المؤلفون: Diogo Cabral, Ana C. Fradinho, Yi Zhang, Hao Zhou, Prithvi Ramtohul, Meera S. Ramakrishnan, Telmo Pereira, Ruikang K. Wang, K. Bailey Freund

المصدر: Scientific Reports, Vol 13, Iss 1, Pp 1-8 (2023)

مصطلحات موضوعية: Medicine, Science

الوصف: Abstract During the past 15 years, new treatment paradigms for neovascular age-related macular degeneration (nvAMD) have evolved due to the advent of intravitreal anti-vascular endothelial growth factor (VEGF) therapy and rapid advances in retinal imaging. Recent publications describe eyes with type 1 macular neovascularization (MNV) as showing more resistance to macular atrophy than eyes with other lesion types. We sought to explore whether the perfusion status of the native choriocapillaris (CC) surrounding type 1 MNV influences its pattern of growth. To evaluate this effect, we analyzed a case series of 22 eyes from 19 nvAMD patients with type 1 MNV exhibiting growth on swept-source optical coherence tomography angiography (SS-OCTA) over a minimum follow-up of 12 months. We observed an overall weak correlation between type 1 MNV growth and CC flow deficits (FDs) average size (τ = 0.17, 95% CI [− 0.20, 0.62]) and a moderate correlation with CC FD % (τ = 0.21, 95% CI [− 0.16, 0.68]). Type 1 MNV was located beneath the fovea in most of the eyes (86%) and median visual acuity was 20/35 Snellen equivalent. Our results support that type 1 MNV recapitulates areas of CC blood flow impairment while serving to preserve foveal function.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/2045-2322Test

الوصول الحر: https://doaj.org/article/58dd2766f14a4369801e3d972427590cTest

المؤلفون: Rita Flores, Ângela Carneiro, Guilherme Neri, Ana C. Fradinho, Bruno Quenderra, Maria João Barata, Sandra Tenreiro, Miguel C. Seabra

المصدر: Diagnostics, Vol 12, Iss 5, p 1290 (2022)

مصطلحات موضوعية: intermediate AMD, chorioretinal vasculature, optical coherence tomography, OCT-angiography, Medicine (General), R5-920

الوصف: Age-related macular degeneration (AMD) is a multifactorial disease, whose complete pathogenesis is still unclear. Local hemodynamics may play a crucial role in its manifestation and progression. To evaluate choroidal and retinal vascular parameters, a total of 134 eyes were analyzed, 100 with intermediate AMD and 34 age matched healthy controls. 131 eyes of 104 patients were eligible for complete image assessment and 3 eyes were excluded for insufficient image quality: Group 1: intermediate AMD (n = 97) and Group 2: healthy controls (n = 34). Spectral domain optic coherence tomography (SD-OCT) with enhanced depth imaging (EDI) and optic coherence tomography angiography (OCT-A) were acquired using Spectralis (Heidelberg Engineering). Choroid and retinal capillary plexus were evaluated and image binarization was used to obtain quantitative data. Mean age was 77.67 years old (YO) and 67.2% were women. Total subfoveal choroidal area and luminal area were significantly reduced in Group 1 compared with Group 2 (0.88 mm2 and 0.40 mm2 vs. 1.24 mm2 and 0.55 mm2, respectively) (p < 0.05). Regarding choriocapillary flow density, AMD eyes recorded reduced values (34.83%) compared with controls (36.25%) (p < 0.05). Chorioretinal vasculature is impaired in intermediate AMD patients and vascular parameters could be attractive new prognostic biomarkers. Future therapeutic approaches may target this vascular dysfunction and delay disease progression.

وصف الملف: electronic resource

العلاقة: https://www.mdpi.com/2075-4418/12/5/1290Test; https://doaj.org/toc/2075-4418Test

الوصول الحر: https://doaj.org/article/5c42b97babd54767ab86d6fa7d82e643Test

المؤلفون: Diogo Cabral, Prithvi Ramtohul, Ana C. Fradinho, K. Bailey Freund

المصدر: Ophthalmology Retina. 6:1185-1193

مصطلحات موضوعية: Ophthalmology, Visual Acuity, Humans, Fluorescein Angiography, Atrophy, Tomography, Optical Coherence, Retina, Retrospective Studies

الوصف: To characterize and distinguish non-neovascular deep retinal age-related microvascular anomalies (DRAMA) from type 3 macular neovascularization (MNV) using volume rendering of OCT and OCT angiography (OCTA).Retrospective, consecutive case series.Consecutive patients with age-related macular degeneration (AMD) exhibiting de novo non-neovascular abnormalities within the deep vascular plexus (DCP), as detected using high-resolution (High-Res) spectral-domain (SD) and swept-source (SS) OCT or OCTA. Patients with retinal vascular alterations attributable to other disease entities were excluded.Complete ophthalmic examination and multimodal imaging, including confocal fundus photography (CFP), SD-OCT, High-Res SD-OCT and OCTA, and volume-averaged SS-OCTA. The volume renderings of High-Res OCTA and averaged SS-OCTA were used to analyze capillary abnormalities and inflow or outflow connectivity pathways.The primary outcomes were the characteristics of capillary abnormalities (number, size, shape, reflectivity, and location) and inflow or outflow connectivity pathways. The secondary outcomes were nearby changes in CFP and structural OCT (hyperreflective foci [HRF], outer retinal atrophy, and retinal pigment epithelium [RPE] atrophy).From 8 eyes of 8 patients, 2 subtypes of DRAMA were identified: small-diameter perifoveal capillary dilations with hyperreflective walls within the inner nuclear layer (type 1, n = 4) and vascular outpouchings, typically multiple, extending posteriorly into the Henle fiber layer, with reflectivity similar to adjacent normal retinal capillaries (type 2, n = 10). Four eyes had both subtypes of DRAMA. The 3-dimensional visualization of OCTA data demonstrated DRAMA corresponding to the dilations of DCP capillaries without direct inflow or outflow connections to the superficial plexus. Fundus photographs showed circular red dots in 3 eyes, all corresponding to type 1 DRAMA. In all the cases, DRAMA colocalized with HRF. No lesions were found anterior to the areas of the RPE or outer retina atrophy. Asymptomatic intraretinal exudation varied through a follow-up duration of up to 6 years, with no lesions progressing to type 3 MNV.In eyes with non-neovascular AMD, DRAMA include 2 types of capillary dilations occurring without the remodeling of the surrounding vascular network. Deep retinal age-related microvascular anomalies can resemble microvascular changes due to other causes and can masquerade as type 3 MNV. Mild intraretinal exudation can vary during follow-up, without progression to type 3 MNV.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::0533bc762f233e4a6d4aadc9c5a14c54Test
https://doi.org/10.1016/j.oret.2022.06.005Test

المؤلفون: Diogo Cabral, Ana C. Fradinho, Telmo Pereira, Meera S. Ramakrishnan, Tommaso Bacci, Dong An, Sandra Tenreiro, Miguel C. Seabra, Chandrakumar Balaratnasingam, K. Bailey Freund

المساهمون: Centro de Estudos de Doenças Crónicas (CEDOC), NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM)

المصدر: Translational vision sciencetechnology. 11(6)

مصطلحات موضوعية: deep vascular complex, Biomedical Engineering, Visual Acuity, Retinal Vessels, high-resolution optical coherence tomography, Retinal Vessels/diagnostic imaging, Fluorescein Angiography/methods, Tomography, Optical Coherence/methods, macular blood flow, Ophthalmology, Cross-Sectional Studies, SDG 3 - Good Health and Well-being, Humans, Fluorescein Angiography, Tomography, X-Ray Computed, Tomography, Optical Coherence

الوصف: Funding: Supported by the Macula Foundation, Inc. (New York, NY, USA) and by Fundação para a Ciência e Tecnologia (FCT)–Portugal, cofunded by FEDER under the PT2020 Partnership Agreement (to MCS, including project PTDC/MED-PAT/30385/2017, iNOVA4Health-UIDB/04462/2020). ACF was funded by a FCT PhD studentship (PD/BD/135503/2018). DC was supported in part by a studentship from Fundação Luso-Americana para o Desenvolvimento (FLAD, USA R&D@PhD–Proj 2020/0140). Purpose: To characterize macular blood flow connectivity in vivo using high-resolution optical coherence tomography (HighRes OCT). Methods: Cross-sectional, observational study. Dense (6-µm interscan distance) perifoveal HighRes OCT raster scans were performed on healthy participants. To mitigate the limitations of projection-resolved OCT-angiography, flow and structural data were used to observe the vascular structures of the superficial vascular complex (SVC) and the deep vascular complex. Vascular segmentation and rendering were performed using Imaris 9.5 software. Inflow and outflow patterns were classified according to vascular diameter and branching order from superficial arteries and veins, respectively. Results: Eight eyes from eight participants were included in this analysis, from which 422 inflow and 459 outflow connections were characterized. Arteries had direct arteriolar connections to the SVC (78%) and to the intermediate capillary plexus (ICP, 22%). Deep capillary plexus (DCP) inflow derived from small-diameter vessels succeeding ICP arterioles. The most prevalent outflow pathways coursed through superficial draining venules (74%). DCP draining venules ordinarily merged with ICP draining venules and drained independently of superficial venules in 21% of cases. The morphology of DCP draining venules in structural HighRes OCT is distinct from other vessels crossing the inner nuclear layer and can be used to identify superficial veins. Conclusions: Vascular connectivity analysis supports a hybrid circuitry of blood flow within the human parafoveal macula. Translational Relevance: Characterization of parafoveal macular blood flow connectivity in vivo using a precise segmentation of HighRes OCT is consistent with ground-truth microscopy studies and shows a hybrid circuitry. publishersversion published

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::65cb2a754d1e59c2e99139ba4208618eTest
https://pubmed.ncbi.nlm.nih.gov/35648637Test

المؤلفون: Clare E. Futter, Ana S. Falcao, Cristina Escrevente, Miguel M. Mesquita, Paul Nicklin, Ana C. Fradinho, Sandra Tenreiro, Pedro Antas, Mafalda Lopes-da-Silva, Thomas Ciossek, Michael J. Hall, Ines S. Ferreira, Daniela Oliveira, M. Helena Cardoso, Miguel C. Seabra

المساهمون: NOVA Medical School|Faculdade de Ciências Médicas (NMS|FCM), Centro de Estudos de Doenças Crónicas (CEDOC), iNOVA4Health - pólo NMS

المصدر: Repositório Científico de Acesso Aberto de Portugal
Repositório Científico de Acesso Aberto de Portugal (RCAAP)
instacron:RCAAP
Investigative Ophthalmology & Visual Science

مصطلحات موضوعية: autofluorescent granules, Swine, Lysosome dysfunction, Blotting, Western, European Regional Development Fund, Library science, Retinal Pigment Epithelium, Lipofuscin, Cellular and Molecular Neuroscience, Phagocytosis, Political science, media_common.cataloged_instance, Animals, Humans, European union, Cells, Cultured, media_common, retinal pigmented epithelium, Flow Cytometry, Rod Cell Outer Segment, lysosome dysfunction, Sensory Systems, Autofluorescent granules, Ophthalmology, Retinal Cell Biology, Models, Animal, Retinal pigment cell, Photoreceptor outer segments, photoreceptor outer segments, Retinal pigmented epithelium, Lysosomes

الوصف: Funding Information: Supported by Funda??o para a Ciência e Tecnologia (FCT) ? Portugal co-funded by FEDER under the PT2020 Partnership Agreement (to MCS, including project PTDC/MED-PAT/30385/2017, iNOVA4Health-UIDB/04462/2020, research infrastructure PPBI-POCI-01-0145-FEDER-022122, M-ERA.NET 2/0005/2016), Boehringer Ingelheim (to MCS), Fight for Sight UK (to MCS), Wellcome Trust grant number 212216/Z/18/Z/ (to CEF). MJH was funded by Moor-fields Eye Charity with the Bill Brown 1989 Charitable Trust PhD studentship 538158, MLS was funded by FCT-CEECIND/01536/2018, ACF was funded by FCT PhD studentship (PD/BD/135503/2018). This work was developed with the support from the research infrastructure PPBI-POCI-01-0145-FEDER-022122, co-financed by FCT (Portugal) and Lisboa2020, under the PORTUGAL2020 agreement (European Regional Development Fund) and this article is supported by the LYSOCIL project funded by the European Union?s Horizon 2020 programme under grant agreement No. 811087. Funding Information: Supported by Fundação para a Ciência e Tecnologia (FCT) – Portugal co-funded by FEDER under the PT2020 Partnership Agreement (to MCS, including project PTDC/MED-PAT/30385/2017, iNOVA4Health-UIDB/04462/2020, research infrastructure PPBI-POCI-01-0145-FEDER-022122, M-ERA.NET 2/0005/2016), Boehringer Ingelheim (to MCS), Fight for Sight UK (to MCS), Wellcome Trust grant number 212216/Z/18/Z/ (to CEF). MJH was funded by Moor-fields Eye Charity with the Bill Brown 1989 Charitable Trust PhD studentship 538158, MLS was funded by FCT-CEECIND/01536/2018, ACF was funded by FCT PhD studentship (PD/BD/135503/2018). This work was developed with the support from the research infrastructure PPBI-POCI-01-0145-FEDER-022122, co-financed by FCT (Portugal) and Lisboa2020, under the PORTUGAL2020 agreement (European Regional Development Fund) and this article is supported by the LYSOCIL project funded by the European Union’s Horizon 2020 programme under grant agreement No. 811087. Publisher Copyright: Copyright 2021 The Authors PURPOSE. We aim to characterize the pathways required for autofluorescent granule (AFG) formation by RPE cells using cultured monolayers. METHODS. We fed RPE monolayers in culture with a single pulse of photoreceptor outer segments (POS). After 24 hours the cells started accumulating AFGs that were comparable to lipofuscin in vivo. Using this model, we used a variety of light and electron microscopical techniques, flow cytometry and Western blot to analyze the formation of AFGs. We also generated a mutant RPE line lacking cathepsin D by gene editing. RESULTS. AFGs seem to derive from incompletely digested POS-containing phagosomes and after 3 days are surrounded by a single membrane positive for lysosome markers. We show by various methods that lysosome-phagosome fusion is required for AFG formation, and that impairment of lysosomal pH or catalytic activity, particularly cathepsin D activity, enhances AF accumulation. CONCLUSIONS. We conclude that lysosomal dysfunction results in incomplete POS degradation and enhanced AFG accumulation. publishersversion published

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::88e27c694cb824b11689ba198596642aTest

المؤلفون: Cristina Escrevente, Ana S Falcão, Michael J Hall, Mafalda Lopes-da-Silva, Pedro Antas, Miguel M Mesquita, Inês S Ferreira, M Helena Cardoso, Daniela Oliveira, Ana C Fradinho, Thomas Ciossek, Paul Nicklin, Clare E Futter, Sandra Tenreiro, Miguel C Seabra

المصدر: Invest Ophthalmol Vis Sci

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=r3c4b2081b22::88e27c694cb824b11689ba198596642aTest