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https://www.readbyqxmd.com/read/29772044/a-phase-1-open-label-dose-escalation-trial-to-investigate-safety-and-tolerability-of-single-intravitreous-injections-of-icon-1-targeting-tissue-factor-in-wet-amd
#1
John A Wells, Christine R Gonzales, Brian B Berger, Victor H Gonzalez, Brian D Sippy, Gabriela Burian
BACKGROUND AND OBJECTIVE: This phase 1 study evaluated the safety and tolerability of single intravitreous injections (IVIs) of ICON-1 (Iconic Therapeutics, South San Francisco, CA) in patients with neovascular age-related macular degeneration (nAMD). ICON-1 is a modified factor VIIa protein linked with the Fc portion of a human immunoglobulin G1. The molecule binds tissue factor overexpressed on choroidal neovascularization (CNV) in AMD. PATIENTS AND METHODS: Open-label, interventional, dose-escalation trial in 18 patients with CNV due to AMD, with six patients per dose cohort...
May 1, 2018: Ophthalmic Surgery, Lasers & Imaging Retina
https://www.readbyqxmd.com/read/29767257/bmp%C3%A2-6-protects-retinal-pigment-epithelial-cells-from-oxidative-stress%C3%A2-induced-injury-by-inhibiting-the-mapk-signaling-pathways
#2
Li Chen, Ming Liu, Yan Luan, Yingfei Liu, Zhichao Zhang, Bo Ma, Xuan Liu, Yong Liu
Worldwide, neovascular age‑related macular degeneration (nAMD) is one of the most common causes of blindness in the elderly. In particular, degeneration of retinal pigment epithelial (RPE) cells represents the main pathological process in the development of nAMD, and oxidative stress serves a major role. The present study aimed to investigate the association between bone morphogenetic protein 6 (BMP‑6) and nAMD. BMP‑6 concentration was significantly reduced in patients with wet nAMD compared with in the control group...
May 14, 2018: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29766021/transduction-patterns-of-adeno-associated-viral-vectors-in-a-laser-induced-choroidal-neovascularization-mouse-model
#3
Si Hyung Lee, Ye Seul Kim, Seung Kwan Nah, Hee Jong Kim, Ha Yan Park, Jin Young Yang, Keerang Park, Tae Kwann Park
Adeno-associated virus (AAV) vector is a promising platform technology for ocular gene therapy. Recently clinical successes to treat choroidal neovascularization (CNV) in wet type age-related macular degeneration have been reported. However, because pathologic conditions of the retina may alter the tropism of viral vectors, it is necessary to evaluate the transduction efficiency of different serotypes of AAV vectors in the retinas with CNVs. Here, we show the patterns and efficacy of transduction of AAV2, -5, and -8 vectors in a laser-induced CNV mouse model...
June 15, 2018: Molecular Therapy. Methods & Clinical Development
https://www.readbyqxmd.com/read/29753123/photodynamic-therapy-in-combination-with-ranibizumab-versus-ranibizumab-monotherapy-for-wet-age-related-macular-degeneration-a-systematic-review-and-meta-analysis
#4
REVIEW
Yongxian Su, Jiawei Wu, Yu Gu
OBJECTIVE: To evaluate the efficacy and safety between photodynamic therapy (PDT) combined with intravitreal ranibizumab (IVR) and ranibizumab monotherapy in treating wet age-related macular degeneration (AMD). METHODS: A systematic search was performed in the PubMed, Embase, Web of Science and the Cochrane Library databases through December 31, 2017. The methodological quality of the references was evaluated according to the Cochrane quality assessment. RevMan 5...
May 9, 2018: Photodiagnosis and Photodynamic Therapy
https://www.readbyqxmd.com/read/29744763/accuracy-of-ultra-wide-field-fundus-ophthalmoscopy-assisted-deep-learning-a-machine-learning-technology-for-detecting-age-related-macular-degeneration
#5
Shinji Matsuba, Hitoshi Tabuchi, Hideharu Ohsugi, Hiroki Enno, Naofumi Ishitobi, Hiroki Masumoto, Yoshiaki Kiuchi
PURPOSE: To predict exudative age-related macular degeneration (AMD), we combined a deep convolutional neural network (DCNN), a machine-learning algorithm, with Optos, an ultra-wide-field fundus imaging system. METHODS: First, to evaluate the diagnostic accuracy of DCNN, 364 photographic images (AMD: 137) were amplified and the area under the curve (AUC), sensitivity and specificity were examined. Furthermore, in order to compare the diagnostic abilities between DCNN and six ophthalmologists, we prepared yield 84 sheets comprising 50% of normal and wet-AMD data each, and calculated the correct answer rate, specificity, sensitivity, and response times...
May 9, 2018: International Ophthalmology
https://www.readbyqxmd.com/read/29734810/theoretical-insights-into-the-retinal-dynamics-of-vegf-in-patients-treated-with-ranibizumab-based-on-an-ocular-pharmacokinetic-pharmacodynamic-model
#6
Laurence A Hutton-Smith, Eamonn A Gaffney, Helen M Byrne, Antonello Caruso, Philip K Maini, Norman Alan Mazer
Neovascular age-related macular degeneration (wet AMD) results from the pathological angiogenesis of choroidal capillaries, which leak fluid within or below the macular region of the retina. The current standard of care for treating wet AMD utilizes intravitreal injections of anti-VEGF antibodies or antibody fragments to suppress ocular VEGF levels. While VEGF suppression has been demonstrated in wet AMD patients by serial measurements of free-VEGF concentrations in aqueous humor samples, it is presumed that anti-VEGF molecules also permeate across the inner limiting membrane (ILM) of the retina as well as the retinal pigmented epithelium (RPE) and suppress VEGF-levels in the retina and/or choroidal regions...
May 7, 2018: Molecular Pharmaceutics
https://www.readbyqxmd.com/read/29721978/vegf-as-a-trophic-factor-for-m%C3%A3-ller-glia-in-hypoxic-retinal-diseases
#7
Shuhua Fu, Shuqian Dong, Meili Zhu, Yun-Zheng Le
Age-related macular degeneration (AMD) and diabetic retinopathy (DR), leading causes of blindness, share a common retinal environment: hypoxia which is a major stimulator for the upregulation of vascular endothelial growth factor (VEGF), a cardinal pathogenic factor for the breakdown of blood-retina barrier (BRB). As a result of intensive studies on VEGF pathobiology, anti-VEGF strategy has become a major therapeutics for wet AMD and DR. To investigate the potential impact of anti-VEGF strategy on major retinal supporting cells, Müller glia (MG), we disrupted VEGF receptor-2 (VEGFR2) in MG with conditional knockout (CKO) and examined the effect of VEGFR2-null on MG viability and neuronal integrity in mice...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29721942/the-role-of-hypoxia-hypoxia-inducible-factor-hif-and-vegf-in-retinal-angiomatous-proliferation
#8
Maya Barben, Marijana Samardzija, Christian Grimm
In industrialized countries, age-related macular degeneration (AMD) is the leading cause of blindness in elderly people. Hallmarks of the non-neovascular (dry) form of AMD are the formation of drusen and geographic atrophy, whereas the exudative (wet) form of the disease is characterized by invading blood vessels. In retinal angiomatous proliferation (RAP), a special form of wet AMD, intraretinal vessels grow from the deep plexus into the subretinal space. Little is known about the mechanisms leading to intraretinal neovascularization, but age-related changes such as reduction of choroidal blood flow, accumulation of drusen, and thickening of the Bruch's membrane may lead to reduced oxygen availability in photoreceptors...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29721926/anaphylatoxin-signaling-in-retinal-pigment-and-choroidal-endothelial-cells-characteristics-and-relevance-to-age-related-macular-degeneration
#9
Bärbel Rohrer
Age-related macular degeneration (AMD) is the leading cause of blindness in the USA. Polymorphisms in various complement components are associated with an increased risk for AMD, and it has been hypothesized that an overactive complement system is partially responsible for the pathology of AMD. AMD is classified as early, intermediate, or late AMD, depending on the degree of the associated pathologies. Late AMD can be characterized as either lesions associated with neovascular AMD or geographic atrophy. Both sets of lesions are associated with pathology at the RPE/choroid interface, which include a thickening of Bruch's membrane, presence of drusen, and pigmentary alterations, and deterioration of the blood-retina barrier has been reported...
2018: Advances in Experimental Medicine and Biology
https://www.readbyqxmd.com/read/29696386/tear-film-proteome-in-age-related-macular-degeneration
#10
Mateusz Winiarczyk, Kai Kaarniranta, Stanisław Winiarczyk, Łukasz Adaszek, Dagmara Winiarczyk, Jerzy Mackiewicz
PURPOSE: Age-related macular degeneration (AMD) is the main reason for blindness in elderly people in the developed countries. Current screening protocols have limitations in detecting the early signs of retinal degeneration. Therefore, it would be desirable to find novel biomarkers for early detection of AMD. Development of novel biomarkers would help in the prevention, diagnostics, and treatment of AMD. Proteomic analysis of tear film has shown promise in this research area. If an optimal set of biomarkers could be obtained from accessible body fluids, it would represent a reliable way to monitor disease progression and response to novel therapies...
April 25, 2018: Graefe's Archive for Clinical and Experimental Ophthalmology
https://www.readbyqxmd.com/read/29683983/fluorescein-angiography-indications-changes-after-optical-coherence-tomography-and-antiangiogenics
#11
Sonia C Labrador-Velandia, María R Sanabria
SIGNIFICANCE: The present study provides quantitative data regarding the change of indications of fluorescein angiography in a tertiary hospital. Exhaustively compiled data over more than 10 years concerning all the angiographic studies including diagnosis, first-visit/follow-up, possible relation with antiangiogenics approval, and optic coherence tomography (OCT) are presented. PURPOSE: The aim of this study was to determine the frequency and indications of fluorescein angiography before and after OCT and anti-vascular endothelial growth factor (anti-VEGF) treatment implantation...
April 20, 2018: Optometry and Vision Science: Official Publication of the American Academy of Optometry
https://www.readbyqxmd.com/read/29682574/baseline-predictors-of-visual-acuity-outcome-in-patients-with-wet-age-related-macular-degeneration
#12
REVIEW
Xinyuan Zhang, Timothy Y Y Lai
Age-related macular degeneration (AMD) is one of the leading causes of severe vision loss in people over 60 years. Wet AMD (wAMD) causes more severe visual acuity (VA) loss compared with the dry form due to formation of choroidal neovascularization (CNV). Antivascular endothelial growth factor (anti-VEGF) agents such as ranibizumab and aflibercept are now the standard of care treatment for wAMD. Unfortunately, up to a quarter of anti-VEGF-treated wAMD patients might not fully benefit from intravitreal injections and CNV activity may not respond to the treatment and these patients are called anti-VEGF nonresponders...
2018: BioMed Research International
https://www.readbyqxmd.com/read/29677356/volume-rendered-projection-resolved-oct-angiography-3d-lesion-complexity-is-associated-with-therapy-response-in-wet-age-related-macular-degeneration
#13
Peter L Nesper, Brian T Soetikno, Alison D Treister, Amani A Fawzi
Purpose: To explore whether quantitative three-dimensional (3D) analysis of choroidal neovascularization (CNV) using projection-resolved optical coherence tomography angiography (PR-OCTA) is associated with treatment response in neovascular age-related macular degeneration (nAMD). Methods: Retrospective, cross-sectional study of 51 eyes of 49 patients undergoing individualized anti-VEGF therapy for nAMD. Patients were classified as "good" or "poor" responders, requiring injections at less or more frequently than 6-week intervals, respectively...
April 1, 2018: Investigative Ophthalmology & Visual Science
https://www.readbyqxmd.com/read/29669378/spontaneous-regression-of-wet-age-related-macular-degeneration-after-termination-of-anti-vegf-injections
#14
Andrea Bräutigam, Heinrich Gerding
No abstract text is available yet for this article.
April 2018: Klinische Monatsblätter Für Augenheilkunde
https://www.readbyqxmd.com/read/29659183/predictors-of-visual-outcomes-in-patients-with-neovascular-age-related-macular-degeneration-treated-with-anti-vascular-endothelial-growth-factor-therapy-post-hoc-analysis-of-the-view-studies
#15
Paolo Lanzetta, Alan F Cruess, Salomon Y Cohen, Jason S Slakter, Todd Katz, Olaf Sowade, Oliver Zeitz, Christiane Ahlers, Paul Mitchell
PURPOSE: Identify predictors for response to anti-vascular endothelial growth factor (VEGF) therapy in patients with neovascular (wet) age-related macular degeneration (nAMD). METHODS: Retrospective, post hoc analysis of VIEW 1/2. Patients were randomized 1:1:1:1 to 0.5 mg intravitreal aflibercept (IVT-AFL) injection every 4 weeks (0.5q4); 2 mg IVT-AFL every 4 weeks (2q4); 2 mg IVT-AFL every 8 weeks (2q8) after an initial three injections at weeks 0, 4 and 8 or 0...
April 16, 2018: Acta Ophthalmologica
https://www.readbyqxmd.com/read/29619125/accuracy-of-a-self-monitoring-test-for-identification-and-monitoring-of-age-related-macular-degeneration-a-diagnostic-case-control-study
#16
Martin K Schmid, Livia Faes, Lucas M Bachmann, Michael A Thiel
Objective: To evaluate diagnostic accuracy of a new self-monitoring device using a Vernier hyperacuity alignment task. Method: A total of 11 wet Age-Related Macular Degeneration (AMD) patients and 9 controls contributing 37 eyes were consecutively enrolled into this prospective diagnostic case-control study at the retina centre of the Cantonal Hospital Lucerne, Switzerland. Vernier acuity testing (index test) and Optical Coherence Tomography (OCT, reference test) were performed in all participants...
2018: Open Ophthalmology Journal
https://www.readbyqxmd.com/read/29616508/an-efficacy-analysis-of-anti-vascular-endothelial-growth-factor-therapy-for-choroidal-neovascularization-secondary-to-multifocal-choroiditis-and-comparison-with-wet-age-related-macular-degeneration
#17
Lei Feng, Jiang-Hua Hu, Jie Chen, Xin Xie
OBJECTIVE: To evaluate the effect of anti-vascular endothelial growth factor (VEGF) on juxtafoveal choroidal neovascularization (CNV) secondary to multifocal choroiditis (MFC) and wet age-related macular degeneration (AMD). METHODS: In this retrospective, comparative study, 20 unique eyes with CNV were divided into two groups: 10 patients affected by MFC and 10 patients diagnosed with wet AMD. They all received local intravitreal (IVT) injections of ranibizumab, with 6 months of follow-up...
2018: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/29611471/peroxisome-proliferated-activated-receptors-ppars-opportunities-and-challenges-for-ocular-therapy
#18
Prachi Khatol, Shivani Saraf, Ankit Jain
Peroxisome proliferator-activated receptors (PPARs) are nuclear transcription factors. They exist in three isoforms (PPAR-α, PPAR-β/δ, and PPAR-Υ) in humans, but mainly PPAR-Υ, and they are expressed in retinal epithelial pigment. PPARs are involved in mediating numerous pathological implications in eye such as diabetic retinopathy (DR), choroidal neovascularization (CNV), glaucoma, diabetic macular edema, and other retinal diseases. Peroxisome proliferator-activated receptors are key players in various biological pathways like lipid degeneration, immune regulation, and reactive oxygen species regulation, regulation of vascular endothelial growth factor, matrixmetalloproteinase-9, and docosahexaenoic acid pathway...
2018: Critical Reviews in Therapeutic Drug Carrier Systems
https://www.readbyqxmd.com/read/29600418/comparison-of-model-averaging-and-model-selection-in-dose-finding-trials-analyzed-by-nonlinear-mixed-effect-models
#19
Simon Buatois, Sebastian Ueckert, Nicolas Frey, Sylvie Retout, France Mentré
In drug development, pharmacometric approaches consist in identifying via a model selection (MS) process the model structure that best describes the data. However, making predictions using a selected model ignores model structure uncertainty, which could impair predictive performance. To overcome this drawback, model averaging (MA) takes into account the uncertainty across a set of candidate models by weighting them as a function of an information criterion. Our primary objective was to use clinical trial simulations (CTSs) to compare model selection (MS) with model averaging (MA) in dose finding clinical trials, based on the AIC information criterion...
March 29, 2018: AAPS Journal
https://www.readbyqxmd.com/read/29563771/age-sex-and-type-of-medication-predict-the-effect-of-anti-vegf-treatment-on-central-retinal-thickness-in-wet-age-related-macular-degeneration
#20
Toke Bek, Sidsel Ehlers Klug
Purpose: Randomized clinical trials studying the effects of VEGF inhibition on wet age-related macular degeneration (wAMD) are designed so that the effects of individually varying risk factors on the treatment response are eliminated. The influence of these risk factors can be studied in large data sets from real-life experience. Patients and methods: All 2,255 patients diagnosed with wAMD requiring anti-VEGF treatment in at least one eye over more than 9 years in a defined Danish population with 0...
2018: Clinical Ophthalmology
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