João Castro-De-Sousa

BackgroundThe ILUVIEN Registry Safety Study was a multicentre, open-label, non-randomised, observational, phase 4 study designed to assess the safety and effectiveness of the fluocinolone acetonide (FAc) implant in all indications in real-world practices in Europe.MethodsThe study included data collected prospectively and retrospectively. Patients receiving FAc implants between 2013 and 2017 were included and monitored until the last patient reached ≥3 years of follow-up. Mean intraocular pressure (IOP) data over the course of the study, along with IOP events, use of IOP-lowering therapy, mean change in visual acuity (VA) and information on supplemental therapy use were analysed post-FAc implantation.ResultsSix hundred and ninety-five eyes from 556 patients, with a mean±SD follow-up of 1150.5±357.36 days, were treated with a FAc implant. 96.7% of eyes had chronic diabetic macular oedema (cDMO). IOP lowering was achieved in 34.5% of eyes using topical agents and 4.3% by surgery. Seve...

Rhegmatogenous retinal detachment (RRD) is a potentially blinding condition characterized by a physical separation between neurosensory retina and retinal pigment epithelium. Quantitative proteomics can help to understand the changes that occur at the cellular level during RRD, providing additional information about the molecular mechanisms underlying its pathogenesis. In the present study, iTRAQ labeling was combined with two-dimensional LC-ESI-MS/MS to find expression changes in the proteome of vitreous from patients with RRD when compared to control samples. A total of 150 proteins were found differentially expressed in the vitreous of patients with RRD, including 96 overexpressed and 54 underexpressed. Several overexpressed proteins, several such as glycolytic enzymes (fructose-bisphosphate aldolase A, gamma-enolase, and phosphoglycerate kinase 1), glucose transporters (GLUT-1), growth factors (metalloproteinase inhibitor 1), and serine protease inhibitors (plasminogen activator...

The aim of this study was to evaluate subfoveal choroidal thickness (SFCT) as a marker of outcome in real-world treatment of diabetic macular edema (DME) and to correlate it with choroidal thicknesses (CT) collected around the fovea. Prospective interventional case series included a total of 126 eyes from 126 patients with recently diagnosed DME treated with a 3-monthly loading dose of ranibizumab or aflibercept and PRN thereafter until 24 months (M). CT was manually measured in the central 3500 μm area, subfoveally (SFCT), at 1750 μm right and left from the center in the horizontal plane and at 1750 μm up and down from the center in the vertical plane, by OCT. Anatomic (10% decrease in central retinal thickness) and functional (gain ≥ 5 letters) responses were assessed using univariate and multivariate analyses. The areas under ROC curves were used to assess whether baseline SFCT was a predictor of outcome. CT significantly decreased in all follow-ups (3 months after the 3 injectio...

Proteomic analysis of human vitreous humor (VH) may elucidate the pathogenesis of retinal ocular diseases and may provide information for the development of potential therapeutic targets due to its pivotal location near lens and retina. The discovery of whole VH proteome involves a complex analysis of thousands of proteins simultaneously. Therefore, in proteomic studies the protein fractionation is important for reducing sample complexity, facilitating the access to the low-abundant proteins, and recognizing them as biotargets for clinical research. Although several separation methods have been used, gel-based proteomics are the most popular and versatile ones applied for global protein separation. However, chromatographic methods and its combination with other separation techniques are now beginning to be used as promising set-ups for VH protein identification. This review attempts to offer an overview of the techniques currently used with VH, exploring its methodological demands, exposing its advantages, and helping the reader to plan future experiences. Moreover, this review shows the relevance of VH proteomic analysis as a tool for the study of the mechanisms underlying some ocular diseases and for the development of new therapeutic approaches.

The vitreous humor (VH) is the largest component of the eye. It is a colorless, gelatinous, highly hydrated matrix that fills the posterior segment of the eye between the lens and retina in vertebrates. In VH, a diversity of proteins that can influence retinal physiology is present, including growth factors, hormones, proteins with transporter activity, and enzymes. More importantly, the protein composition of VH has been described as being altered in a number of disease states. Therefore, attempts aiming at establishing a map of VH proteins and detecting putative biomarkers for ocular illness or protein fluctuations with putative physiologic significance were conducted over the last two decades, using proteomic approaches. Proteomic strategies often involve gel-based or LC techniques as sample fractioning approaches, subsequently coupled with MS procedures. This set of studies resulted in the proteomic characterization of a range of ocular disease samples, with particular incidence...

Oxidative stress is defined as an unbalance between pro-oxidants and antioxidants, as evidenced by an increase in reactive oxygen and reactive nitrogen species production over time. It is important in the pathophysiology of retinal disorders such as diabetic retinopathy, age-related macular degeneration, retinal detachment, and proliferative vitreoretinopathy, which are the focus of this article. Although the human organism’s defense mechanisms correct autoxidation caused by endogenous or exogenous factors, this may be insufficient, causing an imbalance in favor of excessive ROS production or a weakening of the endogenous antioxidant system, resulting in molecular and cellular damage. Furthermore, modern lifestyles and environmental factors contribute to increased chemical exposure and stress induction, resulting in oxidative stress. In this review, we discuss the current information about oxidative stress and the vitreous proteome with a special focus on vitreoretinal diseases. Add...

AimsThe ILUVIEN Registry Safety Study is an ongoing, multicentre, open-label, observational study collecting real-world data on the safety and effectiveness of the 0.2 µg/day fluocinolone acetonide (FAc) implant in patients treated according to the European label requirements.MethodsPatients included in this analysis were treated for the licensed indication of chronic diabetic macular oedema (cDMO; that is, DMO that persists or recurs despite treatment). Data presented in the current analysis were collected from patient records up to 6 March 2017. Visual acuity (VA) data, including mean change in VA over time and at last observation, intraocular pressure (IOP) over the course of the study, IOP events, use of IOP-lowering therapy and cup:disc ratio were analysed. Information on additional DMO treatments post-FAc implant was also captured.ResultsFive hundred and sixty-three patients (593 eyes) were enrolled on the study. Mean IOP for the overall population remained within the normal r...

Records of lightning data in mainland Portugal began in June 2002. Since then, the spatial-temporal variability of lighting in Portugal has been assessed in some previous studies. A first attempt to model days with low or high atmospheric electrical activity is presented in this work. Firstly, dynamically coherent lightning regimes in Portugal are isolated and, secondly, an innovative methodology is implemented for a statistical-dynamical modeling of the lightning intensity over the country (strong or weak). High-resolution reanalysis datasets are used for this purpose and three lightning regimes are then identified for Portugal: winter regional – WREG, winter remote – WREM and summer regime – SREG. WREG is a typical cold-core cut-off low. WREM is associated with intense frontal systems controlled by remote low pressure systems over the North Atlantic at higher latitudes. SREG combines an inverted trough system with a mid-tropospheric cold-core in the proximity of Portugal. The stat...

ABSTRACT Atmospheric lightning is an important atmospheric hazard, as cloud-to-ground discharges (CGD) can affect people, can lead to severe damages in buildings, equipment, and can trigger forest fires. The potential damages directly linked to CGD have been increasing as society develops (e.g. due to greater use of electronic equipment). However, an adequate risk assessment requires an analysis in depth of the CGD spatial-temporal distributions. Further, the climate change impacts on the lightning activity still present many uncertainties. Nevertheless, there is a wide agreement in the scientific community that climate change in Europe is likely to impact on frequency, severity and location of extreme events. The Portuguese meteorological office (IPMA) maintains a lightning detection network (LDN) over mainland Portugal since June 2002. Due to the recent and short time period of available data, there are only few studies using this dataset. The RAIDEN project (contract number PTDC/CTE-ATM/101931/2008) - Lightning activity in Portugal: variability patterns and socioeconomic impacts - aims (1) to characterize the spatial-temporal variability of the lightning activity over mainland Portugal and (2) to assess its corresponding risks and socioeconomic impacts. This study is based on data provided by the Portuguese LDN and follows a multidisciplinary approach. As such, the project is focused on a 7-year period (2003-2009) of CGD data and the research program started studying the main climatological aspects of lightning activity, regarding the spatial patterns of the CGD occurrences, as well as their temporal variability at different time scales (inter-annual, seasonal and daily variability). The spatial patterns of the CGD occurrences over Portugal have also been categorized taking into account their spatial spread and strength using a clustering methodology. Furthermore, the dynamical mechanisms underlying the CGD occurrences, including the identification of the main lightning regimes in Portugal, have been studied. In this analysis a number of driving atmospheric parameters have been isolated in order to develop a dynamical-statistical modeling of the CGD occurrences in Portugal, with a direct application to weather forecasting.

ABSTRACT This paper addresses a predictive control strategy for Unmanned Air Vehicles in the presence of bounded disturbances. The goal is to guarantee tracking capabilities with respect to a reference trajectory which is pre-specified using the differential flatness formalism. Furthermore, an off-line linearization strategy of the nonlinear model of the vehicle along the flat trajectory is proposed. Since the reference trajectory is available beforehand, an optimization problem which minimizes the tracking error for the vehicle is formulated in a predictive control framework. The proposed method exhibits effective performance validated through software-in-the-loop simulations for the control of Unmanned Aerial Vehicles (UAVs).

ABSTRACT The present study employs a dataset of cloud-to-ground discharges over Portugal, collected by the Portuguese lightning detection network in the period of 2003-2009, to identify dynamically coherent lightning regimes in Portugal and to implement a statistical-dynamical modeling of the daily discharges over the country. For this purpose, the high-resolution MERRA reanalysis is used. Three lightning regimes are then identified for Portugal: WREG, WREM and SREG. WREG is a typical cold-core cut-off low. WREM is connected to strong frontal systems driven by remote low pressure systems at higher latitudes over the North Atlantic. SREG is a combination of an inverted trough and a mid-tropospheric cold-core nearby Portugal. The statistical-dynamical modeling is based on logistic regressions (statistical component) developed for each regime separately (dynamical component). It is shown that the strength of the lightning activity (either strong or weak) for each regime is consistently modeled by a set of suitable dynamical predictors (65-70% of efficiency). The difference of the equivalent potential temperature in the 700-500 hPa layer is the best predictor for the three regimes, while the best 4-layer lifted index is still important for all regimes, but with much weaker significance. Six other predictors are more suitable for a specific regime. For the purpose of validating the modeling approach, a regional-scale climate model simulation is carried out under a very intense lightning episode.