bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dysfunction in amino acid synthesis pathways: Potential biomarkers for early glaucoma detection
Authors: Andrés‐Blasco Irene , Bisbal M. Carmen MArtínez , Gallego‐Martínez Alex , Tufanisco Elena Bendala , Martinez Francisco Cavas , Marabotto Marina Botello , Martinez‐Mañez Ramon , Durán Maria Dolores Pinazo 
Published: January 2025

Aims/Purpose: Amino acids have been proposed as preclinical biomarkers of the risk of developing neurodegenerative and metabolic diseases. We used proton nuclear magnetic resonance (1H‐NMR) in tears for the first time to investigate alterations in essential amino acids in patients with primary open‐angle glaucoma (POAG).Methods: We planned an analytical pilot case‐control study for 30 participants aged 40‐80 years, divided into: POAG group (n = 11) and control group (CG; n = 19). Tears were obtained from each eye using capillarity. The samples were studied using 1H‐NMR spectroscopy, acquiring one‐dimensional spectra for each sample, and assigning the peaks according to their chemical shift (profiling) and information from various databases. The data from the chemometric analysis are shown as mean and standard deviation.Results: A total of 40 metabolites were assigned based on their chemical shifts, multiplicity, and scalar coupling between J cores. Our multivariate model included 11 to discriminate between POAG and CG: phenylalanine, phenylacetate, leucine, taurine, glycine, urea, glucose, N‐acetylated compounds, unsaturated fatty acid, formic acid, and uridine. Thus, the most relevant metabolites were phenylalanine, phenylacetate, leucine, taurine, glycine, urea, and glucose, showing a significant reduction in concentration in the tears of the POAG group for phenylalanine, phenylacetate, leucine, N‐acetylated compounds, formic acid, and uridine, compared to the CG.Conclusions: Our results suggested that the alteration in phenylalanine, tyrosine, and tryptophan signaling pathways and their effects are associated with an increased risk for POAG. Their decrease in tears maybe considered a potential biomarker to identify patients in the early stages of glaucoma.
Exploring the interplay between self‐reported glaucoma, physical shape, and exercise: Findings from a Danish eye and vision cohort – Project forever
Authors: Sjö Astrid , Rovelt Jens , Freiberg Josefine , Toft‐Petersen Anne Pernille , Kolko Miriam 
Published: January 2025

Purpose: To investigate the associations between self‐reported glaucoma, intraocular pressure, and self‐reported physical activity and shape in a Danish cohort.Methods: Questionnaire responses from project FOREVER (Finding Ophthalmic Risk and Evaluating the Value of Eye exams and their predictive Reliability) reported information on age, biological sex, height, weight, intraocular pressure status, smoking habits, physical activity and shape, and eye diseases. Generalized linear regression models were used to examine associations between glaucoma and physical exercise. Associations between intraocular pressure and physical shape or physical exercise were investigated using linear regression models. All models were adjusted for age and sex.Results: A total of 34,218 subjects were included in the study, predominantly female (62%), with a median age of 57 years (interquartile range 48‐67). Among them, 545 reported having glaucoma. We observed a significant decrease in the odds of having glaucoma among people reporting to be in good physical shape compared to those in moderate shape (Odds ratio (OR) 0.79, 95% CI 0.65‐0.97, p‐value < 0.05). Increased intraocular pressure was associated with increased odds of being in poor (OR 0.13, 95% CI 0.01‐0.25, p‐value < 0.05) or very poor physical shape (OR 0.21, 95% CI 0.01‐0.40, p‐value < 0.05).Conclusion: Good physical shape was associated with reduced odds of glaucoma whereas increasing intraocular pressure was associated with poor or very poor physical shape. Further research is warranted to elucidate the underlying mechanisms and identify potential preventive interventions, from which patients may benefit.
Impact of citicoline and coenzyme Q10 (COQUN Combo) on retinal ganglion cell survival in a experimental glaucoma model
Authors: Matamoros José A. , Fernández‐Albarral José A. , Salobrar‐Garcia Elena , Elvira‐Hurtado Lorena , López‐Cuenca Inés , Sanchez‐Puebla Lidia , Martínez‐López Miguel A. , Rubio‐Casado Sara , de Hoz Rosa , Gallardo Meritxell Lopez , Marco Eva M. , Ramirez Jose Manuel , Salazar Juan Jose , De La Villa Pedro , Ramirez Ana Isabel 
Published: January 2025

Aims/Purpose: Treatments for glaucoma damage have focused on lowering intraocular pressure (IOP). However, despite controlled IOP, the neurodegenerative process continues. Therefore, it is necessary to study new molecules with neuroprotective properties for treatment. The aim of this study was to investigate the survival of retinal ganglion cells (RGCs) in an experimental model of ocular hypertension (OHT) following the administration of a combination of citicoline and coenzyme Q10 (COQUN Combo).Methods: Four groups of Swiss albino mice were used: vehicle control (Vehicle, n = 6), COQUN Combo control (COQUN Combo, n = 5), laser with vehicle (LG+Veh, n = 6), and laser with COQUN Combo (LG+COQUN Combo, n = 6). COQUN Combo was administered daily mixed with gelatin, 15 days prior to laser induction and 7 days post‐induction in COQUN Combo and LG+COQUN Combo groups. The Vehicle and LG+Veh groups received only neutral gelatin. OHT was induced in the left eye by laser photocoagulation of the limbal and episcleral veins, analyzing hypertensive eyes and their contralateral. IOP was measured different time points after‐laser (24h, 48h, 3, 5, and 7 days). Retinal whole‐mounts were processed with 1) Anti‐Brn3a to semi‐automatically quantify the number of Brn3a+ RGCs; and 2) Anti‐melanopsin to manually quantify the number of melanopsin+ RGCs.Results: At 24 hours post‐laser, both vehicle and COQUN Combo hypertensive eyes exhibited a significant increase in IOP. However, the increase was lower in the COQUN Combo OHT eyes (p value < 0.0001). In vehicle OHT eyes, the number of Brn3a+ RGCs was significantly lower compared to the vehicle control. However, the COQUN Combo‐treated OHT eyes maintained similar values to vehicle control eyes, as did the contralateral vehicle and contralateral COQUN Combo eyes. The number of melanopsin+ RGCs was similar in all study groups.Conclusions: The COQUN Combo may be a neuroprotective strategy in glaucomatous pathology.
Citicoline and coenzyme Q10 (COQUN Combo) reduce inflammation in an experimental glaucoma model
Authors: Matamoros José A. , Fernández‐Albarral José A. , Salobrar‐Garcia Elena , Elvira‐Hurtado Lorena , López‐Cuenca Inés , Sanchez‐Puebla Lidia , Martínez‐López Miguel A. , Rubio‐Casado Sara , de Hoz Rosa , Gallardo Meritxell Lopez , Marco Eva M. , Ramirez Jose Manuel , Salazar Juan Jose , De La Villa Pedro , Ramirez Ana Isabel 
Published: January 2025

Aims/Purpose: To investigate the anti‐inflammatory effects of citicoline and coenzyme Q10 (COQUN Combo) in an experimental model of ocular hypertension (OHT).Methods: Swiss albino mice were used: vehicle control (Vehicle n = 6), COQUN Combo control (COQUN Combo n = 5), laser vehicle (LG+Veh, n = 6), and laser COQUN Combo (LG+COQUN Combo, n = 6). COQUN Combo was administered daily with gelatin 15 days prior to laser induction and 3 days post‐induction in COQUN Combo and LG+COQUN Combo groups. The Vehicle and LG+Veh groups received neutral gelatin. OHT was induced in the left eye by laser photocoagulation of the limbal and episcleral veins, analyzing hypertensive eyes and their contralateral eyes. Retinal whole‐mounts were processed with: 1) Anti Iba‐1 to quantify: Number of Iba‐1+ cells (Iba1‐cn) in outer segments (OS), outer plexiform layer (OPL) and inner plexiform layer (IPL); Retinal area occupied by Iba‐1+ cells (Iba1‐RA) in the nerve fiber layer‐ganglion cell layer (NFL‐GCL); Cell body area (Iba1‐cba) of Iba‐1+ cells in OPL, IPL and NFL‐GCL; and arbor area (Iba1‐aa) of Iba‐1+ cells in OPL and IPL. 2) Anti‐P2RY12 to differentiate activated microglia.Results: No significant differences were observed between the control groups. Both OHT eyes and their contralaterals of LG+Veh, as well as LG+COQUN Combo OHT eyes and their contralaterals, showed significant differences compared to controls in Iba1‐cn, Iba1‐ RA, Iba1‐cba, and Iba1‐aa in all layers analyzed. However, these changes were significantly smaller in LG+COQUN Combo OHT and their contralateral eyes compared to LG+Veh OHT and their contralateral eyes. In the Vehicle, Iba‐1+ cells were P2RY12+. P2RY12 expression was downregulated in both OHT eyes of LG+Veh and LG+ COQUN Combo; however, this downregulation was less pronounced in the OHT eyes of LG+COQUN Combo. In the contralateral eyes, P2RY12 expression remained similar to that of the controlsConclusions: COQUN Combo can attenuate the inflammatory process in glaucoma.
Monitoring glaucoma progression from Fundus photos using a deep learning‐based trend analysis
Authors: Hemelings Ruben , Wong Damon , Stalmans Ingeborg , Schmetterer Leopold 
Published: January 2025

Aims/Purpose: To assess the agreement between established tools to monitor glaucoma progression and a linear regression on deep learning (DL)‐based glaucoma risk predictions obtained from color fundus photos (CFPs).Methods: CFPs and clinical metadata were retrospectively collected from three university hospitals in Belgium. Eyes with at least five CFP visits were included based on the availability of progression ground truth labels.Ground truth labels for glaucoma progression were derived from within‐eye linear regression on either average retinal nerve fiber layer thickness (aRNFL) as measured by optical coherence tomography (OCT) or mean deviation (MD) from visual field testing. A significant MD slope (p < 0.05) from linear regression was selected as a biomarker for functional glaucoma progression, tested with a minimum of 4, 5, and 6 values. For structural progression, a significant aRNFL slope (p < 0.05) was assessed, requiring 3 or 4 visits due to data scarcity and lower test‐retest variability in OCT data.Preprocessed CFPs were input into a previously trained deep learning model (G‐RISK). The within‐eye linear regression of G‐RISK predictions, referred to as the G‐RISK slope, was then obtained. Agreement was evaluated using the area under the receiver operating characteristic curve (AUC) with 95% confidence intervals. We varied the MD slope between 0 and ‐4 dB per year and computed AUC using G‐RISK slopes as predictions. Similarly, we varied the aRNFL slope between 0 and ‐4 μm per year.Results: A total of 5875 eyes had at least four visits with MD values, and 313 eyes had at least three visits with aRNFL values. For functional progression, AUC climbed up to 0.67 [0.58; 0.75] at an MD slope of at least ‐2.5 dB per year. For structural progression, AUC reached up to 0.99 [0.98; 1] with a yearly aRNFL decrease exceeding 3.4 μm.Conclusions: Both MD and RNFL slopes showed significant agreement with G‐RISK slope, supporting its potential as a novel biomarker for glaucoma management.References
Hemelings, R., Elen, B., Barbosa‐Breda, J. et al. Deep learning on fundus images detects glaucoma beyond the optic disc. Sci Rep 11, 20313 (2021).
Improving dynamic vessel analysis: A new pipeline for localized retinal vessel response evaluation
Authors: Beeckmans Lennert , Van Eijgen Jan , Vilser Walthard , Kotliar Konstantin , Hanssen Henner , De Vos Maarten , Stalmans Ingeborg 
Published: January 2025

Aims/Purpose: Dynamic Vessel Analysis (DVA) is a non‐invasive imaging modality that evaluates the reactivity of retinal arteriolar and venular vessels in response to flicker light stimulation. This study aims to introduce a novel data‐processing pipeline that involves noise reduction techniques localized to different locations along the vessel wall. Additionally, it employs standardized parameter extraction, allowing for a more precise assessment of retinal vessel responses across these locations.Methods: Previous studies used robust principal component analysis (RPCA) on averaged time series data for arteries and veins, combining one averaged time series per patient into arterial and venous matrices. Our method retains individual location time series for each arteriole and venule, preserving local responses. We combine these individual time series into arteriolar and venular matrices and apply RPCA, resulting in sparse matrices containing noise and low‐rank matrices capturing common features. The low‐rank matrices, containing the noise‐reduced information, are then used for further analysis. This approach maintains the granularity of local vascular responses.Results: We identified and integrated key parameters from existing literature to delineate vasodilation and vasoconstriction profiles. By applying analysis of covariance (ANCOVA) for age, sex, baseline vessel dilation, and mean arterial pressure, we identified significantly lower Baseline‐Corrected Flicker Response of the proximal retinal venules in normal tension glaucoma patients (2.46%, n = 23) compared to healthy controls (4.23%, n = 21, p = 0.049).Conclusions: Our novel pipeline adds to all previously published methods and effectively identified altered neurovascular responses in glaucoma patients after the necessary adjustments. This standardized and automated approach is a promising catalysator for DVA research, offering a more localized and precise understanding of retinal vascular dynamics.
Inflammation and neurodegeneration in glaucoma: Isolated eye disease or a part of a systemic disorder? ‐ Serum proteomic analysis
Authors: Zarzecki Mateusz , Okruszko Michał , Szabłowski Maciej , Michnowska‐Kobylińska Magdalena , Lisowski Łukasz , Łapińska Magda , Stachurska Zofia , Szpakowicz Anna , Kamiński Karol , Konopińska Joanna 
Published: January 2025

Aims/Purpose: To investigate serum expression of inflammatory and neurotrophic factors in glaucoma patients.Methods: We investigated the serum expression of 92 inflammatory and neurotrophic factors in glaucoma patients. The study group consisted of 26 glaucoma patients and 192 healthy subjects based on digital fundography.Results: Patients with glaucoma had significantly lower serum expression of IL‐2Rβ, TWEAK, CX3CL1, CD6, CD5, LAP TGF‐beta1, LIF‐R, TRAIL, NT‐3, and CCL23 and significantly higher expression of IL‐22Rα1.Conclusions: Our results indicate that patients with glaucoma tend to have lower levels of neuroprotective proteins and higher levels of neuroinflammatory proteins, similar to those observed in psychiatric, neurodegenerative and autoimmune diseases, indicating a potential link between these conditions and glaucoma pathogenesis.References: Glaucoma is the most common optic neuropathy and the leading cause of irreversible blindness worldwide, which affects 3.54% of the population aged 40–80 years. Despite numerous published studies, some aspects of glaucoma pathogenesis, serum biomarkers, and their potential link with other diseases remain unclear. Recent articles have proposed that autoimmune, oxidative stress and inflammation may be involved in the pathogenesis of glaucoma.
Ab‐externo Xen glaucoma microstent implantation in the treatment of glaucoma – A 1‐year retrospective observational study
Authors: Langosz Paulina , Maruszczyk Wojciech , Eder Krzysztof , Mrozek Agnieszka , Dygas Dominik , Porwolik Mateusz , Janiszewska‐Salamon Julia , Wyględowska‐Promieńska Dorota , Smedowski Adrian 
Published: January 2025

Aims/Purpose: The purpose of our work was to evaluate the efficacy and complications of ab‐externo XEN gel microstent (XEN, Aquesys, Inc.) implantations as a treatment modality for various types of glaucoma.Methods: We have analyzed 28 patients (28 eyes) that underwent 32 XEN stent implantations over the past year as a treatment for diverse types of glaucoma. The mean age of the population was 65 (IQR 47‐71), with the mean length of glaucoma pharmacotherapy beforehand of 6.5 (2.0‐12.5) years. 20 eyes were pseudophakic and 22 have undergone a prior invasive glaucoma treatment, with 6 precedent stent implantations.Eyes have been observed for 9±3 months especially in terms of post‐implantation BCVA and IOP profile. Surgical complications, need for further glaucoma pharmacotherapy during the observation period have been analyzed. Subjective ailments reported by the patients have been numbered.Results: We have observed an IOP drop from 30.0 (22.5‐39.5) on admission to 8.0 (8.0‐10.0) on discharge, with further values of 11.0 (7.0‐15.0); 14.0 (11.5‐19.0); 17.0 (14.0‐20.0); 18.0 (14.0‐19.0) at the 1‐week, 1, 3, and 6‐month control points respectively. Number of glaucoma topical medications dropped from 3 (3‐4) pre‐surgery to 0 (0‐0) immediately post‐op. BCVA pre‐op was 0.15 (0.05‐0.61) logMAR and improved to 0.1 (0.00‐0.52) at the 6‐month observation point. 14 of the patients required a surgical revision of the stent and 5 of all the eyes have been further qualified to repeated surgical treatment in different modality.Conclusions: The ab externo method for XEN microstent implantation has been proved to be an effective glaucoma treatment modality, drastically decreasing the necessity for both further pharmacotherapy and/or follow‐up surgical procedures. The subjective ailments reported by patients have been found to be at a acceptable level.
The relationship between social deprivation and glaucoma‐related quality of life (QOL)
Authors: Teo Ryan , Tsakiris Kleonikos 
Published: January 2025

Aims/Purpose: Glaucoma carries a considerable global health burden. As it is generally accepted that glaucoma is incurable, it is critical to maintain or improve the QOL of afflicted patients.Social deprivation is known to be associated with poor vision. However, less is known about the relationship between social deprivation and its impact on glaucoma‐related QOL.It must be noted that QOL is an entirely different concept as a glaucoma patient with poor vision could still maintain a good vision‐related QOL.The purpose of this project was to identify a potential gap in the provision of care for socially deprived glaucoma patients and advance the European Glaucoma Society's aim of glaucoma treatment, which is to maintain QOL in affected patients at a sustainable cost.Methods: The research study included:
Systematic Literature Review to determine the best instruments to measure social deprivation and glaucoma‐related QOL
Patient Questionnaire Study (280 patients) to investigate the correlation between social deprivation and glaucoma‐related QOL
Statistical Analysis of the results from the Patient Questionnaire Study

It was decided that the best tool to assess social deprivation was the Scottish Index of Multiple Deprivation (SIMD) and the best instrument to measure glaucoma‐related QOL in this context was the 25‐item National Eye Institute Visual Functioning Questionnaire (VFQ‐25).Results: 280 patients, 142 males and 138 females, undertook the questionnaire.The mean age was 73, all of Caucasian race.Those with lower SIMD scores (more socially deprived) reported lower VFQ‐25 scores (lower quality of life).Statistical analysis established that Pearson correlation coefficient r = 0.535 with p‐value = 0.011The significance threshold was set at 0.05 for the p‐value.Conclusions: This study has now established that greater social deprivation leads to a lower glaucoma‐related QOL, which encompasses the physical, psychological, emotional and social well‐being of the patient.This is extremely useful as it highlights that more can and should be done to help socially deprived glaucoma patients. The research poster proposes some measures to implement to help improve the overall well‐being of socially deprived glaucoma patients, and thereby maintain their independence and QOL.
Phacolytic glaucoma: About a case report
Authors: Younes Laarif , Nihal El Arari , Ouadghiri Soukayna , Salma Hamidi , Benchekroun Saad , Elhachimi Rim , Abdellah Amazouzi , Oufae Cherkaoui Lalla 
Published: January 2025

Aims/Purpose: We report the case of a 70‐year‐old patient with chronic renal failure secondary to amyloidosis of undetermined etiology as well as multiple episodes of red eye with notion of self‐medication for 2 years consulting for an episode of red eye painful for 3 days.Methods: The ophthalmic examination revealed a best corrected visual acuity at counting fingers at 1 meter and light perception respectively in OD and in OS.Examination of the anterior segment showed a calm anterior segment in OD with normal ocular tonus and a grade 3 nuclear cataract and in OS a slight conjunctival hyperemia, ocular tonus at 30 mmHg, a 1+ flare and a dense morganian cataract.The ocular fundus was inaccessible in both eyes.The ocular ultrasound found a normal posterior segment in both eyes.Results: A phacolytic glaucoma diagnosis has been made and the patient was started on local steroid therapy and local and systemic antiglaucoma treatment and then benefited 3 days later from cataract surgery which took place without notable incident.The post‐operative period was marked by an improvement in visual acuity and a reduction in intraocular inflammation. Phacolytic glaucoma occurs mainly in the context of hypermature or even Morgagnian senile cataract. Over time, the cortical fibers of the lens degenerate into water‐soluble protein aggregates. These high molecular weight lens proteins escape through a grossly intact lens capsule into the anterior chamber, where they induce intense macrophage activity.Conclusions: Although curable, cataract remain the most significant cause of blindness in developing countries, mainly affecting the elderly.Delayed treatment leads to serious complications such as lens induced glaucoma, which can lead to irreversible vision loss. Cataract surgery is the most effective treatment for lowering IOP and restoring vision in these patients if undertaken early enough.References
Macovei ML, Canache M, Neagoe BM. Phacolytic glaucoma ‐ case report. Rom J Ophthalmol. 2021 Apr‐Jun;65(2):191‐195. doi: 10.22336/rjo.2021.38. PMID: 34179587; PMCID: PMC8207859.
A low dose bimatoprost 0.01% & Timolol 0.1% eye gel compared to bimatoprost 0.03% & Timolol 0.5% eye drops: A Phase III Randomized study
Authors: Stalmans Ingeborg , Cordeiro M. Francesca 
Published: January 2025

Aims/Purpose: To compare the efficacy and safety of preservative‐free (PF) fixed combination, bimatoprost 0.01%/timolol 0.1% eye gel (BTFC eye gel) with bimatoprost 0.03%/timolol 0.5% eye drops (BTFC eye drops) in patients with open‐angle glaucoma (OAG) or ocular hypertension (OHT).Methods: Phase III, international, multicentre, randomised, 2 parallel groups, investigator‐masked, 3‐month treatment duration study. Patients with OHT or OAG, insufficiently controlled with a first‐line monotherapy, and requiring a dual therapy, were randomized to receive either PF BTFC eye gel (bimatoprost 0.01%/timolol 0.1%) or PF BTFC eye drops (bimatoprost 0.03%/timolol 0.5%), once daily for 12 weeks. The primary efficacy endpoint was the change from baseline (Day 1) to Week 12 in IOP at 08:00, in the study eye. Noninferiority was based on a predetermined criteria (upper 95% confidence interval margin of 1.5 mmHg at Week 12 at 08:00). Further efficacy and safety endpoints were assessed as secondary outcomes.Results: The mean change from baseline to Week 12 in IOP at 08:00 was −10.96±3.43 mmHg for BTFC eye gel and −11.14±3.56 mmHg for BTFC eye drops. Noninferiority of T4030 was demonstrated, based on the predetermined criteria. IOP‐lowering efficacy was also similar between treatment groups at Week 6 (08:00; 10:00; 16:00) and Week 12 (10:00; 16:00). The safety profile was similar between T4030 and Ganfort; however, more patients withdrew from the study due to a treatment‐related adverse event (AE) with BTFC eye drops (8 patients [21 AEs]), compared to BTFC eye gel (no patients). Global tolerance was considered as satisfactory/very satisfactory by the investigator for more patients in the T4030 (96.4%) versus Ganfort (91.6%) at Week 6, with a statistically significant between group difference (p = 0.020).Conclusions: A low dose PF bimatoprost 0.01%/timolol 0.1% eye gel can be considered as a safe and effective tool in the therapeutic management of glaucoma and OHT.