Undetectable Macular Neovascularization on OCT Angiography in Age Related Macular Degeneration: Comparison between Different Devices.

Background and Objectives: The aim of this study was to report the characteristics of macular neovascularization (MNV) with undetectable flow on optical coherence tomography angiography (OCTA) in neovascular age related macular degeneration (nAMD), and compare them with the characteristics of detectable MNV. Materials and Methods: Patients with a diagnosis of nAMD who underwent dye imaging and OCTA in the same day were included and divided into two groups: undetectable and detectable flow on OCTA. Three OCTA devices were used, two with spectral-domain technology (AngioVue, RTVue 100xAvanti, Optovue, Freemont, CA, USA and Heidelberg OCT2 Beta Angiography Module, Heidelberg Engineering, Germany) and one swept-source OCTA (PlexElite 9000; Carl Zeiss Meditec, Inc., Dublin, CA, USA). We studied the demographics, neovascularization characteristics, and OCTA device and acquisition characteristics for both groups. Results: A global comparison between Group 1 and Group 2 was made, followed by an analysis of variables associated with (un)detectability for each OCTA device. A total of 108 eyes were included: 90 in the detectable group (Group 1) and 18 in the undetectable group (Group 2), corresponding to a global sensitivity of OCTA for the detection of MNV of 83.49%. There was a statistically significant difference between the two groups regarding MNV type (p = 0.02) and PED height (p = 0.017). For the three devices, detection sensitivity with automatic segmentation was significantly lower than with manual segmentation. For Heidelberg, PED Height and scan quality explained 68.3% of the undetectability. For AngioVue, PED Height and absence of hemorrhage explained 67.9% of undetectability. Conclusions: In this study, we found a global sensitivity of 83.49% for the three OCTA devices combined, with a range from 55.5% to 96.26% depending on the segmentation and OCTA device. This means that undetectable/undetected MNV can represent up to 45% of the examinations, eventually misdiagnosing choroidal neovascularization for 1 out every 2 patients.

Evaluation of microvascular density and retinal vessel diameter in gestational and type 2 diabetes using swept-source OCT-A technology.

PURPOSE: To assess foveal and parafoveal retinal and choroidal microvascular changes using optical coherence tomography angiography (OCTA) and changes in retinal vessel caliber in pregnant women with gestational diabetes mellitus (GDM), non-pregnant female patients with type 2 diabetes mellitus (DM2), and healthy pregnant female subjects. METHODS: The study was conducted cross-sectionally and composed of three age-matched groups: 32 near-term pregnant women with GDM (GDM group), 32 non-pregnant female patients with a recent diagnosis of DM2 (DM2 group), and 32 healthy near-term pregnant female subjects. Vessel density (VD) and vessel diameter were the main outcomes. Detailed ophthalmic examinations were performed for each participant, including swept-source OCTA measurements consisting of superficial, deep, outer retinal and choroidal vessel density. RESULTS: The average VD values in the central fovea of the superficial and deep retina were significantly lower in the GDM group (P=0.001 for both, between the three groups), whereas the mean VD in the parafoveal nasal sector of the deep retina was significantly lower in the DM2 group (P=0.008, between the three groups). There were no significant differences in the foveal or parafoveal VD measurements of the outer retina and choriocapillaris (P>0.05 for all). There were statistically significant differences in the retinal venous diameter and arterial vein ratio in the GDM and DM2 groups compared to the control group (P=0.001 for all). CONCLUSION: The microvascular density changes seen on OCTA images of pregnant women with GDM are remarkable. These changes in retinal vessels appeared to occur rapidly after the onset of the metabolic impairment or might be the reflection of previous insulin resistance as well, as in recent diabetes. Our results also suggest that these changes may be more significant in a GDM pregnant woman than in a pregnant, established diabetic patient.

Comparison of swept-source versus spectral-domain optical coherence tomography angiography for detection of macular neovascularization.

PURPOSE: To compare swept-source (SS) versus spectral-domain (SD) optical coherence tomography angiography (OCTA) for the detection of macular neovascularization (MNV). METHODS: In this prospective cohort study, 72 eyes of 54 patients with subretinal hyperreflective material (SHRM) and/or pigment epithelial detachment (PED) on OCT possibly corresponding to MNV in at least one eye were included. OCTA scans were acquired using two devices, the PLEX Elite 9000 SS-OCTA and the Spectralis SD-OCTA. Fluorescein angiography (FA) was used as reference. Two graders independently evaluated en face OCTA images using a preset slab as well as a manually modified slab, followed by a combination of en face and cross-sectional OCTA. RESULTS: Sensitivity (specificity) for the automated slabs was 51.7% (93.0%) for SS-OCTA versus 58.6% (95.3%) for SD-OCTA. Manual modification of segmentation increased sensitivity to 79.3% for SS-OCTA but not for SD-OCTA (58.6%). The combination of en face OCTA with cross-sectional OCTA reached highest sensitivity values (SS-OCTA: 82.8%, SD-OCTA: 86.2%), and lowest number of cases with discrepancies between SS-OCTA and SD-OCTA (4.2%). Fleiss kappa as measure of concordance between FA, SS-OCTA, and SD-OCTA was 0.56 for the automated slabs, 0.60 for the manual slabs, and 0.73 (good agreement) for the combination of en face OCTA with cross-sectional OCTA. Concordance to FA was moderate for the automated slabs and good for manual slabs and combination with cross-sectional OCTA of both devices. CONCLUSION: Both devices reached comparable results regarding the detection of MNV on OCTA. Sensitivity for MNV detection and agreement between devices was best when evaluating a combination of en face and cross-sectional OCTA.

Optical Coherence Tomography Angiography in Macular Neovascularization: A Comparison Between Different OCTA Devices.

Purpose: The purpose of this study is to compare the ability of 3 optical coherence tomography angiography (OCTA) devices to measure lesion area in patients with macular neovascularization (MNV) with type 1, 2 and mixed neovascularization (NV). Methods: OCTA, fluorescein angiography (FA), indocyanine green angiography (ICGA), and structural optical coherence tomography (OCT) were performed. NV lesion area measurements were performed by two graders. Results: Twenty-eight eyes were included: 20 with NV were classified as type 1, 6 as type 2, and 2 as mixed type. AngioVue and Spectralis detected the NV in 26 out of 28 eyes (92.8%). The intraclass correlation coefficient (ICC) between readers for the three different OCTA with the different slabs was high. The NV area was larger in the outer retina to choriocapillaris (ORCC) and choriocapillaris (CC) images for the AngioVue device and the PLEX Elite device compared to avascular images (P < 0.05). The mean values of the NV area were not significantly different among the three instruments (Friedman test, P > 0.05) for the avascular zone (AV), ORCC, and CC images. Median (interquartile range [IQR]) NV were significantly different among avascular images, ORCC images, and CC images of the AngioVue device (P = 0.046), of the Spectralis device (P = 0.015), and the PLEX Elite device (P < 0.001). Conclusions: The ORCC slabs showed the highest detection rate for NV detection independently to the device used, and swept source (SS)-OCTA measurements of ORCC slabs showed the highest detection rate of NVs compared to the spectral domain (SD)-OCTA. Translational Relevance: It is pivotal to realize how much we can rely on OCTA to make a diagnosis of NV.

Sequential imaging of a case of choroidal osteoma using swept-source OCT and optical coherence tomography angiography: A 4-year follow-up study.

A 33-year-old gentleman was presented with metamorphopsia in the left eye due to choroidal osteoma (CO) complicated by choroidal neovascular membrane (CNVM). Optical coherence tomography angiography (OCTA) proved to be a valuable, noninvasive tool in monitoring treatment response of CNVM. The tumor subsequently underwent decalcification over a period of 4 years. In addition, SS-OCT scans were instrumental in documenting the natural course of the tumor and focal choroidal excavations (FCE), which were found in correspondence with tumor decalcification. Close follow-up is warranted in FCE, secondary to decalcification of CO, as CNVM has been documented to occur on the slope or bottom of eyes with FCE.

Retinal and choroidal vasculature changes associated with chronic kidney disease.

PURPOSE: Retinal and choroidal microvascular changes can be related to renal impairment in hypertension and chronic kidney disease (CKD). The study examines the association between retinochoroidal parameters and renal impairment in hypertensive, non-diabetic patients. METHODS: This is a cross-sectional study on Caucasian patients with systemic arterial hypertension with different levels of renal function. All subjects were studied by blood chemistry, urine examination, microalbuminuria and blood pressure. Complete eye examination was completed with swept source optical coherence tomography (SS-OCT) and optical coherence tomography angiography (OCTA) scans of macular region. Patients were divided in groups: LowGFR and HighGFR and CKD- and CKD+, according to the value of glomerular filtrate (GFR) and albuminuria. LowGFR and CKD+ groups included patients with clinical kidney impairment. RESULTS: One hundred and twenty eyes of 120 hypertensive patients were evaluated. The mean retinal thickness was thinner in CKD+ versus CKD- group (p < 0.009). LowGFR and CKD+ groups showed thinner choroidal values than HighGFR (p < 0.02) and CKD- (p < 0.001) groups. OCTA showed lower density in LowGFR than in HighGFR group (p < 0.001) and in CKD+ versus CKD- group (p < 0.001). Albuminuria was inversely related to choroidal and retinal thickness measures (p < 0.001) and to the indices of superficial parafoveal (p < 0.05) and foveal (p < 0.05) vascular densities. CONCLUSIONS: CKD is associated with retinal thinning, eGFR and decreasing renal function with progressive reduction of choroidal and retinal vascular density. SS-OCT and OCTA documented close association between CKD and reduction of both choroidal thickness and paracentral retinal vascular density in hypertensive patients.

Influence of Axial Length on Parafoveal and Peripapillary Metrics from Swept Source Optical Coherence Tomography Angiography.

Purpose: To assess the effect of axial length (AL) on the quantification of superficial vessel density of both macular and disc region using swept source optical coherence tomography angiography (SSOCTA). Methods: This is a cross-sectional clinical study. Seventy-five eyes from 75 Chinese healthy participants (56 females) with a mean age of 26.6 ± 6.8 (range 19-50) years were included in this study. All eyes were imaged with SSOCTA, using a 3 × 3mm scan pattern centered on the macular and optic disc, respectively, and the superficial layer was used for evaluation. The image size was corrected with AL using Bennett formula. Outcome measurements included perfusion density (PD), vessel length density (VLD) in parafoveal and disc regions, averaged peripapillary large vessel diameter and area of foveal avascular zone (FAZ). Image processing and measurements was performed using Image J software. Multivariate regression analysis adjusting for age and signal strength was used to assess the influence of AL on the metrics. Results: AL was the only predictive factor for parafoveal PD (ß = -0.273, P = .047) and VLD (ß = -0.396, P = .003). There was no correlation between AL and area of FAZ, large vessel diameter, or the vessel density on any location in disc region. Age was the only predictor for PD (ß = -0.287, P = .024) and VLD (ß = -0.289, P = .023) on optic nerve head. Conclusions: AL was negatively correlated with superficial parafoveal microvasculature, but not correlated with peripapillary capillaries, suggesting that the inner retina stretches more in the distal end of the disc with increased AL.

Ultra-wide optical coherence tomography angiography in diabetic retinopathy.

BACKGROUND: To implement an ultra-wide optical coherence tomography angiography imaging (UW-OCTA) modality in eyes with diabetic retinopathy (DR) with the aim of quantifying the burden of microvascular disease at baseline and subsequent clinic visits. METHODS: UW-OCTA was implemented on a 1,060 nm swept source (SS) OCTA engine running at 100 kHz A-line rate with a motion tracking mechanism. A montage scanning protocol was used to capture a 100-degree field of view (FOV) using a 4×4 grid of sixteen total individual 6×6 mm2 scans. Typical OCTA images with a FOV of 3×3, 6×6 and 12×12 mm2 were obtained for comparison. DR patients were scanned at baseline and follow-up. They were treated at the clinician's discretion. Vessel density and non-perfusion area maps were calculated based on the UW-OCTA images. RESULTS: Three proliferative DR patients were included in the study. UW-OCTA images provided more detailed visualization of vascular networks compared to 50-degree fluorescein angiography (FA) and showed higher burden of pathology in the retinal periphery that was not captured by typical OCTA. Neovascularization complexes were clearly detected in the two patients with active PDR. Vessel density and non-perfusion maps were used to measure progressive capillary non-perfusion and regression of neovascularization between visits. CONCLUSIONS: UW-OCTA provides approximately 100-degree OCTA images of the fundus comparable to that of wide-angle fundus photography, and may be more applicable in conditions such as DR which affect the peripheral retina in contrast to standard OCTA.

Accurate estimation of choriocapillaris flow deficits beyond normal intercapillary spacing with swept source OCT angiography.

BACKGROUND: To estimate choriocapillaris flow deficits beyond normal intercapillary distance with swept source optical coherence tomography angiography (SS-OCTA). METHODS: Subjects were enrolled and repeated SS-OCTA scans were performed using the 3 mm × 3 mm scan pattern. Blood flow was identified using the complex optical microangiography (OMAGc) algorithm. The choriocapillaris (CC) was defined as a 20 µm slab of the flow volume beneath the outer boundary of Bruch's membrane (BM) and was compensated with the corresponding structural image for flow deficits measurement. Flow deficits were segmented based on one mean standard deviation from a normal database. A histogram based thresholding method was developed to remove small flow deficits that were determined by examining intercapillary spacing within normal CC networks. A registration method based on affine and B-spline transformation was utilized for the CC angiogram averaging. Four repeated scans were averaged, and results were compared with and without removal of small flow deficits after averaging a different number of scans (N=1, group 1; N=2, group 2; N=3, group 3 and N=4, group 4). RESULTS: Seven normal subjects were enrolled. Intercapillary distance was found to be 24 µm for the CC networks under OCTA, which was used as the threshold to exclude small flow deficits for CC quantification. After averaging, significant reduction in background noise and improvement in continuity of blood vessel networks were observed both on retinal and choriocapillaris angiograms. Flow deficit percentages of the choriocapillaris were significantly reduced with averaging (group 1 vs. group 2: P<0.0001; group 2 vs. group 3: P<0.001; group 3 vs. group 4: P<0.001). The flow deficit percentages were also significantly reduced after removing the small flow deficits (≤24 µm in diameter) in all groups (P<0.01). A statistically significant difference was found after removing small flow deficits (≤24 µm in diameter) between group 1 and group 2 (P<0.001), between group 2 and group 3 (P<0.05), and between group 3 and group 4 (P<0.05). However, the significance was decreased compared to that without small flow deficits removal. CONCLUSIONS: A method was developed to improve the robust estimation of choriocapillaris flow deficits by removing the small flow deficits corresponding to normal intercapillary spacing. After the removal of small flow deficits, fewer repeats were required for image averaging to achieve comparable accuracy of flow deficit measurements with SS-OCTA.

Comparing imaging capabilities of spectral domain and swept source optical coherence tomography angiography in healthy subjects and central serous retinopathy.

BACKGROUND: There are two forms of system implementation of optical coherence tomography angiography (OCTA) in ophthalmic imaging, i.e., spectral domain (SD-) and swept source OCTA (SS-OCTA). The purpose of this paper is to compare the SD-OCTA and SS-OCTA for elucidating structural and vascular features associated with central serous retinopathy (CSR), and to evaluate the effects of CSR on SD- and SS-OCTA's imaging capabilities. METHODS: Normal subjects and CSR patients were imaged by SD- and SS-OCTA using 3 × 3 mm and 6 × 6 mm scan patterns. OCT signal strengths at the superficial retina, deep retina, Sattler's layer and Haller's layer were used to compare the ability of SD- and SS-OCTA to image structural features. In addition, the ability to acquire angiograms were discussed by evaluating retinal vessel density. Central serous volume (CSV) was measured and it was correlated with difference in signal strengths (∆S) between two OCTA devices. RESULTS: Seven normal eyes and seven diseased eyes were recruited. Results showed no significant differences between SD- and SS-OCT in detecting structural features of the retinal layer according to the paired t-test. However, when imaging the Sattler's layer for normal eyes, a significant difference is found between SD- and SS-OCT (p < 0.0001 for 3 × 3 mm scan, and p = 0.0002 for 6 × 6 mm); while for CSR eyes, the corresponding values were p < 0.0001 and p = 0.0003, respectively. At Haller's layer for normal eyes, the corresponding values were p = 0.0004 and p = 0.0014; and for CSR eyes, p = 0.0004 and p < 0.0001, respectively. A strong correlation between ∆S and CSV was observed in the Sattler's layer (3 × 3 mm - p = 0.0031 and R2  = 0.951; 6 × 6 mm - p = 0.0075 and R2  = 0.911) and Haller's layer (3 × 3 mm - p = 0.0026 and R2  = 0.955; 6 × 6 mm - p = 0.0013 and R2  = 0.972). CONCLUSIONS: The results suggest no differences between SD- and SS-OCTA for imaging the retinal layers however, when imaging beyond retinal layers, SS-OCTA appears advantageous in detecting returning signals. In CSR cases, the CSV may have an impact on sub-CSR tissue imaging and appears to have more impact on SD- than SS-OCTA.

Quantifying choriocapillaris flow deficits using global and localized thresholding methods: a correlation study.

BACKGROUND: To investigate the correlation and agreement of two previously published choriocapillaris (CC) quantification methods using a normal database with swept-source optical coherence tomography angiography (SS-OCTA). METHODS: Normal adult subjects from all age groups imaged by SS-OCTA were used in this study. Each subject was imaged with 3 mm × 3 mm and 6 mm × 6 mm scan patterns centered on fovea, upon which en face CC images were generated by segmenting volumetric OCTA data. After signal compensation and removal of projection artifacts and noise, CC images were analyzed to identify flow deficits (FD) using two published methods. The first method utilized standard deviation from a young normal database (SD method) as the global thresholding while the second method utilized fuzzy C-means algorithm (FCM method) with local thresholding. Both methods segmented FDs from CC images and quantified FD density (FDD) and mean FD size (MFDS). In each 3 mm × 3 mm scan, three regions were quantified: a 1 mm circle (C1), a 1.5 mm rim (R1.5) and a 2.5 mm circle (C2.5). In each 6 mm × 6 mm scan, five regions were quantified: C1, R1.5, C2.5, a 2.5 mm rim (R2.5) and a 5 mm circle (C5). Spearman correlation and Bland-Altman plot analyses were conducted to compare the two methods. RESULTS: Data obtained from 164 normal subjects (age: 56±19, 59% females) were used in this study. Strong correlations were observed between the two methods in all comparisons (r: 0.78-0.94, all P<0.0001). Overall MFDS provided higher or comparable correlation coefficients (r) compared to FDD. We have also observed stronger correlations in the central macula compared to parafoveal and perifoveal regions for both FDD and MFDS. In regions of C1, R1.5 and C2.5, 6 mm × 6 mm scans resulted in better agreement (smaller mean bias, similar or tighter limit of agreement) between the two methods for both FDD and MFDS compared to 3 mm × 3 mm scans. CONCLUSIONS: There are strong correlations and satisfactory agreement between SD method and FCM method. SD method requires the reference to a normal database for CC quantification while FCM does not. Both methods could be used for the analysis of CC FDs in clinical settings depending on specific study designs such as the availability of a normal database.