To assess the effect of image registration and averaging on the visualization and quantification of the radial peripapillary capillary (RPC) network on optical coherence tomography angiography ...(OCTA).
Twenty-two healthy controls were imaged with a commercial OCTA system (AngioVue, Optovue, Inc.). Ten 10x10° scans of the optic disc were obtained, and the most superficial layer (50-μm slab extending from the inner limiting membrane) was extracted for analysis. Rigid registration was achieved using ImageJ, and averaging of each 2 to 10 frames was performed in five ~2x2° regions of interest (ROI) located 1° from the optic disc margin. The ROI were automatically skeletonized. Signal-to-noise ratio (SNR), number of endpoints and mean capillary length from the skeleton, capillary density, and mean intercapillary distance (ICD) were measured for the reference and each averaged ROI. Repeated measures analysis of variance was used to assess statistical significance. Three patients with primary open angle glaucoma were also imaged to compare RPC density to controls.
Qualitatively, vessels appeared smoother and closer to histologic descriptions with increasing number of averaged frames. Quantitatively, number of endpoints decreased by 51%, and SNR, mean capillary length, capillary density, and ICD increased by 44%, 91%, 11%, and 4.5% from single frame to 10-frame averaged, respectively. The 10-frame averaged images from the glaucomatous eyes revealed decreased density correlating to visual field defects and retinal nerve fiber layer thinning.
OCTA image registration and averaging is a viable and accessible method to enhance the visualization of RPCs, with significant improvements in image quality and RPC quantitative parameters. With this technique, we will be able to non-invasively and reliably study RPC involvement in diseases such as glaucoma.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
To compare perfused capillary density (PCD) in diabetic patients and healthy controls using optical coherence tomography angiography (OCTA).
Forty controls, 36 diabetic subjects without clinical ...retinopathy (NoDR), 38 with nonproliferative retinopathy (NPDR), and 38 with proliferative retinopathy (PDR) were imaged using spectral-domain optical coherence tomography. A 3 × 3-mm full-thickness parafoveal OCTA scan was obtained from each participant. Following manual delineation of the foveal avascular zone (FAZ), FAZ area, perimeter, and acircularity index were determined. Seven consecutive equidistant 200-μm-wide annular segments were drawn at increasing eccentricities from the FAZ margin. Annular PCD (%) was defined as perfused capillary area divided by the corresponding annulus area after subtraction of noncapillary blood vessel areas. Nonparametric Kruskal-Wallis testing with Bonferroni correction was performed in pairwise comparisons of group PCD values.
The NoDR group demonstrated consistently higher PCD compared to the control group in all 7 annuli, reaching statistical significance (36.6% ± 3.30% vs 33.6% ± 3.98%, P = .034) at the innermost annulus (FAZ margin to 200 μm out). The NPDR and PDR groups demonstrated progressively decreasing PCD. Differences in FAZ metrics between the NoDR and control groups did not reach statistical significance.
Relative to healthy controls, increased PCD values in the NoDR group likely represent an autoregulatory response to increased metabolic demand, while the decrease in PCD that follows in NPDR and PDR results largely from an incremental loss of capillary segments. These findings, consistent with previous studies, demonstrate the potential of OCTA as a clinical tool for earlier objective detection of preclinical diabetic retinopathy. NOTE: Publication of this article is sponsored by the American Ophthalmological Society.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To image retinal macrophages at the vitreoretinal interface in the living human retina using a clinical optical coherence tomography (OCT) device.
Eighteen healthy controls and three patients with ...retinopathies were imaged using a clinical spectral-domain OCT. In controls, 10 sequential scans were collected at three different locations: (1) ∼9 degrees temporal to the fovea, (2) the macula, and (3) the optic nerve head (ONH). Intervisit repeatability was evaluated by imaging the temporal retina twice on the same day and 3 days later. Only 10 scans at the temporal retina were obtained from each patient. A 3-µm OCT reflectance (OCT-R) slab located above the inner limiting membrane (ILM) surface was averaged.
In controls, ramified macrophage-like cells with regular spatial separation were visualized in the temporal and ONH OCT-R images; however, cell structures were not resolvable at the macula. Interim changes in cell position suggestive of cell translocation were observed between images collected on the same day and those collected 3 days later. There was considerable variation in cell density and nearest-neighbor distance (NND) across controls. Mean ± SD cell densities measured at the temporal and ONH were 78 ± 23 cells/mm2 and 57 ± 16 cells/mm2, respectively. Similarly, mean ± SD NNDs measured at the temporal and ONH were 74.3 ± 13.3 µm and 93.3 ± 20.0 µm, respectively. Nonuniform spatial distribution and altered morphology of the cells were identified in patients with retinopathies.
Our findings showed regular spatial separation and ramified morphology of macrophage-like cells on the ILM surface with cell translocation over time in controls. Their distribution and morphology suggest an origin of macrophage-like cells such as microglia or hyalocytes.
To compare the use of optical coherence tomography angiography (OCTA) and adaptive optics scanning light ophthalmoscope fluorescein angiography (AOSLO FA) for characterizing the foveal ...microvasculature in healthy and vasculopathic eyes.
Four healthy controls and 11 vasculopathic patients (4 diabetic retinopathy, 4 retinal vein occlusion, and 3 sickle cell retinopathy) were imaged with OCTA and AOSLO FA. Foveal perfusion maps were semiautomatically skeletonized for quantitative analysis, which included foveal avascular zone (FAZ) metrics (area, perimeter, acircularity index) and vessel density in three concentric annular regions of interest. On each set of OCTA and AOSLO FA images, matching vessel segments were used for lumen diameter measurement. Qualitative image comparisons were performed by visual identification of microaneurysms, vessel loops, leakage, and vessel segments.
Adaptive optics scanning light ophthalmoscope FA and OCTA showed no statistically significant differences in FAZ perimeter, acircularity index, and vessel densities. Foveal avascular zone area, however, showed a small but statistically significant difference of 1.8% (P = 0.004). Lumen diameter was significantly larger on OCTA (mean difference 5.7 μm, P < 0.001). Microaneurysms, fine structure of vessel loops, leakage, and some vessel segments were visible on AOSLO FA but not OCTA, while blood vessels obscured by leakage were visible only on OCTA.
Optical coherence tomography angiography is comparable to AOSLO FA at imaging the foveal microvasculature except for differences in FAZ area, lumen diameter, and some qualitative features. These results, together with its ease of use, short acquisition time, and avoidance of potentially phototoxic blue light, support OCTA as a tool for monitoring ocular pathology and detecting early disease.
•Acircularity index and axis ratio can quantify FAZ abnormalities in diabetics.•They do not require axial length measurement.•They can be used to noninvasively stage severity of diabetic retinopathy ...using OCTA.•These metrics show promise as methods to monitor disease over time.
Given the complexity of the current system used to stage diabetic retinopathy (DR) and the risks and limitations associated with intravenous fluorescein angiography (IVFA), noninvasive quantification of DR severity is desirable. We examined the utility of acircularity index and axis ratio of the foveal avascular zone (FAZ), metrics that can noninvasively quantify the severity of diabetic retinopathy without the need for axial length to correct for individual retinal magnification. A retrospective review was performed of type 2 diabetics and age-matched controls imaged with optical coherence tomography angiography (OCTA). Diabetic eyes were divided into three groups according to clinical features: No clinically observable diabetic retinopathy (NoDR), nonproliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR). OCTAs of the superficial and deep vascular layers centered at the fovea were superimposed to form a full vascular layer on which the FAZ was manually traced. Acircularity index and axis ratio were calculated for each FAZ. Significant differences in acircularity index were observed between all groups except for controls vs. NoDR. Similar results were found for axis ratio, although there was no significant difference observed between NPDR and PDR. We demonstrate that acircularity index and axis ratio can be used to help noninvasively stage DR using OCTA, and show promise as methods to monitor disease progression and detect response to treatment.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To assess peripapillary perfused capillary density (PCD) in primary open-angle glaucoma (POAG) across stage of disease.
In this observational, cross-sectional study, 60 eyes with varying stages of ...POAG and 24 control eyes were imaged on a spectral domain optical coherence tomography angiography system (AngioVue, Optovue, Fremont, California, USA) generating images centred on the optic nerve head. Major blood vessels were removed using custom automated software. PCD was calculated as a percentage as the ratio of pixels associated with perfused capillaries to the total number of pixels in the corresponding region-of-interest (ROI). Analysis of covariance was used to compare PCD among the subject groups and control for possible covariates. Area under the receiver operating characteristic curve (AROC) and sensitivity at 95% specificity were calculated to assess the capability of PCD to distinguish mild glaucoma from control. The Pearson's product-moment correlation coefficient was used to assess correlations between PCD and circumpapillary retinal nerve fibre layer thickness (cpRNFLT) and visual field mean deviation (MD).
PCD demonstrated a progressive stepwise decrease from control eyes throughout worsening POAG stage at all ROIs. PCD demonstrated AROC and sensitivity values comparable to cpRNFLT and visual field parameters and exhibited significant correlations with cpRNFLT and MD at all corresponding ROIs.
PCD displayed significant correlations with morphological and functional indices and exhibited diagnostic capabilities comparable to currently employed clinical variables. Our preliminary results suggest that PCD analysis may prove to be a useful tool in monitoring POAG across stage and identifying early POAG.
To compare perfused peripapillary capillary density in primary open-angle glaucoma (POAG), normal-tension glaucoma (NTG), and normal patients using optical coherence tomography angiography (OCT-A).
A ...retrospective review of POAG, NTG, and normal patients imaged with OCT-A was performed. En face OCT angiograms identifying peripapillary vessels were obtained using a spectral-domain OCT system (Avanti RTVue-XR). A custom image analysis approach identified perfused peripapillary capillaries, quantified perfused capillary density (PCD), and generated color-coded PCD maps for 3.5- and 4.5-mm-diameter scans. We compared PCD values, PCD maps, standard automated perimetry (Humphrey visual field HVF) parameters, and OCT retinal nerve fiber layer (RNFL) thickness analyses across all groups.
Forty POAG, 26 NTG, and 26 normal patients were included. Annular PCD in POAG (34.24 ± 6.76%) and NTG (37.75 ± 3.52%) patients was significantly decreased compared to normal patients (42.99 ± 1.81%) in 4.5-mm scans (P < 0.01 and P < 0.01, respectively). Similar trends and statistical significances were seen in 3.5-mm scans. Linear regression analysis resulted in moderate correlations between annular PCD values and other glaucomatous parameters. Pearson coefficients comparing annular PCD from 4.5-mm scans in POAG and NTG groups to HVF mean deviation, HVF pattern standard deviation, and average RNFL thickness all showed statistical significance (P < 0.05). Color maps showed that POAG and NTG patients had a reduction of perfused capillaries that progressed in size when comparing early, moderate, and severe glaucoma groups.
Optical coherence tomography angiography can uniquely identify changes in peripapillary PCD in glaucoma patients. Optical coherence tomography angiography may offer insights into the pathophysiology of glaucomatous damage and risk factors for disease progression.
To investigate the association between the size and shape of the foveal avascular zone and retinal thickness in healthy subjects.
In vivo imaging of the foveal microvasculature was performed on 32 ...subjects by using an adaptive optics scanning laser ophthalmoscope (AOSLO). Motion contrast maps of the AOSLO images were used to generate a montage revealing the foveal capillary network. Foveal avascular zone (FAZ) diameters along the horizontal (FAZH) and vertical (FAZV) meridians were measured on the montages. An asymmetry index (AI) of the FAZ was then computed as the ratio of the FAZH to FAZV. Retinal thickness was investigated by using spectral-domain optical coherence tomography (SDOCT). Inner retinal layer (INLFAZ) thickness and outer nuclear layer (ONLFAZ) thickness were measured at the edges of the FAZ on the horizontal and vertical SDOCT scans on the same eye.
The foveal capillary network was readily visualized in all subjects. As expected there was individual variation in the size and shape of the FAZ. Along the horizontal and vertical meridians, the mean±SD (μm) of the FAZ diameter was 607±217 and 574±155, respectively. The INLFAZ thickness was 68±9 and 66±9, and the ONLFAZ thickness was 103±13 and 105±11, respectively. The mean±SD of the AI was 1.03±0.27. The difference between FAZH and FAZV decreases with increasing FAZ area (P=0.004). Mean ONLFAZ was negatively correlated with FAZ effective diameter (P<0.0001). No significant correlation was found between mean INLFAZ and FAZ effective diameter (P=0.16).
Despite large individual variations in size and shape of the FAZ, the INLFAZ has a relatively constant thickness at the margins of the FAZ, suggesting the presence of retinal capillaries is needed to sustain an INLFAZ thickness greater than 60 μm. A smaller FAZ area is associated with a vertically elongated FAZ.
To improve the ability to image the vascular walls in the living human retina using multiply-scattered light imaging with an adaptive optics scanning laser ophthalmoscope (AOSLO).
In vivo arteriolar ...wall imaging was performed on eight healthy subjects using the Indiana AOSLO. Noninvasive imaging of vascular mural cells and wall structure were performed using systematic control of the position of a 10× Airy disk confocal aperture. Retinal arteries and arterioles were divided into four groups based on their lumen diameters (group 1: ≥100 μm; group 2: 50-99 μm; group 3: 10-49 μm; group 4: <10 μm).
Fine structure of retinal vasculature and scattering behavior of erythrocytes were clearly visualized in all eight subjects. In group 1 vessels the mural cells were flatter and formed the outer layer of regularly spaced cells of a two (or more) layered vascular wall. In the vessels of groups 2 and 3, mural cells were visualized as distinct cells lying along the lumen of the blood vessel, resulting in a wall of irregular thickness. Vascular wall components were not readily identified in group 4 vessels.
Our results show that retinal vascular mural cells and wall structure can be readily resolved in healthy subjects using AOSLO with multiply scattered light imaging for retinal vessels with a lumen diameter greater than or equal to 10 μm. Our noninvasive imaging approach allows direct assessment of the cellular structure of the vascular wall in vivo with potential applications in retinal vascular diseases such as diabetes and hypertension.
Twenty-five years ago, adaptive optics (AO) was combined with fundus photography, thereby initiating a new era in the field of ophthalmic imaging. Since that time, clinical applications of AO ...ophthalmoscopy to investigate visual system structure and function in both health and disease abound. To date, AO ophthalmoscopy has enabled visualization of most cell types in the retina, offered insight into retinal and systemic disease pathogenesis, and been integrated into clinical trials. This article reviews clinical applications of AO ophthalmoscopy and addresses remaining challenges for AO ophthalmoscopy to become fully integrated into standard ophthalmic care.
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