bluuebunny/crossref_metadata_2025_split huggingface dataset:
Gut microbial dysbiosis in age‐related macular degeneration
Authors: Vergroesen Joëlle , Vermeulen Jeroen , Thee Eric , Liefers Bart , Klaver Caroline 
Published: January 2025

Purpose: The gut microbiome is highly influential in diseases with inflammatory components. Multiple studies showed a link between the gut microbiome and age‐related macular degeneration (AMD). However, no consistent taxa have been reported.Methods: We included 1372 participants from the Rotterdam Study (RS). AMD features (e.g. [reticular pseudo‐]drusen, retinal pigment epithelium degeneration, and hyperpigmentation) were graded by human graders on color fundus photographs. Next, areas of these features were automatically quantified by a deep learning segmentation model. Stages were determined according to the RS classification (preliminary = 239, early‐intermediate = 75, late = 6). Propensity score matching was performed on age, sex and BMI. Multivariable associations with taxonomic and functional profiles were assessed using zero‐adjusted models (MaAsLin2; Compound Poisson). p‐values were false discovery rate‐adjusted (q‐values). Taxa associated (q < 0.25) with at least two out of seven AMD(‐related) outcomes are reported.Results: We observed no associations with alpha‐ or beta‐diversity. Nineteen taxa were associated with AMD, of which 7 persisted after additional adjustment for dietary data. Eubacterium xylanophilum group, Lachnoclostridium, Faecalibacterium, Odoribacter splanchnicus and Parabacteroides distasonis were associated with an AMD phenotype. Parabacteroides and Akkermansia were inversely associated with an AMD phenotype. Moreover, 46 MetaCyc pathways were associated with AMD, of which 15 persisted after additional adjustment for dietary data. GLUCARDEG.PWY, PWY.5028, PWY.5347, PWY.5415, PWY.5532, PWY.5971, PWY.6969 and TCA were associated with an AMD phenotype. FOLSYN.PWY, LEU.DEG2.PWY, PANTO.PWY, PANTOSYN.PWY, PWY.6612, PWY0.1586 and PYRIDNUCSYN.PWY were inversely associated with an AMD phenotype.Conclusions: Several gut microbiota were associated with an AMD phenotype. AMD pathophysiology might be linked to changes in gut‐related metabolic pathways.
The cumulative impact of air pollution on dry eye disease: Evidence from the Korea National Health and Nutrition Examination Survey (2017–2020)
Authors: Shin Dong Weon , Cho Yunnie , Rim Tyler , Seo Kyung Yul 
Published: January 2025

Aims/Purpose: This study investigated the relationship between environmental pollution and dry eye disease (DED), focusing on the cumulative impact of air pollutants.Methods: Cross‐sectional data from the 7th and 8th Korea National Health and Nutrition Examination Survey (KNHANES) (2017‐2020) were analyzed alongside air pollution data from the National Ambient Air Quality Management Information System (NAMIS). Non‐smokers aged between 40 and 80 were selected (n = 8,840). The daily cumulative index (CI) of air quality was calculated for each region of residence based on key pollutants, including SO₂, NO₂, PM2.5, and PM10. Using Gaussian mixture models, each day was categorized as usual,poor, or bad based on CI values. Multiple logistic regression analysis assessed the impact of air pollutants on DED while accounting for clinical, demographic, and meteorological factors. Additionally, the Aggregated Air Quality Index (AAQI) was calculated and evaluated for the same dataset.Results: Multiple logistic regression analysis indicated that the proportion of high pollution days within a year significantly increased the odds of DED (OR: 4.19, 95% CI: 1.23–14.25, p = 0.02), after adjusting for factors associated with DED as covariates. Although the AAQI did not show statistical significance, the Cumulative Index effectively demonstrated the aggregated effect of multiple air pollutants on DED.Conclusions: This research highlights the utility of a model using regularly measured air quality indicators, providing a comprehensive assessment of the aggregated effect of air pollutants. Implementing these measures can help identify at‐risk populations and consider environmental factors in managing and preventing DED.References
Saxena, A., & Shekhawat, S. (2017). Ambient Air Quality Classification by Grey Wolf Optimizer Based Support Vector Machine. Journal of environmental and public health, 2017, 3131083. Kyrkilis, G., Chaloulakou, A., & Kassomenos, P. A. (2007). Development of an aggregate Air Quality Index for an urban Mediterranean agglomeration: relation to potential health effects. Environment international, 33(5), 670–676.
Survey of B‐blockers against retinal degeneration
Authors: Makiou Anthi‐Styliani , Kalatanova Anna , del Amo Eva Maria , Leinonen Henri 
Published: January 2025

Aims/Purpose: This project aims at finding the best clinically approved β‐blocker drug for RD prevention. The project is a part of a larger drug repurposing program that utilizes a combination of clinically approved G protein‐coupled receptor drugs as a therapeutic strategy.Methods: Comprehensive literature review of β1‐blockers (including dual blockers of α‐ and β‐adrenoreceptors) focusing on the ability to accumulate in melanin‐rich eye tissues was performed. Physicochemical descriptors of the obtained 17 β‐blockers were generated and principal component analysis (PCA) was used for a concise overview of a dataset in the chemical space for further selection. The efficacy of selected drugs was tested in the acute bright light‐induced RD (LIRD) mouse model using standard ophthalmology imaging methods: electroretinography (ERG) and optical coherence tomography (OCT). LIRD was induced to dark‐adapted Balb/c mice between 4‐ and 5‐weeks of age, and the drug efficacy was examined one week after.Results: Based on the PCA score plot, eight drugs were selected for testing so that the drugs would maximally represent the diversity of this drug class. ERG and OCT experiments revealed that non‐selective‐blockers propranolol, timolol and metipranolol were more efficacious against LIRD than selective β1‐blockers metoprolol, bisoprolol, and levobetaxolol, and more effective than dual α‐/β‐receptor blockers labetalol and carvedilol. Additionally, an experimental β2‐antagonist (ICI‐118551) was tested but its administration did not significantly protect from LIRD.Conclusions: Non‐selective β‐blockers showed better retinal protection than β1‐selective blockers in this context. Future experiments will include testing dual administration of selective β1‐ and β2‐ antagonists. Additionally, the drug efficacy against stressors relevant for RD, such as H2O2 and all‐trans‐retinal, will be assessed using organotypic retina explants and oxidative stress and cell death markers.
Biodistribution of alpha‐lipoic acid in beta‐cyclodextrins: Analyzing ex vivo delivery to the posterior segment of the eye
Authors: Ta Phuong Linh , Just Lucia Bernat , Alambiaga‐Caravaca Adrián , Alarma Vicente Rodilla , Castellano Alicia López , Morell Francisco Bosch 
Published: January 2025

Aims/Purpose: α‐lipoic acid (ALA), a natural antioxidant, has shown significant value in delaying retinal damage progression. The purpose of this study was to quantify the amount of α‐lipoic acid in β‐ cyclodextrins (ALA‐βCD) complexation in various ocular tissues, especially in the posterior segment of the eye and the neuroretina, after administration from solution and ocular inserts containing the drug.Methods: ALA‐βCD was dissolved in phosphate saline solution (PBS) to obtain a 1 mg/mL solution. Inserts containing 1 mg/mL ALA‐βCD were prepared using eye‐compatible polymers: polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), and hyaluronic acid (HA).Porcine eyes were obtained from an abattoir shortly after sacrifice and they were cleaned and placed on a Franz diffusion cell. The solution (250 μl) was administered every 2h and washed after 5 min with PBS. The inserts were placed in contact with either the cornea or the sclera. Both experiments were carried out for 8h at 37°C with humidity control. The eyes were then washed with PBS and stored at ‐80°C for 12 h wrapped in parafilm to maintain their morphology. The frozen eyes were surgically dissected to separate the different eye structures. The ALA from various structures/tissues was extracted by soaking them in acetonitrile: water solution (80: 20, v/v) for 12h under constant stirring. The samples were then filtered, and the concentration of ALA determined by a validated HPLC method.Results: ALA was detected in all ocular tissues. The higher content of ALA found in the inserts was due to its longer contact time than the solution, and it increased bioadhesibility allowed greater biodistribution of ALA in the ocular tissues. Up to 1.5 % of ALA in the inserts reached the neuroretina, the target tissue for the treatment of retinopathies.Conclusions: The data show that in ex vivo, ALA can diffuse from the cornea and the sclera, reaching the posterior segment of the eye, and particularly the neuroretina. This data proves the way to carry out in vivo studies to assess the potential of topically administered ALA in protecting the eye from retinopathies.References
Alambiaga‐Caravaca AM, et al. Biodistribution of progesterone in the eye after topical ocular administration via drops or inserts. Int Jour of Pharma. 2023 Jan; 630: 122453.
Comparative neuroprotective effects of xenogeneic and allogeneic bone marrow‐derived mesenchymal stromal cells in a murine model of sepsis
Authors: Campoverde Jhoana Abigail Guarnizo , Ramírez Kristy Tatiana Rodríguez , Bernal David García , Lucas‐Ruiz Fernando , Vidal‐Sanz Manuel , Agudo‐Barriuso Marta 
Published: January 2025

Aims/Purpose: Sepsis causes systemic inflammation (SI) and induces acute and long‐term neurological dysfunctions. In the retina, SI causes the loss of retinal ganglion cells (RGCs). Advanced cell therapy with bone marrow‐derived mesenchymal stromal cells (BM‐MSCs) is a promising avenue for RGCs neuroprotection in SI due to their immunomodulatory properties. Here we analyze the neuroprotective properties of BM‐MSCs in two transplantation settings: xenogeneic and allogeneic in a murine model of SI induced by lipopolysaccharide (LPS).Methods: 2‐month‐old C57BL/6J male mice were used in all groups. LPS was intraperitoneally injected (5mg/kg) at day 0. At day 1, BM‐MSCs isolated from BALB/C mice (allogenic) or human donors (xenogenic) were intravitreally administered in the left eye. As controls we used intact and LPS‐treated C57BL/6J animals. RGCs survival (Brn3a+) and microglial activation (Iba1+) were studied at 7 days in both retinas, the treated and the contralateral to the injection.Results: BM‐MSCs were found forming an epiretinal membrane in both transplant modalities. RGCs death in LPS controls reached 20% of the original population. The allogeneic transplant rescued all RGCs in both eyes. In contrast, xenogeneic transplant only protected to the contralateral eyes and microglia were more activated and reactive.Conclusions: These preclinical data show that allogeneic BM‐MSCs elicits a greater neuroprotection for sepsis induced RGCs degeneration in both eyes, the treated and contralateral. While the xenogeneic transplant does not neuroprotect RGCs in the treated eye, it does in the contralateral one, a neuroprotection that could be due to paracrine effects. These findings may be the basis to treat sepsis induced neurodegeneration.
Early detection of biochemical changes in tear fluid induced by contact lens wear using raman spectroscopy
Authors: Tavazzi Silvia , Pezzoli Fabio , Ponzini Erika , Duse Alessandro 
Published: January 2025

Aims/Purpose: The aim of this study is to evaluate different approaches to investigate early alterations in tear biomolecular profiles induced by contact lens (CL) wear. This includes assessing the impact of CL wear on tear volume, osmolarity, and biomolecular composition using Raman spectroscopy.Methods: Two participants of the same sex (male), age (23 years), and with a similar lifestyle wore different CLs for two hours. Ocular analysis was performed at three time points: before CL insertion, immediately after CL removal, and two hours post‐removal. The analyses included tear meniscus height and osmolarity measurements. Tear samples were collected at each time point and analyzed using Raman spectroscopy.Results: Tear volume and osmolarity remained unchanged throughout the study. Raman spectroscopy highlighted notable changes in the biomolecular profile of tears after CL wear, particularly in the 2700‐3200 cm‐¹ spectral window.Conclusions: Among the analyses performed, only Raman spectroscopy revealed significant changes. It highlighted alterations in the biomolecular profile of tears post‐CL wear, particularly in the 2700‐3200 cm‐¹ spectral window associated with C‐H stretching. The ability of Raman spectroscopy to detect these subtle, subclinical changes underscores its value as a non‐invasive tool for analyzing individual responses to CLs. Notably, Raman spectroscopy captures molecular‐level alterations, which form the basis of changes in the physical and functional properties of the tear film, including those measured by tear meniscus height and osmolarity. These changes become detectable by traditional techniques only in a late stage, while molecular‐level alterations can be detected earlier, providing an opportunity for proactive intervention and management.
Upregulation of rod ribbon synapse components implies homeostatic presynaptic scaling in early‐stage retinitis pigmentosa
Authors: Roihuvuo Elias , Tabaka Marcin , Montaser Ahmed , Choi Elliot , Palczewski Krzysztof , Vinberg Frans , Leinonen Henri 
Published: January 2025

Aims/Purpose: Photoreceptor death triggers retinal rewiring and remodeling that are generally thought to be detrimental for vision. Some recent research results challenge this dogma. It was recently shown that in early‐stage retinitis pigmentosa (RP), the retina compensates for the reduced rod population activity by upscaling synaptic transmission between the remaining rods and rod bipolar cells. The purpose of the current project is to study the molecular mechanism behind this phenomenon.Methods: To model the primary pathology, P23H mouse model of autosomal dominant RP was used. Notably, wild‐type mice were not used as controls, instead, cone‐transducin (GNAT2) knockout mice that lack cone photoreceptor functionality were used. To produce “rod‐function‐only” RP mice, P23H and Gnat2‐/‐ mice were cross‐bred. Single cell RNA‐sequencing (scRNA‐seq; Gnat2‐/‐, n = 4; P23H/Gnat2‐/‐, n = 4) and retinal global proteomics (Gnat2‐/‐, n = 5; P23H/Gnat2‐/‐, n = 10) analyses were performed at P30. Statistical significance was set at q < 0.05. Additional protein expression analyses for synaptic proteins were performed using immunohistochemistry and immunoblotting.Results: ScRNA‐seq analysis revealed upregulation of several major ribbon synapse genes exclusively in P23H/Gnat2‐/‐ mouse rods. These included genes that are crucial in presynaptic structure and neurotransmitter release, such as the Ca2+ sensor Syt1, snare protein complex component Snap25, ribbon protein Ctbp2, and the synaptic vesicle protein Sv2b. In addition, upregulation of the glutamate transporter Slc1a2 was found. Based on proteomics data, STX1B and SYT7 were overexpressed in whole P23H/Gnat2‐/‐ mouse retinas as compared to controls.Conclusions: Early‐stage RP in mice associates with increased expression of several rod ribbon synapse components that play a role in glutamate release. These results imply that regulation of presynaptic glutamate release may play a role in improving retinal synaptic transmission during RP.
Bilateral levator palpebrae superioris involvement by malt lymphoma
Authors: Ortega Aranzazu Caro , Ferrando Sergio Obiol , Fernando Diego Serrano , Rovira Elena Gracia , García Amparo Lanuza 
Published: January 2025

Aims: Lymphoma is the most common malignant tumour in the ocular region. Among its histopathological subtypes, mucosa‐associated lymphoid tissue (MALT) is the most frequent. Extraocular muscles’ affectation by MALT lymphoma of the eye is uncommon (5%), more if possible, infiltration of levator palpebrae superioris (EPS), have not been described affectation of EPS isolated and none bilateral so far: We report one case of bilateral EPS involvement by MALT lymphoma.Methods: A 67‐year‐old lady noticed of gradually solitary mass increment on the right upper eyelid. Examination revealed a fibrous, nonpitting, hard and non‐tender, subciliary mass measuring 2‐3 cm on this eyelid. The rest of the ophthalmological examination was normal. Orbital magnetic resonance imaging showed infiltration of right EPS. The histological and immunohistochemical result of the biopsy was MALT lymphoma. The serology resulted negative for Chlamydophila psittaci. Three weeks later a similar mass appears in the left upper eyelid.Results: Ann Arbor's stage IV‐A was established. Haematology Committee decided treatment with six cycles of immunochemotherapy with: R‐CVP (Rituximab‐Cyclophosphamide‐Vincristine‐Prednisone). The tumor disappearance after the 4th cycle.Conclusions: MALT lymphoma is the most frequent ocular adnexal lymphoma, although extraocular muscles involvement is rarity entity itself. The most common affected muscle is superior rectus. Eligible treatment for limited type is locoregional radiotherapy. In case of advanced disease chemotherapy is preferred. Hence MALT lymphoma is a rare disease, which frequently recurs locally and has potential for systematic spread and transformation to a high‐grade B cell lymphoma, so warrant alertness to this neoplasm is required to reach an early diagnosis.References
Abalo‐Lojo, J. M., Baleato‐Gonzalez, S., Abdulkader, I., & Gonzalez, F. (2011). Extraocular muscle involvement in MALT lymphomas. Orbit (Amsterdam, Netherlands), 30(4), 186–188.
Hedgehog pathway inhibitors in eyelid tumors
Authors: Funes Elisa , Merino Jacobo Yañez , Sopeña‐Pinilla Maria , Ciobotaru Olga , Bestué Ana Pueyo , Pueyo‐Bestué Ignacio , Fernandez‐Velasco Diego , Mallen Victor , Bermudez Javier , Biescas Andrés 
Published: January 2025

Aims/Purpose: Basal cell carcinoma (BCC) is the most common type of tumor worldwide. Although it has a low capacity for systemic spread, it exhibits a high rate of local invasion. The most frequently affected areas are the face and neck. So far, the most widely used treatment has been surgery in its various forms: excision‐electrodesiccation‐curettage, cryotherapy, or the increasingly common Mohs micrographic surgery. In recent years, various researchers have identified molecules that can reduce or even eliminate these lesions. Among them, we highlight Vismodegib due to the good results obtained. This molecule is the first selective Hedgehog pathway inhibitor approved for the treatment of local and metastatic BCC.Methods: A 57‐year‐old female patient came to our clinic, referred by the dermatology department of our hospital, due to a basal cell carcinoma on the left lower eyelid affecting the free margin.Results: An incisional biopsy of the lesion was performed, diagnosing nodular BCC. After explaining the characteristics of the tumor and the therapeutic options to the patient, it was decided to start treatment with Vismodegib, include her in the surgical waiting list, and perform monthly follow‐up. In subsequent check‐ups, the patient reported good tolerance and adherence to the treatment, without adverse side effects. During the consultations, a clear reduction of the lesion was observed. However, due to the incomplete disappearance of the lesion, it was decided to perform a wedge resection of the tumor.Conclusions: Currently, the patient shows a good alignment of the free margin, with good tension and no signs of tumor activity.
Retrospective review of the annual endophthalmitis rates following intravitreal injections at Royal Bournemouth Hospital over an eight‐year period from 01/02/2016 until 31/01/2024
Authors: Tsokolas Georgios , Tossounis Charalambos , Anderson Owen , Matthews Non 
Published: January 2025

Aims/Purpose: To present the annual rates of post‐intravitreal injection endophthalmitis at Royal Bournemouth Hospital (RBH) over an eight‐year period from 01/02/2016 until 31/01/2024.Methods: The total number of intravitreal injections performed was identified retrospectively from our electronic records. The cases of post‐injection endophthalmitis were identified from the department's written logbook record.Results: Over the above 8‐year‐period, a total number of 13 cases of endophthalmitis were identified. The total number of injections performed over this 8‐year‐period was 54,134. The annual endophthalmitis rates fluctuated from a minimum 0% (year 01/02/2016 until 31/01/20217) to a maximum of 0.05% (year 01/02/2019 until 31/01/2020). Mean annual endophthalmitis rate over this 8‐year‐period was 0.025%. 1 case occurred after an intravitreal Ozurdex injection and 12 following anti‐VEGF injections.Conclusions: Despite the increasing number of injections every year, we noted that our endophthalmitis rates were consistently much lower than the estimated rate of 1 in 1000 (0.1%) in the literature. We postulate that our current standard local protocols and practices which include the use of sterile gloves, sterile drapes, face masks and pre‐injection instillation of povidone iodine in the fornix have played a pivotal role in keeping the annual endophthalmitis rates very low. Furthermore, the introduction of novel agents of biosimilars to Ranibizumab (Ongavia) and Faricimab (Vabysmo) which are withdrawn from vials and are not available in pre‐filled syringes did not have any adverse impact on our endophthalmitis rates. In 2014, the administration of chloramphenicol 0.5% antibiotic eye drops post‐intravitreal injections were stopped permanently. In 2016, specialist nurse injectors were introduced in our clinical practice. Based on our endophthalmitis rates over this 8‐year‐period, these two important changes in the clinical practice do not seem to have had a negative impact in our annual endophthalmitis rates. Our aim is to continue auditing our rates annually in order to ensure that we are a safe to practice macular unit and to maintain high quality patient care.