Retinal vascular reactivity study using optical coherence tomography angiography

A retina, o tecido que mais oxigénio consome por unidade de área, possui um complexo sistema de autorregulação vascular. Este mecanismo permite manter o adequado fornecimento de oxigénio e nutrientes à retina em condições de hipóxia ou alterações da pressão arterial, por exemplo. Na maior parte dos estudos existentes, as respostas vasculares da retina foram avaliadas com recurso a técnicas de imagem que se limitam à avaliação dos vasos de maior calibre. A possibilidade de analisar em maior detalhe estes mecanismos poderá ajudar a compreender melhor os processos envolvidos na autorregulação microvascular da retina, tanto em condições fisiológicas como de doença. A angiografia por tomografia de coerência ótica (OCTA) é um exame rápido, seguro, não-invasivo, tridimensional e de alta resolução da microvasculatura retiniana. O objetivo principal desta tese foi estudar a reatividade vascular da retina usando OCTA, em indivíduos saudáveis e com diabetes tipo 1 (DM1), e discutir potenciais aplicações clínicas. Nesse sentido, desenvolvemos uma série de trabalhos experimentais multidisciplinares. A primeira publicação constitui a prova de conceito sobre a capacidade daOCTA detetar uma resposta vascular retiniana. No segundo artigo, utilizou-se OCTA para estudar alterações microvasculares estruturais da retina em pacientes com DM1 sem retinopatia. O terceiro manuscrito consiste num protocolo metodológico em que a OCTA é utilizado para estudar respostas vasculares retinianas a estímulos vasodilatadores e vasoconstritores, utilizando dois testes padronizados - hipóxia e exercício isométrico, respetivamente. Na última publicação, aplicou-se este protocolo a doentes com DM1 sem evidência de retinopatia, e verificou-se que estes apresentam alterações nas respostas autorregulatórias da retina. Os estudos realizados no âmbito desta tese destacam o potencial de otimização da tecnologia OCTA no sentido de combinar uma análise funcional ao angiograma estrutural atualmente isponível. A metodologia desenvolvida nesta tese para o estudo da microcirculação retiniana constitui um ponto de partida para futuras aplicações clínicas da OCTA, não só em Oftalmologia mas também em outras áreas, como a Medicina Cardiovascular e Neurociências.As the highest oxygen-consuming tissue of the human body, the retina has evolved to have an intricate vascular autoregulatory system. This mechanism ensures adequate supply of oxygen and nutrients to retinal tissues in conditions such as high blood pressure or hypoxia. Most studies on retinal vascular responses used imaging techniques that were limited to the assessment of the larger vessels. Novel and more detailed ways of analysing retinal vascular responses could provide insights on retinal autoregulation in both health and disease. Optical coherence tomography angiography (OCTA) allows a fast, safe, non-invasive and three-dimensional angiographic scan of the retinal microvasculature with unprecedented high-resolution. The main goal of this thesis was to dynamically study retinal vascular reactivity in healthy subjects and in a cohort of patients with type 1 diabetes (T1D) using OCTA, and to explore potential applications in ophthalmology and other medical fields. With this purpose, we developed a series of experimental multidisciplinary works. The first publication constitutes the proof of concept on the capacity of OCTA to detect a retinal vascular response. In the second, OCTA was used to study early structural retinal microvascular changes in patients with T1D before clinically evident retinopathy. The third paper consists of a methodological protocol on the use of OCTA to study retinal vascular responses of both vasodilation and vasoconstriction, using two standardized stress tests – hypoxia and isometric exercise. The last publication applied these methods to the disease setting (i.e. T1D patients with no evidence of retinopathy), and significant changes in retinal autoregulatory responses were found. The studies developed within this thesis highlight the potential of optimizing OCTA technology in order to combine a functional analysis to the currently available single structural angiogram. It provides a basis for future applications of this concept in ophthalmology and many other fields, such as neurological and cardiovascular research.Bolsa de Doutoramento da Universidade de Lisboa14ª Bolsa Investigação Fundação AstraZeneca/FMU

Propriedades da córnea e glaucoma : revisão da literatura e meta-análise

SciELO - Scientific Electronic Library Online. ABO is licensed under a Creative Commons Attribution-NonComercial 4.0 Internacional.Purpose: Studies have suggested that corneal biomechanical properties influence intraocular pressure (IOP) measurements, namely central corneal thickness (CCT) and corneal hysteresis (CH). The present study aimed to investigate the associations of CH and CCT with glaucoma development. Methods: We performed a review of the literature and meta-analysis of observational studies (2006-2016) that included both adult glaucoma patients and controls and reported CCT and CH as outcomes. Nineteen studies were conside red eligible, and the mean difference (MD) between groups (patient and control) for both variables was used for statistical analyses. Results: A total of 1,213 glaucoma and 1,055 healthy eyes were studied. Quan titative analysis suggested that CH was significantly lower in the glaucoma group than in the control group (MD=-1.54 mmHg, 95% CI [-1.68, -1.41], P<0.0001). Additionally, CCT was significantly lower in the glaucoma group than in the control group (MD=-8.49 µm, 95% CI [-11.36, -5.62], P<0.001). Conclusion: Corneal properties appear to differ between glaucoma patients and healthy controls. Our results emphasize the importance of corneal biomechanical properties in IOP interpretation and should support further studies on the influence of CH and CCT in glaucoma screening and diagnosis.Objetivo: A literatura sugere que as propriedades biomecânicas da córnea, nomea-damente a espessura central da córnea (ECC) e a histerese corneana (HC), influenciam a medição da pressão intraocular (PIO). Este estudo teve como objetivo investigar a associação entre a ECC e a HC e o desenvolvimento de glaucoma. Métodos: Revisão da literatura e meta-análise. Foram incluídos estudos observacio-nais, publicados entre 2006 e 2016, que integrassem um grupo controle e um grupo de pacientes com glaucoma em que estes dois grupos apresentassem, igualmente, a ECC e a HC como parâmetros. Dezenove estudos foram considerados elegíveis e a diferença média (MD) daqueles parâmetros nos dois grupos foi utilizada para análise estatística. Resultados: Estudaram-se um total de 1.213 olhos com glaucoma e 1.055 olhos saudáveis. A análise quantitativa revelou que a HC é significativamente mais baixa no grupo de doentes com glaucoma quando comparada com o grupo controle (MD=-1,54 mmHg, intervalo de confiança de 95% [-1,68-1,41], P<0,00001). A ECC foi, também, significativamente mais baixa no grupo glaucoma quando comparada com os indivíduos saudáveis MD=-8,49 μm, intervalo de confiança de 95% [-11,36, -5,62], P<0,001). Conclusão: Os pacientes com glaucoma parecem possuir propriedades corneanas diferentes das que apresentam os indivíduos saudáveis. Os resultados enfatizam a importância das propriedades biomecânicas da córnea na interpretação da PIO e devem contribuir para novos estudos sobre a influência da HC e da ECC no rastreio e diagnóstico do glaucoma.info:eu-repo/semantics/publishedVersio

Analysis of the Cochrane review : anti-vascular endothelial growth factor for prevention of postoperative vitreous cavity hemorrhage after vitrectomy for proliferative diabetic retinopathy : Cochrane Database Syst Rev. 2015;8:CD008214

Copyright © Ordem dos Médicos 2017Postoperative vitreous hemorrhage is a complication following vitrectomy for proliferative diabetic retinopathy, delaying visual recovery and making fundus examination and disease follow-up more difficult. Anti-vascular endothelial growth factor drugs such as bevacizumab, when injected in the vitreous cavity, reduce vascular proliferation and their use has been proposed to reduce the incidence of postoperative vitreous hemorrhage. The authors of this Cochrane systematic review evaluated all randomized controlled trials on the pre- or intraoperative use of anti-vascular endothelial growth factor to reduce postoperative vitreous hemorrhage occurrence after vitrectomy in patients with proliferative diabetic retinopathy. The results suggested that the use of intravitreal bevacizumab was effective in reducing early postoperative vitreous hemorrhage (i.e. at four weeks) occurrence, with a good safety profile. This work aims to summarize and discuss the findings and clinical implications of this Cochrane systematic review.A hemorragia vítrea pós-operatória é uma complicação da cirurgia de vitrectomia por retinopatia diabética proliferativa, que atrasa a melhoria da acuidade visual e dificulta a visualização do fundo ocular e o seguimento da doença. Quando injetados na cavidade vítrea, os fármacos anti-factor de crescimento do endotélio vascular, como o bevacizumab, diminuem a proliferação vascular e o seu uso tem sido proposto na redução da incidência de hemorragia vítrea pós-operatória. Os autores desta revisão sistemática Cochrane reviram os ensaios clínicos aleatorizados sobre o uso pré- ou intraoperatório de anti-factor de crescimento do endotélio vascular na redução da incidência de hemorragia vítrea pós-operatória após vitrectomia em doentes com retinopatia diabética proliferativa. Dos resultados, destaca-se o efeito benéfico da utilização de bevacizumab na diminuição da hemorragia vítrea pós-operatória precoce (i.e. às quatro semanas), com um bom perfil de segurança. Neste trabalho, sumarizam-se e discutem-se os principais achados e implicações práticas desta revisão sistemática Cochrane.info:eu-repo/semantics/publishedVersio

Retropupillary iris claw intraocular lens implantation in aphakia for dislocated intraocular lens

© 2016 Faria et al. This work is published and licensed by Dove Medical Press Limited. The full terms of this license are available at https://www.dovepress.com/terms.php and incorporate the Creative Commons Attribution – Non Commercial (unported, v3.0) License (http://creativecommons.org/licenses/by-nc/3.0/).Background: Nowadays, dislocated intraocular lenses (IOLs) and inadequate capsular support are becoming a challenge for every ophthalmic surgeon. Explantation of dislocated IOL and iris claw IOL (ICIOL) are the techniques that have been used in our ophthalmic department. The aim of this study is to report our technique for retropupillar ICIOL. Methods: This study is a retrospective case series. A total of 105 eyes with dislocated IOL from the patients at the Department of Ophthalmology in Santa Maria Hospital, a tertiary reference hospital in Lisbon, Portugal, from January 2012 until January 2016, had been analyzed. Of these 105 eyes, 66 eyes had dislocated one-piece IOL and 39 eyes had dislocated three-piece IOL. The latter underwent iris suture of the same IOL and were excluded from this study. The remaining 66 eyes with dislocated one-piece IOL underwent pars plana vitrectomy, that is, explantation of dislocated IOL through corneal incision and an implantation of retropupillary ICIOL. Operative data and postoperative outcomes included best corrected visual acuity, IOL position, intraocular pressure, pigment dispersion, clinical signs of endothelial cell loss, and anterior chamber depth. Results: The mean follow-up was 23 months (range: 6–48 months). The mean preoperative best corrected visual acuity was 1.260±0.771 logMAR, and postoperative best corrected visual acuity was 0.352±0.400 logMAR units. Mean vision gain was 0.909 logMar units. The patients had the following complications: 1) retinal detachment was found in one patient, 2) corneal edema was found in three patients, 3) high intraocular pressure was observed in twelve patients, 4) subluxation of the IOL was observed in one patient, and 5) macular edema was found in three eyes. Conclusion: The results demonstrate that retropupillary ICIOL is an easy and effective method for the correction of aphakia in patients not receiving capsule support. The safety of this procedure must be interpreted in the context of a surgery usually indicated in complicated cases.info:eu-repo/semantics/publishedVersio

Anti-TNF drugs for chronic uveitis in adults : a systematic review and meta-analysis of randomized controlled trials

Copyright © 2019 Leal, Rodrigues, Sousa, Duarte, Romão, Marques-Neves, Costa and Fonseca. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.Background: We aimed to assess efficacy and safety of anti-tumor necrosis factor (TNF) drugs for adult chronic non-infectious uveitis (NIU). Methods: CENTRAL, MEDLINE, and EMBASE, were searched from inception to January 2019. Double-masked randomized placebo-controlled trials, assessing any anti-TNF vs. best medical intervention/standard of care in adults with chronic NIU were considered. The PRISMA and SAMPL guidelines were followed. The risk of bias was assessed using the Cochrane risk of bias tool. Overall quality of the evidence was assessed according to GRADE. PROSPERO registration: #CRD42016039068. The primary efficacy and safety outcomes were preservation of visual acuity (VA) and withdrawals due to adverse events, respectively. Meta-analysis of efficacy analysis was not performed due to significant clinical heterogeneity between studies' population and interventions. Results: A total of 1,157 references were considered and 3 studies were included. The overall risk of bias was moderate. In active NIU, adalimumab group showed an increased likelihood of VA preservation (risk ratio (RR) 1.75, 95%CI 1.32 to 2.32, n = 217), whereas the etanercept group did not (RR 0.81, 95%CI 0.57 to 1.14, n = 20). In inactive NIU, adalimumab was associated with increased likelihood of VA preservation (RR 1.31, 95%CI 1.12 to 1.53, n = 226). The rate of adverse events did not differ between anti-TNF and control arms (RR 1.03, 95%CI 0.94 to 1.13, n = 410). Conclusions: There is high quality evidence that adalimumab decreases the risk of worsening VA in active and inactive NIU and very low quality evidence that the risk of etanercept worsening VA in inactive NIU is not different from placebo. Moderate quality evidence suggests that anti-TNF agents are not different from placebo on the risk of study withdrawal.This project received a research grant from a non-profit and scientific organization, Portuguese Society of Ophthalmology (Sociedade Portuguesa de Oftalmologia). UID/BIM/50005/2019, project funded by Fundação para a Ciência e a Tecnologia (FCT)/Ministério da Ciência, Tecnologia e Ensino Superior (MCTES) through Fundos do Orçamento de Estado (Portuguese State Funding).info:eu-repo/semantics/publishedVersio

A protocol to evaluate retinal vascular response using optical coherence tomography angiography

Copyright © 2019 Sousa, Leal, Moreira, do Vale, Silva-Herdade, Aguiar, Dionísio, Abegão Pinto, Castanho and Marques-Neves. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY).The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these termsIntroduction: Optical coherence tomography angiography (OCT-A) is a novel diagnostic tool with increasing applications in ophthalmology clinics that provides non-invasive high-resolution imaging of the retinal microvasculature. Our aim is to report in detail an experimental protocol for analyzing both vasodilatory and vasoconstriction retinal vascular responses with the available OCT-A technology. Methods: A commercial OCT-A device was used (AngioVue®, Optovue, CA, United States), and all examinations were performed by an experienced technician using the standard protocol for macular examination. Two standardized tests were applied: (i) the hypoxia challenge test (HCT) and (ii) the handgrip test, in order to induce a vasodilatory and vasoconstriction response, respectively. OCT-A was performed at baseline conditions and during the stress test. Macular parafoveal vessel density of the superficial and deep plexuses was assessed from the en face angiograms. Statistical analysis was performed using STATA v14.1 and p < 0.05 was considered for statistical significance. Results: Twenty-four eyes of 24 healthy subjects (10 male) were studied. Mean age was 31.8 ± 8.2 years (range, 18–57 years). Mean parafoveal vessel density in the superficial plexus increased from 54.7 ± 2.6 in baseline conditions to 56.0 ± 2.0 in hypoxia (p < 0.01). Mean parafoveal vessel density in the deep plexuses also increased, from 60.4 ± 2.2 at baseline to 61.5 ± 2.1 during hypoxia (p < 0.01). The OCT-A during the handgrip test revealed a decrease in vessel density in both superficial (55.5 ± 2.6 to 53.7 ± 2.9, p < 0.001) and deep (60.2 ± 1.8 to 56.7 ± 2.8, p < 0.001) parafoveal plexuses. Discussion: In this work, we detail a simple, non-invasive, safe, and non-costly protocol to assess a central nervous system vascular response (i.e., the retinal circulation) using OCT-A technology. A vasodilatory response and a vasoconstriction response were observed in two physiologic conditions—mild hypoxia and isometric exercise, respectively. This protocol constitutes a new way of studying retinal vascular changes that may be applied in health and disease of multiple medical fields.This study was supported by the Faculty of Medicine of the University of Lisbon, AstraZeneca Foundation – 14th Grant.info:eu-repo/semantics/publishedVersio

Retinal vascular reactivity in type 1 diabetes patients without retinopathy using optical coherence tomography angiography

Copyright © 2020 The Authors. This work is licensed under a Creative Commons Attribution-Non-Commercial-No-Derivatives 4.0 International License.Purpose: We hypothesize that patients with type 1 diabetes (T1D) may have abnormal retinal vascular responses before diabetic retinopathy (DR) is clinically evident. Optical coherence tomography angiography (OCTA) was used to dynamically assess the retinal microvasculature of diabetic patients with no clinically visible retinopathy. Methods: Controlled nonrandomized interventional study. The studied population included 48 eyes of 24 T1D patients and 24 demographically similar healthy volunteers. A commercial OCTA device (AngioVue) was used, and two tests were applied: (1) the hypoxia challenge test (HCT) and (2) the handgrip test to induce a vasodilatory or vasoconstrictive response, respectively. The HCT is a standardized test that creates a mild hypoxic environment equivalent to a flight cabin. The handgrip test (i.e., isometric exercise) induces a sympathetic autonomic response. Changes in the parafoveal superficial and deep capillary plexuses in both tests were compared in each group. Systemic cardiovascular responses were also comparatively evaluated. Results: In the control cohort, the vessel density of the median parafoveal superficial and deep plexuses increased during hypoxia (F1,23 = 15.69, P < 0.001 and F1,23 = 16.26, P < 0.001, respectively). In the T1D group, this physiological response was not observed in either the superficial or the deep retinal plexuses. Isometric exercise elicited a significant decrease in vessel density in both superficial and deep plexuses in the control group (F1,23 = 27.37, P < 0.0001 and F1,23 = 27.90, P < 0.0001, respectively). In the T1D group, this response was noted only in the deep plexus (F1,23 = 11.04, P < 0.01). Conclusions: Our work suggests there is an early impairment of the physiological retinal vascular response in patients with T1D without clinical diabetic retinopathy.info:eu-repo/semantics/publishedVersio

Broadening risk factor or disease definition as a driver for overdiagnosis: a narrative review

© 2022 The Authors. Journal of Internal Medicine published by John Wiley & Sons Ltd on behalf of Association for Publication of The Journal of Internal Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.Medical overuse—defined as the provision of health services for which potential harms exceed potential benefits—constitutes a paradigm of low-value care and is seen as a threat to the quality of care. Value in healthcare implies a precise definition of disease. However, defining a disease may not be straightforward since clinical data do not show discrete boundaries, calling for some clinical judgment. And, if in time a redefinition of disease is needed, it is important to recognize that it can induce overdiagnosis, the identification of medical conditions that would, otherwise, never cause any significant symptoms or lead to clinical harm. A classic example is the impact of recommendations from professional societies in the late 1990s, lowering the threshold for abnormal total cholesterol from 240 mg/dl to 200 mg/dl. Due to these changes in risk factor definition, literally overnight there were 42 million new cases eligible for treatment in the United States. The same happened with hypertension—using either the 2019 NICE guidelines or the 2018 ESC/ECC guidelines criteria for arterial hypertension, the proportion of people overdiagnosed with hypertension was calculated to be between 14% and 33%. In this review, we will start by discussing resource overuse. We then present the basis for disease definition and its conceptual problems. Finally, we will discuss the impact of changing risk factor/disease definitions in the prevalence of disease and its consequences in overdiagnosis and overtreatment (a problem particularly relevant when definitions are widened to include earlier or milder disease).info:eu-repo/semantics/publishedVersio

Edge caching with mobility prediction in virtualized LTE mobile networks

Abstract Mobile Edge Computing enables the deployment of services, applications, content storage and processing in close proximity to mobile end users. This highly distributed computing environment can be used to provide ultra-low latency, precise positional awareness and agile applications, which could significantly improve user experience. In order to achieve this, it is necessary to consider next-generation paradigms such as Information-Centric Networking and Cloud Computing, integrated with the upcoming 5th Generation networking access. A cohesive end-to-end architecture is proposed, fully exploiting Information-Centric Networking together with the Mobile Follow-Me Cloud approach, for enhancing the migration of content-caches located at the edge of cloudified mobile networks. The chosen content-relocation algorithm attains content-availability improvements of up to 500 when a mobile user performs a request and compared against other existing solutions. The performed evaluation considers a realistic core-network, with functional and non-functional measurements, including the deployment of the entire system, computation and allocation/migration of resources. The achieved results reveal that the proposed architecture is beneficial not only from the users’ perspective but also from the providers point-of-view, which may be able to optimize their resources and reach significant bandwidth savings

Anti-TNF Drugs for Chronic Uveitis in Adults—A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Background: We aimed to assess efficacy and safety of anti-tumor necrosis factor (TNF) drugs for adult chronic non-infectious uveitis (NIU).Methods: CENTRAL, MEDLINE, and EMBASE, were searched from inception to January 2019. Double-masked randomized placebo-controlled trials, assessing any anti-TNF vs. best medical intervention/standard of care in adults with chronic NIU were considered. The PRISMA and SAMPL guidelines were followed. The risk of bias was assessed using the Cochrane risk of bias tool. Overall quality of the evidence was assessed according to GRADE. PROSPERO registration: #CRD42016039068. The primary efficacy and safety outcomes were preservation of visual acuity (VA) and withdrawals due to adverse events, respectively. Meta-analysis of efficacy analysis was not performed due to significant clinical heterogeneity between studies' population and interventions.Results: A total of 1,157 references were considered and 3 studies were included. The overall risk of bias was moderate. In active NIU, adalimumab group showed an increased likelihood of VA preservation (risk ratio (RR) 1.75, 95%CI 1.32 to 2.32, n = 217), whereas the etanercept group did not (RR 0.81, 95%CI 0.57 to 1.14, n = 20). In inactive NIU, adalimumab was associated with increased likelihood of VA preservation (RR 1.31, 95%CI 1.12 to 1.53, n = 226). The rate of adverse events did not differ between anti-TNF and control arms (RR 1.03, 95%CI 0.94 to 1.13, n = 410).Conclusions: There is high quality evidence that adalimumab decreases the risk of worsening VA in active and inactive NIU and very low quality evidence that the risk of etanercept worsening VA in inactive NIU is not different from placebo. Moderate quality evidence suggests that anti-TNF agents are not different from placebo on the risk of study withdrawal