bluuebunny/crossref_metadata_2025_split huggingface dataset:
Vitamin D supplementation modifies clinical and biological markers of keratoconus progression
Authors: Ferrari Giulio , Palombella Silvia , Bartolomeo Nicolò , Tilaro Gianluca , Pederzolli Matteo , Vitar Romina Mayra Lasagni , Fonteyne Philippe , Massimo De Micheli , Bandello Francesco 
Published: January 2025

Aims/Purpose: evaluation of vitamin D (Vit D) supplementation on clinical progression and systemic biomarkers in adolescent patients affected by keratoconus (KC) and Vit D insufficiency.Methods: forty adolescent patients (age range: 12–19) meeting the criteria of KC diagnosis and Vit D insufficiency ( < 30 ng/mL) were enrolled and followed for 12 months. Vit D supplementation was prescribed for the first 6 months and patients were then followed up for additional 6 months. Clinical parameters, including best spectacle‐corrected visual acuity, maximal keratometry, and corneal thickness were measured at month 0, 2, 4, 6, 9, 12 after enrollment to monitor the KC progression. Moreover, at month 0 and 6 after enrollment we evaluated serum biomarkers, including Vit D levels and metabolism, collagen degradation, and inflammation by ELISA and RT‐PCR.Results: after 6 months of Vit D supplementation, serum Vit D levels were significantly increased and remained clinically stable up to month 12. Two‐thirds of patients responded to treatment and showed KC stabilization 12 months after enrollment. Interestingly, Vit D receptor was upregulated only in stable patients (p < 0.01) at month 6. Serum markers indicated that type I collagen degradation product, procollagen type I carboxyl‐terminal propeptide, and the ratio between matrix metalloproteinase 9 and tissue inhibitor of matrix metalloproteinase 1 were statistically decreased (p < 0.05) only in stable patients. Vit D supplementation was associated with increased expression of CD 14 (p < 0.0001) and decreased levels of lactoferrin (p < 0.0001).Conclusions: these data demonstrated that Vit D treatment stabilized KC progression in the majority of patients. These stable patients showed reduced systemic inflammation and collagen catabolism, thus suggesting that KC could be considered a systemic disease.
Performance and safety of a new preservative‐free eye drops in contact lens wearers with dry eye
Authors: Christina Grupcheva 
Published: January 2025

Aims/Purpose: One of the most common reason for contact lens discomfort and drop out is dry eye. The aim of this study was to assess the performance of new preservative‐free eye drops Thealoz®Total containing sodium hyaluronate (SH) 0.15%, trehalose 3%, NAAGA (N‐Acetyl‐Aspartyl‐Glutamic Acid) 2.45% (Laboratoires Théa, Clermont‐Ferrand, France), in patients with subjective appreciation of ocular surface problems due to contact lenses (CL)wear.Methods: A prospective, single‐arm, multicenter, 5‐week study included three visits: Day 1 (D1), D15 and D36 in 34 patients wearing CL daily, applying Thealoz®Total 3 to 6 times daily. The Ocular Surface Disease Index (OSDI) and the Contact Lens Dry Eye Questionnaire‐8 (CLDEQ‐8) were used to evaluate symptoms and quantify discomfort. Standardized clinical tests were performed to assess dry eye.Results: The results for 34 participants were analyzed (FAS). The mean (SD) of the CLDEQ‐8 total score was 22.6 (4.6) at baseline, 13.5 (5.2) at D15 and 10.0 (4.7) with a mean Change From Baseline (CFB) of ‐12.6 (5.0) at D36 (p < 0.001). The mean (SD) OSDI score was 36.85 (16.29) at baseline, 19.37 (14.41) at D15, 12.71 (10.34) at D36 with a mean CFB of ‐24.14 (12.57) at D36 (p < 0.001). The mean CFB in the ocular discomfort score was ‐22.1 ± 18.3 mm at D15 and ‐32.6 ± 19.0 mm at D36 (p < 0.001). The mean CFB in total symptom score was ‐4.4 ± 2.4 at D15 and ‐6.3 ± 3.2 at D36 (p < 0.001). Most patients experienced an improvement of each symptom at D15 (50.0% for itching and 82.4% for dryness) and D36 (67.6% for itching and tearing, and 91.2% for dryness). A soothing sensation upon instillation was judged “important” by 47.1% of patients at D15, and increased to 79.4% at D36. Only two Treatment‐Emergent Adverse Event (TEAE) were experienced by 1 patient, and were non‐serious and of mild intensity (photophobia and instillation site discomfort).Conclusions: This new eye drops containing SH 0.15%, trehalose 3%, NAAGA 2.45% has been shown to be efficacious on dry eye symptoms and ocular discomfort in CL wearers as soon as 15 days, with sustainable improvement in 36 days. This makes the drops safe and efficient, not only for CL users but for variety of therapeutic and postsurgical applications with utilization of CL.
Reducing disconfort in contact lens wearers: Refitting symptomatic users to Kalifilcon A
Authors: Ruiz Jose Miguel Sanchez , Di Pierdomenico Johnny , Ayuso Diego Garcia 
Published: January 2025

Aims/Purpose: The prevalence of discomfort associated with contact lens (CL) wear is estimated to affect up to half of the wearers, often resulting in the discontinuation of CL wear. This study aimed to determine whether refitting symptomatic wearers with a daily disposable CL (Kalifilcon A) reduces symptoms and improves the wearer experience.Methods: 47 symptomatic CL wearers (CLDEQ‐8 > 12) were randomly assigned in a masked fashion to receive either Kalifilcon A or their usual CL (placebo). Following one month of CL wear, participants were switched to Kalifilcon A or placebo, which they wore for another month. Non‐invasive tear break‐up time measurements were performed using a Medmont E300USB topographer. Furthermore, the participants completed the CLDEQ‐8 and NEI VQF‐25 questionnaires to assess symptomatology and vision‐related quality of life while wearing CLs. Finally, the participants were asked to subjectively rate the ease of handling, manipulation and comfort of both CLs.Results: After a one‐month period of wearing both CLs, the results of theCLDEQ‐8 revealed a statistically and clinically significant reduction in symptomatology with Kalifilcon A CL (10.95 ± 8.82) in comparison to the placebo CL (14.65 ± 7.83; p = 0.02). The NEI VFQ‐25 questionnaire outcomes indicate that Kalifilcon A CL exhibits a substantial improvement in the subscales of eye pain, with a score of 59.4 ± 9.9, compared to the score of 47.3 ± 8.2 (p < 0.0001), and in the subscales of role difficulties, with a score of 10.1 ± 13.9, compared to the score of 38.6 ± 8.2 (p < 0.0001).In terms of subjective rate, Kalifilcon A CL demonstrated superior performance in terms of overall satisfaction with comfort (7.78 ± 1.88vs8.5 ± 1.86; p = 0.01) and overall satisfaction with the CL (7.8 ± 1.89vs8.44 ± 1.61; p = 0.04). The results of the tear quality study revealed no statistically significant differences between the two CLs.Conclusions: Refitting individuals who exhibit symptoms while wearing CLs with Kalifilcon A daily disposable contact lenses resulted in a significant reduction in the incidence of symptoms and a noticeable enhancement in the user's overall experience. This presents a valuable solution for those who may otherwise be at risk of discontinuing CL wear.
The physiochemical properties of artificial tears and their impact on human cultured conjunctival goblet cells
Authors: Alnoor Umalbaninn , Ahrensberg Simone , Heegaard Steffen , Kolko Miriam 
Published: January 2025

Aims/Purpose: To investigate the cell survival and mucin release (Muc5AC) of human conjunctival goblet cells (GCs) when incubated with preserved and preservative‐free (PF) artificial tears (AT), and to compare the physicochemical properties of these ATs. Ten different ATs were examined, five containing preservatives (benzalkonium chloride (BAK), PolyQuad, and cetrimide) and five preservative‐free.Methods: Primary cultures of human conjunctival GCs were cultivated from donor conjunctiva. After incubation with ATs diluted 1: 7 or 1: 3.5 in culture media for 2 hours, GC survival was analysed using a lactate dehydrogenase assay and compared to a negative control. Mucin release was evaluated after incubation with ATs (1: 7) for 4 hours using an ELISA assay. The pH values, osmolarity, and surface tension of the ATs were also measured.Results: AT (1: 7) preserved with 0.001% BAK and 0.01% cetrimide reduced cell survival by 26% (p < 0.0001) and 19% (p = 0.0304), respectively, compared to a negative control. When diluted 1: 3.5, ATs preserved with 0.005% and 0.006% BAK also significantly decreased cell survival (p = 0.0014 and p < 0.0001, respectively). Preservative‐free ATs did not significantly alter cell survival. Muc5AC release was increased by 0.01% BAK preserved AT (p = 0.0497). The pH values of all ATs varied significantly between different products and were all significantly different from the physiological pH of the tear film (pH = 7.4). None of the ATs were hyperosmolar. PF ATs had a higher surface tension compared to preserved ATs.Conclusions: BAK‐ and cetrimide‐preserved artificial tears induce goblet cell death in a concentration‐dependent manner, potentially exacerbating dry eye disease (DED). Additionally, BAK appears to increase Muc5AC release. Therefore, preservative‐free or PolyQuad‐preserved artificial tears may be more suitable for DED management. The physicochemical properties of these artificial tears vary which can influence their effectiveness.
Identification of clinical protein markers correlated to the impairment of the lacrimal and meibomian glands in the progression of dry eye syndrome
Authors: Perumal Natarajan , Lindner Anna , Glassmacher Adina , Multani Bettina , Lin Hao , Manicam Caroline 
Published: January 2025

Aims/Purpose: Dry eye syndrome (DES) is a multifactorial pathology of the ocular surface, characterized by disruption of tear film homeostasis. Although prevalent, distinct clinical biomarkers associated with the impairment of the lacrimal (LG) and meibomian glands (MG) that exacerbate the progression of DES are still largely lacking. This study was conducted to identify potential DES markers for precise clinical diagnosis.Methods: Subjects underwent a battery of clinical examinations including the basic secretory test via Schirmer I to evaluate the functional impairment of the LG that leads to aqueous‐deficient DES (DRYaq). Meanwhile, tear break‐up time (TBUT) test was used to evaluate the impairment status of the MG, which leads to evaporative DES (DRYlip). Next, the tear samples (N = 307) were analyzed individually employing mass spectrometry‐based proteomics, followed by in‐depth statistical and bioinformatics analyses.Results: A total of 47 proteins, largely secreted by the LG and annotated to antibacterial response (p = 5.0 × 10‐9) were found to be significantly (p < 0.01) decreased in abundance with the progression of DRYaq, namely LTF (r = ‐0.79), PROL1 (r = ‐0.64) and AZGP1 (r = ‐0.58). On the contrary, as many as 360 proteins were found to be significantly increased in abundance with the progression of DRYaq, namely SFN (r = +0.68), ORM2 (r = +0.67) and TXN (r = +0.66). These proteins are annotated to various biological functions, especially inflammatory response (p = 3.0 × 10‐17), apoptosis (p = 2.1 × 10‐29) and synthesis of reactive oxygen species (p = 3.7 × 10‐29). Only 26 proteins were found to be significantly expressed with the progression of DRYlip, namely ACTN2 (r = ‐0.33) and ARG1 (r = +0.48). These proteins are exclusively annotated to anti‐inflammatory response (p = 8.1 × 10‐5), citrulline biosynthesis (p = 4.5 × 10‐3) and IL‐15 signaling (p = 2.5 × 10‐4).Conclusions: For the first time, our study analyzed the proteome of the largest number of individual tear samples in a clinical setting. Importantly, we identified progressive changes in the expression of specific protein markers correlated to the functionality of the LG and MG that could be potentially leveraged for future development of improved clinical diagnosis and targeted therapeutic interventions to ameliorate DES in a personalized manner.
Optimizing keratoconus treatment with AI‐driven lenticule matching using pentacam indices
Authors: Doroodgar Farideh , Niazi Sana , Nematy Hamidreza 
Published: January 2025

Aims/Purpose: The aim of this study is to develop an advanced artificial intelligence (AI) methodology to optimize the matching of donor and recipient lenticules for the treatment of keratoconus. This approach leverages Pentacam indices related to corneal thickness and topography to minimize the preparatory modifications required for stromal lenticule implantation.Methods: We will construct a comprehensive database of donor and recipient lenticules by systematically collecting Pentacam‐derived indices, including central corneal thickness (CCT), anterior and posterior corneal elevation, and corneal curvature, at preoperative, intraoperative, and postoperative stages. Using these datasets, an AI algorithm capable of identifying the most compatible lenticule pairs will be trained and validated. The algorithm's performance will be assessed based on its accuracy in predicting optimal matches and the practical effectiveness of the process.Results: As this project is in its preliminary phase, no results are currently available. However, we hypothesize that the AI‐assisted matching system will significantly enhance the compatibility of donor and recipient lenticules. Expected outcomes include increased postoperative central corneal thickness, improved corrected distance visual acuity (CDVA), and reduced corneal irregularity.Conclusions: This study aims to validate the potential of AI‐assisted matching of donor and recipient lenticules using Pentacam indices as a transformative approach in the treatment of keratoconus. By refining the customization process, we anticipate improvements in surgical efficiency and patient outcomes.
Quantitative assessment of chitin synthase gene of demodex mite on eyelashes and correlation to symptomatology of blepharitis
Authors: Andriopoulos Georgios , Kalogeropoulos Chris , Katsanos Andreas , Kozobolis Vasileios , Terzidou Chryssa , Dalianis Georgios , Trivli Alexandra 
Published: January 2025

Aims/Purpose: to quantify the presence and activity of Demodex mites and correlate it with patient symptoms, using quantitative determination of gene copy number for the chitin synthase gene.Methods: 61 patients meeting the inclusion criteria were enrolled in the study. 8 eyelashes from each patient were aseptically placed in sterile microtubes. After DNA isolation, quantitative real‐time PCR reactions were performed with specific primers for the chitin synthase gene (DEM) (for Demodex) and beta‐actin (ACTNB) and Factor V (FV) (for human), to amplify the corresponding genes. The quantitative differences for Demodex DNA copies were relative to the simultaneous amplification of the reference human genes (CtDEM‐CtFV/ΔCt1 or CtDEM‐CtACTNB/ΔCt2).Results: 51 subjects completed the protocol. Mean age was 57.08 ± 17.35 years. Mean Ocular Surface Disease Index (OSDI) was 41.79 ± 20.05, while mean Total Ocular Symptom Score (TOSS) was 42.25 ± 23.90. Mean conjunctival hyperemia was 1.43 ± 0.48 (0‐3). Subjects had a mean Non‐Invasive Tear Break‐up Time (NIBUT) of 6.86 ± 4.32 sec. Meibography showed a mean of 1.66 ± 0.51 (0‐3), while Marx Line values were 1.56 ± 0.825 (0‐3). Pearson's correlation coefficient indicated a positive correlation of age and TOSS score (p = 0.035) as well as conjunctival hyperemia (p < 0.001) values. Higher OSDI scores were correlated to higher TOSS scores (p < 0.001), lower NIBUT values (p = 0.001) and worse meibography grade (p = 0.038). Conjunctival hyperemia showed a linear relationship with age (p < 0.001). ΔCt1 (CtDEM‐CtFV) showed a positive correlation with ΔCt2 (CtDEM‐CtACTNB) (p < 0.001).Conclusions: The present study is the first to test the number of Demodex‐severity of symptoms hypothesis, using specific genes and Real‐time PCR. Although no statistically significant correlation was revealed for the specific genes, the clinical data analysis confirmed a correct methodology and sampling, creating a frame for future research on the hypothesis.
Co‐polymer based delivery system for the treatment of ocular surface and cornea diseases
Authors: Astolfi Gloria , Guidotti Giulia , Soccio Michelina , Lotti Nadia , Ponzini Erika , Fontana Luigi , Moramarco Antonio , Versura Piera 
Published: January 2025

Aims/Purpose: The treatment of ocular surface diseases (OSD) requires the administration of therapeutic agents in sufficient quantities for the proper time to reach therapeutic efficacy and relieve from subjective symptoms. Delivery systems avoid systemic routes which may require undesirable concentrations of the agents to reach appropriate levels at the target site. The aim of this work was to standardize two polyester‐based co‐polymers for ophthalmic application.Methods: The cytotoxicity, the morphological changes, and the adhesion behaviour of the copolymers in study were assessed by Human Conjunctival Fibroblasts (HConF) and Epithelial (HCjECs) cell‐culture‐based tests (ISO 10993.5). The controlled release of two model proteins presents in tear fluid, (Human Lactoferrin–LF, and Lysozyme C‐LYS‐C, Sigma) was estimated by uploading both proteins for 24h in a solution with a physiological concentration, and the released kinetic was monitored over time with the Bioanalyzer 2100 (Agilent). The structure of the proteins was monitored by circular dichroism analysis on pure and released proteins.Results: Both copolymers were demonstrated to be non‐cytotoxic, cell viability was preserved after the contact with both materials or their extracts, growth and proliferation of HConF and HCjECs on the wells were also supported, cells failed to adhere to both materials. The release analysis showed a gradual time dependance, reaching a plateau at 180 minutes for LF and 75 min for LYS‐C. The native structures of released LF and LYS were unchanged as compared to their pre‐loaded structure.Conclusions: Data from this study suggest that the copolymers under study might represent a versatile, safe and effective treatment option for chronic OSD, to ensure patient's compliance, and effective treatment.
Residence time and ultrastructural effects of a new formulation of multiple‐action tear substitute: Preliminary results at scanning electron microscopy (SEM) examination
Authors: Troisi Mario , Del Prete Salvatore , Troisi Salvatore , Marasco Daniela , Costagliola Ciro 
Published: January 2025

Aims/Purpose: The aim of the study is to evaluate with SEM the residence time and ultrastructural effects on the ocular surface cells in patients suffering from dry eye disease (DED) treated with a multiple‐acting tear substitute based on 0.15% cross‐linked HA, cationic liposomes and 3% trehalose (Trimix®, Offhealth SpA, Firenze, Italy).Methods: We examined 10 eyes of 10 patients with previous clininal diagnosis of DED (Schirmer test 1 < 10 mm, TBUT < 10 s, OSDI > 13). Exclusion criteria: topical or systemic therapies in the previous 30 days; allergic conjunctivitis; infections and other ocular surface diseases in the last 3 months; previous herpetic keratitis; corneal opacities and ulcers; pregnancy and breastfeeding, age < 18 years.All patients were treated for 30 days BID with Trimix®. At the baseline (T0) and 1h (T1), 6h (T2) and 12h (T3) after the end of the treatment, a cytological sampling of the bulbar conjunctiva with an impression procedure was performed. The cytological smear was examined with SEM for the evaluation of the microvilli, using a preset scale (Del Prete, 2017), and of the persistence of Trimix®, preliminarily identified by SEM on a slide. The results were compared with a control group (CTR) of 10 patients with the same grades of inflammation of DED group, treated with BID balanced salt solution.Results: At T0 6 DED patients presented mild/moderate inflammation (grade 1‐2 of microvillar alteration); 4 medium/severe inflammation, with grade 3‐4 on the microvillar evaluation. At T1 8/10 eyes (80%) showed a complete restoration of the microvillar surface (p < 0.001), 2/10 (20%) an improvement at stage 1 (p < 0.001). The persistence of the Trimix® molecules was detected at T1 and T2 in all cases; in 9 of them (90%) Trimix® partially enveloped the microvilli at T3. No significant microvillar changes were found in CTR group (p > 0.05). The tear substitute resulted well tolerated as no patient reported any significant side effects.Conclusions: Microvilli express the vitality of epithelial cells. Their significant improvement or complete recovery after treatment with Trimix® indicates strong trophic and protective properties of the product, that could continue even 12 hours after the instillation, as confirmed by the high residence time. This could suggest a high effectiveness even when administered twice daily.
Transmigration of neutrophils across the avascular corneal endothelium
Authors: van der Krogt Jeffrey , Dallinga Marchien , Murphy Conor , van der Meulen Ivanka , van Buul Jaap 
Published: January 2025

Aims/Purpose: The corneal endothelium (CE) functions as a tight barrier to regulate nutrient and fluid influx into the corneal stroma. During corneal infections, leukocytes infiltrate the cornea through the conjunctival lymphoid reservoir or via angiogenesis directed by the limbus. In a previous study, neutrophils were found to migrate across the corneal endothelium (CE) upon stimulation with IFN‐γ, mediated by ICAM‐1 [1]. We aim to further elucidate the transmigration of neutrophils across the CE as a possible third route for corneal infiltration.Methods: CE tissue samples were obtained from patients with corneal disease that underwent posterior lamellar corneal transplantation or penetrating keratoplasty. Confocal immunofluorescence microscopy was used to study the expression and distribution of adhesion molecule ligands for leukocyte adhesion and the spatial distribution of neutrophils within the CE.Results: Multiple events of infiltrating neutrophils across the CE monolayer were identified, with the paracellular route being the preferred mode of migration. The expression of the leukocyte ligand ICAM‐1 appeared diffuse but heterogeneous across the CE.Conclusions: Using high‐end microscopy, we found neutrophil infiltration through the CE monolayer and confirmed the presence of ICAM‐1 on the apical surface of CE cells. These data imply that there is a third pathway of corneal immunity. This has implications for anti‐inflammatory therapies instilled systemically or topically and warrants further investigation.References
Elner VM, et al., Intercellular adhesion molecule‐1 in human corneal endothelium. Modulation and function. Am J Pathol. 1991.