Neovascularization detection in diabetic retinopathy from fluorescein angiograms.
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ABSTRACT:
SUBMITTER: Beouche-Helias B
PROVIDER: S-EPMC5689132 | biostudies-literature | 2017 Oct
REPOSITORIES: biostudies-literature
Publications
Neovascularization detection in diabetic retinopathy from fluorescein angiograms.
Béouche-Hélias Benjamin B Helbert David D de Malézieu Cynthia C Leveziel Nicolas N Fernandez-Maloigne Christine C
Journal of medical imaging (Bellingham, Wash.) 20171001 4
Although a lot of work has been done on optical coherence tomography and color images in order to detect and quantify diseases such as diabetic retinopathy, exudates, or neovascularizations, none of them is able to evaluate the diffusion of the neovascularizations in retinas. Our work has been to develop a tool that is able to quantify a neovascularization and the fluorescein leakage during an angiography. The proposed method has been developed following a clinical trial protocol; images are tak ...[more]
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Project description:PurposeThe apoptosis of human umbilical vein endothelial cells has been reportedly induced by the protein transthyretin (TTR). In human ocular tissue, TTR is generally considered to be secreted mainly by retinal pigment epithelial cells (hRPECs); however, whether TTR affects the development of neovascularization in diabetic retinopathy (DR) remains unclear.MethodsNatural and simulated DR media were used to culture human retinal microvascular endothelial cells (hRECs). Hyperglycemia was simulated by increasing the glucose concentration from 5.5 mM up to 25 mM, while hypoxia was induced with 200 µM CoCl2. To understand the effects of TTR on hRECs, cell proliferation was investigated under natural and DR conditions. Overexpression of TTR, an in vitro wound-healing assay, and a tube formation assay were employed to study the repression of TTR on hRECs. Real-time fluorescence quantitative PCR (qRT-PCR) was used to study the mRNA levels of DR-related genes, such as Tie2, VEGFR1, VEGFR2, Angpt1, and Angpt2.ResultsThe proliferation of hRECs was significantly decreased in the simulated hyperglycemic and hypoxic DR environments. The cells were further repressed by added exogenous or endogenous TTR only under hyperglycemic conditions. The in vitro migration and tube formation processes of the hRECs were inhibited with TTR; furthermore, in the hyperglycemia and hyperglycemia/hypoxia environments, the levels of Tie2 and Angpt1 mRNA were enhanced with exogenous TTR, while those of VEGFR1, VEGFR2, and Angpt1 were repressed.ConclusionsIn hyperglycemia, the proliferation, migration, and neovascularization of hRECs were significantly inhibited by TTR. The key genes for DR neovascularization, including Tie2, VEGFR1, VEGFR2, Angpt1, and Angpt2, were regulated by TTR. Under DR conditions, TTR significantly represses neovascularization by inhibiting the proliferation, migration and tube formation of hRECs.
| S-EPMC5063089 | biostudies-literature
Project description:PurposeTo investigate the correlation between quantifiable vessel density, computed in an automated fashion, from ultra-widefield fluorescein angiography (UWFFA) images from patients with proliferative diabetic retinopathy (PDR) with visual acuity and macular thickness.MethodsWe performed a secondary analysis of a prospective randomized controlled trial. We designed and trained an algorithm to automate retinal vessel detection from input UWFFA images. We then used our algorithm to study the correlation between baseline vessel density and best corrected visual acuity (BCVA) and CRT for patients in the RECOVERY study. Reliability of the algorithm was tested using the intraclass correlation (ICC). 42 patients from the Intravitreal Aflibercept for Retinal Non-Perfusion in Proliferative Diabetic Retinopathy (RECOVERY) trial who had both baseline UWFFA images and optical coherence tomography (OCT) data were included in our study. These patients had PDR without significant center-involving diabetic macular edema (central retinal thickness [CRT] ≤320μm).ResultsOur algorithm analyzed UWFFA images with a reliability measure (ICC) of 0.98. A positive correlation (r = 0.4071, p = 0.0075) was found between vessel density and BCVA. No correlation was found between vessel density and CRT.ConclusionsOur algorithm is capable of reliably quantifying vessel density in an automated fashion from baseline UWFFA images. We found a positive correlation between computed vessel density and BCVA in PDR patients without center-involving macular edema, but not CRT.Translational relevanceOur work is the first to offer an algorithm capable of quantifying vessel density in an automated fashion from UWFFA images, allowing us to work toward studying the relationship between retinal vascular changes and important clinical endpoints, including visual acuity, in ischemic eye diseases.
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Project description:BackgroundRetinal neovascularization, which is characterized by the increased proliferation, migration, and tube formation of retinal microvascular endothelial cells (RMECs), contributes to the progression of diabetic retinopathy (DR). MiR-409-5p has been reported to be upregulated in peripheral blood of DR patients and in vascular endothelial growth factor (VEGF)-induced RMECs. However, the role of miR-409-5p in retinal neovascularization of DR remains unelucidated.MethodThe expression of miR-409-5p was measured in retinal tissues of streptozocin-induced and db/db diabetic mice, in high glucose-induced mouse RMECs (mRMECs), and in vitreous fluid of proliferative DR patients. Antagomir of miR-409-5p was intravitreally injected into diabetic mice. Proliferation, migration, and tube formation were detected using cell counting kit-8 assay, transwell assay, and microscope observation, respectively. Luciferase reporter assay was used to detect the direct interaction between miR-409-5p and peroxisome proliferator-activated receptor-α (PPARα).ResultMiR-409-5p was upregulated in retinal tissues of diabetic mice, in high glucose-induced mRMECs, and in vitreous fluid of proliferative DR patients. The knockdown of miR-409-5p attenuated retinal neovascularization in vivo. The overexpression of miR-409-5p promotes the proliferation, migration, and tube formation, and increased VEGF expression and secretion, while the knockdown of miR-409-5p suppressed the VEGF-induced retinal neovascularization in vitro. PPARα is a downstream target of miR-409-5p, and PPARα overexpression negated the promotion of miR-409-5p overexpression on the proliferation, migration, and tube formation of mRMECs.ConclusionOur findings demonstrated that miR-409-5p acted as a neovasculogenic factor in DR, and anti-miR-409-5p therapy may provide a novel strategy in treating DR.
| S-EPMC7469530 | biostudies-literature
Project description:The detection and assessment of intravascular filling defects is important, because they may represent a process central to cerebral malaria pathogenesis: neurovascular sequestration. We have developed and validated a framework that can automatically detect intravascular filling defects in fluorescein angiogram images. It first employs a state-of-the-art segmentation approach to extract the vessels from images and then divide them into individual segments by geometrical analysis. A feature vector based on the intensity and shape of saliency maps is generated to represent the level of abnormality of each vessel segment. An AdaBoost classifier with weighted cost coefficient is trained to classify the vessel segments into normal and abnormal categories. To demonstrate its effectiveness, we apply this framework to 6,358 vessel segments in images from 10 patients with malarial retinopathy. The test sensitivity, specificity, accuracy, and area under curve (AUC) are 74.7%, 73.5%, 74.1% and 74.2% respectively when compared to the reference standard of human expert manual annotations. This performance is comparable to the agreement that we find between human observers of intravascular filling defects. Our method will be a powerful new tool for studying malarial retinopathy.
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Project description:Diabetic retinopathy (DR) is the most common microangiopathic complication of diabetes mellitus, representing a major cause of visual impairment in developed countries. Proliferative DR (PDR) represents the last stage of this extremely complex retinal disease, characterized by the development of neovascularization induced by the abnormal production and release of vascular endothelial growth factor (VEGF). The term VEGF includes different isoforms; VEGF-A represents one of the most important pathogenic factors of DR. Anti-VEGF intravitreal therapies radically changed the outcome of DR, due to combined anti-angiogenic and anti-edematous activities. Nowadays, several anti-VEGF molecules exist, characterized by different pharmacological features and duration. With respect to PDR, although anti-VEGF treatments represented a fundamental step forward in the management of this dramatic complication, a big debate is present in the literature regarding the role of anti-VEGF as substitute of panretinal photocoagulation or if these two approaches may be used in combination. In the present review, we provided an update on VEGF isoforms and their role in DR pathogenesis, on current anti-VEGF molecules and emerging new drugs, and on the current management strategies of PDR. There is an overall agreement regarding the relative advantage provided by anti-VEGF, especially looking at the management of PDR patients requiring vitrectomy, with respect to laser. Based on the current data, laser approaches might be avoided when a perfectly planned anti-VEGF therapeutic strategy can be adopted. Conversely, laser treatment may have a role for those patients unable to guarantee enough compliance to anti-VEGF injections.Key messagesVEGF increased production, stimulated by retinal hypoperfusion and ischaemia, is a major pathogenic factor of neovascular complication onset in diabetic retinopathy and of DR stages progression.Nowadays, several anti-VEGF molecules are available in clinical practice and other molecules are currently under investigation. Each anti-VEGF molecule is characterized by different targets and may interact with multiple biochemical pathways within the eye.All the data agreed in considering anti-VEGF molecules as a first line choice for the management of diabetic retinopathy. Laser treatments may have a role in selected advanced cases and for those patients unable to guarantee enough compliance to intravitreal treatments schemes.
| S-EPMC9891228 | biostudies-literature
Project description:PurposeEvaluate association of retinal nonperfusion (NP) on ultrawide field (UWF) fluorescein angiography (FA) with diabetic retinopathy (DR) severity and predominantly peripheral lesions (PPL).MethodsMulticenter observational study, 652 eyes (361 participants) having nonproliferative DR (NPDR) without center-involved diabetic macular edema in at least one eye. Baseline 200° UWF-color and UWF-FA images were graded by a central reading center for color-PPL and FA-PPL, respectively. UWF-FA was graded for NP index within concentric zones: posterior pole (<10 mm from fovea), midperiphery (10-15 mm), and far periphery (>15 mm).ResultsBaseline Early Treatment Diabetic Retinopathy Study DR severity was 31.7% no DR/mild NPDR, 24.1% moderate NPDR, 14.0% moderately severe NPDR, 25.6% severe/very severe NPDR, and 4.6% proliferative DR. Worse DR severity was associated with increased NP index overall (P = 0.002), in the posterior pole (P < 0.001), midperiphery (P < 0.001), and far periphery (P = 0.03). On average, 29.6% of imaged retinal NP was in the posterior pole, 33.7% in midperiphery, and 36.7% in far periphery. Increased NP index was associated with FA-PPL (P < 0.001) but not with color-PPL (P = 0.65).ConclusionApproximately, 70% of NP in diabetic eyes is located outside the posterior pole. Increased NP is associated with the presence of FA-PPL, suggesting UWF-FA may better predict future DR worsening than UWF-color alone.
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Project description:BackgroundTo analyze the distribution of manifest lesions of diabetic retinopathy (DR) by fundus fluorescein angiography (FFA) and color fundus photography (FP).MethodsA total of 566 eyes of 324 Chinese patients diagnosed with DR were included in this retrospective study. DR severity was graded by the international grading criterion. The distributions of microaneurysms (MA), intraretinal hemorrhages/exudates (He/Ex), intraretinal microvascular abnormality (IRMA), capillary nonperfusion areas (NPA), and neovascularization (NV) were estimated by multiple logistic regression analyse based on nine-field FFA and FP images.ResultsIn mild nonproliferative diabetic retinopathy (NPDR), the highest frequency of MA was found in the posterior pole (67.7%), followed by the inferior nasal (59.4%), and the nasal (55.4%) fields. In moderate NPDR, MA frequently distributed in the posterior pole (98.0%), nasal (97.0%), superior (96.0%), inferior nasal (94.9%), and inferior (92.9%) fields, whereas He/Ex were most prevalent in the posterior pole (69.7%). In severe NPDR and proliferative DR, IRMA, NPA, and NV were more frequent in the nasal field, particularly in the inferior nasal field (60.3, 38.7, and 76.0%, respectively). All lesions were more observed in the combined posterior pole, nasal, and inferior nasal fields than in the posterior pole or combined two fields in the early and severe stages of DR (P < 0.05).ConclusionsThe manifest lesions of DR were common in the nasal field besides the posterior pole in Chinese patients. A combined examination of the posterior pole, nasal, and inferior nasal mid-peripheral retina would help to detect different retinal lesions of DR.Trial registrationClinicalTrial. gov, NCT03528720 . Registered 18 May 2018 - Retrospectively registered.
| S-EPMC7709243 | biostudies-literature
Project description:Background:Diabetic retinopathy (DR) is a leading cause of blindness due to diabetic macular edema (DME) or complications of proliferative diabetic retinopathy (PDR). Optical coherence tomography (OCT) is a noninvasive imaging technique well established for DME but less used to assess neovascularization in PDR. Developments in OCT imaging and the introduction of OCT angiography (OCTA) have shown significant potential in PDR. Objectives:To describe the tomographic features of PDR, namely of neovascularization, both of the optic disc (NVD) and elsewhere (NVE), intraretinal microvascular abnormalities (IRMA), retinal nonperfusion areas (NPA), status of the posterior vitreous, vitreoschisis and vitreous and subhyaloid/sub-ILM hemorrhages. Data sources:Electronic database search on PubMed and EMBASE, last run on December 19th 2019. Study eligibility criteria participants and interventions:Publications assessing OCT and/or OCTA findings in PDR patients. All study designs were allowed except for case-reports, conference proceedings and letters. Study appraisal:Newcastle-Ottawa Scale for observational studies was used for purposes of risk of bias assessment. Results:From the 1300 studies identified, 283 proceeded to full-text assessment and 60 were included in this comprehensive review. OCT was useful in detecting NVD and NVE, such as in characterizing disease activity and response to laser and/or anti-VEGF therapies. The absence of posterior vitreous detachment seemed determinant for neovascular growth, with the posterior hyaloid acting as a scaffold. OCTA allowed a more detailed characterization of the neovascular complexes, associated NPA and disease activity, allowing the quantification of neovessel area and flow index. However, changes in OCTA blood flow signal following local therapies did not necessarily correlate with structural regression. Widefield and ultra-widefield OCTA were highly sensitive in the detection of PDR, adding value to disease staging and monitoring. Compared to fluorescein angiography, OCTA was more sensitive in detecting microvascular changes indicating disease progression. Limitations:Publication languages were restricted. Most included studies were observational and non-comparative. Risk of bias regarding case representativeness. Conclusions:OCT-based retinal imaging technologies are advancing rapidly and the trend is to be noninvasive and wide-field. OCT has proven invaluable in diagnosing, staging and management of proliferative diabetic disease with daily application in clinical and surgical practices.
| S-EPMC7322867 | biostudies-literature
Project description:PurposeTo assess inter-rater reliability in the detection of proliferative diabetic retinopathy (PDR) changes using wide-field optical coherence tomography angiography (WF-OCTA) versus fluorescein angiography (FA).MethodsThis retrospective, cross-sectional study included patients with severe nonproliferative and PDR. Images were acquired with 12 × 12 mm WF-OCTA and FA with a 55° lens. Images were cropped to represent the exact same field of view. Qualitative (detection of neovascularization at the disc [NVD] and elsewhere [NVE], enlarged foveal avascular zone [FAZ], vitreous hemorrhage [VH]) and quantitative analyses (FAZ area, horizontal, vertical, and maximum FAZ diameter) were performed by 2 masked graders using ImageJ. Inter-rater reliability was calculated using unweighted Cohen's kappa coefficient (κ) for qualitative analyses and intraclass correlation coefficients (ICC) for quantitative analyses.ResultsTwenty-three eyes of 17 patients were included. Inter-rater reliability was higher for FA than for WF-OCTA in qualitative analyses: κ values were 0.65 and 0.78 for detection of extended FAZ, 0.83 and 1.0 for NVD, 0.78 and 1.0 for NVE, and 0.19 and 1 for VH for WF-OCTA and FA, respectively. In contrast, inter-rater reliability was higher for WF-OCTA than for FA in the quantitative analyses: ICC values were 0.94 and 0.76 for FAZ size, 0.92 and 0.79 for horizontal FAZ diameter, 0.82 and 0.72 for vertical FAZ diameter, and 0.88 and 0.82 for maximum FAZ diameter on WF-OCTA and FA, respectively.ConclusionsInter-rater reliability of FA is superior to WF-OCTA for qualitative analyses whereas inter-rater reliability of WF-OCTA is superior to FA for quantitative analyses.Translational relevanceThe study highlights the specific merits of both imaging modalities in terms of reliability. FA should be preferred for qualitative parameters, whereas WF-OCTA should be preferred for quantitative parameters.
| S-EPMC10351024 | biostudies-literature
Project description:The detection and assessment of leakage in retinal fluorescein angiogram images is important for the management of a wide range of retinal diseases. We have developed a framework that can automatically detect three types of leakage (large focal, punctate focal, and vessel segment leakage) and validated it on images from patients with malarial retinopathy. This framework comprises three steps: vessel segmentation, saliency feature generation and leakage detection. We tested the effectiveness of this framework by applying it to images from 20 patients with large focal leak, 10 patients with punctate focal leak, and 5,846 vessel segments from 10 patients with vessel leakage. The sensitivity in detecting large focal, punctate focal and vessel segment leakage are 95%, 82% and 81%, respectively, when compared to manual annotation by expert human observers. Our framework has the potential to become a powerful new tool for studying malarial retinopathy, and other conditions involving retinal leakage.
| S-EPMC4450752 | biostudies-other