bluuebunny/crossref_metadata_2025_split huggingface dataset:
Translational research in ophthalmology. Some examples
Authors: JImeno Jose Carlos Pator 
Published: January 2025

Translational research is a bidirectional process that involves multidisciplinary integration among basic, clinical, practice, population, and policy‐based research. The goal of translational research is to speed up scientific discovery into patient and community benefit.In my opinion, the most accessible research to a clinician like me is translational, and must be intimately linked to training and clinical practice. But the environment is very important and although our national health system has many benefits, research was not stimulated, at least in 1981 when I became a professor in Valladolid.For this reason, and taking advantage of a reform of the University Law (LRU), in 1994 we created the IOBA. Thirty years later, we have our own building and more than 100 people work, 40 of whom are researchers.Every five years we are evaluated by the University Quality System and in the last evaluation we obtained 88.5 points out of a total of 100. In 2003, we also took advantage of another reform of the University's Law, and created the first start‐up of the University of Valladolid, which 21 years later is still alive. And it allows us, among other things, to retain talented researchers until they find their place at the university.And finally, in 2010 we stimulated the creation of a cluster dedicated to Ophthalmology and Vision Sciences called "Cluster4Eye". This cluster is currently focalized in the application of the so named Medical Device Regulation of the European Union which has been implemented affecting not only manufacturers but also sanitary personnel.As an example of applied research, I will comment on some aspects of our research on the so‐called "endotamponades" in vitreoretinal surgery. Liquid perfluorocarbons and silicone oil.In 2015 we took on the challenge of finding out why hundreds of people had irreparably lost vision in one eye after successful retinal detachment surgery. We were able to find out, we were part of the international ISO standards committee modifying the standard on ocular endotamponades and making an international patent and we are now part of the European Union's expert group for ocular medical devices.Regarding silicone oil, I started working with Miguel Refojo in Boston in 1990 and we have continued to improve it continuously and produce improvements that have been incorporated into the market.
The need for standardization in methodologies for tear fluid biomarkers
Authors: Gijs Marlies 
Published: January 2025

Tear fluid is a complex mixture of proteins, lipids, and other molecules essential for maintaining ocular surface health. In recent years, tear fluid has emerged as an invaluable source of biomarkers, reflecting not only ocular health, but also providing glimpses into systemic and neurological well‐being. Tears can be used to gather abundant molecular information that can be harnessed for diagnostic, monitoring, predictive, and prognostic purposes. The unique tear fluid molecular profile of each patient facilitates tailored interventions, enhancing treatment efficacy and minimizing adverse effects.Besides being continuously accessible, tear fluid can be sampled in a non‐invasive and inexpensive way. This makes the sampling process patient friendly, thereby enhancing patient compliance and reducing the risk of potential complications associated with invasive sampling techniques. The non‐invasive nature of tear fluid sampling makes it suitable for repeated measurements over time, allowing for longitudinal studies and monitoring of dynamic changes in biomarkers. Additionally, tear fluid requires minimal storage requirements, as it can be collected and stored using simple and readily available equipment.To date, hundreds of tear biomarkers have been discovered, but only a few have made it to the clinic. Major progress in translating newly discovered tear biomarkers into diagnostic tests is still missing because of the unique challenges that have yet to be addressed. Variability in tear fluid results poses a significant challenge in ocular research due to the lack of standardized methods for collection, analysis, interpretation, and reporting. This variation makes it difficult to draw consistent conclusions across different studies. Inconsistent research findings result from differences in methodologies and small sample sizes, leading to conflicting reports on disease‐specific tear proteins and outcomes. Moreover, the lack of standardization hampers our understanding of tear fluid physiology and its role in diseases, impeding the development of diagnostic tools and therapies. This lack of consensus also hinders the clinical translation of tear‐based diagnostics and therapies, potentially delaying accurate diagnoses and appropriate treatments for patients.Recognizing the importance of methodological standardization, various initiatives have been proposed to address these challenges. Collaborative efforts involving researchers, clinicians, industry partners, and regulatory agencies aim to establish consensus guidelines for sample collection, processing, and analysis. These guidelines emphasize the importance of rigorous validation studies, quality control measures, and transparent reporting practices to enhance the reliability and reproducibility of tear fluid biomarker research. Through collaborative efforts and adherence to consensus guidelines, the field can realize the full potential of tear fluid biomarkers in revolutionizing the diagnosis, monitoring, and treatment of ocular diseases.
Bacterial keratitis
Authors: Modis Laszlo 
Published: January 2025

The number of infectious keratitis cases is increasing worldwide. The vast majority of cases are bacterial in origin. Both gram positive (Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus pneumoniae Corynebacterium diphtheriae) and gram negative (Pseudomonas aeruginosa, Acinetobacter species) bacteria can cause serious infections.One of the most common causes is related to contact lens wear. This can be in connection with overwear, overnight wear (orthokeratology), inadequate lens cleaning with tap water, lack of hygiene, and contamination of different solutions. Uncontrolled use of lenses ordered from the internet is also a source of danger. The other main cause is trauma, resulting from surface injuries (e.g. nails, plants), foreign bodies, mechanical and chemical injuries. Certain ophthalmological conditions also predispose to bacterial keratitis, such as dry eye, blepharitis, non‐healing ulceration, and previous eye surgery. Immunosuppressive treatment, autoimmune diseases, diabetes mellitus may also result in development of infection.In serious cases patients typically complain of pain, sensitivity to light, blurred vision, tearing, yellowish purulent discharge and various degree of visual loss. Clinical appearance includes epithelial defect and erosions, ulceration, stromal infiltrates with indistinct margins. In serious forms Descemetocele, even perforation can be present. Hypopyon may also appear in the anterior chamber.Diagnosis is based on the clinical picture. Culturing and smear sampling are necessary when the infiltrate is large and central, when there in contact lens wear in the history, the process is resistant to therapy, and appearance is atypical.Most cases can be successfully treated with empiric therapy. The first choice of treatment is usually fluroquinolone therapy. In severe cases moxifloxacin or cefazolin with tobramycin or gentamycin is advised. Eye drops in every hour should be applied both day and night for the first 48 hours as saturation dose. If there is no improvement in the clinical picture after 48 hours, repeat sampling for microbiological culture recommended. Corticosteroids may be considered after 2 days when the infective organism is identified, and the keratitis is responding to therapy. Cycloplegia may also decrease pain as well as synechia formation. In therapy resistant cases crosslinking may be an additional option if herpetic origin can be excluded. Amniotic membrane transplantation is recommended for non‐healing epithelial defects. In cases of non‐healing and rapidly progressive cases therapeutic corneal transplantation is recommended. However, surgery has a better prognosis in quiet eye.
Underground drivers
Authors: Garrido‐Mercado Rafaela 
Published: January 2025

Introduction: Some professional occupations have visual requirements. For underground drivers, requirements include good photopic visual acuity, color vision, stereopsis, and normal campimetry. However, there are other visual functions that may be important in this occupation, especially mesopic tests, as their work is done in darkness, and they are the first functions to be altered with age.Our objective was to describe the state of different visual functions in a population of underground drivers.Methods: A total of 430 randomly selected underground drivers, aged between 27 and 65, participated in the study. 94,41% were males. High and low‐contrast monocular best corrected visual acuity (VA) was tested using EDTRS charts under photopic and mesopic conditions. Photopic (cone‐enhanced) and mesopic (rod‐enhanced) flicker modulation thresholds (FMT) were measured at the fovea and at an eccentricity of 5° in each of the four quadrants using the Flicker‐Plus test (Advance Vision and Optometric test, City Occupational Ltd, London). Subjective refraction and stereopsis were also measure. Myopia was defined as the spherical equivalent ≤ ‐0.5 D.The study was conducted at the Optometry Clinic of the Complutense University of Madrid, Spain.Results: 32.8% of the subjects had myopia, most of which (23.3%) were less than 3 D. 1.63% of the subjects had no stereopsis. For the analysis of the results, we divided the subjects into those under or ≥50 years of age. Mean high contrast photopic visual acuity was ‐0.13 logMAR in subjects under 50 years of age and ‐0.1 logMAR in those over 50, with a significant difference between the two groups (p = 0.004). Mean mesopic visual acuity was 0.05 logMAR in subjects under 50 years of age and 0.07 logMAR in the older group (p = 0.048). None of the subjects had mesopic VA values > 0.3 logMAR. Results of low‐contrast VA showed a mean under photopic conditions of 0.05 logMAR in those under 50 years of age and 0.08 logMAR in those older. Under mesopic conditions, the mean was 0.38 logMAR and 0.41 logMAR in both groups, respectively. In both conditions there were significant differences between the groups (p = 0.04 and 0.03). The median central threshold of Flicker‐plus test under photopic conditions was 4.1 in those under 50 years of age and 5.37 in those over 50. Under mesopic conditions, median values were 8.18 and 10.18 respectively. Values were different between groups (both p < 0.001). Median photopic threshold values for parafovea were 3.93 in those under 50 years of age, and 4.56 in those over 50. Under mesopic conditions, medians were 6.16 and 7.75 in both groups, respectively. Significant differences were found between the groups (both, p < 0.001). We did not find differences in the values of AV or FMT depending on the years of work in the underground.Conclusions: We found good results for visual acuity and flicker modulation thresholds in this population of underground drivers, both in photopic and mesopic conditions. It does not appear that working conditions have influenced the outcome.
Tips to improve ocular surface problems in patients using glaucoma medication
Authors: ∅yo‐Szerenyi Karin 
Published: January 2025

Ocular surface disease is a frequently met challenge in our daily ophthalmology practice; even more so in glaucoma patients, who often need long term topical medication. The risk factors for ocular surface disease are many, including age, systemic disease, drug side effects, ocular conditions and lifestyle habits, such as smoking or computer use. More often than not, our glaucoma therapy is worsening the symptoms.Knowing the different effects and side effects of our therapy will help us chose the optimal local agents for our individual patients and, by addressing this issue with the patient, we can ensure a better adherence to our therapy and find an optimal and tolerable daily regimen for the necessary treatment of glaucoma.
Deciphering the differentiation of human induced pluripotent stem cell‐derived corneal stem cells by gene regulatory networks analysis
Authors: Cunha Dulce Lima , Vatulainen Meri , Arts Julian , Melin Outi , Ilmarinen Tanja , Skottman Heli , Zhou Jo 
Published: January 2025

The cornea is the transparent tissue situated at the surface of the eye, with crucial protective and light refraction properties. Limbal epithelial stem cells (LESC), residing in the limbus in the peripheral cornea, play a crucial role in sustaining corneal clarity by continuously renewing the corneal epithelium. Due to this regenerative capacity, LESC loss or malfunction result in limbal stem cell deficiency (LSCD) and subsequent corneal opacity. Therefore, elucidating LESC development and lineage determination is paramount for the advancement and refinement of LESC‐based therapies.In this project, we have differentiated induced pluripotent stem cells (iPSC) into LESC using established in‐house protocols spanning a 25‐day period. Subsequently, we conducted single‐cell Assay for Transposase‐Accessible Chromatin with high‐throughput sequencing (scATACseq) at three distinct stages of differentiation (days 0, 11, and 25) to examine chromatin accessibility changes throughout the process. These findings were integrated with previously conducted single‐cell RNA sequencing (scRNAseq) on cells at equivalent differentiation stages. Analysis revealed six distinct cell populations based on overall chromatin accessibility profiles, aligning with the major cell clusters identified in scRNA‐seq data. We are currently conducting gene regulatory network analysis using both scATACseq and scRNAseq data to pinpoint the critical transcription factors driving LESC fate and comprehend the mechanisms underlying cellular heterogeneity during differentiation.This research aims to unveil novel epigenetic mechanisms and crucial factors potentially implicated in the dynamic process of LESC lineage determination, potentially benefiting the generation of LESC populations suitable for transplantation as well as providing novel insights for LSCD treatment options.
Objective assessment of corneal transparency using densitometry distribution analysis
Authors: Consejo Alejandra 
Published: January 2025

Advancing the assessment of eye diseases necessitates novel biomarkers that surpass conventional morphological analysis. Historically, the exploration of microstructural details in corneal research has heavily relied on histological examination, a process necessitating post‐mortem tissue samples and inapplicable in vivo. The cornea comprises densely arranged collagen fibers and specialized cell types including keratocytes, endothelial cells, and epithelial cells. These intricate details are inaccessible through widely used clinical instrumentation, such as Scheimpflug or OCT imaging. However, it is possible to analyze in‐vivo microstructure indirectly using Densitometry Distribution Analysis (DDA). This method involves extracting microstructure‐related biomarkers, such as tissue transparency and homogeneity, from low‐resolution clinical corneal images using image processing supported by artificial intelligence. Indirect in‐vivo microstructure analysis requires evaluating the distribution of pixel intensities. In ophthalmic instruments, image formation is influenced by how light, after being emitted from the source, backscatters upon interacting with the cornea. Given the cornea's nonhomogeneous nature, its internal arrangement affects how light traverses through different layers and regions. This variation in light propagation leads to differing pixel intensities in the resultant images. By examining these intensity variations, we can derive microstructure‐related biomarkers, such as tissue transparency and homogeneity.In this talk, we will describe the DDA methodology and revisit its early successes in detecting eye diseases such as keratoconus before any clinical signs are apparent, with a 97% success rate, and up to 100% if clinical signs are observed. The DDA has also been used for early glaucoma detection, with a success rate of over 80%. Additionally, the DDA has been successfully applied to study the effects of contact lens wear on our eyes and to investigate certain rare genetic disorders affecting the cornea.
CXL: Challenges and updates
Authors: Doroodgar Farideh 
Published: January 2025

Corneal cross‐linking (CXL) is a critical treatment for keratoconus that combines UVA light and riboflavin (vitamin B2). This procedure received FDA approval in 2016 based on studies by Sykakis et al. (2015) which indicated that CXL could stabilize keratoconus, prevent myopia progression, and improve uncorrected distance visual acuity (UDVA). Despite the promising results, the studies had potential biases and a low number of randomized controlled trials (RCTs).The two primary methods of CXL are epithelium‐off (epi‐off) and epithelium‐on (epi‐on or transepithelial). Epi‐off CXL involves removing the corneal epithelium to allow riboflavin penetration, whereas epi‐on CXL retains the epithelium, reducing patient discomfort but potentially being less effective. NG et al. (2021) found no significant difference in outcomes between these methods, though epi‐on showed fewer side effects such as corneal haze.Accelerated CXL protocols have been developed to increase efficiency. Karam et al. (2023) compared these protocols, revealing that a 10‐minute protocol with 9 mW/cm2 UVA exposure provided better outcomes than a 5‐minute protocol with 18 mW/cm2. Accelerated methods are becoming more common due to their reduced treatment time.In pediatric cases, both conventional and accelerated CXL are effective, although the transepithelial method had a lesser impact, as concluded by Mahdavi Fard et al. (2020). Additionally, combined procedures known as CXL+ integrate CXL with other treatments like laser ablation. The Athens Protocol, developed by Dr. Kanellopoulos, combines topography‐guided laser ablation with CXL to address irregular astigmatism and coma in keratoconus patients.New riboflavin formulations and delivery methods, such as isotonic riboflavin and iontophoresis, have been developed to enhance riboflavin penetration and effectiveness. Glaukos' (Avedro) Mosaic System and the "sub400" protocol for ultrathin corneas are notable advancements, offering customized treatments based on individual corneal characteristics.
Genetic findings in paediatric patients with nystagmus
Authors: Arruti Natalia 
Published: January 2025

Nystagmus, a condition characterized by involuntary eye movements, can be classified into two primary categories: infantile nystagmus (IN) and acquired nystagmus. IN typically manifests within the first 3‐6 months of life and can be idiopathic or associated with various ocular conditions, including inherited retinal dystrophies (IRD), albinism, or congenital cataracts. Acquired nystagmus appears later in life.Diagnostic approaches for nystagmus involve comprehensive eye examinations, including optical coherence tomography (OCT), and electrophysiology testing to differentiate underlying ocular diseases. The advent of new medical devices allows for detailed recording of eye movements, capturing data on gaze positions, amplitude, frequency, intensity, phase speed, and other parameters, thereby enhancing diagnosis and management.Recent advancements in genetics have significantly impacted the diagnostic process for nystagmus. Genetic testing is increasingly recognized as a crucial component, especially given the development of gene therapies for ocular conditions. We advocate for the routine use of genetic testing in paediatric patients with nystagmus to achieve definitive diagnoses and inform treatment strategies.This study presents a retrospective review of paediatric nystagmus cases referred to our Genetics Department from January 1, 2020, to January 1, 2024. Our findings indicate a significant increase in molecular diagnostic rates following clinical phenotyping.Genetic testing is instrumental in the diagnosis and management of paediatric nystagmus, particularly in the context of ongoing advancements in gene therapy for IRDs.
Tear biomarkers for alzheimer's disease screening and diagnosis (the tearad study)
Authors: Gijs Marlies 
Published: January 2025

The etiology of Alzheimer's disease (AD) can be determined with the use of biomarkers of amyloid‐beta (Aβ) deposition, neurofibrillary tangles and neurodegeneration. Cerebral spinal fluid (CSF) analysis or amyloid positron emission tomography (PET) imaging are currently used for biomarker determination. However, these tests are invasive, expensive and not widely available, thereby limiting their potential as a front‐line screener. Considering the expected increase of people affected by AD (152 million cases by 2050 worldwide), there will be a growing need for non‐invasive and cost‐effective tools allowing identification of patients in the earlier phases of the disease. Timely diagnosis is important to promote early and optimal management of the disease. Furthermore, this will be essential for future therapies as they may be more effective when started earlier in the disease process.Tear fluid is an excellent source of neurological biomarkers. It can be obtained non‐invasively, making the process patient friendly and reducing the risk of complications. Additionally, tear fluid sampling is cost‐effective and requires minimal storage, making it accessible and practical for diagnostic purposes in the memory clinic and outpatient hospitals. For research purposes, tear fluid offers an attractive option for longitudinal studies and monitoring biomarker changes over time.The main interest of the TearAD study is the use of tear biomarkers for AD. Tears covering the ocular surface are an important bio‐fluid containing thousands of molecules, including proteins, lipids, metabolites, nucleic acids, vitamins and electrolytes. We recently demonstrated that Aβ38, Aβ40 and Aβ42, total‐tau (t‐tau) and phosphorylated‐tau (p‐tau) are detectable in tear fluid. Tear t‐tau levels were significantly elevated in AD dementia patients compared to SCD patients, whereas tear p‐tau levels were only detectable in SCD, MCI and AD dementia patients, but not in cognitively healthy controls. Recently, Gharbiya and colleagues was able to reproduce the detection of p‐tau and Aβ42 in the tear fluid of MCI and AD dementia patients. In their study, levels of Aβ42 in tear fluid were significantly lower in MCI and AD dementia patients compared to cognitively healthy controls.Our study is in line with others efforts that identified tear biomarkers for different neurological conditions, such as TNF‐alpha and oligomeric alpha‐synuclein for Parkinson's disease, alpha‐1 anti‐chymotrypsin for multiple sclerosis and mutant huntingtin for Huntington's disease. Together, these studies support the hypothesis that tear fluid may predispose to mirror pathophysiological changes in the central nervous system.