Mayss Al-Sheikh

Swept-source OCT angiography imaging of the foveal avascular zone and macular capillary network density in diabetic retinopathy

PURPOSE We compared the area of the foveal avascular zone (FAZ) and macular capillary network density at different retinal layers using swept-source optical coherence tomography angiography (OCT-A) in normal individuals and patients with diabetic retinopathy (DR). METHODS Images (a 3 × 3 mm cube centered on the fovea) were acquired in 40 eyes of 22 normal individuals and 28 eyes of 18 patients with varying levels of DR using a swept-source OCT-A device (central wavelength 1050 nm; A-scan-rate of 100,000 scans per second). En face images of the retinal vasculature were generated from the superficial and deep retinal layers (SRL/DRL). Quantitative analysis of the vessel density (VD) and FAZ area was performed. Vessel density was assessed as the ratio of the retinal area occupied by vessels. RESULTS Among the DR subjects (mean age, 72 years; 61% male), 35.7% of the eyes had mild, 35.7% moderate, and 7.1% severe nonproliferative DR (NPDR), and 21.4% and proliferative DR (PDR). The mean FAZ area in patients with DR and in normal individuals was 0.518 and 0.339 mm2, respectively, for the SRL (P = 0.003), and 0.615 and 0.358 mm2, respectively, for the DRL (P < 0.001). The mean VD (ratio) at the SRL and DRL was statistically significantly lower in patients with DR (SRL, P < 0.001; DRL, P = 0.028). CONCLUSIONS Swept-source OCT-A of the microcirculation in eyes of patients with DR can be used to quantitatively demonstrate alterations in the FAZ and VD in the SRL/DRL of the macula compared to normal eyes. Future longitudinal studies may use these metrics to evaluate changes over time or in response to treatment.

Quantitative OCT Angiography of the Retinal Microvasculature and the Choriocapillaris in Myopic Eyes

Purpose To study the retinal capillary microvasculature and the choriocapillaris (CC) in myopic eyes using quantitative optical coherence tomography angiography (OCTA) analysis. Methods Macular OCTA images of 3 × 3 mm were obtained using the RTVue-XR Avanti with AngioVue. Quantitative measurements of the retinal capillary microvascular layers and the CC were analyzed using en face projection images. Vessel density and fractal dimension of the superficial and deep retinal capillary plexus, and area and density of flow reduction in the CC were analyzed, quantified, and compared with an age-matched control group. Results Fifty eyes with myopia and 34 age-matched healthy eyes were included in this study. The vessel density and the vessel branching complexity using fractal dimension of the retinal capillary microvasculature were significantly lower in myopic eyes (P < 0.001 and P = 0.001). The total number of flow voids in the CC was lower (108.93 vs. 138.63, P = 0.001) but the total and average flow void area was significantly higher (total area 3.715 ± 0.257 vs. 3.596 ± 0.194 mm2, P = 0.026; average area 0.044 ± 0.029 vs. 0.028 ± 0.010 mm2, P = 0.002) compared with the healthy control group. Average choroidal thickness was lower in the myopic group versus the normal control cohort (123.538 ± 73.477 vs. 246.97 ± 41.745 μm, P < 0.05) and significantly reduced in eyes with lacquer cracks (LC) compared with myopic eyes without LC formation (P = 0.003). There was no correlation between choroidal thickness and quantitative parameters of the CC in the myopic eyes. Conclusions The density of the retinal capillary microvasculature is reduced and the area of flow deficit in the CC is increased in eyes with greater myopia. The relevance of microvascular alterations in the setting of myopia warrants further study.

Image artefacts in swept-source optical coherence tomography angiography

Purpose To describe optical coherence tomography angiography (OCTA) image artefacts in eyes with and without ocular pathologies. Methods The OCTA images of healthy subjects and patients with age-related macular degeneration, diabetic retinopathy and retinal vascular occlusions were retrospectively reviewed. All OCTA images were obtained using a swept-source OCTA instrument (Triton, Topcon). The frequency of various image artefacts including segmentation, banding, motion, projection, masking, unmasking, doubling of the retinal vessels, blink, stretching, out-of-window and crisscross artefacts was assessed. The impact of the artefact on the grading of the images for the foveal avascular zone in deep and superficial retinal layers, capillary non-perfusion and choroidal neovascularisation (CNV) was evaluated. Results OCTA images of 57 eyes of 48 subjects including 23 eyes (40.3%) with CNV, 13 eyes (22.8%) with dry age-related macular degeneration, 9 eyes (15.7%) with cystoid macular oedema due to diabetic retinopathy or retinal vein occlusion and 12 normal eyes (21.1%) were available for evaluation. At least one type of artefact was present in the images from 51 eyes (89.4%). Banding artefact, segmentation, motion, unmasking, blink, vessel doubling, masking and out-of-window artefacts were found in 51 (89.4%), 35 (61.4%), 28 (49.1%), 9 (15.8%), 5 (8.8%), 1 (1.7%), 1 eye (1.7%) and 1 eye (1.7%), respectively. Projection artefact, stretch artefact or crisscross artefact was not observed. Banding, motion and segmentation artefacts were statistically significantly more frequent in eyes with ocular pathology compared with control eyes (all p<0.001). Eyes with choroidal diseases had significantly higher rate of segmentation error in the choriocapillaris slab compared with eyes with only retinal disease (p=0.02). In nine eyes (17.6%), the artefacts were deemed severe enough by the graders to preclude accurate grading of the image. Conclusions Image artefacts occur frequently in OCTA images. The artefacts are more frequent in eyes with pathology.

Repeatability of automated vessel density measurements using optical coherence tomography angiography

Aims To determine the repeatability of optical coherence tomography angiography (OCT-A)-derived automated vessel density measurements in the superficial retinal layer (SRL) and deep retinal layer (DRL) in healthy individuals. Methods 41 eyes of 21 healthy individuals were included in this study. OCT-A was performed using the NIDEK RS-3000 Advance with prototype OCT-A software. Each subject underwent two scanning sessions with 5–10 min in between. En face images of the retinal vasculature were generated using the default segmentation for SRL and DRL. Automated vessel density measurements were compared between the two sessions. The intraclass correlation coefficients (ICCs) and coefficient of repeatability were used as a measure for repeatability. Results The mean±SD age of the subjects was 36.8±7.5 years. Overall vessel density measured in the first and second session was 19.43±3.10 and 19.72±3.78 for the SRL, and 34.67±1.801 and 34.55±1.64 for the DRL, respectively. The mean difference in vessel density between sessions was −0.3 (95% CI 3.3 to −3.9) for the SRL and 0.1 (95% CI 2.6 to −2.5) for the DRL. The two measurements were highly correlated with an ICC=0.90 (p=0.33) for the SRL and 0.83 (p=0.589) for the DRL. The coefficient of variation was 0.052 for the SRL and 0.02 for the DRL. Conclusions Commercial automated vessel density measurements using OCT-A showed excellent repeatability in healthy individuals. Although repeatability will also need to be established in the setting of disease, the level of reproducibility should be useful for assessing the significance of differences in capillary density over time or under different conditions.

Repeatability and Reproducibility of Superficial Macular Retinal Vessel Density Measurements Using Optical Coherence Tomography Angiography En Face Images

Importance The repeatability and reproducibility of quantitative metrics from optical coherence tomographic angiography (OCTA) must be assessed before these data can be confidently interpreted in clinical research and practice. Objective To evaluate the repeatability and reproducibility of OCTA-derived retinal vascular quantitative metrics. Design, Setting and Participants In this cross-sectional study, 21 healthy volunteers (42 eyes) and 22 patients with retinal disease (22 eyes), including 14 with age-related macular degeneration, 3 with epiretinal membrane, 2 with diabetic retinopathy, 2 with myopic macular degeneration, and 1 with retinal vein occlusion, were enrolled. Participants were recruited from September 1 through November 31, 2016. Each eye underwent 3 repeated scans with 3 instruments for a total of 9 acquisitions. Eyes were randomly assigned to scanning with a 3 × 3-mm or 6 × 6-mm pattern. Eyes were excluded from subsequent analysis if any acquisition had a signal strength of less than 7. Repeatability (defined as the agreement in measurements within a device) and reproducibility (defined as the agreement between devices of the same type) were assessed by intraclass correlation coefficient (ICC) and coefficient of variation. Exposures All eyes underwent scanning using 3 separate devices. Main Outcomes and Measures Vessel length density (VLD) and perfusion density (PD) of the superficial retinal vasculature. Results A total of 21 healthy volunteers (8 men and 13 women; mean [SD] age, 36 [6] years) and 22 patients with retinal disease (15 men and 7 women; mean [SD] age, 79 [9] years) underwent evaluation. Of these, 40 of 42 normal eyes and 15 of 22 eyes with retinal disease met signal strength criteria and were included in this analysis. The ICC among the 3 consecutive scans ranged from 0.82 to 0.98 for VLD and from 0.83 to 0.95 for PD. The coefficient of variation (CV) ranged from 2.2% to 5.9% for VLD and from 2.4% to 5.9% for PD. For reproducibility, the ICC ranged from 0.62 to 0.95 and the CV was less than 6% in all groups. The agreement was highest for the 3 × 3-mm pattern in the inner ring (ICC range, 0.92 [95% CI, 0.85-0.96] to 0.96 [95% CI, 0.93-0.98]) and 6 × 6-mm pattern in the outer ring (ICC range, 0.93 [95% CI, 0.86-0.97] to 0.96 [95% CI, 0.92-0.98]). Conclusions and Relevance Vessel length density and PD of the superficial retinal vasculature can be obtained from OCTA images with high levels of repeatability and reproducibility but can vary with scan pattern and location.

Choriocapillaris Imaging Using Multiple En Face Optical Coherence Tomography Angiography Image Averaging

Importance Imaging of the choriocapillaris in vivo is challenging with existing technology. Optical coherence tomography angiography (OCTA), if optimized, could make the imaging less challenging. Objective To investigate multiple en face image averaging on OCTA images of the choriocapillaris. Design, Setting, and Participants Observational, cross-sectional case series at a referral institutional practice in Los Angeles, California. From the original cohort of 21 healthy individuals, 17 normal eyes of 17 participants were included in the study. The study dates were August to September 2016. Exposures All participants underwent OCTA imaging of the macula covering a 3 × 3-mm area using OCTA software (Cirrus 5000 with AngioPlex; Carl Zeiss Meditec). One eye per participant was repeatedly imaged to obtain 9 OCTA cube scan sets. Registration was first performed using superficial capillary plexus images, and this transformation was then applied to the choriocapillaris images. The 9 registered choriocapillaris images were then averaged. Quantitative parameters were measured on binarized OCTA images and compared with the unaveraged OCTA images. Main Outcome and Measure Vessel caliber measurement. Results Seventeen eyes of 17 participants (mean [SD] age, 35.1 [6.0] years; 9 [53%] female; and 9 [53%] of white race/ethnicity) with sufficient image quality were included in this analysis. The single unaveraged images demonstrated a granular appearance, and the vascular pattern was difficult to discern. After averaging, en face choriocapillaris images showed a meshwork appearance. The mean (SD) diameter of the vessels was 22.8 (5.8) µm (range, 9.6-40.2 µm). Compared with the single unaveraged images, the averaged images showed more flow voids (1423 flow voids [95% CI, 967-1909] vs 1254 flow voids [95% CI, 825-1683], P < .001), smaller average size of the flow voids (911 [95% CI, 301-1521] µm2 vs 1364 [95% CI, 645-2083] µm2, P < .001), and greater vessel density (70.7% [95% CI, 61.9%-79.5%] vs 61.9% [95% CI, 56.0%-67.8%], P < .001). The distribution of the number vs sizes of the flow voids was skewed in both unaveraged and averaged images. A linear log-log plot of the distribution showed a more homogeneous distribution in the averaged images compared with the unaveraged images. Conclusions and Relevance Multiple en face averaging can improve visualization of the choriocapillaris on OCTA images, transforming the images from a granular appearance to a level where the intervascular spaces can be resolved in healthy volunteers.

Retinal vessel calibre measurements by optical coherence tomography angiography

Purpose To compare the vessel calibre measurements between optical coherence tomography angiography (OCTA) and colour fundus photography. Methods In this retrospective comparative study, OCTA and colour fundus images of healthy eyes and eyes with optic atrophy were evaluated. The colour fundus image was registered manually using Image J software to the OCTA image of the optic disc. Two independent graders measured the vessel calibre of the widest vein and artery in each peripapillary quadrant on a 3.4 mm diameter circle centred on the optic disc in the same location on both images. The difference in vessel calibre between the two techniques was assessed. Results A total of 312 vessels from 29 healthy eyes and 20 eyes with atrophic optic discs were included. There was a high level of agreement between graders for measurement of vessel calibre in both colour fundus (intraclass correlation coefficient=0.93, coefficient of variation=0.07) and OCTA images (intraclass correlation coefficient=0.94, coefficient of variation=0.05). The mean vessel calibre in colour fundus images (94.5±23.2 µm) and OCT images (112.2±26.1 µm) was correlated (r=0.8, p<0.001), but the difference was statistically significant (mean difference: 17.6±1.5 µm, p<0.001). This difference was evident for both arteries (mean difference: 18.2±16.3 µm, p<0.001) and veins (mean difference: 15.1±16.2 µm, p<0.001) individually, with a similar magnitude of difference for both vessel types (p=0.08). In addition, the magnitude of difference between imaging modalities was similar in atrophic and healthy discs (17.1±15.9 vs 18.4±15.2 µm, respectively, p=0.4). The difference, however, was significantly higher in vessels with a calibre of ≤94.5 compared with larger vessels (19.3±16.3 vs 15.6±14.4 µm, respectively, p=0.02). Conclusions Vessel calibre measurements were significantly larger in OCTA images compared with colour fundus photographs, particularly for smaller vessels. These differences may need to be accounted for when using OCTA-derived metrics.

BIOMARKERS OF NEOVASCULAR ACTIVITY IN AGE-RELATED MACULAR DEGENERATION USING OCT ANGIOGRAPHY

Purpose: To study the qualitative and quantitative features of choroidal neovascular (NV) membranes in age-related macular degeneration using optical coherence tomography angiography in patients with active and quiescent NV lesions before and after treatment with anti–vascular endothelial growth factor. Methods: Macular optical coherence tomography angiography images were obtained using RTVue XR Avanti with AngioVue. Morphologic features and quantitative measurements of the NV lesion were analyzed using en face projection images. The NV lesion was subdivided into inner segment and outer fringe for further fractal dimension analysis. Results: In a series of 31 eyes, 11 eyes with active NV lesions at baseline and after consecutive follow-up after treatment with anti–vascular endothelial growth factor therapy and 20 eyes with quiescent NV lesions were included in this study. Morphologically, all the quiescent NV lesions versus 63.6% of the active NV lesions demonstrated a prominent central vessel and active leasions demonstrated a greater rate of small vessels branching (82%) and peripheral arcades (82%) than quiescent lesions (30% and 40% respectively) and this was statistically significant. The lesion area and vessel density was not statistically significantly different after treatment or versus quiescent lesions although the latter lesions were reduced in area. Lesion pattern complexity measured by the fractal dimension was statistically significantly lower in the inner part of the lesion after treatment and statistically significantly lower in the total lesion of the quiescent NV compared with the active NV. Conclusion: Optical coherence tomography angiography is a new, noninvasive imaging modality that can be used to perform qualitative and quantitative analyses of NV lesions. In the future, OCT angiography may provide biomarkers of activity and guide the evaluation and treatment and monitoring of neovascularization in age-related macular degeneration.

Quantitative Features of the Choriocapillaris in Healthy Individuals Using Swept-Source Optical Coherence Tomography Angiography

BACKGROUND AND OBJECTIVE To quantify vessel density (VD) and grey value (GV) as a measure of flow in the choriocapillaris (CC) in healthy subjects with optical coherence tomography angiography (OCTA). PATIENTS AND METHODS In this prospective, noncomparative case series, 3 mm × 3 mm OCTA images of 36 eyes of 22 healthy individuals were obtained using a swept-source instrument. VD and GV levels were calculated on CC en face slabs in the central 1-mm (subfoveal field) and surrounding 2.5-mm parafoveal ring. VD was calculated as a ratio of vessel area over nonvessel area following image binarization. GV was computed as the mean, un-normalized greyscale intensity value for all pixels in the region of interest. For each eye, the procedure was repeated 1 minute to 2 minutes later and intersession repeatability was analyzed. The choroidal thickness (CT) was automatically measured in the subfoveal and parafoveal regions and compared to VD and GV values. RESULTS The VD ratio and GV was lower in the subfoveal field than in the parafoveal four sectors. The intersession intraclass correlation coefficients were high for both VD and GV measurements. There was no correlation observed between CT and VD or GV. CONCLUSIONS Quantitative metrics can be obtained from CC OCTA en face images. These values show moderate to good intersession repeatability. These normative data may be of value as a reference of comparison in future studies of eyes with disease. [Ophthalmic Surg Lasers Imaging Retina. 2017;48:623-631.].

Choroidal thickness and structural glaucoma parameters in glaucomatous, preperimetric glaucomatous, and healthy eyes using swept-source OCT.

Purpose To evaluate choroidal thickness (CT) and its relationship with retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer thickness (GCIPLT) in glaucomatous, preperimetric glaucomatous, and healthy eyes using swept-source optical coherence tomography (SS-OCT). Methods Fifty eyes with primary open-angle glaucoma, 20 eyes with preperimetric glaucoma, and 20 age-matched healthy eyes were enrolled. Three-dimensional wide-field (12 × 9 mm) images were obtained using a SS-OCT instrument. Peripapillary CT and RNFL thickness, as well as macular CT and GCIPLT, were recorded. The correlation of the CT with nerve fiber layer and GCIPLT measurements was assessed. The association between CT and potential confounding variables including age, sex, axial length, intraocular pressure, and central corneal thickness was also examined. Results Mean peripapillary CTs were 111.7 ± 41.7, 127.7 ± 40.1, and 120.8 ± 35.4 μm in glaucomatous, preperimetric glaucomatous, and normal eyes, respectively. There was statistically significant but weak correlation for the mean RNFL and mean peripapillary CT in glaucomatous subjects (r = 0.341, p = 0.04). There was a significant correlation between RNFL thickness and peripapillary CT in 1, 2, 5, and 6 clock hours of glaucomatous eyes (r = 0.410, p = 0.005; r = 0.316, p = 0.03; r = 0.346, p = 0.02; r = 0.35, p = 0.04, respectively). Mean macular CT was 181.5 ± 70.5, 187.4 ± 65.5, and 185.4 ± 76.4 μm in glaucomatous, preperimetric glaucomatous, and healthy eyes, respectively (p = 0.7). There was no statistically significant correlation between the mean GCIPLT and mean macular CT in all subjects (p>0.05). Conclusions Choroidal thinning and its correlation with other parameters in patients with glaucoma should be further investigated with the proprietary software of SS-OCT.