Ultra-widefield Fluorescein Angiography Images Research Articles

Reassessment of arterial versus venous perfusion of diabetic retinal neovascularization using ultrawide-field fluorescein angiography.

The purpose of this study was to assess whether diabetic NV is perfused by the arterial or the venous circulation. This is a retrospective, consecutive case series evaluating patients with proliferative diabetic retinopathy (PDR) imaged with ultrawide-field (UWF) fluorescein angiography (FA). Areas of neovascularization elsewhere (NVE) and neovascularization of the disc (NVD) were assessed. Perfusion was defined as arterial, arteriovenous, or venous if the area of diabetic neovascularization (NV) began to hyperfluoresce either prior, during, or after laminar venous flow, respectively. A total of 180 eyes from 176 patients with 928 NV were identified (830 NVE, 98 NVD). Of those, 5.1% of NVE were classified as arterial and 58.2% of NVD were classified as arterial. The remaining NV were classified as arteriovenous except for a small subset (6.1%) which were indeterminate. None of the NV were classified as venous. Noteworthy examples demonstrated NV that nearly fully perfused prior to any detectable fluorescence within nearby veins as well as clear shunting of blood from a feeding artery to a draining vein. UWF FA images suggest that some NV is perfused by retinal arteries. This may be useful in devising strategies for early detection and treatment of NV precursors. What is known • Diabetic retinal neovascularization has long been thought to be perfused by the retinal venous circulation. • Vascular endothelial growth factor has been shown to play key roles in both angiogenesis and arteriogenesis. What is new • Ultrawide-field fluorescein angiography demonstrates that at least some diabetic neovascularization is perfused by the retinal arterial circulation. • This supports the hypothesis that diabetic neovascularization may arise from arterially-perfused intraretinal microvascular abnormalities in the capillary bed.

Assessment of Baseline Ultrawidefield Fluorescein Angiographic Quantitative Leakage Parameters with Ultrawidefield Fundus Features and Clinical Parameters in Diabetic Retinopathy in Protocol AA

PurposeEvaluate quantitative leakage parameters on ultra-widefield fluorescein angiography (UWF-FA) images and explore their association with Diabetic Retinopathy Severity Scale (DRSS), predominantly peripheral lesions (PPLs), visual acuity, and clinical characteristics. DesignA post-hoc analysis of baseline UWF-FA images in the DRCR Retina Network observational study Protocol AA. ParticipantsN = 575 eyes from 384 adults across 38 sites in the US and Canada with gradable UWF-FA. MethodsA machine learning-enhanced feature extraction platform provided initial leakage segmentation of UWF-FA images sequentially reviewed and corrected by two certified readers for segmentation accuracy. UWF-FA leakage was measured in five retinal zones: panretinal (whole retina), central macular (3-disc diameter fovea-centered circle), posterior pole (6-disc diameter fovea-centered circle), peripheral (outside 6-disc diameter circle) and widefield far peripheral (outside 9-disc diameter circle); associations with clinical factors were evaluated with marginal beta regression models. Main Outcome MeasuresUWF-FA leakage index, calculated as the area with leakage divided by the analyzable retinal area. ResultsThe mean quantitative leakage index was 3.5% for panretinal, 6.6% for macular, 4.8% for posterior pole, 3.3% for peripheral and 2.8% for wide-field far peripheral retinal zones. Panretinal leakage was associated with DRSS (mean 2.2% for no to mild NPDR, 3.4% for moderate NPDR, 4.2% for moderately severe NPDR, 4.8% for severe NPDR and 5.1% for PDR; P<.001), HbA1c (3.2% for HbA1c <8% vs. 3.8% for HbA1c ≥8%; P=.01 for continuous HbA1c), visual acuity (3.3% for 20/25 or better vs. 4.7% for 20/32 or worse; continuous P<.001), and UWF-FA-PPL types of IRMA (4.3% vs. 3.3%; P=.005) or NVE (5.7% vs. 3.4%; P=.003). DRSS was also statistically significant for leakage within all retinal zones (P<.001); eyes with non-central DME versus no DME had higher mean leakage in the central macular (11.2% vs. 5.9%; P=0.005) and posterior pole regions (9.2% vs. 4.2%; P=.002). ConclusionQuantitative UWF-FA leakage analysis identified associations between leakage and DRSS, visual acuity, and presence of DME. In the future, quantitative UWF-FA leakage parameters may be explored as potential biomarkers for disease progression risk.

RELIABILITY OF CLINICAL GRADING OF DIABETIC RETINOPATHY COMPARED WITH GRADING OF ULTRA-WIDEFIELD IMAGES.

To evaluate the reliability of clinical grading of diabetic retinopathy (DR) severity compared with grading on ultra-widefield pseudocolor fundus (UWF-CF) and ultra-widefield fluorescein angiography (UWF-FA) images and their relative detection of sight-threatening DR and referable DR. A total of 184 diabetic eyes were analyzed. UWF-CF and UWF-FA images were graded based on the International Clinical Diabetic Retinopathy severity scale. Agreement between clinical and UWF-based severity grading was evaluated using Cohen's kappa coefficient. The rate of sight-threatening DR and referable DR was evaluated for each grading method. Moderate agreement was found between clinical grading and UWF-CF (k = 0.456, P < 0.001) and between UWF-CF and UWF-FA (k = 0.443, P < 0.001). The agreement between clinical grading and UWF-FA was fair (k = 0.397, P < 0.001). UWF-based grading identified a higher DR grade in 56 eyes (30%) on UWF-CF and 85 eyes (46.2%) on UWF-FA. Compared with clinical grading, UWF-FA detected a higher rate of sight-threatening DR (44%; 81/184 vs. 22.3%; 41/184), while UWF-CF detected more referable eyes (58.1%; 107/184 vs. 45.65%; 84/184). Ultra-widefield pseudocolor fundus is a valuable tool for identifying referable eyes and can be a useful, noninvasive adjunct to clinical grading. The results suggest that UWF-FA is particularly useful for detecting unsuspected sight-threatening DR in eyes with clinically referable DR.

Ultrawide-field fluorescein angiography features in patients with anterior uveitis

PurposeTo evaluate the utility of ultrawide-field fluorescein angiography (UWFFA) in patients with anterior uveitis by investigating the detection of retinal vascular leakage (RVL) and the subsequent implications on disease diagnosis and management.Study design/materials and methodsPatients, who were referred to the National Eye Institute (NEI) for evaluation of anterior uveitis and underwent UWFFA imaging at the initial visit, were included in this study. The electronic medical records of eligible patients were reviewed. The UWFFA images were assessed for severity of retinal vascular leakage, presence of macular leakage, and optic disc leakage by a two-grader system, and intergrader agreement was calculated using the κ-value. Patients with altered diagnoses and management attributable to UWFFA results were noted.ResultsA total of 93 eyes of 63 patients were included in the study. Of 93 eyes, 31 (33.3%) eyes had RVL on UWFFA, with 26 (28.0%) eyes and 5 (5.4%) eyes showing mild and moderate-severe RVL, respectively. Twenty-five (26.9%) eyes showed macular leakage, and 7 (7.5%) eyes showed optic disc leakage. The κ-values ranged from 0.85 – 0.87 indicating excellent intergrader agreement. Of the 31 eyes with RVL, the diagnosis was changed to anterior/intermediate uveitis for 9 (29.0%) eyes and to panuveitis for 4 (12.9%) eyes. Systemic treatment was escalated in 5 patients.ConclusionOur results suggest that UWFFA imaging is useful in detecting subclinical posterior involvement in patients with anterior uveitis. Moreover, UWFFA results in altered diagnosis and treatment approaches in a portion of patients.

Macula vs periphery in diabetic retinopathy: OCT-angiography and ultrawide field fluorescein angiography imaging of retinal non perfusion.

To investigate the association between peripheral non-perfusion index (NPI) on ultrawide-field fluorescein angiography (UWF-FA) and quantitative OCT-Angiography (OCT-A) metrics in the macula. In total, 48 eyes with UWF-colour fundus photos (CFP), UWF-FA (California, Optos) and OCT-A (Spectralis, Heidelberg) were included. OCT-A (3 × 3 mm) was used to determine foveal avascular zone (FAZ) parameters and vessel density (VD), perfusion density (PD), fractal dimension (FD) on superficial capillary plexus (SCP). NPI's extent and distribution was determined on UWF-FA within fovea centred concentric rings corresponding to posterior pole (<10 mm), mid-periphery (10-15 mm), and far-periphery (>15 mm) and within the total retinal area, the central macular field (6×6 mm), ETDRS fields and within each extended ETDRS field (P3-P7). Macular PD was correlated to NPI in total area of retina (Spearman ρ = 0.69, p < 0.05), posterior pole (ρ = 0.48, p < 0.05), mid-periphery (ρ = 0.65, p < 0.05), far-periphery (ρ = 0.59, p < 0.05), P3-P7 (ρ = 0,55 at least, p < 0.05 for each), central macula (ρ = 0.47, p < 0.05), total area in ETDRS (ρ = 0.55, p < 0.05). Macular VD and FD were correlated to NPI of total area of the retina (ρ = 0.60 and 0.61, p < 0.05), the mid-periphery (ρ = 0.56, p < 0.05) and far-periphery (ρ = 0.60 and ρ = 0.61, p < 0.05), and in P3-P7 (p < 0.05). FAZ perimeter was significantly corelated to NPI at posterior pole and central macular area (ρ = 0.37 and 0.36, p < 0.05), and FAZ area to NPI in central macular area (ρ = 0.36, p < 0.05). Perfusion macular metrics on OCT-A correlated with UWF-FA's non-perfusion (NP), particularly in the retina's mid and far periphery, suggesting that OCT-A might be a useful non-invasive method to estimate peripheral retinal NP.

Relationship between ischemic index, leakage index, and macular edema in branch retinal vein occlusion.

To investigate the combined association of the ischemic index and leakage index with macular edema on ultra-widefield fluorescein angiography (UWFFA) in patients with branch retinal vein occlusion (BRVO). Retrospective image analysis study. The leakage index and ischemic index were calculated using Fiji after aligning early and late UWFFA images. Differences in the ischemic index, leakage index, and central macular thickness (CMT) between ischemic and non-ischemic BRVO were compared. Moreover, the association between the ischemic index, leakage index, and macular edema was analyzed. Eighty-three patients with BRVO were enrolled, including 53 non-ischemic BRVO and 30 ischemic BRVO patients. No significant differences were observed in leakage index and CMT between ischemic BRVO and non-ischemic BRVO (all P > 0.05). In all included patients, CMT correlated with the panretina and all subregion leakage indexes (all P < 0.01), but not with the ischemic index (all P > 0.05). In the ischemic BRVO group, CMT showed a correlation with the leakage index in several regions, but not with the ischemic index. After adjusting for the ischemic index and other clinical features, CMT remained significantly correlated with the leakage index in all regions. The leakage index may be a more effective biomarker for monitoring BRVO-associated macular edema compared to the ischemic index. Further follow-up studies are warranted to validate these findings.

Association between macrophage-like cell density and ischemia metrics in diabetic eyes

We previously showed that macrophage-like cells (MLCs) are increased in eyes with advanced diabetic retinopathy (DR). Here, we hypothesized that MLC density was correlated with ischemia using optical coherence tomography angiography (OCTA) and ultra-widefield fluorescein angiography (UWF-FA). Treatment-naïve diabetic eyes were prospectively imaged with repeated OCTA (average 5.3 scans per eye) and UWF-FA imaging. OCTA images were registered and averaged to generate a superficial capillary plexus (SCP), deep capillary plexus (DCP), and MLC slab. We calculated geometric perfusion deficit (GPD), vessel length density, and vessel density for the SCP and DCP. MLC density was quantified by two masked graders and averaged. Ischemia on UWF-FA was measured to generate a non-perfusion area (NPA) and index (NPI). Since MLC density was non-parametrically distributed, MLC density was correlated with ischemia metrics using Spearman correlations. Forty-five treatment-naïve eyes of 45 patients (59 ± 12 years of age; 56% female) were imaged. We included 6 eyes with no DR, 7 eyes with mild non-proliferative DR (NPDR), 22 moderate NPDR, 4 severe NPDR, and 6 PDR eyes. MLC density between graders was highly correlated (r = 0.9592, p < 0.0001). MLC density was correlated with DCP GPD (r = 0.296, p = 0.049), but no other OCTA ischemia metrics. MLC density was also correlated with UWF-FA NPA (r = 0.330, p = 0.035) and NPI (r = 0.332, p = 0.034). MLC density was correlated with total ischemia on UWF-FA and local DCP GPD. Since both UWF-FA and DCP non-perfusion are associated with higher risk for DR progression, MLC density could be another potential biomarker for DR progression.

Distribution of leakage index using ultra-widefield fluorescein angiography in patients with non-ischemic branch retinal vein occlusion and its association with macular edema

BackgroundTo investigate the distribution of leakage index in patients with non-ischemic branch retinal vein occlusion (BRVO) and its correlation with the severity of macular edema. MethodsRetrospective observational study. Forty-five eyes of 45 patients with BRVO were included. Late ultra-widefield fluorescein angiography images of the affected eyes were processed and analyzed for their leakage index using Fiji software. The visible panretinal area was further divided into the peri‑macular area (PMA), near-peripheral area (NPA), midperipheral area (MPA), and far-peripheral area (FPA). The relationship between the leakage index and central retinal thickness (CMT) was analyzed for the panretina and each subregion. ResultsThe median (interquartile range) leakage indexes of the panretina, PMA, NPA, MPA, and FPA were 5.532% (7.667%), 23.127% (26.073%), 8.303% (16.807%), 1.588% (6.204%), and 0.408% (2.215%), respectively, with a mean CMT of 552.800 ± 183.335 μm. The CMT was positively correlated with the leakage index in the panretina, PMA, NPA, MPA and FPA (r = 0.468, 0.426, 0.463, 0.447, 0.320, respectively; all p < 0.05). ConclusionsThe leakage index in non-ischemic BRVO patients is associated with macular edema severity. The leakage index has the potential to be a useful indicator for monitoring and guiding treatment of macular edema in BRVO patients.

Deep learning for automated detection of neovascular leakage on ultra-widefield fluorescein angiography in diabetic retinopathy

Diabetic retinopathy is a leading cause of blindness in working-age adults worldwide. Neovascular leakage on fluorescein angiography indicates progression to the proliferative stage of diabetic retinopathy, which is an important distinction that requires timely ophthalmic intervention with laser or intravitreal injection treatment to reduce the risk of severe, permanent vision loss. In this study, we developed a deep learning algorithm to detect neovascular leakage on ultra-widefield fluorescein angiography images obtained from patients with diabetic retinopathy. The algorithm, an ensemble of three convolutional neural networks, was able to accurately classify neovascular leakage and distinguish this disease marker from other angiographic disease features. With additional real-world validation and testing, our algorithm could facilitate identification of neovascular leakage in the clinical setting, allowing timely intervention to reduce the burden of blinding diabetic eye disease.

ULTRA-WIDEFIELD OPTICAL COHERENCE TOMOGRAPHY ANGIOGRAPHY IN MILD FAMILIAL EXUDATIVE VITREORETINOPATHY.

To investigate ultra-widefield optical coherence tomography angiography (UWF-OCTA) to detect and evaluate mild familial exudative vitreoretinopathy and compare the detective ratio of UWF-OCTA with ultra-widefield scanning laser ophthalmoscopy and ultra-widefield fluorescein angiography. The patients with familial exudative vitreoretinopathy were included in this study. UWF-OCTA, using a 24- × 20-mm montage, was performed for all patients. All images were independently tested for the presence of familial exudative vitreoretinopathy-associated lesions. Statistical analysis was performed with SPSS V.24.0. Forty-six eyes of 26 participants were included in the study. Ultra-widefield optical coherence tomography angiography was found to be greatly superior to ultra-widefield scanning laser ophthalmoscopy in detecting peripheral retinal vascular abnormality ( P < 0.001) and peripheral retinal avascular zone ( P < 0.001). The detection rates of peripheral retinal vascular abnormality, peripheral retinal avascular zone, retinal neovascularization, macular ectopia, and temporal midperipheral vitreoretinal interface abnormality were comparable with ultra-widefield fluorescein angiography images ( P > 0.05). Furthermore, vitreoretinal traction (17/46, 37%) and small foveal avascular zone (17/46, 37%) were detected effectively on UWF-OCTA. Ultra-widefield optical coherence tomography angiography is a reliable noninvasive tool to detect familial exudative vitreoretinopathy lesions, especially in mild patients or asymptomatic family members. The unique manifestation of UWF-OCTA offers an alternative to ultra-widefield fluorescein angiography for the screening and diagnosis of FEVR.

Non-perfusion severity correlates with central macular thickness and microvascular impairment in branch retinal vein occlusions.

To study peripheral capillary non-perfusion (PCN-P) in branch retinal vein occlusion (BRVO) by means of ultra wide-field fluorescein angiography (UWFFA), and to correlate its extent and severity with optical coherence tomography (OCT) and OCT-angiography (OCTA) parameters and best corrected visual acuity (BCVA). Prospective case series with 2 years of planned follow-up. We recruited patients from June 2019 to December 2019. Ophthalmologic examination included BCVA, UWFFA, OCT and OCTA. Partial (p) and complete (c) ischemic index (ISI) were evaluated on UWFFA images. Vessel density (VD) in both the macular region and the optic nerve head (ONH) was calculated. Twelve BRVO subjects and 12 healthy controls were recruited. Mean age was 63.8 ± 8.74 years. Mean BCVA improved from 0.43 ± 0.25 logMAR to 0.15 ± 0.18 after two years (p < 0.01), while mean central macular thickness (CMT) decreased from 463.83 ± 200.85 µm to 353.17 ± 108.85 µm (p > 0.05). Mean cISI, pISI and total ISI were 25.2 ± 13.0%, 6.3 ± 5.0% and 31.5 ± 12.0%, respectively. Except for VDs of the superficial capillary plexus and choriocapillaris in the macular region, all VDs were lower in the BRVO group (p < 0.01). cISI and tISI negatively correlated with mDCP (p < 0.01), whereas only pISI correlated with CMT at baseline (p < 0.05). Additionally, cISI also negatively correlated with VD at the ONH (p < 0.05). The amount of complete and partial ischemia may have different implications in BRVO, with the former being more associated with microvascular impairment and the latter with macular edema.

Retinal neovascularization as self-organized criticality on ultra-widefield fluorescein angiography imaging of diabetic retinopathy.

Do the distributions of surface area of non-perfusion (NP) and neovascularization (NV) on ultra-widefield fluorescein angiography (UWF FA) in patients with diabetic retinopathy (DR) differ significantly? Inclusion criteria were patients who had a UWF FA taken for DR at the Kellogg Eye Center from January 2009 to May 2018. Exclusion criteria included previous panretinal photocoagulation and significant media opacity (e.g., vitreous haemorrhage or significant cataract). UWF FAs were manually segmented for surface areas of NP and NV. The total areas per patient were organized in a histogram, and logarithmically binned to test against power law and exponential distributions. Then, a computational model was constructed in Python 3.7 to suggest a mechanistic explanation for the observed distributions. Analysis of areas of NV across 189 images demonstrated a superior fit by the least squares method to a power law distribution (p = 0.014) with an R2 fit of 0.9672. Areas of NP over 794 images demonstrated a superior fit with an exponential distribution instead (p = 0.011). When the far periphery was excluded, the R2 fit for the exponential distribution was 0.9618. A computational model following the principles of self-organized criticality (SOC), akin to earthquake and forest fire models, matched these datasets. These distributions inform what useful statistics may be applied to study of these imaging characteristics. Further, the difference in event distribution between NV and NP suggests that the two phenomena are mechanistically distinct. NV may follow SOC, propagating as a catastrophic event in an unpredictable manner.

Quantitative Analysis of Retinal Vascular Leakage in Retinal Vasculitis Using Machine Learning

Retinal vascular leakage is known to be an important biomarker to monitor the disease activity of uveitis. Although fluorescein angiography (FA) is a gold standard for the diagnosis and assessment of the disease activity of uveitis, the evaluation of FA findings, especially retinal vascular leakage, remains subjective and descriptive. In the current study, we developed an automatic segmentation model using a deep learning system, U-Net, and subtraction of the retinal vessel area between early-phase and late-phase FA images for the detection of the retinal vascular leakage area in ultrawide field (UWF) FA images in three patients with Behçet’s Disease and three patients with idiopathic uveitis with retinal vasculitis. This study demonstrated that the automated model for segmentation of the retinal vascular leakage area through the UWF FA images reached 0.434 (precision), 0.529 (recall), and 0.467 (Dice coefficient) without using UWF FA images for training. There was a significant positive correlation between the automated segmented area (pixels) of retinal vascular leakage and the FA vascular leakage score. The mean pixels of automatic segmented vascular leakage in UWF FA images with treatment was significantly reduced compared with before treatment. The automated segmentation of retinal vascular leakage in UWF FA images may be useful for objective and quantitative assessment of disease activity in posterior segment uveitis. Further studies at a larger scale are warranted to improve the performance of this automatic segmentation model to detect retinal vascular leakage.

Automated segmentation of ultra-widefield fluorescein angiography of diabetic retinopathy using deep learning

Background/AimsRetinal capillary non-perfusion (NP) and neovascularisation (NV) are two of the most important angiographic changes in diabetic retinopathy (DR). This study investigated the feasibility of using deep learning (DL) models...

RETINAL VASCULAR BED AREA IN EYES WITH RETINAL VEIN OCCLUSION ON ULTRA-WIDEFIELD FLUORESCEIN ANGIOGRAPHY: WAVE Study.

To compute retinal vascular bed area (RVBA) in square millimeters on distortion corrected ultra-widefield fluorescein angiography images in eyes with retinal vein occlusion (RVO). Prospective observational study. The peripheral distortion of baseline ultra-widefield fluorescein angiography (Optos 200Tx) images of 30 patients with RVO from the WAVE study (NCT01710839) and 13 control eyes of normal subjects was corrected using the stereographic projection method to compute RVBA in square millimeters. In comparison with age- and sex-matched normal control eyes, eyes with RVO had a decreased global RVBA for the entire retina (50.5 ± 20.4 mm 2 vs. 62.6 ± 12.2 mm 2 , P = 0.023). Eyes with RVO and the unaffected fellow eye had a similar RVBA globally (50.5 ± 20.4 mm 2 vs. 46.2 ± 18.9 mm 2 , P = 0.523). The RVBA was observed to negatively correlate with nonperfusion area (R = -0.47, P = 0.009). However, RVBA was not related to the severity of macular edema ( P > 0.05). Eyes with RVO have a similar RVBA to the unaffected fellow eyes but with a reduction when compared with normal control eyes. Retinal vascular bed area appears to be a surrogate biomarker of retinal ischemia on ultra-widefield fluorescein angiography but not the extent of macular edema.

Association of Ultra-Widefield Fluorescein Angiography–Identified Retinal Nonperfusion and the Risk of Diabetic Retinopathy Worsening Over Time

Presence of predominantly peripheral diabetic retinopathy (DR) lesions on ultra-widefield fluorescein angiography (UWF-FA) was associated with greater risk of DR worsening or treatment over 4 years. Whether baseline retinal nonperfusion assessment is additionally predictive of DR disease worsening is unclear. To assess whether the extent and location of retinal nonperfusion identified on UWF-FA are associated with worsening in Diabetic Retinopathy Severity Scale (DRSS) score or DR treatment over time. This cohort study was a prospective, multicenter, longitudinal observational study with data for 508 eyes with nonproliferative DR and gradable nonperfusion on UWF-FA at baseline. All images were graded at a centralized reading center; 200° ultra-widefield (UWF) color images were graded for DR at baseline and annually for 4 years. Baseline 200° UWF-FA images were graded for nonperfused area, nonperfusion index (NPI), and presence of predominantly peripheral lesions on UWF-FA (FA PPL). Treatment of DR or diabetic macular edema was at investigator discretion. Association of baseline UWF-FA nonperfusion extent with disease worsening, defined as either 2 or more steps of DRSS worsening within Early Treatment Diabetic Retinopathy Study fields on UWF-color images or receipt of DR treatment. After adjusting for baseline DRSS, the risk of disease worsening over 4 years was higher in eyes with greater overall NPI (hazard ratio [HR] for 0.1-unit increase, 1.11; 95% CI, 1.02-1.21; P = .02) and NPI within the posterior pole (HR for 0.1-unit increase, 1.35; 95% CI, 1.17-1.56; P < .001) and midperiphery (HR for 0.1-unit increase, 1.08; 95% CI, 1.00-1.16; P = .04). In a multivariable analysis adjusting for baseline DRSS score and baseline systemic risk factors, greater NPI (HR, 1.11; 95% CI, 1.02-1.22; P = .02) and presence of FA PPL (HR, 1.89; 95% CI, 1.35-2.65; P < .001) remained associated with disease worsening. This 4-year longitudinal study has demonstrated that both greater baseline retinal nonperfusion and FA PPL on UWF-FA are associated with higher risk of disease worsening, even after adjusting for baseline DRSS score and known systemic risk. These associations between disease worsening and retinal nonperfusion and FA PPL support the increased use of UWF-FA to complement color fundus photography in future efforts for DR prognosis, clinical care, and research.

NEW BIOMARKER QUANTIFYING THE EFFECT OF ANTI-VEGF THERAPY IN EYES WITH PROLIFERATIVE DIABETIC RETINOPATHY ON ULTRAWIDE FIELD FLUORESCEIN ANGIOGRAPHY: RECOVERY Study.

To quantify changes of the retinal vascular bed area (RVBA) in mm2 on stereographically projected ultrawide field fluorescein angiography images in eyes with proliferative diabetic retinopathy after antivascular endothelial growth factor injection. This is a prospective, observational study. The early-phase ultrawide field fluorescein angiography images (Optos 200Tx) of 40 eyes with proliferative diabetic retinopathy and significant nonperfusion obtained at baseline and after six months (NCT02863354) were stereographically projected by correcting peripheral distortion. The global retinal vasculature on ultrawide field fluorescein angiography was extracted for calculating RVBA by summing the real size (mm2) of all the pixels automatically. For the entire cohort, the global RVBA for the entire retina decreased from 67.1 ± 15.5 to 43.6 ± 18.8 mm2 after anti-VEGF treatment at six months (P < 0.001). In the subgroup receiving monthly anti-VEGF injections, the global RVBA decreased from 68.7 ± 16.2 to 33.9 ± 13.3 mm2 (P < 0.001). In the subgroup receiving anti-VEGF every three months, the global RVBA decreased from 65.6 ± 15.1 to 50.8 ± 19.3 mm2 (P = 0.004). RVBA seems to be a new biomarker to indicate efficiency of retinal vascular changes after anti-VEGF injection. Eyes with proliferative diabetic retinopathy and significant nonperfusion demonstrate reduced RVBA after anti-VEGF treatment.

Ultra-Widefield Fluorescein Angiography Image Brightness Compensation Based on Geometrical Features

Ultra-widefield fluorescein angiography (UWFA) is an emerging imaging modality used to characterise pathologies in the retinal vasculature, such as microaneurysms (MAs) and vascular leakages. Despite its potential value for diagnosis and disease screening, objective quantitative assessment of retinal pathologies by UWFA is currently limited because laborious manual processing is required. In this report, we describe a geometrical method for uneven brightness compensation inherent to UWFA imaging technique. The correction function is based on the geometrical eyeball shape, therefore it is fully automated and depends only on pixel distance from the center of the imaged retina. The method’s performance was assessed on a database containing 256 UWFA images with the use of several image quality measures that show the correction method improves image quality. The method is also compared to the commonly used CLAHE approach and was also employed in a pilot study for vascular segmentation, giving a noticeable improvement in segmentation results. Therefore, the method can be used as an image preprocessing step in retinal UWFA image analysis.

Quantitative analysis of retinal vasculature in normal eyes using ultra-widefield fluorescein angiography.

To quantify the area and density of retinal vascularity by ultra-widefield fluorescein angiography (UWFA). In a retrospective study, UWFA images were obtained using an ultra-widefield imaging device in 42 normal eyes of 42 patients. Central and peripheral steered images were used to define the edge of retinal vasculature by a certified grader. The length from the center of the optic disc to the edge of retinal vascularity (RVL) in each quadrant and the total retinal vascular perfusion area (RVPA) were determined by the grader using OptosAdvance software. The density of retinal vascularity (RVD) was quantified in different zones of central-steered images using Image J software. Among 42 healthy eyes, the values for mean RVL in each quadrant were 19.007±0.781 mm (superior), 18.467±0.869 mm (inferior), 17.738±0.622 mm (nasal) and 24.241±1.336 mm (temporal). The mean RVPA was 1140.117±73.825 mm2. The mean RVD of the total retina was 4.850%±0.638%. RVD varied significantly between different retina zones (P<0.001), and significant differences existed in the RVD values for total retinal area in patients over 50 years old compared to those under 50 years old (P=0.033). No gender difference was found. The UWFA device can be a promising tool for analyzing the overall retinal vasculature and may provide a better understanding of retinal vascular morphology in normal eyes. Aging may be related to lower RVD.

Automated Grading of Diabetic Retinopathy with Ultra-Widefield Fluorescein Angiography and Deep Learning.

Purpose The objective of this study was to establish diagnostic technology to automatically grade the severity of diabetic retinopathy (DR) according to the ischemic index and leakage index with ultra-widefield fluorescein angiography (UWFA) and the Early Treatment Diabetic Retinopathy Study (ETDRS) 7-standard field (7-SF). Methods This is a cross-sectional study. UWFA samples from 280 diabetic patients and 119 normal patients were used to train and test an artificial intelligence model to differentiate PDR and NPDR based on the ischemic index and leakage index with UWFA. A panel of retinal specialists determined the ground truth for our data set before experimentation. A confusion matrix as a metric was used to measure the precision of our algorithm, and a simple linear regression function was implemented to explore the discrimination of indexes on the DR grades. In addition, the model was tested with simulated 7-SF. Results The model classification of DR in the original UWFA images achieved 88.50% accuracy and 73.68% accuracy in the simulated 7-SF images. A simple linear regression function demonstrated that there is a significant relationship between the ischemic index and leakage index and the severity of DR. These two thresholds were set to classify the grade of DR, which achieved 76.8% accuracy. Conclusions The optimization of the cycle generative adversarial network (CycleGAN) and convolutional neural network (CNN) model classifier achieved DR grading based on the ischemic index and leakage index with UWFA and simulated 7-SF and provided accurate inference results. The classification accuracy with UWFA is slightly higher than that of simulated 7-SF.