bluuebunny/crossref_metadata_2025_split huggingface dataset:
ODDB: An interactive database for clinical and translational research in ocular diseases
Authors: Seemab Umair , Kalatanova Anna , Hassan Saad , Tanoli Ziaurrehman , Leinonen Henri 
Published: January 2025

Aims/Purpose: To develop and validate a comprehensive web‐based interactive database of ocular diseases, including information of, for instance, associated genes, biomarkers, and medications.Methods: Initially, a thorough literature review was conducted to identify key ocular diseases and their associated genes and biomarkers. Data was then curated from multiple reputable sources, including peer‐reviewed journals, clinical trial repositories and drug regulatory agency databases. Advanced data integration techniques were employed to link various data types. The database interface was designed to allow intuitive navigation and robust querying capabilities, ensuring ease of access and data utilization. The database underwent internal testing to ensure user friendliness as well as data accuracy and reliability.Results: The resulting web‐based database encompasses detailed information on a wide array of ocular diseases. The diseases are categorized based on location of primary pathology in various parts of the eye, such as the cornea, retina, and optic nerve, among others. For each disease, the database provides a comprehensive list of biomarkers and associated genes, derived from scientific literature. Additionally, the database includes information of drug regulatory agency‐approved drugs and drugs currently undergoing clinical trials, with detailed descriptions of their therapeutic targets, mechanisms of action and clinical efficacy. The database also features tools for epidemiological analysis.Conclusions: This user‐friendly database of ocular diseases is a valuable resource for the scientific community, providing a wealth of information that can aid in the advancement of ophthalmology research. By consolidating data of biomarkers, genes, drugs and epidemiology, the database supports basic and clinical research, and facilitates the development of new therapeutic strategies. This initiative sets a precedent for future databases in other medical disciplines.
GPT wars: Creating and detecting fake ophthalmology data sets with artificial intelligence
Authors: Taloni Andrea , Coco Giulia , Pellegrini Marco , Lucisano Andrea , Scalzo Giovanna Carnovale , Scorcia Vincenzo , Giannaccare Giuseppe 
Published: January 2025

Aims/Purpose: Recently, our group demonstrated how the Large Language Model GPT‐4 can fabricate fake ophthalmology data sets, designed to support false scientific evidence. The objectives of this study were: (1) to identify peculiar statistical patterns of AI‐generated data sets, (2) to attempt at enhancing the quality of fabricated data for eliminating any discernible mark of non‐authenticity, and (3) to develop a custom GPT trained to detect signs of fabrication.Methods: Three fictional studies were designed to compare treatment outcomes for a specific ocular disease. First, prompts were submitted to the custom GPT “Data Analyst” to produce 12 “unrefined” fake data sets for the three studies. Then, the custom GPT “Fake Data Creator” was developed to generate 12 “refined” fake data sets, specifically designed to evade authenticity checks. Forensic analysis was performed on all data sets using IBM SPSS. Finally, the custom GPT “Fake Data Detector” (FDD) was developed to replicate the forensic analysis and assign 1 point for each sign of fabrication.Results: Forensic analysis of the unrefined fake data sets revealed numerous flaws, most notably: name/gender mismatch (n = 12), non‐uniform distribution (n = 11) and repetitive patterns of last digits (n = 7), absence of correlation between study variables (n = 12), and distribution shape anomalies (n = 11). In refined fake data sets, the forensic analysis did not reveal statistical flaws, except for distribution shape anomalies (n = 7). Overall, 5 refined fake data sets (41.7%) passed forensic analysis as authentic. The results of the statistical analyses performed by GPT FDD were identical to those obtained with IBM SPSS, with a mean of 9.67±2.13 (95% IC 8.46‐10.87) and 1.00±1.00 (95% IC 0.43‐1.57) points respectively allocated to unrefined and refined data sets.Conclusions: Sufficiently sophisticated custom GPTs can perform complex statistical tasks and may be abused to fabricate seemingly authentic ophthalmology data sets, passing forensic analysis.References
Taloni A, Scorcia V, Giannaccare G. Large Language Model Advanced Data Analysis Abuse to Create a Fake Data Set in Medical Research. JAMA Ophthalmol. 2023; 141(12):1174–1175. doi:10.1001/jamaophthalmol.2023.5162
Localized acute exanthematous pustulosis, a rare reaction on eyelids
Authors: Borghi Luca Manuel Bueno , Simón Cristina Calvo , Remacha Carla Sánchez , Duarte Javier Ramos , Pascual Ana María Abad , González Pablo Tejada , de la Cámara Sahuquillo Edurne , Sánchez Inma Herrero , Fernández Miguel Castillo , Martínez Marta Suñer , Clavería Julia Aramburu , Arias Pablo Cisneros , de Rivas Marta Orejudo , Moscarda Eva Josefina Nuñez , Puyuelo Javier Ascaso 
Published: January 2025

Aims/Purpose: The aim of this study is to present a case of localized acute exanthematous pustulosis (ALEP) on the eyelids, a rare adverse cutaneous reaction primarily induced by drugs, with a focus on its clinical features, diagnosis, and management.Methods: We describe the case of a 21‐year‐old female patient who presented with multiple painful vesicles and pustules on the eyelids, predominantly on the right upper eyelid, with no other body involvement. Initially, she did not report any contact with new cosmetics or other treatments. The initial treatment involved doxycycline and Terramycin. During a second visit, when symptoms worsened, the patient reported that she had used a new cosmetic product. The treatment was modified to topical hydrocortisone, mupirocin, and cefadroxil, and withdrawal of the previous treatment. The patient's progress was monitored.Results: At the follow‐up visit conducted three weeks later, both the cutaneous lesions and palpebral edema had completely resolved. Mild palpebral hyperpigmentation persisted; however, the symptoms of pruritus and pain had entirely disappeared.Conclusions: ALEP is a rare, drug‐induced condition that can be effectively managed with proper diagnosis and treatment. This case highlights the importance of having a high suspicion of adverse effects of local treatments and makeup, even when they are not recounted by the patient. Early recognition and intervention are crucial to prevent complications and ensure favorable outcomes.References1.	Parisi R, Shah H, Navarini AA, Muehleisen B, Ziv M, Shear NH, et al. Acute Generalized Exanthematous Pustulosis: Clinical Features, Differential Diagnosis, and Management. Am J Clin Dermatol [Internet]. 2023 Jul 1 [cited 2024 May 29];24(4):1. Available from: /pmc/articles/PMC10166469/2.	Momin S, Rosso J Del, Michaels B, Cutis NM‐, 2009 U. Acute generalized exanthematous pustulosis: an enigmatic drug‐induced reaction. cutis [Internet]. 2009 [cited 2024 Jun 1]; Available from: https://cdn.mdedge.com/files/s3fs-public/Document/September-2017/083060291.pdf
5XFAD/LC3 mice as a model to investigate autophagy mechanism in the eye
Authors: Ruuth Johanna , Toropainen Elisa , Koskela Ali , Hyttinen Juha , Tanila Heikki , Kaarniranta Kai 
Published: January 2025

Purpose: Disturbed proteostasis leads to intracellular protein aggregation and decreased activity of autophagy seen in age‐related macular degeneration (AMD) and Alzheimer's disease (AD). Autophagy is a cellular catabolic recycling process which degrades damaged and aged cellular organelles and protein aggregates. Removed material is sealed by autophagosome which fuses with the lysosome to form an autolysosome. However, autophagy research in vivo is challenging due to lack of specific markers to follow autophagic structures i.e., formation of autophagosomes and autolysosomes. LC3 (microtubule associated protein 1A/1B‐light chain 3) family members are major markers of the autophagosomes located on the autophagosomal membrane. CAG‐RFP‐EGFP‐LC3 (LC3 reporter mice) mice strain enables following the quantity and quality of autophagic structures in the cells. In this study, we investigated the suitability of LC3 reporter mice to study autophagic structures in the 5xFAD mouse eye developing AMD‐like pathogenesis.Methods: 5xFAD and LC3 reporter mice strains were combined. 5xFAD mice develop AD‐ and AMD‐like pathology and LC3 reporter mice express red fluorescent protein (RFP) and pH sensitive enhanced green fluorescent protein (EGFP) attached to a LC3. Therefore, autophagosomes shows both fluorescence signals (yellow) whereas autolysosomes show only RFP signal. The eyes of 3‐ and 6‐months‐old mice (n = 3‐5) were examined by fluorescence microscopy for autophagic structures.Results: Fluorescence microscopy revealed that LC3 reporter mice express fluorescent colors especially in the cornea and the retina. 5xFAD/LC3 strain showed accumulation of autophagic structures in the retinal pigment epithelium. Also, the number of autolysosomes were higher suggesting increased autophagy as a response to a cellular damage.Conclusions: 5xFAD/LC3 reporter mice model seems to be a good model to investigate autophagy mechanism in the eye and degenerative retina processes.
Cryopreservation of corneal endothelial cells in vitro, ex vivo, and on a tissue engineered endothelial graft
Authors: Sagnial Tomy , Coban Melis , Aouimeur Inès , Coulomb Louise , Philippe Gain , He Zhiguo 
Published: January 2025

Aims/Purpose: In response to the global shortage of corneas, alternatives such as cell injection therapy and tissue‐engineered endothelial keratoplasty (TEEK) have emerged, both relying on the mass production of primary cultured corneal endothelial cells (CECs). Cryopreservation of corneas (the primary cell culture source), cultured CECs (in vitro), and TEEK grafts (final products) is crucial to facilitate their industrialization and clinical application. While corneal cryopreservation has long been a challenge, advancements in cryoprotectants warrant a renewed investigation. This study aims to assess various cryopreservation methods for CECs n the three different states.Methods: Ten cryopreservation media and varying cooling rates (‐2°C/min, ‐1°C/min, or ‐0.5°C/min) were first tested on cultured CECs. After thawing, cell survival rates were assessed using Trypan blue staining and an automated cell counter. Subsequently, the best conditions identified for cultured CECs were applied to native CECs adhered to their Descemet's membrane and CECs on TEEKs. Post‐thawing viability was assessed using triple labeling with Hoechst, Ethidium, and Calcein‐AM (Pipparelli et al. IOVS 2011).Results: A gradual cooling rate of ‐1°C per minute and the cryopreservation medium CryoStor CS10 provided the best conditions for in vitro CECs, ensuring an average viability of 91±1% post‐cryopreservation. However, applying the same conditions to native CECs on corneas or CECs on TEEK grafts resulted in a viability of less than 80%. Upon thawing, CECs tended to detach easily from the DM or bio‐engineered grafts, leading to significant areas without cells.Conclusions: Cryopreservation is effective for in vitro cultured CECs but remains very challenging for CECs attached to the DM or TEEKs. The next step will be to address cell attachment issues during cryopreservation.References: Aurélien Pipparelli, Gilles Thuret, David Toubeau, Zhiguo He, Simone Piselli, Sabine Lefèvre, Philippe Gain, Marc Muraine; Pan‐Corneal Endothelial Viability Assessment: Application to Endothelial Grafts Predissected by Eye Banks. Invest. Ophthalmol. Vis. Sci. 2011;52(8):6018‐6025. https://doi.org/10.1167/iovs.10-6641.
Prescribing patterns for preservative‐free glaucoma drops in United Kingdom ophthalmology clinics: A 5‐year multi‐centre study
Authors: Ansari Ejaz , Scott Robert 
Published: January 2025

Aims/Purpose: To establish differences in prescribing patterns between various UK glaucoma clinics with respect to preserved (P) versus preservative‐free (PF) drops. To establish the rate of switching between the drop classes and the overall use of PF drops over 5 years.Methods: This was a multi‐centre cohort study with retrospective case note review (n = 267). The outcome measures included:
Percentage of cases prescribed preserved drops as first‐line treatment,
Percentage of cases switching from preserved to preservative‐free over 5 years,
Percentage of cases switching from preservative‐free to preserved over 5 years,
Average number of switches over 5 years,
Reasons for switching treatment.

A chi‐squared test was used to examine if categorical variables were independent in influencing the test statistics. Statistical significance was determined at the level p = 0.05.Results: Preserved drops were prescribed first‐line in 72% (192) of cases, of these 48% were switched to preservative‐free drops. Of the 67 (25%) cases where preservative‐free drops were prescribed first‐line by the Hospital Eye Services, 68% were switched to preserved drops by community medical services. The average number of switches over 5 years was 1.7+/‐1.96. This varied from 1.1 to 2.7 switches in each geographical region. The commonest indications for switching from P to PF drops were ocular surface disease, hyperaemia, ocular pain and discomfort. There was no significant difference between centres in the proportion of patients receiving initial treatment with P drops (p = 0.12), but there was a significant difference between centres in switching from P to PF drops (p = 0.01).Conclusions: Most centres initiated treatment with preserved drops, but 48% of these cases were switched to PF within 5 years due to intolerance of preserved drops. Where PF drops were initiated, the majority were switched to preserved drops by community physicians for unspecified reasons against the recommendations of their glaucoma specialists.
Safety and efficacy of subliminal cyclophotocoagulation in the treatment of glaucoma
Authors: Ramanathan Priyanka , Kaliaperumal Subashini , Behera Geeta 
Published: January 2025

Aim: This study was conducted to determine the efficacy of subliminal cyclophotocoagulation in reducing intraocular pressure (IOP) in all subtypes of glaucoma and to study any associated complications of the procedure.Methods: This was a prospective interventional study conducted on patients with glaucoma on medical therapy requiring > 3 topical medications. Twenty‐seven patients underwent subliminal cyclophotocoagulation with Vitra 810 laser machine (Quantel Medicals, France). The primary outcome measures were IOP control, postoperative complications, and a reduction in the number of antiglaucoma medications (AGM).Results: 27 eyes were analysed, of which 26 had 6 months follow‐up. Intraocular pressure reduced from 22 mmHg (18,28) at baseline to 16(14,18) at 6 months post‐procedure. The number of anti‐glaucoma medications reduced from 3 (2,3) to 2 (1,3) at 6 months. The reduction in atleast one glaucoma medication was achieved in 61.5% of eyes at 6 months. Most complications, like mydriasis and drop in vision, were transient and self‐limited. Significant complications like vitreous, vitreous hemorrhage and choroidal detachment were seen in 3 patients. The cumulative success rate at 6 months was found to be 84.61%.Conclusions: Subliminal cyclophotocoagulation is effective in glaucoma patients with IOP control on maximum topical medications. It can reduce the drug burden by at least one medication in the short term.References
Radhakrishnan S, Wan J, et al. Micropulse Cyclophotocoagulation: A Multicenter Study of Efficacy, Safety, and Factors Associated With Increased Risk of Complications. J Glaucoma. 2020;29:1126–31.
Mohammed F, Jyothi PT, et al. Efficacy and safety of subliminal transscleral cyclophotocoagulation in uncontrolled glaucoma. Indian J Ophthalmol. 2022;70:2911–4.
Tan AM, Aquino MC, Lim ZIL, et al. Micropulse transscleral diode laser cyclophotocoagulation in the treatment of refractory glaucoma. Clin Experiment Ophthalmol. 2010;38:266–72.
Shah P, Bhakta A, Vanner EA, et al. Safety and Efficacy of Diode Laser Transscleral Cyclophotocoagulation in Eyes With Good Visual Acuity. J Glaucoma. 2018;27:874–9.
Chow JY, Wan Norliza WM, Bastion MC. Outcomes of Subliminal Transscleral Cyclophotocoagulation treatment in glaucoma. Med J Malaysia. 2021 Mar;76(2):236‐240.
Molecular responses of the aging retina are sexually divergent in Ephx2−/− mice
Authors: Manicam Caroline , Zare Elahe , Pfeiffer Norbert , Perumal Natarajan 
Published: January 2025

Aims/Purpose: Aberrant molecular changes are a major driver of age‐related retinopathies. Furthermore, sexual dimorphism is a key variable in disease predilection, although it is not well defined in preclinical studies. Among the potential targets for mitigating age‐related proteome modifications attributed to vision impairment, we recently unraveled the protective effects of soluble epoxide hydrolase (sEH/ Ephx2) inhibition in glaucoma. Here, we hypothesized that molecular responses of the aging retina are also sexually divergent in the Ephx2‐/‐ (KO) mice.Methods: Retinae were isolated from 160 young (3‐5 months) and old (12‐24 months) wild type (WT) and KO mice of both sexes. Samples were pooled (n = 5 mice/group/replicate) with 4 biological replicates per group and subjected to robust proteomic and bioinformatic analyses to elucidate the underlying mechanistic changes.Results: We observed age‐ and sex‐related body weight changes in mice of both sexes, with no significant differences between the WT and KO mice. Proteome profiling showed significant (p < 0.05) differential expression of proteins between the genders, with a significant involvement in the eIF2 and ferroptosis signaling pathways in both sexes. Remarkably, the female sex exhibited striking resilience against ferroptosis, while the male counterpart demonstrated profound activation of this pathway in both WT (p = 4.2×10‐4; z‐score: 1.3) and KO mice (p = 4.2×10‐4; z‐score: 2). Intriguingly, aged WT females were highly susceptible to retinal diseases (p = 9.6×10‐4) and neurodegeneration (p = 9.9×10‐4), but KO significantly regulated proteins related to synaptogenesis (p = 3.8×10‐2) and neurotransmission (p = 1.7×10‐2). In addition, KO significantly activated neuritogenesis (p = 5.4×10‐5) and cell‐cell contact (p = 1.2×10‐3) in both sexes. It is noteworthy that a major upstream transcription regulator, X‐box binding protein 1 (XBP1), which is responsible for maintaining protein homeostasis by ameliorating ER stress, was found only in aged male retinae (WT: p = 3.9×10‐4; KO: p = 8.1×10‐3).Conclusions: Taken together, we showed for the first time a sex‐related trend in the proteome of aging KO retina, which is crucial for understanding the pathomechanistic underpinnings of age‐related retinal diseases and potential targeted intervention.
Effectiveness of intravitreal antitNF‐ALFA for neuroinflammation control and neuroprotection in experimental rabbit glaucoma model
Authors: Tarlabolen Okyanus Bulut , Baris Mine Esen , Soylu Emrah , Yaman Banu , Kose Timur , Guvenyilmaz Suzan 
Published: January 2025

Aims/Purpose: The aim of the study is to create a microbead induced ocular hypertension (OHT) model in rabbits, and to evaluate the effects of intravitreal and intraperitoneal injections of Adalimumab (ADA) on the number of retinal ganglion cells (RGC), retinal nerve fiber layer (RNFL) and ganglion cell complex (GCC) thickness.Methods: 15 rabbits of mixed strain (9–12 months old, 3.5‐4kg) were randomized into 4 groups. OHT was induced with microbead injection into the anterior chamber of right eyes. On 7th, 14th days of OHT, ADA was injected at one of two concentrations (2.5mg group 1: G1/5mg group 2:G2) into right eyes of two groups, intraperitoneally 5mg/kg into the third group (G3), and balanced salt solution into fourth group (sham). The left eyes were used as controls. At 40th day, the rabbits were euthanized. Retinal and optic nerve head (ONH) histology was studied with hematoxylin‐eosin and toluidine blue staining.Results: OHT was induced with microbeads in 13 eyes. 2 rabbits were excluded (endophthalmitis, total hyphema). The average pre‐OHT IOP from all eyes 9.7±09mmHg (8‐11). Statistically significant IOP increase was observed in all subject eyes on day 7 (14±1.4 (12‐18)) (p = 0.01) and maintained until ADA injection (day 21). RGCs in the eyes with elevated IOP were 7.2±1.2 and 7.6±1.5, 6.3+1.1 cells in ADA treated groups, G1, G2, G3, respectively. There was no statistically significant difference between treatment groups. The average RNFL was 125.9±10.9 μm in control, 60.2±9.4 μm in G1, 45.7±2.9 μm in G2, 22.8±2.9 μm in G3, 21.7±10 μm in sham. Significant elevation was observed in G1 compared to all treatment groups. (p = 0.01). The average GCC of control was 45.5±1.9 μm, G1 41.2±2.2 μm, G2 39.3±3.3 μm, G3 34.1±1.6 μm, sham was 38.3±1.1 μm. Significant increase was observed in G1 compared to G3. (p = 0.01).Conclusions: OHT triggers inflammatory response in which TNF‐α expression is increased around the ONH. Blocking TNF‐α might prevent axonal degeneration and RGC loss by inhibiting this response. These findings may further contribute to the literature for a new treatment strategy for glaucoma using TNF‐α antagonists or inflammation suppressors.
miRNAs from tear fluid‐derived extracellular vescicles to identify patients at high risk of fibrotic lesions after glaucoma surgery
Authors: Sanroque‐Muñoz Marta , Garcia Sergio G. , Clos‐Sansalvador Marta , Font‐Morón Miriam , Botella‐Garcia Jessica , Franquesa Marcella , Loscos‐Arenas Jordi , Borràs Francesc E. 
Published: January 2025

Aims/Purpose: Glaucoma is a progressive optic neuropathy characterized by elevated intraocular pressure (IOP). Initial treatment involves topical medication, but surgical intervention is indicated for patients with uncontrolled IOP (1). Yet, post‐surgical tissue fibrosis is a major challenge in 30‐40% of operated patients after 3 years (2). In this work, we investigated the potential of tear fluid‐derived extracellular vesicles (tEVs) from glaucoma‐operated patients to identify specific biomarkers associated with surgery failure secondary to fibrosis.Methods: Tear samples from 14 healthy controls and 41 glaucoma‐operated patients were collected using the Schrimer's test. Patients were divided into two groups CAGDS1 (one surgical procedure) and CAGDS2 (two surgical procedures due to previous surgical failure). EV‐associated microRNA (miRNA) extraction from tear samples was performed using the Urine Exosome RNA Isolation kit (NORGEN). Total RNA quality was evaluated using an Agilent BioAnalyzer 2100, and miRNA expression was assessed by RNA‐seq using 8 μL of each sample to prepare the libraries.Results: Bioanalyzer results showed that miRNAs constituted between 70‐95% of the total small RNA content in tEVs, with a miRNA concentration of 2 to 15 ng/μL in all samples. No differences in RNA quality and concentration were detected between them. RNA sequencing was performed loading 500 pM library pools into two independent NEXtSeq‐1000 runs, and 20 million reads of each sample were obtained. Preliminary analysis showed differential expression of several miRNAs between the groups. Fully analyzed results will be presented and discussed.Conclusions: Tear EV‐derived small RNA extraction is an easy, rapid, and minimally‐invasive method that yields high‐quality miRNA samples starting from a small volume of tears. Similarly to that observed from other sources, RNA sequencing analysis of tEVS could be useful to identify specific glaucoma risk biomarkers, that may help clinicians in their decision making well before therapeutic interventions.