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  • 1
    Language: English
    In: Clinical & experimental ophthalmology, 2021-09, Vol.49 (7), p.652-663
    Description: The use of vascular endothelial growth factor (VEGF) inhibitors has revolutionised the treatment of neovascular age‐related macular degeneration (nAMD) since the pivotal Phase III studies demonstrated their efficacy more than 10 years ago. The Fight Retinal Blindness! project was developed to track the treatment outcomes of patients with nAMD in real‐world practice. Data from this registry have been used to answer several clinically relevant questions related to the treatment of nAMD including the effect of under‐treatment, the comparative effectiveness of different anti‐vascular endothelial growth factor agents, long‐term treatment outcomes, identifying optimal treatment regimens and the rate and outcomes of rare adverse events. Observational studies are a valuable complement to the shortcomings of clinical trials and a combination of data from real‐world settings and clinical trials are necessary to provide evidence on how to achieve the best outcomes for individual patients with nAMD.
    Subject(s): Blindness ; disease registry ; Endothelium ; Macular degeneration ; Medical research ; Medicine, Experimental ; neovascular age‐related macular degeneration ; Physiological aspects ; real‐world evidence ; Vascular endothelial growth factor ; vascular endothelial growth factor inhibitors
    ISSN: 1442-6404
    E-ISSN: 1442-9071
    Source: Alma/SFX Local Collection
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  • 2
    Language: English
    In: Graefe's archive for clinical and experimental ophthalmology, 2017-11-25, Vol.256 (2), p.325-332
    Description: Purpose Various hypoxia-related proteins are differentially expressed in the retina and secreted to the vitreous and/or aqueous humor of patients affected by dry or neovascular age-related macular degeneration (nAMD). To determine whether these conditions alter concentrations of cytokines also in the systemic circulation, we measured plasma levels of six hypoxia-related proteins. Methods Plasma was prepared from EDTA blood that was collected from patients affected by dry AMD ( n  = 5), nAMD ( n  = 11), proliferative diabetic retinopathy (PDR; n  = 9), and patients with an epiretinal membrane (ERM; n  = 11). ERM samples served as negative controls, PDR samples as positive controls. Protein concentrations of vascular endothelial growth factor (VEGF), erythropoietin (EPO), angiopoietin-like 4 (ANGPTL4), placental growth factor (PlGF), tumor necrosis factor alpha (TNF-α), and pigment epithelium-derived factor (PEDF) were determined by enzyme-linked immunosorbent assay (ELISA). Results The concentration of PlGF was significantly increased in plasma of patients affected by nAMD. Although no statistically significant differences were found for EPO, ANGPTL4, PlGF, TNF-α, and PEDF, the mean concentration of VEGF was lowest in the nAMD group. Plasma concentrations of the six factors did not correlate with gender or age of patients. Conclusions nAMD may increase plasma concentrations of PlGF, making it a candidate as a biomarker for the neovascular form of AMD. Other factors, however, were not differentially regulated, suggesting that their systemic concentrations are not generally increased in hypoxia-related retinal diseases.
    Subject(s): Age-related macular degeneration ; Basic Science ; Care and treatment ; Cytokines ; Diabetic retinopathy ; Endothelial growth factors ; Endothelium ; Enzyme-linked immunosorbent assay ; Enzymes ; Glycoproteins ; Macular degeneration ; Medicine ; Medicine & Public Health ; Ophthalmology ; Physiological aspects ; Plasma ; Vascular endothelial growth factor
    ISSN: 0721-832X
    E-ISSN: 1435-702X
    Source: Alma/SFX Local Collection
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  • 3
    Language: English
    In: Frontiers in pharmacology, 2021-05-10, Vol.12, p.675295-675295
    Description: Purpose: To evaluate efficacy of eplerenone therapy vs. observation on resolution of subretinal fluid (SRF) in patients with acute and chronic central serous chorioretinopathy (CSCR) in routine clinical practice.Methods: Retrospective comparative case series of eyes diagnosed with CSCR treated with eplerenone or observation. Primary outcome measure was maximum height of SRF at 12 months. Secondary outcome was percentage of eyes with complete resolution of SRF, percentage of eyes with reduction of SRF ≥50%, and best corrected visual acuity (VA) at 12 months. Separate analysis was conducted for eyes with acute and chronic CSCR.Results: Sixty-eight eyes of 60 patients (82% male) were included. Eleven of the 38 eyes with acute CSCR, and seven of the 30 eyes with chronic CSCR, received eplerenone. Subretinal fluid decreased from baseline to 12 months in acute (287 ± 221 to 31 ± 63 µm) and chronic (148 ± 134 to 40 ± 42 µm) CSCR. Kaplan-Meier curves were similar for treated and observed eyes and COX regression analysis did not show a significant difference in SRF resolution in treated vs. observed eyes (p = 0.6 for acute, p = 0.2 for chronic CSCR).Conclusion: This routine clinical practice outcome study did not show evidence of efficacy of eplerenone on resolution of SRF in acute nor chronic CSCR.
    Subject(s): aldosterone antagonists ; central serous chorioretinopathy ; eplerenone ; medical retina ; Pharmacology ; retinal disease
    ISSN: 1663-9812
    E-ISSN: 1663-9812
    Source: PubMed Central
    Source: DOAJ Directory of Open Access Journals - Not for CDI Discovery
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  • 4
    Language: English
    In: Graefe's archive for clinical and experimental ophthalmology, 2017-12-12, Vol.256 (3), p.641-641
    Description: The original publication of this paper contains mistakes due to incorrect order of first and last names.
    Subject(s): Care and treatment ; Cells ; Correction ; Macular degeneration ; Medicine ; Medicine & Public Health ; Ophthalmology ; Physiological aspects
    ISSN: 0721-832X
    E-ISSN: 1435-702X
    Source: Alma/SFX Local Collection
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  • 5
    Language: English
    In: Scientific reports, 2016-06-29, Vol.6 (1), p.28755-28755
    Description: Inherited monogenic diseases of the retina and vitreous affect approximately 1 in 2000 individuals. They are characterized by tremendous genetic heterogeneity and clinical variability involving mutations in approximately 250 genes and more than 20 different clinical phenotypes. Clinical manifestations of retinal dystrophies (RDs) range from mild retinal dysfunctions to severe congenital forms of blindness. A detailed clinical diagnosis and the identification of causative mutations are crucial for genetic counseling of affected patients and their families, for understanding genotype-phenotype correlations and developing therapeutic approaches. Using whole exome sequencing (WES) we have established a reliable and efficient high-throughput analysis pipeline to identify disease-causing mutations. Our data indicate that this approach enables us to genetically diagnose approximately 64% of the patients (n = 58) with variant(s) in known disease-associated genes. We report 20 novel and 26 recurrent variants in genes associated with RDs. We also identified a novel phenotype for mutations in C2orf71 and provide functional evidence for exon skipping due to a splice-site variant identified in FLVCR1. In conclusion, WES can rapidly identify variants in various families affected with different forms of RDs. Our study also expands the clinical and allelic spectrum of genes associated with RDs in the Swiss population.
    Subject(s): Eye Proteins - genetics ; Female ; High-Throughput Nucleotide Sequencing ; Humans ; Male ; Membrane Transport Proteins - genetics ; Mutation ; Receptors, Virus - genetics ; Retinal Dystrophies - epidemiology ; Retinal Dystrophies - genetics ; Switzerland - epidemiology ; Whole Exome Sequencing
    ISSN: 2045-2322
    E-ISSN: 2045-2322
    Source: Nature Open Access
    Source: Academic Search Ultimate
    Source: PubMed Central
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  • 6
    Language: English
    In: Eye (London), 2020-11-25, Vol.35 (10), p.2793-2801
    Description: BACKGROUND/OBJECTIVESome clinicians may be forced to temporarily extend treatment intervals in neovascular age-related macular degeneration (nAMD) eyes with frequent retreatments to reduce the number of visits during the COVID-19 pandemic. To provide an indication of what these outcomes may be, we studied eyes with active lesions with unplanned treatment interval extensions before the pandemic occurred. METHODSWe compared eyes with active disease despite ≤6 weekly injections whose next injection was extended to ≥7 weeks and those whose intervals were not extended. We identified 1559 (16%) of 9602 eyes from the Fight Retinal Blindness! (FRB!) registry (2013 and 2018) that fit this criteria. Eyes were further stratified into four groups by the mean interval over the following 6 months: (1) ≤6 weeks (81%), (2) 7-9 weeks (9%), (3) 10-12 weeks (5%) and (4) 〉12 weeks (5%). RESULTSThere was a significant loss in VA in eyes extended to 〉12 weeks compared to the non-extended group (adjusted VA change, mean (95% CI): ≤6 weeks, 0.4 (-1.5 to 2.2), versus 〉12 weeks, -4.7 (-7.4 to -2.1), letters, p = 0.03 and a threefold increase in relative risk of losing ≥15 letters (absolute risk (14% versus 4%, p 〈 0.01)). CONCLUSIONMean VA remained stable for 6 months in eyes requiring frequent treatment despite retreatment interval extension up to 10-12 weeks. There was a significant short-term risk to vision when retreatment interval was extended beyond 12 weeks, hence extensions to this level should be considered cautiously. These data may be useful for physicians who are considering reducing visits to mitigate the risk of COVID-19.
    ISSN: 0950-222X
    E-ISSN: 1476-5454
    Source: Alma/SFX Local Collection
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  • 7
    Language: English
    In: Cell death and differentiation, 2018-12, Vol.25 (12), p.2071-2085
    Description: Reduced choroidal blood flow and tissue changes in the ageing human eye impair oxygen delivery to photoreceptors and the retinal pigment epithelium. As a consequence, mild but chronic hypoxia may develop and disturb cell metabolism, function and ultimately survival, potentially contributing to retinal pathologies such as age-related macular degeneration (AMD). Here, we show that several hypoxia-inducible genes were expressed at higher levels in the aged human retina suggesting increased activity of hypoxia-inducible transcription factors (HIFs) during the physiological ageing process. To model chronically elevated HIF activity and investigate ensuing consequences for photoreceptors, we generated mice lacking von Hippel Lindau (VHL) protein in rods. This activated HIF transcription factors and led to a slowly progressing retinal degeneration in the ageing mouse retina. Importantly, this process depended mainly on HIF1 with only a minor contribution of HIF2. A gene therapy approach using AAV-mediated RNA interference through an anti-Hif1a shRNA significantly mitigated the degeneration suggesting a potential intervention strategy that may be applicable to human patients.
    ISSN: 1350-9047
    E-ISSN: 1476-5403
    Source: PubMed Central
    Source: Alma/SFX Local Collection
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  • 8
    Language: English
    In: American Journal of Ophthalmology, 2016, Vol.168, p.1
    Description: PURPOSE: To define a minimum set of outcome measures for tracking, comparing, and improving macular degeneration care. DESIGN: Recommendations from a working group of international experts in macular degeneration outcomes registry development and patient advocates, facilitated by the International Consortium for Health Outcomes Measurement (ICHOM). METHODS: Modified Delphi technique, supported by structured teleconferences, followed by online surveys to drive consensus decisions. Potential outcomes were identified through literature review of outcomes collected in existing registries and reported in major clinical trials. Outcomes were refined by the working group and selected based on impact on patients, relationship to good clinical care, and feasibility of measurement in routine clinical practice.
    Subject(s): Clinical Medicine ; Klinisk medicin ; Medical and Health Sciences ; Medicin och hälsovetenskap ; Oftalmologi ; Ophthalmology
    ISSN: 1879-1891
    ISSN: 0002-9394
    E-ISSN: 1879-1891
    Source: SWEPUB Freely available online
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  • 9
    Language: English
    In: Clinical & experimental ophthalmology, 2018-05, Vol.46 (4), p.407-411
    Description: Importance To assess the impact of injection frequency on visual outcomes in patients with neovascular age‐related macular degeneration (nAMD) treated with intravitreal aflibercept. Background The UK licence for treatment of nAMD with aflibercept is based on the VIEW protocol. We tested the hypothesis that patients receiving fewer than the eight recommended injections in the first year would experience worse visual outcomes. Design Retrospective, single‐centre observational study. Participants There were 42 eyes from 42 patients included. Methods Fight Retinal Blindness! software was used to record real‐world outcomes of all treatment‐naïve eyes receiving aflibercept for at least 1 year. Main Outcome Measures Visual acuity (VA) at 1 year in eyes which received the recommended eight injections versus those receiving seven or fewer injections. Results There were 21 eyes (50%) that received the recommended eight aflibercept injections in the first year of treatment, whilst 14 eyes received seven injections, five received six injections and two received only five injections, with median VA change +7.0, +5.0, −4.0 and −6.5 LogMAR letters, respectively. Those eyes receiving seven or fewer injections had worse baseline vision. The main reasons for patients being undertreated were insufficient clinic capacity and non‐attendance due to illness. Conclusions and Relevance Patients in the real‐world receiving aflibercept for nAMD at fixed intervals as per UK licence could achieve similar visual improvement at 1 year compared with phase III clinical trials. Undertreated patients had worse visual outcomes. Measures need to be introduced to increase clinic capacity and closely follow non‐attenders to improve future outcomes.
    Subject(s): aflibercept ; Aged ; Aged, 80 and over ; age‐related macular degeneration ; Blindness ; Care and treatment ; Drug Administration Schedule ; Female ; Follow-Up Studies ; Humans ; Incidence ; Intravitreal Injections ; Macula Lutea - pathology ; Macular degeneration ; Male ; neovascular ; Patient outcomes ; Physiological aspects ; real‐world outcomes ; Receptors, Vascular Endothelial Growth Factor - administration & dosage ; Receptors, Vascular Endothelial Growth Factor - antagonists & inhibitors ; Recombinant Fusion Proteins - administration & dosage ; Retrospective Studies ; Tomography, Optical Coherence ; Treatment Outcome ; United Kingdom - epidemiology ; Visual Acuity ; Wet Macular Degeneration - diagnosis ; Wet Macular Degeneration - drug therapy ; Wet Macular Degeneration - epidemiology
    ISSN: 1442-6404
    E-ISSN: 1442-9071
    Source: Academic Search Ultimate
    Source: Alma/SFX Local Collection
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  • 10
    Language: English
    In: British journal of ophthalmology, 2019-09, Vol.103 (9), p.1337-1341
    Description: AimsTo compare 24 months outcomes of eyes with retinal angiomatous proliferations (RAPs) treated with antivascular endothelial growth factor (anti-VEGF) with a group of controls diagnosed with other neovascular age-related macular degeneration (nAMD) subtypes in a real-world setting.MethodsTreatment-naïve nAMD eyes that commenced anti-VEGF between January 2006 and November 2015 were identified from a registry of nAMD treatment outcomes. Cases were defined as eyes diagnosed with RAP. Three controls per case were selected among nAMD eyes with non-RAP lesions and matched on baseline visual acuity (VA), year of treatment initiation, anti-VEGF agent first injected and follow-up. Baseline VA was compared with 12 and 24 months VA. Change in VA, number of injections received, proportion of visits with active nAMD and time to first inactivation were compared between RAPs and controls.Results157 RAPs and 469 controls were included. Baseline VA (mean (SD)) increased at 12 months (61.4 (15.5) vs 68.7 (14.7) letters, p〈0.001) and remained higher (66.6 (17.3) letters) at 24 months (p〈0.001) in RAPs. The change from baseline VA (mean(95% CI)) was significantly higher in RAPs than in controls at 12 months (7.3 (5.4 to 9.1) vs 4.1 (2.8 to 5.4) letters, p=0.01) and at 24 months (5.1 (2.8 to 7.3) vs 2.5 (1 to 4) letters, p=0.056). Both groups received a median of 13 injections. RAPs inactivated earlier and were less active than controls (both p〈0.001).ConclusionsRAPs responded well to anti-VEGF, with a significant improvement in VA persisting at 24 months. RAPs had better visual outcomes than controls at 12 and 24 months, tended to inactivate earlier and were less active throughout 2 years follow-up.
    Subject(s): Age ; Aged ; Aged, 80 and over ; Angiogenesis Inhibitors - therapeutic use ; Case-Control Studies ; Choroidal Neovascularization - drug therapy ; Databases ; Epidemiology ; Female ; Fluorescein Angiography ; Humans ; Intravitreal Injections ; Life Sciences & Biomedicine ; Macular degeneration ; Macular Degeneration - complications ; Male ; Middle Aged ; Ophthalmology ; Patients ; Ranibizumab - therapeutic use ; Science & Technology ; Survival analysis ; Tomography, Optical Coherence ; Vascular endothelial growth factor ; Visual Acuity
    ISSN: 0007-1161
    E-ISSN: 1468-2079
    Source: Web of Science - Science Citation Index Expanded - 2019〈img src="http://exlibris-pub.s3.amazonaws.com/fromwos-v2.jpg" /〉
    Source: Alma/SFX Local Collection
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