Publications by authors named "Maria F Cordeiro"

The term inherited retinal dystrophies (IRDs) refers to a diverse range of conditions characterized by retinal dysfunction, and mostly deterioration, leading to a gradual decay of the visual function and eventually to total vision loss. IRDs have a global impact on about 1 in every 3000 to 4000 individuals. However, the prevalence statistics might differ significantly depending on the exact type of dystrophy and the demographic being examined.

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Macular atrophy (MA) is an irreversible endpoint of age-related macular degeneration (AMD), which is the leading cause of blindness in the world. Early detection is therefore an unmet need. We have developed a novel automated method to identify MA in patients undergoing follow-up with optical coherence tomography (OCT) for AMD based on the combination of 2D and 3D Unet architecture.

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/: Optic neuropathies are a category of illnesses that ultimately cause damage to the optic nerve, leading to vision impairment and possible blindness. Disorders such as dominant optic atrophy (DOA), Leber hereditary optic neuropathy (LHON), and glaucoma demonstrate intricate genetic foundations and varied phenotypic manifestations. This narrative review study seeks to consolidate existing knowledge on the genetic and molecular mechanisms underlying ocular neuropathies, examine genotype-phenotype correlations, and assess novel therapeutic options to improve diagnostic and treatment methodologies.

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Glaucoma stands as a primary cause of irreversible blindness globally, characterized by the progressive dysfunction and loss of retinal ganglion cells (RGCs). While current treatments primarily focus on controlling intraocular pressure (IOP), many patients continue to experience vision loss. Therefore, the research focus has shifted to therapeutic targets aimed at preventing or delaying RGC death and optic nerve degeneration to slow or halt disease progression.

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Primary open angle glaucoma (POAG) is defined as a "genetically complex trait", where modifying factors act on a genetic predisposing background. For the majority of glaucomatous conditions, DNA variants are not sufficient to explain pathogenesis. Some genes are clearly underlying the more "Mendelian" forms, while a growing number of related polymorphisms in other genes have been identified in recent years.

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Objectives: To compare intraocular pressure (IOP) during the water drinking test (WDT) and modified diurnal tension curve (mDTC) in open-angle glaucoma (OAG) patients, using multimodal, observer-masked tonometry.

Methods: Open-angle glaucoma subjects were prospectively enroled, excluding those who had undergone glaucoma filtration or laser surgery. Two-hourly mDTC Goldmann applanation (GAT) and rebound tonometry (RT) was performed between 8:00 and 16:00, and every 15 min for 45 min after ingestion of 800mls of water.

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. Retinitis pigmentosa (RP) is the most common inherited rod-cone dystrophy (RCD), resulting in nyctalopia, progressive visual field, and visual acuity decay in the late stages. The autosomal dominant form (ADRP) accounts for about 20% of RPs.

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The process of senescence impairs the function of cells and can ultimately be a key factor in the development of disease. With an aging population, senescence-related diseases are increasing in prevalence. Therefore, understanding the mechanisms of cellular senescence within the central nervous system (CNS), including the retina, may yield new therapeutic pathways to slow or even prevent the development of neuro- and retinal degenerative diseases.

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DARC (detection of apoptosing retinal cells) uses fluorescently tagged Annexin A5 to identify retinal apoptosis non-invasively in vivo using a confocal laser scanning ophthalmoscope (cSLO). This can provide insights into the presence and progression of disease pathology and the efficacy of neuroprotective intervention. The methods of administration, imaging, and quantification of DARC, including the operation of the cSLO, are described here.

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Glaucoma is currently considered one of the leading causes of severe visual impairment and blindness worldwide. Topical medical therapy represents the treatment of choice for many glaucoma patients. Introduction of latanoprost, 25 years ago, with an entirely new mechanism of action from that of the antiglaucoma drugs used up to that time was a very important milestone.

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Here, we have developed a deep learning method to fully automatically detect and quantify six main clinically relevant atrophic features associated with macular atrophy (MA) using optical coherence tomography (OCT) analysis of patients with wet age-related macular degeneration (AMD). The development of MA in patients with AMD results in irreversible blindness, and there is currently no effective method of early diagnosis of this condition, despite the recent development of unique treatments. Using OCT dataset of a total of 2211 B-scans from 45 volumetric scans of 8 patients, a convolutional neural network using one-against-all strategy was trained to present all six atrophic features followed by a validation to evaluate the performance of the models.

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Introduction: Age-related macular degeneration (AMD) is a leading cause of irreversible visual impairment worldwide. The endpoint of AMD, both in its dry or wet form, is macular atrophy (MA) which is characterized by the permanent loss of the RPE and overlying photoreceptors either in dry AMD or in wet AMD. A recognized unmet need in AMD is the early detection of MA development.

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Motile and non-motile cilia are associated with mutually-exclusive genetic disorders. Motile cilia propel sperm or extracellular fluids, and their dysfunction causes primary ciliary dyskinesia. Non-motile cilia serve as sensory/signalling antennae on most cell types, and their disruption causes single-organ ciliopathies such as retinopathies or multi-system syndromes.

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This case-control study aims to compare the efficacy, safety, and postoperative burden of MicroShunt versus trabeculectomy. The first consecutive cohort of MicroShunt procedures (n = 101) was matched to recent historical trabeculectomy procedures (n = 101) at two London hospital trusts. Primary endpoints included changes in intraocular pressure (IOP) and glaucoma medications.

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Objective: Propose a theoretical framework for retinal biomarkers of Alzheimer's disease (AD).

Background: The retina and brain share important biological features that are relevant to AD. Developing retinal biomarkers of AD is a strategic priority but as yet none have been validated for clinical use.

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The resident macrophages of the central nervous system, microglia, are becoming increasingly implicated as active participants in neuropathology and ageing. Their diverse and changeable morphology is tightly linked with functions they perform, enabling assessment of their activity through image analysis. To better understand the contributions of microglia in health, senescence, and disease, it is necessary to measure morphology with both speed and reliability.

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Diabetic retinal disease remains one of the most common complications of diabetes mellitus (DM) and a leading cause of preventable blindness. The mainstay of management involves glycemic control, intravitreal, and laser therapy. However, intravitreal therapy commonly requires frequent hospital visits and some patients fail to achieve a significant improvement in vision.

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Microglia are the resident immune cells of the central nervous system (CNS), including the retina. Similar to brain microglia, retinal microglia are responsible for retinal surveillance, rapidly responding to changes in the environment by altering morphotype and function. Microglia become activated in inflammatory responses in neurodegenerative diseases, including multiple sclerosis (MS).

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DARC (Detection of Apoptosing Retinal Cells) is a retinal imaging technology that has been developed within the last 2 decades from basic laboratory science to Phase 2 clinical trials. It uses ANX776 (fluorescently labelled Annexin A5) to identify stressed and apoptotic cells in the living eye. During its development, DARC has undergone biochemistry optimisation, scale-up and GMP manufacture and extensive preclinical evaluation.

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Purpose: To investigate the efficacy of intravitreal dexamethasone implants (DEX) after anti-VEGF failure in retinal vein occlusion macular oedema.

Methods: Retrospective cohort study of DEX implant (0.7 mg) given after anti-VEGF 'failure'.

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Article Synopsis
  • The study evaluated a new convolutional neural network (CNN) called DARC, which predicts the formation of subretinal fluid in patients with Age-related Macular Degeneration (AMD).
  • Using 427 OCT images from 29 AMD eyes, researchers found that a DARC count greater than 5 at baseline was significantly linked to new subretinal fluid development over three years.
  • The results showed that DARC could effectively identify early signs of neovascular activity in AMD, suggesting its potential as a biomarker for preventing vision loss, though more extensive studies are needed to confirm its effectiveness.
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Gastro-intestinal function plays a vital role in conditions ranging from inflammatory bowel disease and HIV through to sepsis and malnutrition. However, the techniques that are currently used to assess gut function are either highly invasive or unreliable. Here we present an alternative, non-invasive sensing modality for assessment of gut function based on fluorescence spectroscopy.

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With the increasing global burden of glaucoma-caused blindness there is a significant need to develop therapies that both enable early detection of retinal neurodegeneration, and help protect cells from the neurodegenerative processes of glaucoma. In this chapter, we discuss potential neuroprotective agents that are present naturally and examine their role and suitability as therapies in glaucoma. These agents have been found to have anti-apoptotic and anti-inflammatory mechanisms of action which may aid the resilience of retinal ganglion cells and enable them to withstand potential insults that trigger cell death.

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In this article, using the integration of paper microfluidics within laser-inscribed commercial contact lenses, we demonstrate the multiplexed detection of clinically relevant analytes including hydrogen ions, proteins, glucose, nitrites and l-ascorbic acid, all sampled directly from model tears. In vitro measurements involved the optimization of colorimetric assays, with readouts collected, stored and analyzed using a bespoke Tears Diagnostics smartphone application prototype. We demonstrate the potential of the device to perform discrete measurements either for medical diagnosis or disease screening in the clinic or at the point-of-care (PoC), with future applications including monitoring of ocular infections, uveitis, diabetes, keratopathies and assessing oxidative stress.

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Background: A key objective in glaucoma is to identify those at risk of rapid progression and blindness. Recently, a novel first-in-man method for visualising apoptotic retinal cells called DARC (Detection-of-Apoptosing-Retinal-Cells) was reported. The aim was to develop an automatic CNN-aided method of DARC spot detection to enable prediction of glaucoma progression.

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