsis models, 6-h severe sepsis without treatment and 30-h moderate sepsis maintaining mean arterial pressure, and volume controlled hemorrhagic shock and fluid resuscitation model were used to see the change of microcirculation. The blood flow index (BFI), which was calculated from the OCTA images to represent the average relative blood flow, was decreasing during the 6-h severe sepsis model. Its change is in parallel with the mean arterial blood pressure (MAP) and blood lactate levels. In the 30-h moderate sepsis model, the BFI was decreased while maintaining MAP, and lactate was increased. In the hemorrhagic shock model, the change of BFI is in line with MAP and lactate levels. In all models, BFI change is more sensitive in choroid than in retina. This study presents the OCTA-based retinal and choroidal microcirculatory blood flow monitoring method and shows its utility for assessment of critical illness.

High-Speed, Ultrahigh-Resolution Spectral-Domain OCT with Extended Imaging Range Using Reference Arm Length Matching.

Purpose: To develop high-speed, extended-range, ultrahigh-resolution spectral-domain optical coherence tomography (UHR SD-OCT) and demonstrate scan protocols for clinical retinal imaging. Methods: A UHR SD-OCT operating at 840-nm with 150-nm bandwidths was developed. The axial imaging range was extended by dynamically matching reference arm length to the retinal contour during acquisition. Two scan protocols were demonstrated for imaging healthy participants and patients with dry age-related macular degeneration. A high-definition raster protocol with intra-B-scan reference arm length matching (ReALM) was used for high-quality cross-sectional imaging. A cube volume scan using horizontal and vertical rasters with inter-B-scan ReALM and software motion correction was used for en face and cross-sectional imaging. Linear OCT signal display enhanced visualization of outer retinal features. Results: UHR SD-OCT was demonstrated at 128- and 250-kHz A-scan rates with 2.7 µm axial resolution and a 1.2-mm, 6-dB imaging range in the eye. Dynamic ReALM was used to maintain the retina within the 6-dB imaging range over wider fields of view. Outer retinal features, including the rod and cone interdigitation zones, retinal pigment epithelium, and Bruch's membrane were visualized and alterations observed in age-related macular degeneration eyes. Conclusions: Technological advances and dynamic ReALM improve the imaging performance and clinical usability of UHR SD-OCT. Translational Relevance: These advances should simplify clinical imaging workflow, reduce imaging session times, and improve yield of high quality images. Improved visualization of photoreceptors, retinal pigment epithelium, and Bruch's membrane may facilitate diagnosis and monitoring of age-related macular degeneration and other retinal diseases.

A Framework for Multiscale Quantitation of Relationships Between Choriocapillaris Flow Impairment and Geographic Atrophy Growth.

PURPOSE: To develop a multiscale analysis framework for investigating the relationships between geographic atrophy (GA) growth rate and choriocapillaris (CC) blood flow impairment using optical coherence tomography (OCT) and OCT angiography (OCTA). DESIGN: Retrospective case series. METHODS: We developed an OCT/OCTA analysis framework that quantitatively measures GA growth rates at global and local scales and CC impairment at global, zonal, and local scales. A geometric GA growth model was used to measure local GA growth rates. The utility of the framework was demonstrated on 7 eyes with GA imaged at 2 time points using a prototype 400-kHz, 1050-nm swept-source OCTA system. RESULTS: Qualitatively, there was a trend of increasing GA growth rate with increasing CC impairment. The local analysis model enabled growth rates to be estimated at each point on the GA boundary. However, there was no generally observed trend between local GA growth rates and local CC impairment. CONCLUSIONS: The global, zonal, and local analysis framework may be useful for investigating relationships between GA growth and CC impairment at different spatial scales. The geometric GA growth model enables spatially resolved growth measurements that capture the anisotropy of GA growth and may improve the characterization of GA progression.

Controlling for Artifacts in Widefield Optical Coherence Tomography Angiography Measurements of Non-Perfusion Area.

The recent clinical adoption of optical coherence tomography (OCT) angiography (OCTA) has enabled non-invasive, volumetric visualization of ocular vasculature at micron-scale resolutions. Initially limited to 3 mm × 3 mm and 6 mm × 6 mm fields-of-view (FOV), commercial OCTA systems now offer 12 mm × 12 mm, or larger, imaging fields. While larger FOVs promise a more complete visualization of retinal disease, they also introduce new challenges to the accurate and reliable interpretation of OCTA data. In particular, because of vignetting, wide-field imaging increases occurrence of low-OCT-signal artifacts, which leads to thresholding and/or segmentation artifacts, complicating OCTA analysis. This study presents theoretical and case-based descriptions of the causes and effects of low-OCT-signal artifacts. Through these descriptions, we demonstrate that OCTA data interpretation can be ambiguous if performed without consulting corresponding OCT data. Furthermore, using wide-field non-perfusion analysis in diabetic retinopathy as a model widefield OCTA usage-case, we show how qualitative and quantitative analysis can be confounded by low-OCT-signal artifacts. Based on these results, we suggest methods and best-practices for preventing and managing low-OCT-signal artifacts, thereby reducing errors in OCTA quantitative analysis of non-perfusion and improving reproducibility. These methods promise to be especially important for longitudinal studies detecting progression and response to therapy.

Quantifying Microvascular Changes Using OCT Angiography in Diabetic Eyes without Clinical Evidence of Retinopathy.

OBJECTIVE: To compare quantitative OCT angiography (OCTA) parameters of macular ischemia in diabetic eyes without retinopathy with those in healthy nondiabetic controls. DESIGN: Cross-sectional study from August 2014 through June 2017. SUBJECTS: Thirty-nine eyes of 39 diabetic patients without clinical evidence of diabetic retinopathy and 40 eyes of 40 healthy nondiabetic subjects. METHODS: Subjects underwent OCTA imaging using prototype AngioVue software (RTVue XR Avanti). Analyses of the foveal avascular zone (FAZ) and vasculature surrounding the FAZ were performed on the automatically generated en face OCTA images of the superficial and deep retinal vasculatures using vessel-based and FAZ-based metrics. MAIN OUTCOME MEASURES: Comparison of measurements made in the superficial and deep retinal capillary plexuses of diabetic eyes and normal eyes. RESULTS: FAZ-based analysis revealed statistically significant differences between diabetic and normal eyes in FAZ area (superficial and deep layers), perimeter (superficial layer), major axis length (superficial layer), and minor axis layer (superficial and deep layers). Vessel-based analysis revealed statistically significant differences in the binarized flow index (superficial and deep layers), both including and excluding the FAZ area. CONCLUSIONS: Quantitative OCTA parameters reveal subclinical macular ischemia at both the superficial and deep retinal capillary plexuses in diabetic eyes that do not manifest clinical retinopathy. Vessel-based and FAZ-based metrics applied to OCTA images may serve as effective tools for screening and disease monitoring in patients with diabetes without clinical evidence of retinopathy.

Analyzing Relative Blood Flow Speeds in Choroidal Neovascularization Using Variable Interscan Time Analysis OCT Angiography.

PURPOSE: Longitudinally visualizing relative blood flow speeds within choroidal neovascularization (CNV) may provide valuable information regarding the evolution of CNV and the response to vascular endothelial growth factor (VEGF) inhibitors. DESIGN: Retrospective, longitudinal case series conducted at the New England Eye Center. PARTICIPANTS: Patients with either treatment-naïve or previously treated CNV secondary to neovascular age-related macular degeneration. METHODS: Optical coherence tomography angiography (OCTA) was performed using a 400-kHz, 1050-nm swept-source OCT system with a 5-repeat B-scan protocol. Variable interscan time analysis (VISTA) was used to compute relative flow speeds from pairs of B-scans having 1.5- and 3.0-ms separations; VISTA signals then were mapped to a color space for display. MAIN OUTCOME MEASURES: Quantitative outcomes included OCTA-based area and volume measurements of CNV at initial and follow-up visits. Qualitative outcomes included VISTA OCTA analysis of relative blood flow speeds, along with analysis of contraction, expansion, densification, and rarefication of CNV. RESULTS: Seven eyes of 6 patients (4 women and 2 men) with neovascular age-related macular degeneration were evaluated. Two eyes were treatment naïve at the initial visit. Choroidal neovascularization in all eyes at each visit showed relatively higher flow speeds in the trunk, central, and larger vessels and lower flow speed in the small vessels, which generally were located at the periphery of the CNV complex. Overall, the CNV appeared to expand over time despite retention of good visual acuity in all patients. In the treatment-naïve patients, slower-flow-speed vessels contracted with treatment, whereas the larger vessels with higher flow speed remained constant. CONCLUSIONS: Variable interscan time analysis OCTA allows for longitudinal observations of relative blood flow speeds in CNV treated with anti-VEGF intravitreal injections. A common finding in this study is that the main trunk and larger vessels seem to have relatively faster blood flow speeds compared with the lesions' peripheral vasculature. Moreover, an overall growth of chronically treated CNV was seen despite retention of good visual acuity. The VISTA framework may prove useful for developing clinical end points, as well as for studying hemodynamics, disease pathogenesis, and treatment response.

Photoreceptor Layer Thickness Changes During Dark Adaptation Observed With Ultrahigh-Resolution Optical Coherence Tomography.

Purpose: To examine outer retinal band changes after flash stimulus and subsequent dark adaptation with ultrahigh-resolution optical coherence tomography (UHR-OCT). Methods: Five dark-adapted left eyes of five normal subjects were imaged with 3-µm axial-resolution UHR-OCT during 30 minutes of dark adaptation following 96%, 54%, 23%, and 0% full-field and 54% half-field rhodopsin bleach. We identified the ellipsoid zone inner segment/outer segment (EZ[IS/OS]), cone interdigitation zone (CIZ), rod interdigitation zone (RIZ), retinal pigment epithelium (RPE), and Bruch's membrane (BM) axial positions and generated two-dimensional thickness maps of the EZ(IS/OS) to the four bands. The average thickness over an area of the thickness map was compared against that of the dark-adapted baselines. The time-dependent thickness changes (photoresponses) were statistically compared against 0% bleach. Dark adaptometry was performed with the same bleaching protocol. Results: The EZ(IS/OS)-CIZ photoresponse was significantly different at 96% (P < 0.0001) and 54% (P = 0.006) bleach. At all three bleaching levels, the EZ(IS/OS)-RIZ, -RPE, and -BM responses were significantly different (P < 0.0001). The EZ(IS/OS)-CIZ and EZ(IS/OS)-RIZ time courses were similar to the recovery of rod- and cone-mediated sensitivity, respectively, measured with dark adaptometry. The maximal EZ(IS/OS)-CIZ and EZ(IS/OS)-RIZ response magnitudes doubled from 54% to 96% bleach. Both EZ(IS/OS)-RPE and EZ(IS/OS)-BM responses resembled dampened oscillations that were graded in amplitude and duration with bleaching intensity. Half-field photoresponses were localized to the stimulated retina. Conclusions: With noninvasive, near-infrared UHR-OCT, we characterized three distinct, spatially localized photoresponses in the outer retinal bands. These photoresponses have potential value as physical correlates of photoreceptor function.