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3.
Medicine (Baltimore) ; 99(17): e19081, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32332595

RESUMEN

Previous studies evaluating the association of dietary fat and risk of age-related macular degeneration (AMD) yield discrepant results. The objective of this systematic review (SR) and meta-analysis is to establish whether an association exists between dietary fat and AMD. This protocol was developed in line with the quality requirements of the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols (PRISMA-P) statement. PubMed and EMBASE will be searched for randomized controlled trials (RCTs), non-randomized trials (NRTs), cross-sectional studies, cohort studies, and case-control studies that evaluate the total incidence of AMD. The data extraction content and quantitative analysis will be carried out systematically. Newcastle-Ottawa Scale (NOS), the Cochrane risk of bias tool, and quality assessment tools will be used for quality assessment. This SR will synthesize evidence to determine if there is an association between dietary fat and AMD. The evidence would provide rationale for future research and serve as a basis for the development of future guidelines. Results are expected to be publicly available in mid 2020.PROSPERO registration number: CRD42019137086.


Asunto(s)
Grasas de la Dieta/administración & dosificación , Degeneración Macular/epidemiología , Humanos , Proyectos de Investigación
4.
Medicine (Baltimore) ; 99(17): e19955, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32332680

RESUMEN

The aim of this study was to identify any changes that occur in the retinal nerve fiber layer (RNFL) and ganglion cell-inner plexiform layer (GC-IPL) in patients with exudative age-related macular degeneration (AMD) during treatment with anti-vascular endothelial growth factor (VEGF) injections.Patients were enrolled in this retrospective study if they had exudative AMD, had received at least 3 injections of ranibizumab or aflibercept, and had a minimum of 12 months of follow-up. We analyzed the changes in the RNFL and GC-IPL using spectral-domain optical coherence tomography in rescan mode.Fifty-two eyes of 52 patients who had been treated with repeated anti-VEGF injections for exudative AMD were included. At the final visit, there was no significant between-group difference in best-corrected visual acuity or intraocular pressure. There was a significant decrease in central macular thickness in all groups (P < .05). There was a decrease in RNFL thickness that was only statistically significant in the ranibizumab group and when the ranibizumab or aflibercept groups were combined (P = .036 and .044, respectively). The thickness of the GC-IPL layer was significantly decreased in the aflibercept and total group (P = .035 and P = .048, respectively).The thicknesses of the RNFL and GC-IPL decreased in patients with exudative AMD who underwent repeated anti-VEGF injections.


Asunto(s)
Degeneración Macular/tratamiento farmacológico , Retina/patología , Factores de Crecimiento Endotelial Vascular/uso terapéutico , Pesos y Medidas , Anciano , Anciano de 80 o más Años , Inhibidores de la Angiogénesis/farmacología , Inhibidores de la Angiogénesis/uso terapéutico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Ranibizumab/farmacología , Ranibizumab/uso terapéutico , Receptores de Factores de Crecimiento Endotelial Vascular/uso terapéutico , Proteínas Recombinantes de Fusión/farmacología , Proteínas Recombinantes de Fusión/uso terapéutico , Retina/fisiopatología , Estudios Retrospectivos , Estadísticas no Paramétricas , Factores de Crecimiento Endotelial Vascular/farmacología
7.
PLoS One ; 15(3): e0230260, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32196538

RESUMEN

INTRODUCTION: For quantification of Optical Coherence Tomography Angiography (OCTA) images, Vessel Density (VD) and Vessel Skeleton Density (VSD) are well established parameters and different algorithms are in use for their calculation. However, comparability, reliability and ability to discriminate healthy and impaired macular perfusion of different algorithms are unclear, yet, of potential high clinical relevance. Hence, we assessed comparability and test-retest reliability of the most common approaches. MATERIALS AND METHODS: Two consecutive 3×3mm OCTA en face images of the superficial and deep retinal layer were acquired with swept-source OCTA. VD and VSD were calculated with manual thresholding and six automated thresholding algorithms (Huang, Li, Otsu, Moments, Mean, Percentile) using ImageJ and compared in terms of intra-class correlation coefficients, measurement differences and repeatability coefficients. Receiver operating characteristic analyses (healthy vs. macular pathology) were performed and Area Under the Curve (AUC) values were calculated. RESULTS: Twenty-six eyes (8 female, mean age: 47 years) of 15 patients were included (thereof 15 eyes with macular pathology). Binarization thresholds, VD and VSD differed significantly between the algorithms and compared to manual thresholding (p < 0.0001). Inter-measurement differences did not differ significantly between patients with healthy versus pathologic maculae (p ≥ 0.685). Reproducibility was higher for the automated algorithms compared to manual thresholding on all measures of reproducibility assessed. AUC was significantly higher for the Mean algorithm compared to the manual approach with respect to the superficial retinal layer. CONCLUSIONS: Automated thresholding algorithms yield a higher reproducibility of OCTA parameters and allow for a more sensitive diagnosis of macular pathology. However, different algorithms are not interchangeable nor results readily comparable. Especially the Mean algorithm should be investigated in further detail. Automated thresholding algorithms are preferable but more standardization is needed for clinical use.


Asunto(s)
Angiografía/métodos , Degeneración Macular/diagnóstico por imagen , Tomografía de Coherencia Óptica/métodos , Algoritmos , Angiografía/normas , Automatización/métodos , Automatización/normas , Femenino , Humanos , Masculino , Persona de Mediana Edad , Reproducibilidad de los Resultados , Tomografía de Coherencia Óptica/normas
10.
Invest Ophthalmol Vis Sci ; 61(3): 2, 2020 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-32150251

RESUMEN

Purpose: The purpose of this study was to examine changes in the ganglion cell layer (GCL) of individuals with intermediate age-related macular degeneration (AMD) using grid-wise analysis for macular optical coherence tomography (OCT) volume scans. We also aim to validate the use of age-correction functions for GCL thickness in diseased eyes. Methods: OCT macular cube scans covering 30° × 25° were acquired using Spectralis spectral-domain OCT for 87 eyes with intermediate AMD, 77 age-matched normal eyes, and 254 non-age-matched normal eyes. The thickness of the ganglion cell layer (GCL) was defined after segmentation at 60 locations across an 8 × 8 grid centered on the fovea, where each grid location covered 0.74 mm2 (approximately 3° × 3°) within the macula. Each GCL location of normal eyes (n = 77) were assigned to a specific iso-ganglion cell density cluster in the macula, based on patterns of age-related GCL thickness loss. Analyses were then performed comparing AMD GCL grid-wise data against corresponding spatial clusters, and significant AMD GCL thickness changes were denoted as values outside the 95% distribution limits. Results: Analysis of GCL thickness changes revealed significant differences between spatial clusters, with thinning toward the fovea, and thickening toward the peripheral macula. The direction of GCL thickness changes in AMD were associated more so with thickening than thinning in all analyses. Results were corroborated by the application of GCL thickness age-correction functions. Conclusions: GCL thickness changed significantly and nonuniformly within the macula of intermediate AMD eyes. Further characterization of these changes is critical to improve diagnoses and monitoring of GCL-altering pathologies.


Asunto(s)
Mácula Lútea/patología , Degeneración Macular/patología , Células Ganglionares de la Retina/patología , Anciano , Anciano de 80 o más Años , Envejecimiento/patología , Estudios de Casos y Controles , Femenino , Humanos , Mácula Lútea/diagnóstico por imagen , Degeneración Macular/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Tomografía de Coherencia Óptica/métodos
11.
Invest Ophthalmol Vis Sci ; 61(3): 10, 2020 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-32176261

RESUMEN

Purpose: To investigate the clinical and genetic characteristics of occult macular dystrophy (OMD) based on a Chinese patient cohort. Methods: Fifteen Chinese OMD patients from nine unrelated families underwent genetic testing, and all of them harbored a pathogenic RP1L1 variant. Comprehensive ophthalmic examinations were performed in nine probands, including spectral-domain optical coherence tomography (SD-OCT), near-infrared reflectance (NIR), fundus autofluorescence (AF), and multifocal electroretinography. Results: The RP1L1 variants p.R45W and p.S1199C were identified in 13 patients and two patients, respectively, and one was a de novo mutation. Among the nine probands, the median ages at onset and examination were 25.0 years (range, 6-51 years) and 27.0 years (range, 14-55 years), respectively. The median decimal visual acuity was 0.20 (range, 0.04-0.5). Foveal photoreceptor thickness and visual acuity showed a significant correlation (r = 0.591; P = 0.01). All eyes presented with an absent interdigitation zone and blurred ellipsoid zone of photoreceptors when examined by SD-OCT. In addition, central round lesions with low NIR reflectance were observed in 66.7% (12/18) of eyes by NIR reflectance imaging, corresponding to the regions with abnormal photoreceptor microstructures observed by SD-OCT. Of the 18 eyes, only four eyes showed ring-like faint hyperfluorescence around the macula by AF. Conclusions: To the best of our knowledge, this is the largest study in a cohort of Chinese OMD patients with RP1L1 mutations. Our findings revealed that the two recurrent RP1L1 variants are related to OMD in the Chinese population. Furthermore, multimodal imaging combined with genetic testing is valuable for diagnosing and monitoring OMD progression.


Asunto(s)
Grupo de Ascendencia Continental Asiática/genética , Proteínas del Ojo/genética , Degeneración Macular/genética , Mutación , Adolescente , Adulto , Edad de Inicio , Niño , Estudios de Cohortes , Electrorretinografía , Femenino , Angiografía con Fluoresceína , Predisposición Genética a la Enfermedad , Humanos , Degeneración Macular/diagnóstico por imagen , Degeneración Macular/fisiopatología , Masculino , Persona de Mediana Edad , Imagen Multimodal/métodos , Linaje , Tomografía de Coherencia Óptica , Agudeza Visual/genética , Adulto Joven
12.
Invest Ophthalmol Vis Sci ; 61(3): 18, 2020 03 09.
Artículo en Inglés | MEDLINE | ID: mdl-32176267

RESUMEN

Purpose: To study the levels of complement activation in different disease stages of AMD and the influence of genetic polymorphisms in complement genes. Methods: We included 797 patients with AMD and 945 controls from the European Genetic Database. Patients were grouped into five AMD stages: early AMD, intermediate AMD, central geographic atrophy, active choroidal neovascularization or inactive choroidal neovascularization. Differences in complement activation, as defined by the systemic C3d/C3 ratio, between AMD stages were evaluated using general linear modeling. In addition, we evaluated the influence of 18 genetic AMD polymorphisms in complement genes and their effect on complement activation. Differences in complement activation between stages were evaluated stratifying by complement associated haplotypes. Results: Complement activation levels differed significantly between AMD disease stages. As compared with controls, the C3d/C3 ratio was higher in patients with intermediate AMD (P < 0.001) and central geographic atrophy (P = 0.001). Two polymorphisms in CFH (rs10922109 and rs570618) and one in CFB (rs116503776) were significantly associated with complement activation. The association between AMD disease stage and complement activation was more pronounced in patients with haplotypes associated with the highest complement activation. Conclusions: In general, consecutive AMD disease stages showed increasing levels of complement activation, especially in individuals with a genetic burden in complement genes. These findings contribute to the discussion on the pathogenesis of AMD in relation to complement activation and might suggest refinement in patient selection and the optimum window of treatment with complement inhibitors. Prospective studies are needed to confirm these results.


Asunto(s)
Activación de Complemento/genética , Degeneración Macular/genética , Degeneración Macular/inmunología , Polimorfismo de Nucleótido Simple , Anciano , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Complemento C3/análisis , Complemento C3d/análisis , Bases de Datos Genéticas , Haplotipos , Humanos , Persona de Mediana Edad , Índice de Severidad de la Enfermedad , Triglicéridos/sangre
13.
PLoS One ; 15(3): e0229694, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32142523

RESUMEN

PURPOSE: To assess the 5-year change in abnormal fundus autofluorescence (FAF) patterns and retinal sensitivity in the fellow eye of Japanese patients with unilateral exudative age-related macular degeneration (AMD). METHODS: Patients with unilateral exudative AMD who developed abnormal FAF in the fellow eyes were enrolled. FAF imaging and microperimetry were performed at baseline and follow-ups. FAF findings were classified into 8 patterns based on the International Fundus Autofluorescence Classification Group to assess retinal sensitivity. Forty-five points covering the central 12 degrees on microperimetry were superimposed onto the FAF images. Each point was classified depending on the distance from the abnormal FAF. "Close" was defined as the portion within 1 degree from the border of any abnormal FAF, and "Distant" was defined as the portion over 1 degree from the border of abnormal FAF. To investigate the association between the retinal sensitivity and distance from the abnormal FAF, hierarchical linear mixed-effect models were used with the distance, time and time squared from baseline (months), and angle (degrees) as fixed effects. Differences among patients, eyes, and test point locations were considered successively nested random effects. RESULTS: We studied 66 fellow eyes with abnormal FAF. Twenty-seven eyes were followed-up during the 5 years. In the 13 of 27 eyes (48%), the abnormal FAF patterns had changed during the 5 years. We found retinal sensitivity was associated significantly with the distance from the abnormal FAF ("Distant": p<0.001, time2 from baseline: p<0.001, angle: p<0.001). The mean retinal sensitivity of the "Close" tended to deteriorate after the third year and eventually showed the similar sensitivity as the portion within the abnormal FAF. CONCLUSION: FAF patterns can change about half during the 5 years and the retinal sensitivity near abnormal FAF tends to deteriorate after the third year.


Asunto(s)
Degeneración Macular/diagnóstico por imagen , Degeneración Macular/fisiopatología , Imagen Óptica , Anciano , Anciano de 80 o más Años , Progresión de la Enfermedad , Femenino , Estudios de Seguimiento , Fondo de Ojo , Humanos , Japón , Modelos Lineales , Masculino , Persona de Mediana Edad , Retina/diagnóstico por imagen , Retina/fisiopatología , Factores de Tiempo , Pruebas del Campo Visual
14.
PLoS One ; 15(3): e0230305, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32168355

RESUMEN

PURPOSE: To describe epidemiologic features of patients with presumed ocular histoplasmosis syndrome (POHS) in the United States using insurance claims data and compare POHS patients with and without choroidal neovascularization (CNV). DESIGN: Retrospective cohort study. METHODS: Patients with International Classification of Diseases, Ninth Revision, Clinical Modification diagnosis codes for histoplasmosis retinitis on an outpatient claim in the 2014 IBM® MarketScan® Commercial Database and the Medicare Supplemental Database who were enrolled for at least 2 years after the POHS code. MAIN OUTCOME MEASURES: Data related to testing, treatment, and direct medical costs. RESULTS: Among >50 million total MarketScan enrollees, 6,678 (13 per 100,000) had a POHS diagnosis code. Of those, 2,718 were enrolled for 2 years; 698 (25%) of whom had a CNV code. Eleven of the 13 states with the highest POHS rates bordered the Mississippi and Ohio rivers. CNV patients had significantly more eye care provider visits (mean 8.8 vs. 3.2, p<0.0001), more ophthalmic imaging tests, higher rates of treatment with anti-vascular endothelial growth factor injections (45% vs. 4%, p<0.0001), and incurred higher mean total yearly costs ($1,251.83 vs. $251.36, p<0.0001) than POHS patients without CNV. CONCLUSIONS: Although the relationship between Histoplasma and POHS remains controversial, geographic patterns of POHS patient residence were consistent with the traditionally reported range of the fungus. CNV in the context of POHS was associated with additional healthcare use and costs. Further research to understand POHS etiology, risk factors, prevalence, and complications is needed, along with early diagnosis and treatment strategies.


Asunto(s)
Neovascularización Coroidal/economía , Histoplasmosis/economía , Seguro de Salud/economía , Degeneración Macular/economía , Retinitis/economía , Adolescente , Adulto , Anciano , Niño , Preescolar , Neovascularización Coroidal/complicaciones , Neovascularización Coroidal/patología , Neovascularización Coroidal/terapia , Ojo/patología , Oftalmopatías/economía , Oftalmopatías/epidemiología , Femenino , Personal de Salud , Histoplasmosis/complicaciones , Histoplasmosis/patología , Histoplasmosis/terapia , Humanos , Lactante , Recién Nacido , Revisión de Utilización de Seguros , Degeneración Macular/patología , Degeneración Macular/terapia , Masculino , Persona de Mediana Edad , Oftalmología/economía , Retinitis/complicaciones , Retinitis/patología , Retinitis/terapia , Estados Unidos/epidemiología , Visión Ocular/fisiología , Adulto Joven
15.
PLoS One ; 15(3): e0230344, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32214330

RESUMEN

In age-related macular degeneration (AMD) or diabetic retinopathy (DR), hypoxia and inflammatory processes lead to an upregulation of the vascular endothelial growth factor (VEGF) expression and thereby to pathological neovascularisation with incorrectly formed vessels prone to damage, thus increasing the vascular permeability and the risk of bleeding and oedema in the retina. State of the art treatment is the repeated intraocular injection of anti-VEGF molecules. For developing improved individualized treatment approaches, a minimally invasive, repeatable method for in vivo quantification of VEGF in the eye is necessary. Therefore, we designed single molecule eBRET2 VEGF biosensors by directly fusing a Renilla luciferase mutant (Rluc8) N-terminal and a green fluorescent protein (GFP2) C-terminal to a VEGF binding domain. In total, 10 different VEGF biosensors (Re01- Re10) were generated based on either single domains or full length of VEGF receptor 1 or 2 extracellular regions as VEGF binding domains. Full length expression of the biosensors in HEK293-T cells was verified via Western Blot employing an anti-Rluc8-IgG. Expression of alternative splice variants was eliminated through the deletion of the donor splice site by introduction of a silent point mutation. In all ten biosensors the energy transfer from the Rluc8 to the GFP2 occurs and generates a measurable eBRET2 ratio. Four biosensors show a relevant change of the BRET ratio (ΔBR) after VEGF binding. Furthermore, each biosensor shows a unique detection range for VEGF quantification and especially Re06 and Re07 have a high sensitivity in the range of in vivo VEGF concentrations in the eye, previously measured by invasive methods. In conclusion, we generated several eBRET2 biosensors that are suitable for VEGF quantification in vitro and could identify two eBRET2 biosensors, which may be suitable for non-invasive in vivo VEGF quantification with an implantable device.


Asunto(s)
Técnicas Biosensibles/instrumentación , Mediciones Luminiscentes/instrumentación , Proteínas Recombinantes de Fusión/química , Factor A de Crecimiento Endotelial Vascular/análisis , Animales , Córnea/patología , Retinopatía Diabética/diagnóstico , Retinopatía Diabética/patología , Transferencia de Energía , Proteínas Fluorescentes Verdes/química , Proteínas Fluorescentes Verdes/genética , Células HEK293 , Células Endoteliales de la Vena Umbilical Humana , Humanos , Luciferasas de Renilla/química , Luciferasas de Renilla/genética , Degeneración Macular/diagnóstico , Degeneración Macular/patología , Unión Proteica , Dominios Proteicos , Proteínas Recombinantes de Fusión/genética , Proteínas Recombinantes de Fusión/metabolismo , Retina/patología , Transfección , Regulación hacia Arriba , Factor A de Crecimiento Endotelial Vascular/metabolismo , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo
16.
Expert Opin Pharmacother ; 21(7): 773-784, 2020 May.
Artículo en Inglés | MEDLINE | ID: mdl-32153203

RESUMEN

INTRODUCTION: Age-related macular degeneration (AMD) is the most common cause of blindness among the elderly in the industrialized world. While effective treatment is available for neovascular AMD, no therapy is successful for the non-neovascular form. Herein, the authors report the current knowledge on non-neovascular AMD pathogenesis and the promising research on treatments. AREAS COVERED: In the present review, the authors summarize the most recent advances in the treatment of non-neovascular AMD and provide an update on current treatment strategies. Evidence available from preclinical and clinical studies and from a selective literature search is reported. EXPERT OPINION: When investigating AMD, numerous pathological cascades and alterations of physiological processes have been investigated. It is well-known that AMD is a multifactorial disease, with environmental causes and genetics playing a role. Perturbations in multiple pathogenic pathways have been identified and this led to the development of several molecules directed at specific therapeutic targets. However, despite the huge research effort, the only proven approach so far is oral antioxidant supplementation. We believe that, in addition to successful advancement of promising drugs, further research should be directed at tailoring therapy to specific patient groups, eventually employing a combinational therapy strategy.


Asunto(s)
Antiinflamatorios/uso terapéutico , Antioxidantes/uso terapéutico , Degeneración Macular/tratamiento farmacológico , Agudeza Visual/efectos de los fármacos , Vitaminas/uso terapéutico , Anciano , Antiinflamatorios/administración & dosificación , Antioxidantes/administración & dosificación , Ensayos Clínicos como Asunto , Suplementos Dietéticos , Terapia Genética , Humanos , Degeneración Macular/metabolismo , Degeneración Macular/patología , Trasplante de Células Madre , Resultado del Tratamiento , Vitaminas/administración & dosificación
18.
Ophthalmology ; 127(4): e21-e22, 2020 04.
Artículo en Inglés | MEDLINE | ID: mdl-32200844
20.
PLoS One ; 15(3): e0229342, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32155173

RESUMEN

We aimed to construct a better model for predicting treatment outcomes of anti-vascular endothelial growth factor therapy for neovascular age-related macular degeneration (nAMD) using the concentrations of aqueous humour proteins at baseline and during treatment. From the data of 48 treatment-naïve nAMD eyes that received intravitreal ranibizumab pro re nata for up to 12 months, we used the aqueous humour concentrations of C-X-C motif chemokine ligand 1 (CXCL1), CXCL12, CXCL13, interferon-γ-induced protein 10, monocyte chemoattractant protein 1 (MCP-1), C-C motif chemokine ligand 11, interleukin 6 (IL-6), IL-10, and matrix metalloproteinase 9 (MMP-9). After stepwise regression, multivariate analysis was performed to identify which predictors were significantly associated with best-corrected visual acuity (BCVA) changes and the number of injections. The results demonstrated that besides male sex (ß coefficient = -0.088, P = 0.040) and central retinal thickness (ß coefficient = 0.00051 per µm, P = 0.027), MCP-1 (ß coefficient = 0.44, P < 0.001) and IL-10 (ß coefficient = -0.16, P = 0.033) were significantly correlated with baseline BCVA. Additionally, high MCP-1 at baseline (ß coefficient = -0.20, P = 0.015) and low CXCL13 at baseline (ß coefficient = 0.10, P = 0.0054) were independently associated with better BCVA change at 12 months. High MMP-9 at the first injection (ß coefficient = 0.56, P = 0.01), CXCL12 at the third injection (ß coefficient = 0.10, P = 0.0002), and IL-10 at the third injection (ß coefficient = 1.3, P = 0.001) were predictor variables associated with the increased number of injections. In conclusion, aqueous humour protein concentrations may have predictive abilities of BCVA change over 12 months and the number of injections in pro re nata treatment of exudative nAMD.


Asunto(s)
Humor Acuoso/metabolismo , Proteínas del Ojo/metabolismo , Regulación de la Expresión Génica/efectos de los fármacos , Degeneración Macular/tratamiento farmacológico , Neovascularización Patológica/tratamiento farmacológico , Ranibizumab/uso terapéutico , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , Anciano , Inhibidores de la Angiogénesis/uso terapéutico , Femenino , Humanos , Degeneración Macular/metabolismo , Degeneración Macular/patología , Masculino , Neovascularización Patológica/metabolismo , Neovascularización Patológica/patología , Estudios Prospectivos , Resultado del Tratamiento
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