Neovascularization Segmentation via a Multilateral Interaction-Enhanced Graph Convolutional Network.

Tears of the retinal pigment epithelium (RPE) usually cause a deleterious loss in visual acuity and are most commonly associated with previous vascularized retinal pigment epithelium detachment (vPED) due to age-related macular degeneration (AMD) (Pauleikhoff et al. 2002). Recent studies suggest an increase in RPE tear incidences since the introduction of anti-vascular endothelial growth factor (VEGF) therapies. Therefore, clinicians increasingly direct the focus on the challenge of RPE tear prevention. Several prognostic markers for an impending RPE tear have been described such as vPED lesion's height, hyper-reflective lines in near-infrared images, subretinal clefts, microrips and duration of vPED (Clemens & Eter 2016). Chan and co-workers (2007) firstly described the morphologic proportions of choroidal neovascularization (CNV) and PED lesion as particularly relevant for the likelihood of tear development. A small ratio of CNV size to PED size turned out to correlate with a higher rate of RPE tears. This concept of CNV/PED ratio was based on fluorescence angiographic (FA) data. We report the applicability of the CNV/PED ratio to optical coherence tomography angiography (OCT-A) imaging. Two patients underwent spectral-domain optical coherence tomography and FA imaging as well as OCT-A examinations (Fig. 1). The first patient showed a serous-vascularized PED due to AMD. Fluorescence angiography (FA) shows a shading background fluorescence in the area of the PED in the early phase, followed by an irregular hyperfluorescence at the margin of the PED corresponding to the CNV, which results in a CNV/PED ratio of approximately 0.2 (Fig. 1A). Correspondingly, OCT-A reveals a distinct flow signal within a neovascular network underneath the PED lesion. The entire network is contained in the detached area resulting in a comparable ratio of 0.3 (Fig. 1C). In the second patient, FA imaging revealed a fibrovascular PED with underlying occult CNV and a CNV/PED ratio of approximately 0.7 (Fig. 1B). Corresponding OCT-A shows a neovascular network almost entirely filling out the PED lesion resulting in a CNV/PED ratio of 0.8 (Fig. 1D). OCT-A imaging produces three-dimensional data. Therefore, measurements of vPED lesions can be performed in different retinal layers. Accordingly, vPED and CNV dimensions may vary in OCT-A. Two-dimensional FA images usually visualize the largest lesion diameter. Accordingly, OCT-A measurements were performed in the layer in which vPED and CNV dimensions showed their maximum diameters. Notably, projection artefacts from retinal vessels may influence the visualization of sub-RPE CNV in OCT-A imaging, which must be taken into consideration when determining CNV dimensions (Spaide et al. 2015). OCT-A imaging may be a useful adjunct to the conventional method of FA for CNV/PED ratio assessment as OCT-A visualizes the actual CNV dimensions, whereas CNV measurement in FA is significantly confounded by dye leakage and usually remains an estimate. A critical issue in OCT-A imaging of CNVs under PED represents the slab thickness. A thin slab may not include the maximal dimensions of the CNV membrane resulting in a false CNV/PED ratio, while a thick slab is prone to produce image artefacts. In conclusion, OCT-A allows for a non-invasive assessment of the CNV/PED ratio in vPED patients that represents an important predictive factor of RPE tear development at the beginning as well as in the course of an anti-VEGF treatment. A future study including a higher number of patients must evaluate in how far dimensions of CNV membrane under the PED agree between FA and OCT-A, which will be crucial regarding the relevance as well as the clinical interpretation of the CNV/PED ratio assessed by OCT-A as a risk factor for impending RPE tear development.

Objective To compare the consistency and difference of optical coherence tomography angiography (OCTA) and traditional multimodal fundus imaging in the diagnosis and activity evaluation of choroidal neovascularization (CNV) in exudative age-related macular degeneration (AMD). Methods A total of 112 exudative AMD patients (130 eyes) were included in this retrospective study, 62 were men (71 eyes) and 50 were women (59 eyes). The mean age was (68.250±9.789) years (range 50–91 years). All patients were underwent traditional multimodal fundus imaging including fundus fluorescein angiography (FFA), indocyanine green angiography (ICGA) and spectral domain optical coherence tomography (OCT); OCTA was performed at the same time. The CNV type was divided into active and non-active according to the results of traditional multimodal fundus imaging. The vascular pattern was divided into active and non-active according to the results of OCTA. Using traditional multimodal fundus imaging as the standard, the sensitivity and specialty of OCTA was evaluated. Results In 130 eyes, CNV was visualized on traditional multimodal fundus imaging in 109 eyes (83.8%); CNV was visualized on OCTA in 103 eyes (79.2%), which including 7 eyes of false negative and 1 eye of false positive. The sensitivity of OCTA for CNV diagnosis was 93.6%, with specificity of 95.2%. The CNV detection rate between two methods had no significant difference (Youden index=0.89, Kappa value=0.796, P=0.07). In 109 eyes diagnosed with CNV by traditional multimodal fundus imaging, 73 eyes (67.0%) were active CNV and 36 eyes (33.0%) were non-active CNV; the vascular pattern was active in 60 eyes (55.0%) and non-active in 49 eyes (45.0%). The sensitivity of OCTA for the detection of active CNV was 82.2%, with specificity of 100.0%. The active CNV detection rate between two methods had no significant difference (Youden index=0.82, Kappa value=0.753, P=0.00). Conclusion In the diagnosis and activity evaluation of CNV in exudative AMD, there is remarkable consistency between OCTA and traditional multimodal fundus imaging. Key words: Choroidal neovascularization /diagnosis; Tomography, optical coherence; Fluorescein angiography; Indocyanine green/diagnostic use

We analyzed and compared the sensitivity of choroidal neovascularization (CNV) detection according to CNV type in patients with active neovascular age-related macular degeneration (AMD) using swept-source optical coherence tomography (OCT) angiography (OCTA). A retrospective chart review was performed in patients with neovascular AMD. OCTA images were classified into three groups: Group A (well-circumscribed vascular complex); Group B (moderately circumscribed vascular complex); and Group C (poorly circumscribed vascular complex), according to CNV appearance. Demographic characteristics, OCT parameters, neovascularization subtypes, and OCTA image quality were analyzed to determine the effect on visualization of the neovascular complex. A total of 130 patients with CNV secondary to active neovascular AMD were analyzed. Among them, 52 eyes from 47 patients were included in the study. Eighteen eyes (34.6%) were classified into Group A, 24 (46.2%) into Group B, and 10 (19.2%) into Group C. Statistical analysis showed no significant differences in demographic characteristics or OCT parameters between the three groups. Overall sensitivity of active CNV detection was 80.7% (42/52 eyes). In 73.5% (25/34) of eyes with type 1 CNV (sub-retinal pigment epithelial type), 100.0% (9/9) of eyes with type 2 CNV (sub-retinal type), and 88.9% (8/9) of eyes with type 3 CNV (retinal angiomatous proliferation type), the vascular complex was well visualized on OCTA. OCTA provides adequate noninvasive imaging of CNV in patients with neovascular AMD, which may assist in CNV diagnosis and activity monitoring. In particular, type 2 CNV was well detected in OCTA in comparison with type 1 and type 3 CNV.

To characterize the features of choroidal neovascularization (CNV) in neovascular age-related macular degeneration with spectral domain optical coherence tomography angiography (OCTA) and to determine whether OCTA can be used to determine clinical activity of CNV. Observational, retrospective, consecutive case series. Optical coherence tomography angiography revealed CNV in 28 eyes (62.2%) while 17 eyes (37.8%) did not demonstrate CNV vessels. Choroidal neovascularization was classified as well circumscribed in 12 eyes (42.8%) and poorly circumscribed in 16 eyes (57.2%). Twenty-two eyes with a CNV on OCTA were clinically active, whereas six eyes with visible CNV on OCTA were clinically inactive. Of the 17 eyes that did not have evidence of CNV on OCTA imaging, 14 were clinically inactive and 3 were clinically active. Presence of CNV on OCTA correlated with clinical activity and absence of CNV correlated with inactivity (P < 0.0001). Optical coherence tomography angiography is a noninvasive imaging technique that can be used to visualize blood flow comprising CNV. Optical coherence tomography angiography detects CNV vessels in some albeit not all eyes with neovascular age-related macular degeneration. Although the presence or absence of CNV vessels on OCTA highly correlated with clinical activity of CNV, the morphologic appearance of CNV on OCTA did not have significant correlation with clinical activity.

PurposeThe present study aimed to quantify various factors of vessel morphology, including vessel diameter, length, and complexity (fractal dimension and lacunarity) of both choroidal neovascularization (CNV) and en face Haller vessels using optical coherence tomography angiography (OCTA) and en face structural optical coherence tomography in typical neovascular age-related macular degeneration (nAMD) and polypoidal choroidal vasculopathy (PCV) and to identify factors associated with visual acuity (VA) loss and number of injections within a year after the day of OCTA.MethodsWe retrospectively analyzed 43 eyes of nAMD patients and 33 eyes of PCV patients whose OCTA was performed at least 12 months after an initial anti-vascular endothelial growth factor treatment. Quantitative parameters, including vessel area, vessel diameter, vessel length, fractal dimension, and lacunarity were analyzed from en face images of CNV and Haller vessels. Clinical information, including logarithm of the minimum angle of resolution visual acuity and injection number of anti-vascular endothelial growth factor were acquired after 12 months from OCTA date. Using logistic regression analyses, parameters associated with logarithm of the minimum angle of resolution VA loss of 0.2 or more (VA loss group) and a number of injections of four or more (unstable group) after 12 months were analyzed.ResultsIn typical nAMD, the VA loss group was associated with a smaller number of intersections of Haller vessels. The unstable group was associated with an increased lacunarity of CNV in typical nAMD. In PCV, both VA loss and unstable groups were associated with a higher maximal diameter of Haller vessels.ConclusionsVA loss and injection number of nAMD and PCV 12 months after OCTA imaging were associated with different morphological parameters of CNV and Haller vessels. Therefore, quantitative analyses of both CNV and Haller vessels from OCTA and en face optical coherence tomography might provide prognostic information about visual outcome and injection frequency within 12 months after OCTA imaging.

To evaluate morphologic changes of choroidal neovascularization (CNV) on optical coherence tomography angiography (OCTA) during the nonexudative period and to correlate the features and timing of recurrence in neovascular age-related macular degeneration. (AMD). Two hundred thirty-eight eyes with type 1 CNV were retrospectively reviewed. For cases with exudative recurrence, OCTA images were tracked for analysis between the recurrences. Qualitative parameters of morphologic changes of CNV on OCTA, including tiny branching vessels, anastomotic loops, peripheral vascular arcade, and perilesional halo, were correlated with the features of exudative recurrence. Exudative recurrence was identified in 163 cases, and among them, nonexudative morphological changes in CNV were identified using OCTA in 45 cases. For the cases with nonexudative changes on OCTA, exudative recurrence eventually developed within 0.5-3.5months (mean, 2.3 ± 2.0months) after identifying morphologic changes OCTA. The following changes in CNV were revealed on OCTA: tiny branching vessels in 53.3% (24/45) of cases, anastomotic loops in 40.0% (18/45), peripheral vascular arcades in 44.4% (20/45), and perilesional halo in 35.6% (16/45). Among the morphologic parameters, development of tiny branching vessels was significantly associated with early exudative recurrence (1.5 ± 1.2months, p = 0.019), higher incidence of intraretinal fluid (IRF) (p = 0.016), and subretinal or subretinal pigment epithelial hemorrhage (p = 0.023) at recurrence, compared with other morphologic changes. Development of tiny branching vessels of CNV on OCTA during the nonexudative period was associated with early exudative recurrence, including IRF or hemorrhage. Identifying the nonexudative changes of CNV on OCTA might predict exudative recurrence and provide additional parameters for monitoring neovascular AMD.

Optical coherence tomography angiography (OCT-A) in an animal model of laser-induced choroidal neovascularization

Quantitative Optical Coherence Tomography Angiography of Choroidal Neovascularization in Age-Related Macular Degeneration

Background/AimsTo evaluate the ability of optical coherence tomography angiography (OCTA) to identify the presence or absence of choroidal neovascularisation (CNV) and CNV activity in age-related macular degeneration (AMD).MethodsClinical parameters, fundus...

To compare the capability of indocyanine green angiography (ICGA) and optical coherence tomography angiography (OCTA) in detecting choroidal neovascularization (CNV). In this prospective study, patients with CNV detected with fluorescein angiography (FA) underwent ICGA and OCTA, spectral domain OCT (SD-OCT), and infrared or fundus color photographs. CNV lesions were outlined on ICGA and OCTA images, and the composition and size of the CNV was documented. One hundred eighty-two eyes were included. With ICGA, well-defined lesions were observed in 37.9%, partly defined in 44.5%, and undefined in 17% of eyes. On OCTA, well-defined, partly defined, and undefined vessels were observed in 53.8%, 27.5%, and 18.7% of eyes, respectively. There was a good correlation between CNV size measured with the two instruments (r = 0.84). However, OCTA underestimated CNV area by about 4.5% (slope coefficient with linear regression: 0.55, 95% confidence interval [CI]: 0.46 to 0.65; intercept: 0.27, 95% CI: -0.2 to 0.56). On ICGA, CNV composition was capillary in 28%, mature in 14.3%, and mixed (capillary and major neovascular complex) in 57.7% of eyes. Similarly, OCTA revealed capillary, mature, and mixed CNV in 28.9%, 15.9%, and 55.5% of eyes, respectively. OCTA provides the clinician the ability to perform precise structural and vascular assessment of CNV noninvasively. Our study is, to our knowledge, the largest OCTA analysis to date of CNV secondary to neovascular AMD analyzed simultaneously by ICGA and OCTA.

The aim of this study was to characterize the longitudinal changes of treated type 2 choroidal neovascularization (CNV) (Freund et al. 2010) [showing neither intra- nor subretinal fluid on B-scan spectral-domain optical coherence tomography (SD-OCT)]. We used AngioVue OCT Angiography (OCTA; RTVue XR Avanti; Optovue, Inc., Freemont, CAm, USA) to image eyes undergoing monthly ranibizumab (Lucentis; Genentech, Inc., South San Francisco, CA, USA and Novartis AG, Basel, Switzerland) injection for neovascular age-related macular degeneration (nAMD). The local institutional review board approved this study. Fourteen consecutive treatment-naïve patients with nAMD, underwent monthly ranibizumab injections, were prospectively enrolled and after the loading phase, evaluated monthly with comprehensive ophthalmological examination and SD-OCT B-scan. As per protocol, patients continued to undergo monthly treatment even after the lesion was no longer active. Before the first injection, to establish the presence of new active CNV, we required evidence of leakage on fluorescein angiography (FA) and the association with presence of typical SD-OCT findings, including intra- or subretinal fluid. Choroidal neovascularization (CNV) was defined as type 2 if the lesion was above retinal pigment epithelium (RPE). Optical coherence tomography angiography (OCTA) (3 × 3 mm and 6 × 6 mm macular cube) was performed starting 1 month after the loading phase and the plane of CNV identified (de Carlo et al. 2015). Also, the CNV area on OCTA en face images was manually delineated 1 month after the loading phase (first of 3 consecutive monthly visits showing no more active AMD after the loading phase) using Imagej software version 1.48v (National Institutes of Health; available at http://imagejnihgov/ij/; Fig. 1A) (Kuehlewein et al. 2015). In addition, CNV size in the early phase on FA images was measured at the time of diagnosis (before the loading phase) (IMAGEnet; TRC-50× Topcon Instrument Corp, Tokyo, Japan). Measurements were taken by two different trained graders (MS, DDG). Two authors (LQ, FS), masked to the timing of the images, analysed qualitatively the OCTA images with respect to CNV appearance at baseline examination and its change over time, including shrinkage of vessels at the edge of the main neovascular complex, the decrease in the density of fine vessels and also the appearance of subretinal fluid on B-scans. The CNV size during the follow-up (one-way analysis of variance with the Dunnett) and the relationship between changes in CNV size and different variables at baseline (linear regression analysis) were explored (p < 0.05). Twelve eyes of 12 patients with treated type 2 CNV (mean age 75.6+/−9.4 years) for three consecutive monthly visits after the loading phase were investigated (two eyes excluded because of low-quality images). Mean duration of symptoms at time of diagnosis was 30.2+/− 27.1 days, and mean size of CNV at FA was 5.65+/−10.35 mm2. Mean time from CNV diagnosis to the lesion being no more active was 3.9 months (average of 3.9 intravitreal injections). Quantitative OCTA analysis revealed a CNV area of 4.99+/−3.99 mm2 at baseline examination, which did not change significantly (5.15+/−4.27 mm2; p = 0.99) after 3 monthly ranibizumab injections (Fig. 1A). Qualitative OCTA analysis revealed the persistence of the main neovascular complex in 9/10 eyes (Fig. 1B). However, a subtle shrinkage of vessels at the edge of the lesion and reduction in the capillary network of fine vessels within the neovascular lesion was observed in all eyes (Fig. 1B). No significant relationships were found between age, gender, duration of symptoms, CNV area on FA at time of diagnosis and change in CNV size on OCTA during follow-up (p > 0.05). Our quantitative and qualitative analysis of treated type 2 CNV undergoing monthly anti-VEGF treatment reveals that while the size of the lesion as well as the main neovascular complex does not change during the short-term follow-up, the capillary plexus shows attenuation. These results suggest that anti-VEGF therapy might not be effective in reducing the main neovascular complex size possibly because of the presence of pericytes overlying the endothelial cells, even in the monthly regimen (Benjamin et al. 1998). The main limitation could be related to the inability to be sure that the image quality of the OCTA signal in the area analysed was the same in all visits. Our findings, in line with previous publications (Jia et al. 2014; de Carlo et al. 2015; Kuehlewein et al. 2015), suggest that OCTA can be considered as a valuable tool for monitoring treated CNV. In conclusion, using en face measurements of OCTA images, we showed that further reduction in size is not seen once the type 2 CNV lesion becomes no more active.

Long-term Progression of Type 1 Neovascularization in Age-related Macular Degeneration Using Optical Coherence Tomography Angiography

Using optical coherence tomography angiography to assess and compare changes in pathological vascular tissue, including choroidal neovascularization in neovascular age-related macular degeneration and polypoidal complex in polypoidal choroidal vasculopathy, after treatment with anti-vascular endothelial growth factor. This is a retrospective observational case series study. Clinical data were collected, including that on the best-corrected visual acuity and images of spectrum domain optical coherence tomography and optical coherence tomography angiography of consecutive patients with macula-involved lesions, active pathological vascular tissue in neovascular age-related macular degeneration, and polypoidal complex in polypoidal choroidal vasculopathy who were treated with anti-vascular endothelial growth factor injection. The primary outcome measures were the lesion area, flow density, and flow area of the pathological vascular tissue obtained in optical coherence tomography angiography before treatment, as well as week-1 (W1) and week-5 (W5) after treatment. The secondary outcome measures were the best-corrected visual acuity and the anatomic changes in spectrum domain optical coherence tomography at the same periods. A total of 86 eyes in 79 patients (mean age: 73.10 ± 10.10 (range = 50-91) years, 45 males (57%), of which two eyes were treatment-naïve) underwent one section of intravitreal treatment. Of which 44 eyes (40 patients) were diagnosed as typical neovascular age-related macular degeneration and 42 eyes (39 patients) as polypoidal choroidal vasculopathy. The sensitivity for detecting choroidal neovascularization in neovascular age-related macular degeneration and polypoidal complex in polypoidal choroidal vasculopathy was 75.00% (33/44) and 69.05% (29/42), respectively. There was no significant difference in the detection rate between neovascular age-related macular degeneration and polypoidal choroidal vasculopathy (p = 0.54). In the detectable group, there were significant decrease in lesion area and flow area in the optical coherence tomography angiography images after anti-vascular endothelial growth factor treatment in both the neovascular age-related macular degeneration group (lesion area: W1 = -26.94 ± 19.50%, W5 = -35.52 ± 30.85%, all ps < 0.001; flow area: W1 = -26.22 ± 25.23%, W5 = -32.24 ± 32.07%, all ps < 0.001) and the polypoidal choroidal vasculopathy group (lesion area: W1 = -25.19 ± 20.27%, W5 = -31.55 ± 27.04%, all ps < 0.001; flow area: W1 = -21.83 ± 26.29%, W5 = -28.31 ± 30.72%, all ps < 0.001). The central subfield retinal thickness in spectrum domain optical coherence tomography also showed similar amelioration in both groups. However, the flow density in optical coherence tomography angiography image and the visual outcome did not reveal any significant difference before or after intravitreal injections, and neither were there significant differences between the neovascular age-related macular degeneration and polypoidal choroidal vasculopathy groups. Concerning the effect on the optical coherence tomography angiography images of pathological vascular tissue, there were no statistical differences among different anti-vascular endothelial growth factor agents (i.e. aflibercept, ranibizumab, and bevacizumab). Our study revealed that optical coherence tomography angiography can be used noninvasively and quantitatively to assess the detailed pathologic vascular structures in both neovascular age-related macular degeneration and polypoidal choroidal vasculopathy. Our study also demonstrated that anti-vascular endothelial growth factor could effectively decrease the lesion size and flow area of both the choroidal neovascularization in neovascular age-related macular degeneration cases and the polypoidal complex in polypoidal choroidal vasculopathy cases; the effects were similar in both diseases.

PurposeVessel maturation is considered to proceed by pruning branches resulting in less branching vessels. This study investigated the vessel junction densities of type 1 and type 2 choroidal neovascularizations (CNVs) using optical coherence tomography angiography (OCTA).MethodsWe collected consecutive data from treatment-naïve eyes diagnosed with typical age-related macular degeneration (AMD). The OCTA images with CNV were analyzed to calculate vessel areas, vessel lengths, and vessel junction densities.ResultsOf 60 eyes in 60 patients, type 1 CNV diagnoses had been made in 40 eyes, and type 2 CNV in 20 eyes. We found no significant difference in vessel areas between type 1 CNV and type 2 CNV (type 1 CNV, 0.44 ± 0.37 mm2; type 2 CNV, 0.37 ± 0.48 mm2), and no significant difference in vessel lengths (type 1 CNV, 18.24 ± 15.96 mm; type 2 CNV, 16.13 ± 21.45 mm). However, the vessel junction density of type 1 CNV was significantly lower than that of type 2 CNV by 16.0% (P = 0.008).ConclusionOCTA revealed that the vessel junction densities of type 1 CNVs were lower than those of type 2 CNVs, suggesting type 1 CNV vessels are more mature than type 2 CNV vessels.

PurposeTo describe optical coherence tomography angiography (OCTA) image artefacts in eyes with and without ocular pathologies.MethodsThe OCTA images of healthy subjects and patients with age-related macular degeneration, diabetic retinopathy and...