Optical coherence tomography angiography macular biomarkers of peripheral retinal ischemia in diabetic macular edema: secondary endpoints from the clinical study "FOVEA".

PURPOSE: To investigate the relationship between the macular values of fractal dimension (FD) and lacunarity (LAC) on optical coherence tomography angiography (OCTA) images and the presence of peripheral retina non-perfusion areas (NPAs) on fluorescein angiography (FA) in patients with treatment-naïve diabetic macular edema (DME). METHODS: Fifty patients with treatment-naïve DME underwent a full ophthalmic examination, including best-corrected visual acuity measurement, FA, spectral-domain optical coherence tomography, and OCTA. Specifically, FA was performed to detect the presence of retinal NPAs, whereas fractal OCTA analysis was used to determine macular FD and LAC values at the level of the superficial and deep capillary plexus (SCP and DCP). FA montage frames of the posterior pole and peripheral retina, as well as macular OCTA slabs of the SCP and DCP, were obtained. RESULTS: Thirty (60%) eyes with FA evidence of peripheral retinal NPAs in at least one quadrant showed significantly lower FD and higher LAC in both SCP and DCP, when compared with eyes presenting a well-perfused peripheral retina. Furthermore, macular FD and LAC values were found to be significantly associated with the extent of retinal NPAs. CONCLUSIONS: Macular FD and LAC of both SCP and DCP seem to be strongly associated with the extent of peripheral retinal NPAs, thus suggesting that may be useful predictive biomarkers of peripheral ischemia in treatment-naïve DME eyes.

Predictive Factors of Visual Outcome in Treatment-Naïve Diabetic Macular Edema: Preliminary Results from the Clinical Study "FOVEA".

Diabetic macular edema (DME) is a common cause of vision impairment in diabetic retinopathy. The aim of this study was to analyze the relationship between visual outcome and anatomic changes detected by traditional multimodal retinal imaging and optical coherence tomography angiography (OCTA) in DME eyes under treatment with Aflibercept. METHODS: Sixty-six DME eyes of 62 patients under treatment with intravitreal Aflibercept and with one-year follow-up were enrolled. All participants underwent a full ophthalmic evaluation, including best correct visual acuity (BCVA) measurement, spectral-domain optical coherence tomography, fluorescein angiography and OCTA, both at baseline and final examination. Fractal OCTA analysis of the superficial and deep capillary plexus (SCP and DCP) was performed to estimate vascular perfusion density and lacunarity (LAC). RESULTS: At the final examination, there was a significant improvement in terms of BCVA and central macular thickness (CMT). Furthermore, eyes with CMT <373 µm at baseline reached the higher BCVA at the last follow-up. Eyes with CMT ≥373 µm and DCP LAC <0.41 reached a higher final BCVA, if compared with eyes showing the same CMT but higher initial LAC. CONCLUSION: A 12-month treatment with intravitreal Aflibercept for DME resulted in significant visual and anatomic improvement. Multimodal retinal imaging, together with fractal OCTA analysis, may provide useful biomarkers, predictive of visual outcome in DME.

POLYPOIDAL CHOROIDAL NEOVASCULARIZATION VERSUS TYPE 1 CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION: A Fractal Analysis Study.

PURPOSE: To compare quantitative optical coherence tomography angiography parameters between polypoidal choroidal neovascularizations (PCNVs) and Type 1 choroidal neovascularizations (CNVs) in patients with age-related macular degeneration. METHODS: PCNV and Type 1 CNV lesions were retrospectively recruited in a cohort of patients with age-related macular degeneration. All the patients underwent a comprehensive ophthalmic evaluation, including best-corrected visual acuity, fluorescein and indocyanine green angiography, structural optical coherence tomography (OCT), and optical coherence tomography angiography.Vascular perfusion density, fractal dimension, and lacunarity were computed by means of fractal analysis of neovascular en face optical coherence tomography angiography slabs. RESULTS: Sixty-eight eyes were included in the analysis. Of them, 35 of 68 eyes (51.5%) had PCNV and 33 of 68 (48.5%) had Type 1 CNV. Patients with PCNV were significantly younger (P = 0.0003) and had a higher best-corrected visual acuity (P < 0.0001). The mean vascular perfusion density was 0.83 ± 0.11% in PCNVs and 0.46 ± 0.10% in Type 1 CNVs (P < 0.0001). The mean fractal dimension was 1.44 ± 0.1 in PCNVs and 1.45 ± 0.09 in Type 1 CNVs (P = 0.86) while the mean lacunarity was 2.46 ± 1.03 in PCNVs and 1.86 ± 0.52 in Type 1 CNVs (P = 0.006). CONCLUSION: PCNVs resulted to be more heterogeneous and characterized by higher vascular perfusion density and lacunarity values than Type 1 CNVs. These interesting findings seem to support the idea that PCNVs and Type 1 CNVs are two separate clinical entities. However, future studies based on optical coherence tomography angiography fractal analysis, but also involving other relevant parameters such as demographics, presentation, morphology on multimodal imaging, and response to treatment, are necessary before drawing any definitive conclusions on whether PCNV is a specific clinical entity or a neovascular age-related macular degeneration variant.

OCT-Angiography as a reliable prognostic tool in laser-treated proliferative diabetic retinopathy: The RENOCTA Study.

PURPOSE: To quantitatively assess retinal neovascularizations (RNVs) in proliferative diabetic retinopathy (PDR) before and after photocoagulative laser treatment (PLT) using Optical Coherence Tomography Angiography (OCT-A). METHODS: Consecutive patients with PDR were examined with fluorescein angiography (FA) and OCT-A before and after PLT. Baseline and after-treatment FA images were quantitatively analyzed to assess both the RNVs area and leakage area. On OCT-A RNVs area, vascular perfusion density (VPD), vessel length density (VLD) and fractal dimension were computed. VPD of the full-retina OCT-A underneath the RNV was determined to evaluate potential laser-induced changes in vascular perfusion. RESULTS: Fifteen eyes of 13 patients with PDR were enrolled. The mean area of the RNVs was 0.47 ± 0.50 mm2 in the baseline OCT-A and 0.32 ± 0.40 mm2 in the post-treatment assessment (p = 0.0002). The mean RNV VPD of RNV was 2% ± 4% in pre-treatment and 1% ± 1% for the post-treatment (p = 0.0001). The mean VLD of RNV was 7.26 ± 1.53 at baseline and 6.64 ± 1.65 in the post treatment (p = 0.0002). A significant difference in terms of mean RNVs area and VPD reduction between eyes that needed additional treatment and those that did not (~40% vs ~20%; p < 0.05), was observed. Mean VPD of full-retinal thickness OCT-angiogram was 55% ± 10% for the pre-treatment and 53% ± 8% for the post treatment scan (p = 0.02). CONCLUSION: The quantitative OCT-A assessment of laser-induced changes of RNVs can be a useful non-invasive approach for determining treatment efficacy. A reduction of RNVs area or VPD ⩾ 40% might reveal those eyes that won't require additional treatment. Retinal perfusion impairment seemed to progress independently from the treatment.

QUANTITATIVE OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY FEATURES OF INACTIVE MACULAR NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To compare quantitative optical coherence tomography angiography parameters between treatment-naïve quiescent macular neovascularizations (MNVs) and previously treated nonexudative Type 1 MNVs, in patients with age-related macular degeneration. METHODS: The eyes included in the study were analyzed by fluorescein angiography, indocyanine green angiography, spectral-domain optical coherence tomography, and optical coherence tomography angiography. According to their medical history and multimodal imaging evaluation, Type 1 MNVs were divided into 2 groups: 1) treatment-naïve quiescent MNVs; 2) previously treated nonexudative Type 1 MNVs. Quantitative optical coherence tomography angiography parameters, including perfusion density (PD), fractal dimension (FD), and lacunarity (LAC) were calculated. Receiver operating characteristic curves, showing the ability of PD, FD, and LAC to discriminate between the two MNV groups, were built. RESULTS: Twenty-two eyes with treatment-naïve quiescent MNVs and 20 eyes with MNVs previously treated nonexudative Type 1 MNVs were analyzed. Mean FD and LAC were statistically different between the two study groups (P < 0.05). Lacunarity showed the best discrimination ability, followed by FD and PD (area under curve = 0.83, 0.78, 0.62, respectively). CONCLUSION: Results suggest that FD and LAC may be useful optical coherence tomography angiography biomarkers to objectively discriminate inactive MNVs with different prognosis, such as treatment-naïve quiescent MNVs and previously treated nonexudative Type 1 MNVs, in age-related macular degeneration patients.

IMPLICATIONS OF THE MORPHOLOGIC PATTERNS OF TYPE 1 MACULAR NEOVASCULARIZATION ON MACULAR ATROPHY GROWTH ON PATIENTS UNDER ANTI-VASCULAR ENDOTHELIAL GROWTH FACTOR TREATMENT.

PURPOSE: To evaluate the correspondence between macular atrophy (MA) progression and Type 1 macular neovascularization morphology during long-term anti-vascular endothelial growth factor treatment for exudative neovascular age-related macular degeneration. METHODS: Retrospective review of consecutive patients with complete retinal pigment epithelium and outer retina atrophy overlying or in the proximity of macular neovascularization. The assessment of MA was based on spectral domain optical coherence tomography, en-face near infra-red imaging and fundus autofluorescence. Macular neovascularization blood flow morphology was evaluated by swept-source optical coherence tomography-angiography. Qualitative features were categorized per ETDRS sector as: immature, mature; and hypermature pattern. An automatic analysis was designed in MATLAB coding language to compute MA per ETDRS. Measurements were compared between the baseline and the last follow-up visit. RESULTS: Twenty eyes from 20 patients were included; the mean age was 85.4 (8.3) years. The median follow-up was 1.85 (1.0-2.4) years and the median anti-vascular endothelial growth factor injection rate during follow-up was 4.0 (2.0-5.0) injections/year. During follow-up, sectors with persistence of an immature blood flow pattern had a lower MA growth rate than sectors with mature macular neovascularization flow patterns (P = 0.001). CONCLUSION: The presence of an immature blood flow pattern on optical coherence tomography-angiography is associated with a lower progression rate of MA.

Fractal analysis of polypoidal choroidal neovascularisation in age-related macular degeneration.

AIM: To describe optical coherence tomography angiography (OCTA) features of polypoidal choroidal neovascularisation (PCNV) secondary to age-related macular degeneration. METHODS: A retrospective consecutive series of 51 patients with a diagnosis of PCNV, based on clinical and multimodal imaging, was analysed. All patients with PCNV underwent a comprehensive ophthalmological examination, including fluorescein and indocyanine green angiography, structural optical coherence tomography (OCT) and OCTA. Two blinded retinal specialists carefully reviewed OCTA slabs in order to assess the morphological patterns of PCNV lesions. Furthermore, fractal analysis of PCNV en face images on OCTA, including vascular perfusion density (VPD), fractal dimension (FD) and lacunarity (LAC), was performed. RESULTS: Fifty-one PCNV eyes were included in the study. In all, the branching vascular network appeared hyper-reflective. Polyps showed two different patterns: in 34/51 (67%) eyes, they corresponded to hypo-reflective structures, whereas in the remaining 17 (33%) eyes, they appeared as hyper-reflective lesions. In all PCNV eyes, mean VPD, FD and LAC were 0.76±0.17%, 1.46±0.12 and 2.4±0.87, respectively. No significant difference was found between PCNVs showing a different OCTA pattern, in terms of quantitative OCTA parameters. CONCLUSION: Fractal analysis provides quantitative parameters demonstrating that PCNVs with different OCTA patterns share the same neovascular architecture and branching complexity. These new findings improve our ability to interpret OCTA slabs, opening new areas of discussion about this type of neovascular lesion.

Quantitative Optical Coherence Tomography Angiography Biomarkers in a Treat-and-Extend Dosing Regimen in Neovascular Age-Related Macular Degeneration.

Purpose: To evaluate the association between quantitative optical coherence tomography angiography (OCT-A) parameters and clinical outcomes in treatment-naïve neovascular age-related macular degeneration (nAMD) patients treated with a treat-and-extend dosing regimen on a 12-month follow-up interval. Methods: Observational, prospective study of consecutive patients. The treatment protocol was based on a loading dose of three anti-vascular endothelial growth factor (VEGF) intravitreal injections (IVI) followed by a treat-and-extend regimen. Eyes were evaluated by swept-source OCT-A at baseline, 1 month after the loading dose and at 12 months. A quantitative analysis was issued for fractal dimension (FD), lacunarity index (LAC), blood flow surface area (SA), and vessel density (VD). An association of these parameters with the anatomic response and functional responses, and IVI number at 12 months of follow-up was assessed. A level of significance α = 0.05 was considered. Results: Sixty-four patients were included, 52 of whom (81%) completed the 12-month study protocol. The median number of injections at 12 months was 7 (P25-P75: 6-12). FD and SA were reduced 1 month after the loading dose of anti-VEGF (P < 0.001). The generalized linear models using baseline FD and baseline SA achieved the best performance in discriminating a lower treatment burden (area under the curve [AUC] = 0.78; 95% confidence interval [CI]: 0.64-0.91 and AUC = 0.76; 95% CI: 0.63-0.90, respectively). Conclusions: Baseline OCT-A may provide useful biomarkers for the treatment burden in nAMD. Translational Relevance: The application of fractal dimension and automatic blood flow area algorithms to OCT-A data can distinguish patients with distinct treatment burdens in the first year of nAMD.

Functional correlation between choroidal and retinal vascularity in low-grade diabetic retinopathy.

AIMS: To perform an automated functional assessment of retinal and choroidal microvasculature in eyes with low-grade diabetic retinopathy (DR) using optical coherence tomography angiography (OCT-A) and to identify potential perfusion changes in case of early vascular damage. METHODS: This is an observational, case-control study of consecutive diabetic patients with level 20 DR severity scale score and age-matched healthy subjects. A prototypal OCT-angiography was used to obtain the OCT-angiograms of the superficial capillary plexus (SCP), deep capillary plexus (DCP) and choriocapillaris (CC) layer. A validated automated microstructural analysis provided data on SCP, DCP and CC vascular perfusion density (VPD). A comparative assessment between different vascular layers and different groups was performed. RESULTS: Twenty-nine diabetic patients (7 females, 24%) and 20 healthy controls were enrolled. VPD values were significantly lower in the DCP (25.1% vs. 26.5%; p = 0.04) and CC (71.2% vs. 86.6%; p = 0.0001) of diabetic patients compared with controls. A statistically significant negative linear correlation was reported between CC VPD and DCP VPD in diabetic patients; at the reverse, a positive linear correlation between the same parameters was noticed in controls. CONCLUSION: Retinal and choroidal vascular networks, although distinct entities, seem functionally interconnected: varying the degree of perfusion may be a mutual compensatory mechanism in response to an ischemic injury.

PREDICTIVE ACTIVATION BIOMARKERS OF TREATMENT-NAIVE ASYMPTOMATIC CHOROIDAL NEOVASCULARIZATION IN AGE-RELATED MACULAR DEGENERATION.

PURPOSE: To assess the long-term evolution of treatment-naive quiescent choroidal neovascularization (CNV), in age-related macular degeneration (AMD), to identify predictive activation biomarkers. METHODS: Patients with quiescent CNV underwent a comprehensive ophthalmological examination, including fluorescein and indocyanine green angiographies, structural optical coherence tomography (OCT), and OCT angiography. Qualitative and quantitative analyses of structural OCT and OCT angiography images were performed during the study period. At the last follow-up evaluation, the enrolled eyes were divided into two groups: eyes with quiescent CNV converting to exudative AMD (eAMD) and those not progressing to eAMD. RESULTS: Sixty-eight eyes of 68 patients were enrolled in the study. Mean follow-up duration was 40 ± 28 months using multimodal imaging and 22 ± 13 months using OCT angiography. On structural OCT, quiescent CNV not converting to eAMD showed a preferential growth of the pigment epithelium detachment greatest linear diameter (P = 0.009), whereas the eAMD group presented a preferential growth of the pigment epithelium detachment maximal height (P < 0.0001) during the study period. Quantitative analysis of choriocapillaris OCT angiograms confirmed the CNV area growth during follow-up (from 4.18 ± 4.77 mm at baseline to 5.10 ± 5.06 mm at the last follow-up visit; P = 0.02). CONCLUSION: A close follow-up is recommended to early identify predictive activation biomarkers of treatment-naive quiescent CNV.

Consensus Nomenclature for Reporting Neovascular Age-Related Macular Degeneration Data: Consensus on Neovascular Age-Related Macular Degeneration Nomenclature Study Group.

PURPOSE: To establish a process to evaluate and standardize a state-of-the-art nomenclature for reporting neovascular age-related macular degeneration (AMD) data. DESIGN: Consensus meeting. PARTICIPANTS: An international panel of retina specialists, imaging and image reading center experts, and ocular pathologists. METHODS: During several meetings organized under the auspices of the Macula Society, an international study group discussed and codified a set nomenclature framework for classifying the subtypes of neovascular AMD and associated lesion components. MAIN OUTCOME MEASURES: A consensus classification of neovascular AMD. RESULTS: The study group created a standardized working definition of AMD. The components of neovascular AMD were defined and subclassified. Disease consequences of macular neovascularization were delineated. CONCLUSIONS: The framework of a consensus nomenclature system, a definition of AMD, and a delineation of the subtypes of neovascular AMD were developed. Establishing a uniform set of definitions will facilitate comparison of diverse patient groups and different studies. The framework presented is modified and updated readily, processes that are anticipated to occur on a periodic basis. The study group suggests that the consensus standards outlined in this article be used in future reported studies of neovascular AMD and clinical practice.

Biomarkers of Peripheral Nonperfusion in Retinal Venous Occlusions Using Optical Coherence Tomography Angiography.

PURPOSE: To study the association between the assessment of central macular vascular layers by optical coherence tomography angiography (OCT-A) and peripheral nonperfusion evaluated by fluorescein angiography (FA) in patients with retinal venous occlusion (RVO). METHODS: Retrospective review of RVO patients without macular edema. Patients underwent a comprehensive ophthalmic examination including FA, spectral-domain OCT, and OCT-A. Significant ischemia was defined as nonperfusion areas superior or equal to the equivalent of one retinal quadrant on FA. Vascular density (VD) and foveal avascular zone were measured using AngioAnalytics software. Fractal dimension (FD) and lacunarity (LAC) were computed using an algorithm designed by MATLAB (MathWorks, Natick, MA). These variables were used to build a model that translates their association with OCT-A parameters. RESULTS: There were 48 eyes (48 patients) of which 19 had significant peripheral nonperfusion. Deep capillary plexus FD, VD, and LAC were associated with significant ischemia. In fact, regarding the association with this outcome, LAC alone had the highest area under the curve (AUC = 0.88) followed by FD (AUC = 0.85) and VD (AUC = 0.73). The multivariable model that included LAC and VD, adjusted by best-corrected visual acuity (BCVA) achieved the best performance for the identification of severe nonperfusion on wide-field FA (AUC = 0.93). CONCLUSIONS: The characteristics of the central macular deep capillary plexus on OCT-A may be associated with peripheral nonperfusion on FA, particularly the combination of LAC and vessel density after adjusting by BCVA. TRANSLATIONAL RELEVANCE: Fractal-based metrics applied to OCT-A may become a valuable marker of ischemia in RVO and help guide the clinical decision to perform invasive angiography.

Multimodal OCT Reflectivity Analysis of the Cystoid Spaces in Cystoid Macular Edema.

PURPOSE: To compare and evaluate images of macular cysts with different degrees of reflectivity (from gray to black signal) as observed in B scan spectral domain OCT (SDOCT) and EnFace OCT with decorrelation signal obtained with OCT-angiography (OCTA) in eyes with cystoid macular edema (CME) secondary to diabetic retinopathy (DR) and retinal vein occlusion (RVO). METHODS: Images from 3033 patients affected by CME secondary to diabetes or RVO examined OCTA (Optovue XR Avanti, Optovue, USA) at the University Eye Clinic of Créteil, Hôpital Intercommunal, France, and at the University Eye Clinic of Cagliari, "San Giovanni di Dio" Hospital, Italy, were retrospectively examined. The deep capillary plexus OCTA images and the corresponding EnFace OCT images, both acquired with the same automatic segmentation, had been overlapped to compose RGB color images as red and green channels, respectively, using ImageJ software (National Institutes of Health, Bethesda, MD). Afterward, linear regions of interest were traced on the color images to obtain the profiles of OCTA and EnFace gray values. Number of pixels, mean gray value and standard deviation of the area traced in OCT-A, and EnFace image were analyzed and statistically correlated. Data were exported to Excel to create the plots. RESULTS: 94 patients with DME and 27 patients with RVO showed intraretinal macular cystoid spaces with similar homogeneous, gray-looking content; 73 patients with DME and 113 patients with RVO showed macular cystoid spaces with homogeneous, black-looking content, as observed at SD-OCT, EnFace and OCTA scans. Interestingly, the limits of macular cystoid spaces were clearly detectable with OCTA. The analysis of red and green profiles demonstrated a clearly visible overlap between average OCTA and EnFace signal observed around cystoid spaces that could be attributed to a relationship between the dynamic vascularization and the structural density of the tissue. CONCLUSIONS: This is the first investigation that characterizes and correlates OCTA and EnFace signals on images of macular cystoid spaces in DR and RVO. The low intensity OCTA signals observed inside cystoid spaces raise a relevant question about their nature, as to whether they are due to the presence of corpusculated material pouring out from bloodocular-barrier or they should be considered OCTA artifacts.

Optical coherence tomography angiography in exudative age-related macular degeneration: a predictive model for treatment decisions.

AIMS: To evaluate on optical coherence tomography angiography (OCT-A), the predictive role of different qualitative findings of choroidal neovascularisations (CNV) in assessing the status of exudative age-related macular degeneration (eAMD) and to develop a potential model to predict the CNV activity. METHODS: Retrospective review of the multimodal imaging records of patients with eAMD obtained during treatment for type 1 or type 2 CNV. The qualitative analysis of CNVs on OCT angiograms assessed the presence or absence of tiny branching vessels, loops, peripheral anastomotic arcades and choriocapillaris hypointense halo. These findings were then correlated with those of structural OCT scans. A score forecast was built and validated. RESULTS: One hundred and twenty-six eAMD eyes were enrolled in the study. Exudation was observed in 90 eyes (71%) on structural OCT. The qualitative OCT-A analysis revealed: tiny branching vessels in 82.5% of the cases, vascular loops in 81.7%, peripheral anastomotic arcades in 66.7% and choriocapillaris hypointense halo in 54.8%. In the univariate analysis, each OCT-A parameter showed a statistically significant correlation with exudation on structural OCT (p<0.001). The overall analysis demonstrated a sensitivity of 96.7% and a positive predictive value of 87.9%. In the multivariate analysis, a model with four criteria predicted an exudative lesion in 97.6% of cases and one with two criteria (tiny branching vessels and peripheral anastomotic arcades) in 71.2%. CONCLUSIONS: The presence of tiny branching vessels and a peripheral anastomotic arcade appears to predict the lesion activity with a good accuracy and the model based on four criteria enables optimal decisions regarding retreatment in eAMD.

Quantitative optical coherence tomography angiography biomarkers for neovascular age-related macular degeneration in remission.

PURPOSE: To characterize quantitative optical coherence tomography angiography (OCT-A) parameters in active neovascular age-related macular degeneration (nAMD) patients under treatment and remission nAMD patients. DESIGN: Retrospective, cross-sectional study. PARTICIPANTS: One hundred and four patients of whom 72 were in Group 1 (active nAMD) and 32 in Group 2 (remission nAMD) based on SD-OCT (Spectral Domain OCT) qualitative morphology. METHODS: This study was conducted at the Centre Ophtalmologique de l'Odeon between June 2016 and December 2017. Eyes were analyzed using SD-OCT and high-speed (100 000 A-scans/second) 1050-nm wavelength swept-source OCT-A. Speckle noise removal and choroidal neovascularization (CNV) blood flow delineation were automatically performed. Quantitative parameters analyzed included blood flow area (Area), vessel density, fractal dimension (FD) and lacunarity. OCT-A image algorithms and graphical user interfaces were built as a unified tool in Matlab coding language. Generalized Additive Models were used to study the association between OCT-A parameters and nAMD remission on structural OCT. The models' performance was assessed by the Akaike Information Criterion (AIC), Brier Score and by the area under the receiver operating characteristic curve (AUC). A p value of ≤ 0.05 was considered as statistically significant. RESULTS: Area, vessel density and FD were different (p<0.001) in the two groups. Regarding the association with CNV activity, Area alone had the highest AUC (AUC = 0.85; 95%CI: 0.77-0.93) followed by FD (AUC = 0.80; 95%CI: 0.71-0.88). Again, Area obtained the best values followed by FD in the AIC and Brier Score evaluations. The multivariate model that included both these variables attained the best performance considering all assessment criteria. CONCLUSIONS: Blood flow characteristics on OCT-A may be associated with exudative signs on structural OCT. In the future, analyses of OCT-A quantitative parameters could potentially help evaluate CNV activity status and to develop personalized treatment and follow-up cycles.

Optical coherence tomography angiography in age-related macular degeneration: The game changer.

Optical coherence tomography angiography is one of the biggest advances in ophthalmic imaging. It enables a depth-resolved assessment of the retinal and choroidal blood flow, far exceeding the levels of detail commonly obtained with dye angiographies. One of the first applications of optical coherence tomography angiography was in detecting the presence of choroidal neovascularization in age-related macular degeneration and establishing its position in relation to the retinal pigmented epithelium and Bruch's membrane, and thereby classifying the CNV as type 1, type 2, type 3, or mixed lesions. Optical coherence tomography angiograms, due to the longer wavelength used by optical coherence tomography, showed a more distinct choroidal neovascularization vascular pattern than fluorescein angiography, since there is less suffering from light scattering or is less obscured by overlying subretinal hemorrhages or exudation. Qualitative and quantitative assessments of optical coherence tomography angiography findings in exudative and nonexudative age-related macular degeneration have been largely investigated within the past 3 years both in clinical and experimental settings. This review constitutes an up-to-date of all the potential applications of optical coherence tomography angiography in age-related macular degeneration in order to better understand how to translate its theoretical usefulness into the current clinical practice.

OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN RETINAL VEIN OCCLUSION: Correlations Between Macular Vascular Density, Visual Acuity, and Peripheral Nonperfusion Area on Fluorescein Angiography.

PURPOSE: To study correlations in patients with retinal vein occlusion between the automatically quantified macular vascular densities in the superficial and deep capillary plexus (DCP) obtained using optical coherence tomography angiography (OCTA) and the data from conventional examination, particularly visual acuity and peripheral retinal nonperfusion assessed using fluorescein angiography (FA). METHODS: Retrospective, observational study of patients with retinal vein occlusion who underwent a comprehensive ophthalmic examination including FA and OCTA using the AngioVue OCTA system version 2015.100.0.35 (OptovueRTVue XR 100; AVANTI, Inc, Fremont, CA). Vascular densities in the superficial capillary plexus and DCP, as well as the area of the foveal avascular zone, were measured using the AngioAnalytics software. RESULTS: Our study of 65 eyes of 61 patients (33 men, mean age: 67 years) showed a significant correlation between peripheral nonperfusion on FA and (1) automatically quantified global vascular density in both plexus (P = 0.021 for the DCP) and (2) foveal avascular zone area (P = 0.037). We also found significant correlations between capillary dropouts in both plexus and peripheral nonperfusion (P < 0.001 for both) and between visual acuity and vascular densities (P = 0.002 for the global density in the DCP). Global density less than 46% in the DCP was associated to the presence of peripheral nonperfusion area on FA (P = 0.003) and to enlargement of the superficial foveal avascular zone (P = 0.002). CONCLUSION: Our study demonstrated a significant correlation between automatically quantified macular vascular density on OCTA and peripheral nonperfusion on FA; OCTA could help identify high-risk retinal vein occlusion patients who may benefit from further evaluation using FA.

Optical Coherence Tomography Angiography in Healthy Subjects and Diabetic Patients.

Fluorescein angiography and indocyanine green angiography provide information about the normal retinal and choroidal vascular perfusion. They allow the evaluation of different diseases and increase the capability to define and diagnose several pathological conditions. Fluorescein angio graphy is the "gold standard" in imaging the retinal vascular bed and its changes, although not all the different layers of the capillary network can be visualized in a bidimensional examination. Optical coherence tomography angiography allows a depth-resolved visualization of the retinal and choroidal microvasculature, by calculating the difference (decorrelation) between static and nonstatic tissue. Given that the main moving elements in the eye fundus are contained in vessels, determining a vascular decorrelation signal permits a three-dimensional visualization of the retinal and choroidal vascular network without the administration of an intravenous dye. Moreover, a complete morphofunctional assessment may help in defining both the origin and the clinical activity of different vascular diseases such as diabetic retinopathy.

Evaluation of pseudophakic cystoid macular edema using optical coherence tomography angiography.

PURPOSE: To compare the optical coherence tomography angiography (OCT-A) findings of the superficial capillary plexus (SCP) and deep capillary plexus (DCP) in eyes with pseudophakic cystoid macular edema (PCME) with those of fluorescein angiography (FA) and spectral-domain optical coherence tomography (SD-OCT) and to compare PCME vascular density values of the SCP and DCP with those of healthy eyes. METHODS: In this retrospective observational study, 13 eyes (12 patients) with PCME underwent comprehensive ophthalmologic examinations including visual acuity, FA, SD-OCT, and OCT-A. The vascular density of the SCP and DCP were measured using AngioAnalytics software in all PCME eyes and compared with 46 healthy eyes of 25 subjects. RESULTS: In patients with PCME, at the level of SCP, the mean vascular density in the whole en face image was 44.48 ± 3.61% while it was 50.27 ± 5.30% at the level of the DCP. In contrast, the vascular density in the whole en face image was 50.35 ± 3.22 at the level of SCP while it was 56.15 ± 3.28 at the level of DCP in 46 healthy eyes of 25 subjects. The vascular density of patients with PCME was significantly lower than in healthy subjects at the SCP (p<0.0001) and at the DCP (p<0.0001). CONCLUSION: We report the OCT-A appearance of PCME and vascular density map with values that can be easily interpreted for quantitative evaluation of retina perfusion status using OCT-A. This approach might be the first step in helping us fully understand the pathophysiologic mechanisms underlying PCME.