bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct metabolic profiles in ocular hypertensive individuals responding
Authors: Langbøl Mia , Andreasen Jens Rovelt , Bocca Cinzia , Saruhanian Sarkis , Tiedemann Daniel , Vohra Rupali , Lenaers Guy , Kolko Miriam 
Published: January 2024

Aims/Purpose: To determine the effect of hypoxia on the plasma metabolic signature of patients with normal‐tension glaucoma (NTG) and ocular hypertension (OHT), compared to healthy controls.Methods: Metabolomic profiles of plasma from patients with NTG (n = 10) and OHT (n = 10) were compared to age‐matched controls (n = 10) to investigate the signature of hypoxia. Participants underwent two hours of exposure to normobaric hypoxia, followed by a 30‐min recovery period in normobaric normoxia. Blood samples were collected at baseline, during hypoxia, and recovery. Plasma samples were analysed using a non‐targeted metabolomics approach based on liquid chromatography coupled with high‐resolution mass spectrometry (LC‐HRMS). Multivariate analyses were conducted using principal component analysis (PCA) and orthogonal partial least squares‐discriminant analysis (OPLS‐DA), as well as univariate analysis with Wilcoxon signed‐rank test and false discovery rate (FDR) correction.Results: Overall, controls, OHT, and NTG patients had similar regulatory patterns. Only few metabolites involved in fatty acid biosynthesis, ketone body metabolism and kynurenine pathway were affected in OHT patients exposed to hypoxia, whereas metabolites related to energy production were not modified in NTG and OHT patients. No differences were found when comparing them pairwise at baseline, or during hypoxia and recovery.Conclusions: OHT patients have altered regulation of ketogenesis and kynurenine pathway, that may explain why they do not suffer from degeneration of the optic nerve. The metabolomes of NTG and OHT patients are regulated differently from controls, and omit to regulate metabolites that are important for energy production. This can potentially contribute to neurodegeneration and ultimately cell death in retinal ganglion cells.
Ocular manifestations of juvenile lupus erythematosus: An 2023 update
Authors: Nikolaidou Anna , Frantzidis Christos 
Published: January 2024

Aims/Purpose: Juvenile Systemic Lupus Erythematosus (jSLE) is a chronic multisystem inflammatory disease that manifests before the age of 16 years, following a remitting ‐ relapsing course. The range of clinical presentations of juvenile Systemic Lupus Erythematosus (jSLE) in children is multifaceted. Ocular manifestations are uncommon for children with jSLE but can have a significant effect on their vision if not diagnosed early. Any part of the visual pathway can be affected by jSLE. The aim of this report is to systematically review the ocular manifestations of jSLE.Methods: A systematic review according to Preferred Reporting Items for Systematic Reviews and Meta‐Analyses (PRISMA) 2020 Guidelines was conducted searching MEDLINE and Scopus, including reference lists with appropriate terms for jSLE ocular manifestations. Epidemiological studies, preferably cross‐sectional studies, that describe the prevalence of ocular manifestations in children with a diagnosis or upon diagnosis of jSLE were assessed.Results: Our search yielded 131 results, screened by two independent reviewers. 33 studies were finally included in the review after preliminary assessment. Keratoconjunctivitis sicca, dry eye syndrome, retinopathy and optic neuritis are among the conditions that have been reported. Ocular manifestations in jSLE may be the result of three different mechanisms: the disease itself, infections related to immunosuppression and side effects of drug therapy. Retinal involvement is one of the most important manifestations, implying high possibility of visual loss. It is usually caused by immune complexes and autoantibodies deposition to the retinal vessels or hypertension resulting from kidney disease.Conclusions: Ocular manifestations can occur early in the course of jSLE, sometimes even before other systemic symptoms and can serve as markers of disease activity. Diagnosing ocular manifestations in children with jSLE is important for early intervention, monitoring disease activity, preventing vision loss and providing comprehensive care. By addressing ocular manifestations alongside systemic lupus management, healthcare providers can optimize outcomes and improve the overall well‐being of children with jSLE.
Brain‐derived neurotrophic factor alleviates clinical symptoms of experimental autoimmune uveoretinitis and supports retinal regeneration
Authors: Zloh Miloslav , Štofková Andrea 
Published: January 2024

Purpose: Brain‐derived neurotrophic factor (BDNF) is one of the most important neurotrophins that has a fundamental role in the regulation of neuronal growth, proliferation, and regeneration, as well as an important modulatory effect on the immune cells. In addition, BDNF potentiates the neurodifferentiation of Müller cells (MCs), thus supporting retinal regeneration. Therefore, we aimed to investigate the anti‐inflammatory effect of BDNF in experimental autoimmune uveoretinitis (EAU), a severe neuroinflammatory condition, and whether BDNF could facilitate the regenerative capacity of MCs in EAU.Methods: EAU in mice was induced by s.c. administration of retinal antigen IRBP1‐20 emulsified in a complete Freud's adjuvant, followed by i.v. administration of Pertussis toxin. BDNF was administered daily in the form of eye drops from day 8 to day 14 after immunization. On day 14, fundoscopy was performed to assess clinical signs of EAU. Mice were then euthanized, and their eyes and retinas were isolated for further Western blot, RT‐qPCR, flow cytometry, and immunohistochemistry analyses.Results: The treatment with BDNF significantly improved the clinical manifestations of EAU, including optic disc oedema, vasculitis, and inflammatory infiltrates in the retina. BDNF significantly decreased the infiltration of CD4+ T cells, CD8+ T cells, and CD11b+ myeloid cells into the retina and also suppressed the expression of several pro‐inflammatory cytokines and chemokines. In addition, BDNF administration significantly increased the expression of markers of neurogenesis in retinal MCs.Conclusions: Together, our results demonstrate that BDNF has important anti‐inflammatory and neurogenic properties and that it may serve as a promising target for developing novel therapeutic strategies for neurodegenerative and neuroinflammatory diseases of the retina.Support.This study was supported by the following grant projects: GAUK 378421, 260 648/SVV/2023, and COOPERATIO Neurosciences.
Combined treatment of a giant palpebral keratoacanthoma
Authors: Sanchez Manuel Morales , Revuelta Alvaro Diaz‐Rato , Hernandez Eduardo Conesa , Artola Ines , Pernas Sergio 
Published: January 2024

Aims/Purpose: To highlight the relevance of a therapeutic approach adapted to the clinical characteristics of the eyelid lesion found at the time of surgery to ensure an optimal functional and aesthetic result.Methods: Clinical case assessed, intervened and followed up at our centre.Results: A 76‐year‐old woman consulted for a nodular umbilicated lesion of recent appearance on the outer third of the upper eyelid of the left eye (UELE) measuring 0.5 cm in greatest diameter and 0.5 cm in elevation. The patient was placed on the waiting list for surgical excision and subsequent pathological examination (PE) of the lesion to confirm the initial clinical suspicion of keratoacanthoma (KA). One month later, the patient went to the operating room for surgery. During this time the lesion increased its initial size by more than 4 times, had a large necrotic centre, active borders and generated an evident left mechanical ptosis. As an alternative to the complete excisional surgery initially proposed, we offered the injection of neoadjuvant intralesional chemotherapy (CT) with the aim of reducing the size of the lesion to obtain a better functional and aesthetic result. The patient accepted this therapeutic alternative. KA was treated with weekly intralesional injections of 1 mL of methotrexate (MTX) 12.5 mg/mL. In our case, 3 injections were necessary to achieve a 78% reduction in the diameter of the lesion to allow reconstruction of the UELE with grafting of the contralateral upper eyelid. One week after the third injection of MTX, reconstruction of the UELE was performed after excisional surgery with wide margins for PE. One week later, the PE result ruled out malignancy and the graft had a pink appearance with complete vascular permeability, so the sutures were removed. Two weeks after reconstruction, the functional and aesthetic results were satisfactory.Conclusions: Therefore, in our experience, we recommend the above combined treatment for giant palpebral KA and stress the relevance of a therapeutic approach adapted to the clinical characteristics of the palpebral lesion at the time of surgery to ensure an optimal functional and aesthetic outcome.References1. Patel NP, Cervino AL. Treatment of keratoacanthoma: is intralesional methotrexate an option? Can J Plast Surg 2011; 19: e15‐8.
Microglial involvement in ocular hypertension
Authors: Salobrar‐Garcia Elena 
Published: January 2024

Glaucoma, a chronic and multifactorial neurodegenerative disease, is the leading cause of irreversible blindness. It is characterized by the degeneration of retinal ganglion cells (RGCs), loss of their axons, and damage to the lamina cribrosa. To study glaucomatous optic neuropathy, experimental rodent models are commonly used due to their low cost, ease of handling, and similarities to the human retina. The ideal model must reproduce tissue changes observed in human glaucoma, such as alterations of the optic nerve head, thinning of the retinal nerve fibre layer, activation of glial cells, and progressive degeneration of RGCs.The DBA/2J transgenic mouse model is the most commonly used genetic model, characterized by a gradual increase in intraocular pressure (IOP) with age, leading to rapid and progressive loss of RGCs and optic nerve degeneration. However, limitations such as iris atrophy and peripheral anterior synechiae can alter the anterior segment and influence IOP measurement. Induced models of ocular hypertension (OHT) have a predictable IOP increase following experimental procedures, but this increase is usually rapid and sustained for a relatively short time, which may not represent the slow and sustained IOP elevation observed in primary open‐angle glaucoma. Nonetheless, induced models produce similar pathophysiological mechanisms to genetic models. Other models include the injection of hypertonic saline into episcleral veins to cause scarring of the trabecular meshwork and elevate IOP, and the intracameral injection of polystyrene or magnetic microbeads to obstruct normal drainage flow of aqueous humour, resulting in an IOP increase. A new model employs an intracameral injection of a cross‐linking polymer that produces a viscosity increase, impeding normal drainage of the aqueous humour and resulting in an IOP increase and loss of RGCs.In this SIS, we review the different glaucoma models, their methods, and the retinal tissue changes, with a focus on microglial cell changes.
Retinal glial cell response in a neurodevelopmental disease such as the Dravet syndrome
Authors: Fernández‐Albarral José A. 
Published: January 2024

Dravet syndrome (DS) is an epileptic encephalopathy caused by mutations in the Scn1a gene encoding the α1 subunit of the Nav1.1 sodium channel, which is associated with recurrent and generalized seizures, highly resistant to antiepileptic drugs, which is related to cognitive impairment, developmental delays, hyperactivity, dysautonomia, attention deficit, language impairment, autistic features, even leading to death. GABAergic interneurons are particularly affected, where the Nav1.1 channel is mainly located and the consequent imbalance between excitation and inhibition triggers brain hyperexcitability and seizures, altering the correct functioning of neural networks involved in cognitive processes.Glial reactivity and neuroinflammatory processes have been shown to be present in childhood epileptic processes and therefore cytokines may exert a neuromodulatory role directly impacting neuronal excitability. Indeed, astrocytes have been documented to be involved in the pathogenesis of epilepsy, regulating neurotransmitter and ion concentrations.In our experimental model of DS (Syn‐Cre/Scn1aWT/A1783V), inflammatory events in the prefrontal cortex and dentate gyrus of the hippocampus expressed as an increase in GFAP (astrocyte marker) and Iba‐1 (microglia marker) immunoreactivity have been observed, in addition to morphological changes compatible with activated astrocytes and microglia.The retina is a projection of the brain, and in several pathologies affecting the central nervous system, such as neurodegenerative diseases, correlation between changes occurring in the brain and those occurring in the retina has been shown. Therefore, the analyse of the changes that may occur in retinal glial cells (astrocytes and microglia) in an experimental model of DS, and the correlation with the alterations observed in some specific cerebral areas of these animals could be good predictive and prognostic biomarkers for future treatment.This study analyzes the retinal histological changes in glial cells (microglia and astrocytes), retinal ganglion cells (RGCs) and GABAergic amacrine cells in an experimental model of DS (Syn‐Cre/Scn1aWT/A1783V) compared to a control group at postnatal day (PND) 25. Retinal whole‐mounts were labelled with anti‐GFAP, anti‐Iba‐1, anti‐Brn3a and anti‐GAD65/67. Signs of microglial and astroglial activation and the number of Brn3a+ and GAD65+ 67+ cells were quantified. We found retinal activation of astroglial and microglial cells but not death of RGCs and GABAergic amacrine cells. These changes are similar to those found at the level of the hippocampus in the same experimental model in PND25, indicating a relationship between brain and retinal changes in DS. This suggests that the retina could serve as a possible biomarker in DS.
Biomarkers in macular hole surgery
Authors: Motta Lorenzo 
Published: January 2024

A macular hole is a condition that affects the central part of the retina, the macula. It is characterized by the formation of a hole or tear in the tissue, which can lead to blurred or distorted vision. Early detection and treatment of macular holes are critical to prevent permanent vision loss. Biomarkers are measurable indicators of biological processes that can aid in the diagnosis and management of macular holes.One of the most commonly used biomarkers for macular holes is optical coherence tomography (OCT). OCT uses light waves to create high‐resolution images of the retina, allowing for the detection and monitoring of macular holes. OCT can also be used to measure the size and depth of the hole, which can help guide treatment decisions.Another biomarker for macular holes is the presence of cytokines and growth factors in the vitreous, the gel‐like substance that fills the eye. Cytokines and growth factors are signalling molecules that play a role in the inflammatory response and tissue repair. In patients with macular holes, the levels of certain cytokines and growth factors are altered, indicating the presence of inflammation and tissue damage.Recent studies have also identified genetic biomarkers associated with the development and progression of macular holes. For example, mutations in the FZD4 gene have been linked to an increased risk of macular holes, while variations in the CX3CR1 gene have been associated with a more severe form of the condition.Biomarkers can also be used to monitor the response to treatment in patients with macular holes. For example, changes in cytokine and growth factor levels following treatment can indicate whether the treatment is effective in reducing inflammation and promoting tissue repair. Similarly, changes in OCT measurements can indicate whether the hole is closing and vision is improving.Overall, biomarkers play an important role in the diagnosis, management, and monitoring of macular holes. By providing objective measures of disease progression and response to treatment, biomarkers can improve outcomes for patients with this condition. However, more research is needed to fully understand the role of biomarkers in macular holes and to identify new biomarkers that may aid in the diagnosis and treatment of this condition.
Biomarkers in diabetic retinopathy
Authors: Zaman Anwar 
Published: January 2024

Diabetic retinopathy (DR) is a leading cause of blindness in working‐age adults worldwide, affecting up to 80% of patients who have had diabetes for more than 10 years. Biomarkers are measurable indicators that can be used to diagnose diseases or monitor their progression. In DR, biomarkers can be found in various structures of the eye, including the retina, vitreous, and aqueous humour.One of the most commonly used biomarkers in DR is glycated haemoglobin (HbA1c), which reflects long‐term blood glucose control. Elevated HbA1c levels are associated with an increased risk of developing DR, and strict glycemic control can help to prevent or delay its onset.Other biomarkers in DR include imaging techniques such as optical coherence tomography (OCT) and fundus photography, which can provide detailed images of the retina and allow for the detection of microaneurysms, haemorrhages, and exudates. OCT angiography (OCTA) can also visualize changes in retinal blood flow, which may be indicative of early DR.In addition to structural biomarkers, there are also functional biomarkers that can be used to evaluate visual function, such as contrast sensitivity and visual field testing. These measures are often used to monitor the progression of DR and assess the efficacy of treatment.Recent advances in biomarker research have led to the discovery of new markers for DR, including genetic markers, inflammatory markers, and metabolic markers. Genetic markers, such as single nucleotide polymorphisms (SNPs), have been associated with an increased risk of developing DR. Inflammatory markers, such as cytokines and chemokines, are elevated in the aqueous humour and vitreous of patients with DR and may contribute to the development and progression of the disease. Metabolic markers, such as advanced glycation end‐products (AGEs), are elevated in patients with DR and may play a role in the pathogenesis of the disease.Overall, biomarkers are an important tool in the diagnosis, monitoring, and management of DR. They may also help to improve our understanding of the disease and facilitate the development of new therapies. By identifying patients at high risk of developing DR, biomarkers may enable earlier interventions to prevent or delay the onset of vision loss.
Biomarkers in epiretinal membrane surgery
Authors: Vakalis Athanasios 
Published: January 2024

Vitreoretinal Surgery for the removal of Epiretinal membranes is a well‐established surgical indication. Despite refinement of surgical techniques and the revolution in imaging brought by the advent of Optical Coherence Tomography, a significant proportion of patients fails to gain vision postoperatively.In this talk we will discuss OCT biomarkers that help as distinguish those who can improve most following surgery from those unlikely to respond.
Analysis of vitreous by optical coherence tomography as biomarker in neurodegenerative diseases
Authors: Maria Jesús Rodrigo , Ana Pueyo , Alberto Montolío , Amaya Perez del Palomar , José Cegoñino , Luis Pablo , Rocío Herrero‐Vanrell , Irene Bravo‐Osuna , Elena García‐Martín 
Published: January 2024

Purpose: Neurodegeneration is multifactorial and the immune factor is key. Chronic and acute inflammation can be analysed as hyperreflective opacities in the vitreous (HOV) by optical coherence tomography (OCT) imaging. This study analyzes vitreous cellularity by OCT in two neurodegenerative diseases, chronic glaucoma (CG) and relapsing remitting multiple sclerosis (RRMS) compared to healthy individuals.Methods: Four models of CG generated in rats by episcleral veins sclerosis (EVS n = 35) or injection of biodegradable microspheres into the anterior chamber of the eye non‐loaded (Ms n = 28) and loaded with dexamethasone (Dex n = 43) and Dex‐fibronectin (DexFibro n = 44), compared to healthy rats (n = 32). In addition, patients with RRMS treated (n = 20) and healthy subjects (n = 20) were analysed. The relative intensity of vitreous/retinal pigment epithelium (VIT/RPE) obtained from OCT (for animal and human use) images was quantified. A custom program computational analysis characterizes in vivo the HOV (number and size), identified histologically as hyalocyte‐like Iba‐1+ (microglial marker) cells in animals. For humans, artificial intelligence methods and Image J software were used.Results: Both image analysis techniques identified HOV in animals with chronic glaucoma, in patients with RRMS and in healthy (both animals and humans). Chronic glaucoma models presented more HOV than healthy (decreasing from 100 ‐EVS‐ to 15 ‐healthy‐) (p < 0.05). Corticosteroid models presented an anti‐inflammatory profile (with non‐activated cells as the highest population). However, according VIT/RPE intensity, patients with RRMS treated did not show differences vs. healthy humans (p > 0.44).Conclusions: HOV analysed by OCT were identified in neurodegenerative diseases of chronic course, in outbreaks, and healthy individuals. The presence of anti‐inflammatory drugs (dexamethasone in animals) and immunemodulators (in humans) decreased the VIT/RPE intensity resembling healthy conditions.Acknowledgments: Grants MAT2017‐83858‐C2‐1 and MAT2017‐83858‐C2‐2 funded by MCIN/AEI/ 10.13039/501100011033 and by “ERDF A way of making Europe”. Grants PID2020‐113281RB‐C21 and PID2020‐113281RB‐C22 funded by MCIN/AEI/ 10.13039/501100011033. Research Group UCM920415 (InnOftal). MJR thanks for the grants M17/00213 and JR22_00057.