33,534 research outputs found

    Characterization of subretinal hyperreflective material in patients with neovascular age-related macular degeneration treated with antiangiogenics

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    Prop贸sito: Analizar las caracter铆sticas morfol贸gicas del material hiperreflectivo subretiniano (MHRS) y resultados visuales a corto plazo en pacientes con degeneraci贸n macular relacionada con la edad neovascular (DMREn) tratados con antiangiog茅nicos en la Fundaci贸n Oftalmol贸gica Nacional entre el 2011 y 2017. Metodolog铆a: Estudio descriptivo longitudinal, en el que se incluyeron 65 pacientes con DMREn no tratada previamente, entre enero del 2011 y diciembre del 2017. Se revis贸 la tomograf铆a de coherencia 贸ptica (OCT) estructural para determinar las caracter铆sticas cuantitativas y cualitativas del MHRS, y la agudeza visual mejor corregida (AVMC) en LogMAR antes y despu茅s del tratamiento. Resultados: La mediana de edad fue 76 a帽os (rango 68-84). La mayor铆a de pacientes fueron mujeres en 56.9%. La lateralidad del ojo m谩s afectado fue el derecho en 50.8%. Aflibercept fue el antiangiog茅nico m谩s empleado en el 40% de los pacientes. La mediana de AVMC fue de 0.7 (rango 0.5-1.2) logMAR y 0.7 (rango 0.4-1) logMAR de base y despu茅s del tratamiento, respectivamente. Los par谩metros de base con una correlaci贸n positiva por an谩lisis bivariado antes y despu茅s del tratamiento fueron la AVMC, reflectividad, bordes y extensi贸n del MHRS. Los par谩metros que se asociaron a una mejor铆a en la AVMC despu茅s del tratamiento fueron la presencia de zona elipsoide (ZE) y membrana limitante externa (MLE), la reflectividad, homogeneidad y extensi贸n del MHRS. Conclusi贸n: Este estudio proporciona caracter铆sticas tomogr谩ficas del MHRS asociadas con resultados visuales a corto plazo en ojos con DMREn tratados con antiangiog茅nicos.Purpose: To analyze the morphological characteristics of subretinal hyperreflective material (SHRM) and short-term visual outcomes in patients with neovascular age-related macular degeneration (nAMD) treated with anti-vascular endothelial grown factor (anti-VEGF) at the Fundacion Oftalmologica Nacional between 2011 and 2017. Methodology: Descriptive longitudinal study, including 65 patients with previously untreated nAMD, between January 2011 and December 2017. The structural optical coherence tomography (OCT) was reviewed to determine quantitative and qualitative characteristics of SHRM, and best corrected visual acuity (BCVA) in LogMAR before and after treatment. Results: The median age was 76 years (range 68-84). The majority of patients were women in 56.9%. The laterality of the most affected eye was the right in 50.8%. Aflibercept was the most widely used antiangiogenic in 40% of the patients. The median BCVA was 0.7 (range 0.5-1.2) logMAR and 0.7 (range 0.4-1) logMAR at baseline and after treatment, respectively. The baseline parameters with a positive correlation by bivariate analysis before and after treatment were the BCVA, reflectivity, edges and extension of the SHRM. The parameters that were associated with an improvement in BCVA after treatment were the presence of the ellipsoid zone (EZ) and external limiting membrane (ELM), reflectivity, homogeneity and extension of the SHRM. Conclusion: This study provides tomographic features of the SRHM associated with short-term visual outcomes in eyes with nAMD treated with anti-VEGF

    Molecular role of alphaB-crystallin in hypoxic retinal pigment epithelium

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    Molecular role of Crystallins in hypoxic Retinal Pigment Epithelium Background: Age-Related Macular Degeneration (AMD) causes gradual breakdown of vision due to insoluble deposits accumulation, called 鈥漝rusen鈥. The macula, a area near the center of the retina, holds the highest concentration of light-sensing cells that provide the image which we see. There are two kinds of AMD conditions, 鈥漝ry鈥 and 鈥漺et鈥. We focus on wet form, that is characterized by the presence of drusen between the retinal pigment epithelium (RPE) and Bruch's membrane, concomitantly with choroidal neovascularization (CNV) and is designated neovascular AMD (nAMD). During nAMD the retinal pigment epithelium (RPE) undergoes a hypoxic state (low oxygen), which causes growth of blood vessels to improve oxygen supply. Cells deficient in oxygen produce hypoxia-inducible factor (HIF-1), a transcription factor responsible for the upregulation of a multitude of angiogenic factors in response to hypoxia. Chaperones are a group of proteins assisting protein folding in cells under physiological and stress conditions. Chaperones recognize and bind proteins in their native form thus preventing unspecific aggregation. Small Heat-Shock Proteins (HSP) 20kd (HSP20) is a protein belonging to the family of chaperones; these are also known as alpha Crystallins. ARPE-19 is a human retinal pigment epithelial cell line which will be exposed to shock treatments, causing crystallin reactions. Cas9/CRISPR technologies can be used to generate crystallin mutant cells to deepen our hypothesis and methodology. Aims: The purpose of the present study will be to address the role alpha-B Crystallin in ARPE-19 cells exposed to hypoxia. Hypothesis: The hypothesis is that there is an interaction with crystallins and the Hypoxia-inducible factors (HIF) pathway. Standing question: how do crystallins interact with HIF pathway protein members, as well as their functional role and implication

    Clinical validation of saliency maps for understanding deep neural networks in ophthalmology.

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    Deep neural networks (DNNs) have achieved physician-level accuracy on many imaging-based medical diagnostic tasks, for example classification of retinal images in ophthalmology. However, their decision mechanisms are often considered impenetrable leading to a lack of trust by clinicians and patients. To alleviate this issue, a range of explanation methods have been proposed to expose the inner workings of DNNs leading to their decisions. For imaging-based tasks, this is often achieved via saliency maps. The quality of these maps are typically evaluated via perturbation analysis without experts involved. To facilitate the adoption and success of such automated systems, however, it is crucial to validate saliency maps against clinicians. In this study, we used three different network architectures and developed ensembles of DNNs to detect diabetic retinopathy and neovascular age-related macular degeneration from retinal fundus images and optical coherence tomography scans, respectively. We used a variety of explanation methods and obtained a comprehensive set of saliency maps for explaining the ensemble-based diagnostic decisions. Then, we systematically validated saliency maps against clinicians through two main analyses 鈥 a direct comparison of saliency maps with the expert annotations of disease-specific pathologies and perturbation analyses using also expert annotations as saliency maps. We found the choice of DNN architecture and explanation method to significantly influence the quality of saliency maps. Guided Backprop showed consistently good performance across disease scenarios and DNN architectures, suggesting that it provides a suitable starting point for explaining the decisions of DNNs on retinal images

    Pigment epithelium-derived factor (PEDF) alone or in combination with an anti-VEGF drug as a possible treatment of choroidal neovascularization and ischemic ocular diseases

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    Ocular neovascular diseases such as choroidal neovascularization (CNV) and age-related macular degeneration (AMD) are today the most common causes of visual loss and blindness. Although intravitreal anti-vascular endothelial growth factor (VEGF) therapy has achieved major breakthroughs in the treatment of CNV and wet AMD, it does not always successfully suppress CNV, and no efficacious treatment is yet available to prevent photoreceptor degeneration. The formation of CNV is a compensatory response to ocular ischemia. If CNV can be stabilized, it may be helpful for photoreceptor survival and maintaining the normal physiological function of the retina. With a wide use of optical coherence tomography angiography (OCTA) in the clinic, quiescent CNVs without exudation are much more frequently found than previously assumed. In this study, I examined the efficacy of a pigment epithelium derived factor (PEDF) protein alone or combined with a VEGF antagonist (Avastin) in the treatment of rat quiescent CNV in vivo. The rat quiescent CNV was established by subretinal injection of an adeno-associated viral (AAV)-VEGF-A165 vector, which expresses VEGF and leads to vascular growth from the choroid into the subretinal space. The fluorescein angiography (FA), indocyanine green angiography (ICG) and optical coherence tomography (OCT) were performed at the third week, fourth week, sixth week and seventh week after subretinal injection of the AAV-VEGF-A165 vector. The maximal thickness of CNV was measured in the OCT images. Picrosirius red stain was used to quantify mature and immature collagen content in the formalin-fixed, paraffin-embedded quiescent CNV samples. The collagen 鈪, VEGF and PEDF were examined in the quiescent CNV samples by immunohistochemistry (IHC), and the percentage of positive staining area to the total CNV area was calculated by ImageJ software. To analyze the effect of PEDF on retinal photoreceptor cells, the outer nuclear layer (ONL) area as a percentage of the corresponding CNV area was quantified. The apoptosis of ONL cells above the CNV area was detected by TUNEL staining. PEDF combined with anti-VEGF therapy significantly inhibits VEGF expression in quiescent CNV. The ONL area as a percentage of the corresponding CNV area is increased in the PEDF treatment group (92.29, 120.27) and decreased in the Avastin treatment group (55.11, 75.59) (P 锕0.001, Wilcoxon test with Kruskal-Wallis test). The apoptosis of ONL cells above the CNV area is reduced in the PEDF treatment group (0.95 卤 0.60, n/1000渭m) compared to the vehicle treatment group (2.26 卤 0.95, n/1000渭m) (P 锕0.001, one-way ANOVA test). Thus, PEDF shows a neuroprotective effect for the retinal photoreceptor cells. In this in vivo experiment, a VEGF antagonist (Avastin) can significantly inhibit the formation of CNV in this rat quiescent CNV model and reduce its thickness. However, quiescent CNV can supply oxygen to the photoreceptor cells and protect photoreceptor cells from degeneration, thus maintaining vision. Although anti-VEGF (Avastin) treatment alone inhibits CNV, it also accelerates photoreceptor cell degeneration in this in vivo quiescent CNV model. In the clinic, development of macular geographic atrophy and fibrosis are found in patients with wet AMD under long term anti-VEGF treatment. PEDF has no effect on mature and immature collagen in this quiescent CNV model. The information on the therapeutic effect is shown in Table 1. PEDF is a potential vascular stabilizing and neuroprotective factor for stabilizing CNV and maintaining vision. Ischemic/hypoxic retinopathy is a common condition that can cause visual impairment and blindness. However, the changes of the choroidal blood vessels under ischemic/hypoxic conditions are not clearly known. The apoptosis of retinal ganglion cells (RGCs) and the retinal degeneration under ischemic/hypoxic conditions cannot be treated. In this study, I established an ischemic/hypoxic ex vivo eye model by incubating the freshly enucleated rat eyes in Dulbecco's modified eagle medium (DMEM) at 4 掳C for 14 hours. After 14 hours, eyes (including control eyes, eyes intravitreally injected with vehicle or PEDF protein) were fixed for electron microscopy (EM) and immunohistochemistry (IHC) respectively. The area of lumen (渭m2/渭m of Bruch鈥檚 membrane) and the area of the whole vessel (渭m2/渭m of Bruch鈥檚 membrane) were analyzed and immunohistochemical staining for VEGF and PEDF in the retina and choroidal vessels was performed. The effects of PEDF on the choriocapillaris and retinal neural cells under ischemia/hypoxia were investigated. In addition, the oxygen concentration within the vitreous was measured by an oxygen-sensitive microsensor in both the ischemic/hypoxic ex vivo eye model and the living rats under anesthesia. TUNEL staining was performed and the apoptosis of retinal neural cells was analyzed. In the living rats, the concentration of oxygen within the vitreous was on average 16.4 % of the oxygen concentration in the air. In the ischemic/hypoxic ex vivo eyes, the oxygen concentration within the vitreous was gradually decreased and the concentration was about 50% of the value in the eyes immediately after enucleation after about 400 minutes of incubation, indicating mild hypoxia during this process. After 14 hours of ischemia/hypoxia, the endothelial cells of the choroidal vessel were ultra-structurally similar with respect to cell organelles compared to the immediately fixed control eyes, but the morphology of the choroidal vessels changed dramatically. In the ischemic/hypoxic eyes, filopodia-like projections filled out the choroidal vessel lumen and appeared identical to the labyrinth-capillaries found in surgically extracted choroidal neovascular membranes from patients with wet AMD. The structural changes within the choriocapillaris in this ischemic/hypoxic eye model can mimic early changes in the process of pathological angiogenesis as observed in patients with CNV or wet AMD. This ex vivo eye model can be used to investigate short term drug effects on the choriocapillaris after ischemia/hypoxia. PEDF inhibited the filopodia-like projection formation and kept the choroidal lumen open as in vivo. The area of lumen is significantly reduced in the ischemic/hypoxic group (0.308卤0.087渭m2/渭m) compared to the PEDF-treated group (1.034卤0.077渭m2/渭m) (P锛0.001, t test). The area of vessel is significantly reduced in the ischemic/hypoxic group (0.675卤0.048 渭m2/渭m) compared to the PEDF-treated group (1.583卤0.094渭m2/渭m) (P锛0.001, t test). The intravitreally injected PEDF protein located in the whole retina and the choroidal vessels, indicating that PEDF protein can penetrate the retina and is transported into the choroid. The apoptosis of RGCs (2.36, 2.89; percentage of positive cells per 100渭m) and inner nuclear cells (15.81, 22.89; number of positive cells per 1000渭m) was significantly reduced in the PEDF-treated eyes compared to the ischemic/hypoxic eyes [ RGCs (3.14, 3.75; percentage of positive cells per 100渭m) (P = 0.015), inner nuclear cells (33.69, 45.22; number of positive cells per 1000渭m) (P = 0.001) Wilcoxon test]. The detailed information is shown in Table 2. Thus, PEDF is a promising candidate for treating ischemic/hypoxic retinopathy or human CNV alone or combined with other drugs. In short, PEDF protected retinal neural cells in both the in vivo quiescent CNV model and the ex vivo ischemic/hypoxic eye model. PEDF inhibits the formation of filopodia-like projections and keeps the choroidal vessel lumen open in this ex vivo ischemic eye model.Dissertation ist gesperrt bis 17.02.202

    Silicone oil injection and removal in 27-gauge vitreous surgery

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    Functional Nanomaterials and Polymer Nanocomposites: Current Uses and Potential Applications

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    This book covers a broad range of subjects, from smart nanoparticles and polymer nanocomposite synthesis and the study of their fundamental properties to the fabrication and characterization of devices and emerging technologies with smart nanoparticles and polymer integration

    Implementing Predictive Models in Artificial Intelligence through OCT Biomarkers for Age-Related Macular Degeneration

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    Artificial intelligence (AI) represents a growing and promising branch of computer science that is expanding the horizon of prediction, screening, and disease monitoring. The use of multimodal imaging in retinal diseases is particularly advantageous to valorize the integration of machine learning and deep learning for early diagnosis, prediction, and management of retinal disorders. In age-related macular degeneration (AMD) beyond its diagnosis and characterization, the prediction of AMD high-risk phenotypes evolving into late forms remains a critical point. The main multimodal imaging modalities adopted included color fundus photography, fundus autofluorescence, and optical coherence tomography (OCT), which represents undoubtful advantages over other methods. OCT features identified as predictors of late AMD include the morphometric evaluation of retinal layers, drusen volume and topographic distribution, reticular pseudodrusen, and hyperreflective foci quantification. The present narrative review proposes to analyze the current evidence on AI models and biomarkers identified to predict disease progression with particular attention to OCT-based features and to highlight potential perspectives for future research.artificial intelligence; age-related macular degeneration; deep learning; multimodal imagin

    LIGHTSITE II Randomized Multicenter Trial: Evaluation of Multiwavelength Photobiomodulation in Non-exudative Age-Related Macular Degeneration.

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    INTRODUCTION Photobiomodulation (PBM) represents a potential treatment for non-exudative age-related macular degeneration (AMD). PBM uses wavelengths of light to target components of the mitochondrial respiratory chain to improve cellular bioenergetic outputs. The aim of this study was to further investigate the effects of PBM on clinical, quality of life (QoL) and anatomical outcomes in subjects with intermediate stage non-exudative AMD. METHODS The multicenter LIGHTSITE II study was a randomized clinical trial evaluating safety and efficacy of PBM in intermediate non-exudative AMD. The LumiThera Valeda庐 Light Delivery System delivered multiwavelength PBM (590, 660 and 850聽nm) or sham treatment 3鈥壝椻塸er week over 3-4聽weeks (9 treatments per series) with repeated treatments at baseline (BL), 4 and 8聽months. Subjects were enrolled with 20/32 to 20/100 best-corrected visual acuity (BCVA) and no central geographic atrophy (GA) within the central fovea (500聽渭m). RESULTS LIGHTSITE II enrolled 44 non-exudative AMD subjects (53 eyes). PBM-treated eyes showed statistically significant improvement in BCVA at 9聽months (n鈥=鈥32 eyes, p鈥=鈥0.02) with a 4-letter gain in the PBM-treated group versus a 0.5-letter gain in the sham-treated group (ns, p鈥<鈥0.1) for patients that received all 27 PBM treatments (n鈥=鈥29 eyes). Approximately 35.3% of PBM-treated eyes showed鈥夆墺鈥5-letter improvement at 9聽months. Macular drusen volume was not increased over time in the PBM-treated group but did show increases in the sham-treated group. While PBM and sham groups both showed GA lesion growth in the trial period, there was 20% less growth in the PBM group over 10聽months, suggesting potential disease-modifying effects. No safety concerns or signs of phototoxicity were observed. CONCLUSION These results confirm previous clinical testing of multiwavelength PBM and support treatment with Valeda as a novel therapy with a unique mechanism of action as a potential treatment for non-exudative AMD. TRIAL REGISTRATION Clinicaltrial.Gov Registration Identifier: NCT03878420
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