bluuebunny/crossref_metadata_2025_split huggingface dataset:
The influence of strain on human keratocyte redox homeostasis and behavior
Authors: Zhang Qian , Backman Ludvig , Danielson Patrik 
Published: January 2025

Aims/Purpose: To study the influence of strain on the expression of specific proteins in human keratocytes and its consequential effects on keratocyte intracellular redox homeostasis and behavior.Methods: Strain was applied to human keratocytes using the Flexcell® Tension Systems. Proteomics and western blot were used to identify proteins regulated in response to strain. Immunofluorescence (IF) staining and live‐cell imaging were employed to monitor reactive oxygen species (ROS) production and mitochondrial membrane potential (ΔΨM). Expression of oxidative stress‐related protein, and its influence on nuclear factor kappa‐light‐chain‐enhancer of activated B cells (NF‐κB) nuclear translocation and keratocyte proliferation and migration, were assessed by western blot, IF staining and bromodeoxyuridine (BrdU) assay. Mouse injury models and keratocytes from keratoconus patients were used to assess how strain (intraocular pressure, IOP) influences downstream protein in vivo.Results: The expression of protein Cytochrome P450 1B1 (CYP1B1) and Aldehyde Dehydrogenase 3 Family Member A1 (ALDH3A1) was significantly upregulated in strained keratocytes. Increased CYP1B1 effectively suppressed H2O2‐induced ROS production and mitigated the dissipation of ΔΨM. ALDH3A1 expression was negatively related to ROS accumulation. When the expression of ALDH3A1 was knocked down, NF‐κB nuclear translocation was promoted, ultimately resulting in increased keratocyte proliferation and migration. Mice and keratoconus patients with increased corneal strain also showed elevated ALDH3A1.Conclusions: Corneal strain significantly upregulates the expression of CYP1B1 and ALDH3A1. Increased CYP1B1 helps maintain keratocyte intracellular redox homeostasis and subsequently regulates keratocyte proliferation and migration via ALDH3A1.
Perfluorohexyloctane eye drops in treating dry eye disease associated with meibomian gland dysfunction: A post‐hoc analysis of responses in subgroups based on symptoms and signs
Authors: Jie Ying 
Published: January 2025

Aims/Purpose: In a randomized trial of dry eye disease (DED) associated with meibomian gland dysfunction (MGD), patients received either perfluorohexyloctane eye drops (n = 156) or sodium chloride (NaCl) solution (n = 156) four times daily. The trial showed that perfluorohexyloctane significantly improved DED signs and symptoms with rapid efficacy and satisfactory safety compared to NaCl. This post hoc analysis evaluated efficacy in subgroups based on signs and symptoms, specifically discordant signs and symptoms.Methods: Patients were grouped according to median changes in total corneal fluorescein staining (tCFS), eye dryness score (EDS), and ocular surface disease index (OSDI) between baseline and day 57 after treatment. Responses at day 57 were defined as: tCFS Response, decrease of ≥ 3 points from baseline; EDS Response, reduction of ≥ 30% from baseline; OSDI Response, reduction of ≥ 30% from baseline.Results: In the tCFS ≤ 6 & EDS ≥ 60 group, the tCFS & EDS Response was 52.7% (29 patients) with perfluorohexyloctane vs. 28.4% (19) with NaCl (OR 95% CI: 2.82, 1.33–5.96, p = 0.0068). In the tCFS > 6 & EDS ≥ 60 group, the tCFS & EDS Response was 72.1% (31) vs. 36.6% (15) (OR 95% CI: 4.48, 1.78–11.25, p = 0.0014). In the tCFS ≤ 6 & OSDI ≥ 60 group, the tCFS & OSDI Response was 61.4% (27) vs. 28.2% (11) (OR 95% CI: 4.58, 1.79–11.74, p = 0.0015). In the tCFS > 6 & OSDI < 60 group, the tCFS & OSDI Response was 72.2% (26) vs. 42.9% (15) (OR 95% CI: 3.47, 1.29–9.33, p = 0.0138).Conclusions: The post hoc analysis showed that perfluorohexyloctane eye drops significantly improved DED symptoms and signs in subgroups where symptoms and signs were discordant, such as those with tCFS ≤ 6 & EDS ≥ 60, tCFS ≤ 6 & OSDI ≥ 60, and tCFS > 6 & OSDI < 60, as well as in cases where both symptoms and signs were more severe, such as tCFS > 6 & EDS ≥ 60.
Efficacy and safety of perfluorohexyloctane eye drops in ametropic patients with dry eye disease associated with meibomian gland dysfunction: A subgroup analysis from a phase 3 clinical trial
Authors: Zhao Shaozhen 
Published: January 2025

Aims/Purpose: The randomized clinical trial demonstrated the efficacy and safety of perfluorohexyloctane (SHR8058) eye drops for dry eye disease (DED) associated with meibomian gland dysfunction (MGD). This post‐hoc analysis aimed to evaluate the efficacy and safety of perfluorohexyloctane eye drops in ametropic patients with DED associated with MGD.Methods: This subgroup analysis based on a randomized, double‐masked, saline‐controlled, phase 3 trial included ametropic patients with DED and MGD. In the original study, participants were randomized to receive either perfluorohexyloctane or 0.6% sodium chloride (NaCl) drops four times daily for 57 days. Primary endpoints were changes in total corneal fluorescein staining (tCFS) and eye dryness score at day 57.Results: A total of 121 ametropic patients were included (57 in the perfluorohexyloctane group, 64 in the NaCl group). At day 57, the perfluorohexyloctane group showed a significant improvement in tCFS score (mean reduction: −5.2) vs. NaCl (mean reduction: −3.3), with an estimated least squares mean (LSmean) difference of −1.9 (95% CI: −2.7 to −1.1). Eye dryness score improved significantly in the perfluorohexyloctane group (mean reduction: −42.4) vs. NaCl (mean reduction: −26.9), with an estimated LSmean difference of −15.5 (95% CI: −22.1 to −8.8). Additionally, perfluorohexyloctane eye drops alleviated symptoms including pain, awareness of DED symptoms, and frequency of dryness compared to the control. Ocular treatment‐emergent adverse events were similar between groups (15.8% in the perfluorohexyloctane group vs. 14.1% in the NaCl group).Conclusions: Perfluorohexyloctane eye drops significantly improved both objective signs and subjective symptoms of DED in ametropy patients with MGD, demonstrating favorable efficacy and safety.
Perfluorohexyloctane eye drops for dry eye disease associated with meibomian gland dysfunction: A subgroup analysis by menopausal status from a phase 3 trial
Authors: Shi Xiaoru 
Published: January 2025

Aims/Purpose: In a randomized, double‐masked, phase 3 trial (NCT05515471), perfluorohexyloctane eye drops effectively improved signs and symptoms of dry eye disease (DED) associated with meibomian gland dysfunction (MGD). This post‐hoc analysis of the phase 3 trial provides efficacy and safety results by menopausal status subgroup.Methods: As previously detailed, patients with DED associated with MGD were randomly assigned 1: 1 to receive perfluorohexyloctane eye drops or 0.6% sodium chloride [NaCl]). Primary endpoints were changes from baseline in total corneal fluorescein staining (tCFS) and eye dryness scores at day 57. Menopause was defined as at least 12 consecutive months without menstruation. A random effects model adjusted for center and baseline values analyzed the efficacy data.Results: In total, 94 patients were menopausal (48 on perfluorohexyloctane, 46 on NaCl) and 151 patients were premenopausal (70 on perfluorohexyloctane, 81 on NaCl). At day 57, premenopausal patients treated with perfluorohexyloctane showed greater decreases from baseline in tCFS score and eye dryness score than the NaCl group, with differences between treatment groups of ‐1.35 (95% CI: ‐2.22, ‐0.48) and ‐14.51 (95% CI: ‐20.85, ‐8.17), respectively. In menopausal patients, decreases from baseline in tCFS score and eye dryness score at day 57 were noted in the perfluorohexyloctane group, with no evidence of between‐group differences (tCFS score difference: ‐0.98, 95% CI: ‐1.98, 0.03; eye dryness score difference: ‐7.09, 95% CI: ‐15.12, 0.94). Perfluorohexyloctane led to significantly greater improvements in burning/stinging sensation, awareness of DED symptoms, frequency of dryness, and ocular surface disease index score in both subgroups. Perfluorohexyloctane were well‐tolerated with similar safety profiles across subgroups.Conclusions: Perfluorohexyloctane eye drops showed efficacy and well tolerability for DED associated with MGD in both menopausal and premenopausal patients.
Modified descemet's stripping automated endothelial keratoplasty (DSAEK) after failed visco‐assisted dalk: Case report
Authors: Mancini Alessandra , Lucisano Andrea , Giannaccare Giuseppe , Pietropaolo Rocco , Taloni Andrea , Carnevali Adriano , Scorcia Vincenzo 
Published: January 2025

Aims/Purpose: This case report aims to describe the posterior lamellar approach to manage stromal interface irregularity after deep anterior lamellar keratoplasty (DALK).Methods: A 42‐year‐old woman previously underwent DALK with visco‐bubble failed for keratoconus associated with intraoperative perforation. One year after surgery, she presented to our center with loss visual acuity. The recipient bed appeared wrinkled and opaque. The anterior optical surface was regular, with low and regular astigmatism. Endothelial cell density (ECD) could not be assessed. The planned surgical procedure consisted of a modified small diameter (7mm) DSAEK technique, in which only the small optic zone was replaced, resulting in a two‐piece mushroom graft configuration.Results: Corneal clarity was restored and complete attachment of the donor lamella was achieved. Postoperative best‐ corrected visual acuity (BCVA) reached 20/20. No intraoperative or postoperative complications were reported.Conclusions: To achieve the clearance of the recipient bed in eyes that have undergone manual DALK, the least invasive surgical strategy should be planned, preserving the healthy corneal tissue of the patient. Small diameter posterior lamellar keratoplasty has a lower incidence of postoperative complications, decreases immunological risk and accelerates functional recovery
Tears as a repository for particulate matter PM 1.0, 2.5 and 10 in an urban environment
Authors: Porru Emanuele , Astolfi Gloria , Ciavarella Carmen , Violante Francesco , Versura Piera 
Published: January 2025

Aims/Purpose: This study investigates the potential of tear fluid analysis as a non‐invasive method to monitor air pollution impact on an exposed body tissue, represented by the ocular surface [1,2]. In particular, we characterized the particulate matter (PM) in tears in healthy volunteers exposed or not to an urban environment.Methods: Twenty healthy volunteers were enrolled from personnel staff, ten were exposed to urban traffic in Bologna, Italy in the period January‐April 2024 for a minimum of 2 hours, and ten were not. A minimum of 5 μL tear were sampled from the lower conjunctival sac, deposited onto glass slides or polycarbonate filters, allowed to dry and stored at room temperature in a sterile Petri dishes, until observation. Scanning electron microscopy (SEM, Zeiss) was employed to analyze and characterize the PM present in the samples. Particles were categorized by size, morphology, and elemental composition using energy‐dispersive X‐ray spectroscopy (EDS). PM analysis and characterization in tears was compared to filters obtained for gravimetric analysis of airborne PM collected via filtration in Milan.Results: SEM analysis revealed predominantly fine particles (PM2.5), with occasional larger ones (PM10). Elemental analysis identified common PM pollutants such as carbon, oxygen, sulfur, nitrogen, and trace metals like iron and calcium. The particle count per unit area (15 eV, 400x) showed a range of densities across different samples, with a difference in PM levels between exposed and non exposed subjects.Conclusions: The study demonstrated that SEM analysis of tear samples is a viable method for detecting PM levels in tears, and a notable difference between exposed and non exposed subjects. This highlights the potential role of tear analysis in monitoring environmental pollution. This non‐invasive approach could be pivotal in understanding the impact of air pollution on the ocular surface.References
M.A. Gutiérrez, D Giuliani, A.A. Porta, D. Andrinolo D, J Ophthalmic Vis Res 2019, 14(4), 419‐427.
O. Girshevitz, N. Cohen‐Sinai, A. Zahavi, Y. Vardizer, D. Fixler, N. Goldenberg‐Cohen, J. Pers. Med. 2022, 12, 1633.
Ultrastructure alteration of post intacs cornea
Authors: Akhtar Saeed , Kirat Omar , Alkanaan Aljohara , Almubrad Turki 
Published: January 2025

Aims/Purpose: To Investigate the organization and distribution of lamellae, and collagen fibrils of 3 post‐INTACS‐corneas. INTACS SK were surgically inserted into the cornea to remodel the keratoconus shape of the corneal curvature of three patients.Methods: Three patients had INTACS inserted with IntraLase femtosecond laser [Advanced Medical Optics (AMO), Santa Ana, CA]. Patient 1 returned to the clinic after 6 years, Patient 2 after 8 and Patient 3 after 9 years due to dissatisfaction with their vision. Each patient was referred for lamellar keratoplasty. The lamellae above the INTACS were removed and were processed for light and electron microscopy. Digital images of lamellae, collagen fibrils and proteoglycans were captured by a bottom mounted camera and analyzed by iTEM software.Results: The ultrastructure of the epithelium and stroma were similar in both central and peripheral parts of the cornea in all three patients. The epithelium contained a large number of electron lucent spaces in the cytoplasm of the wing cells and basal epithelial cells. A large number of aggregates of fibrillar material were present in the Bowman's layer and throughout the stroma. The lamellae at the anterior stroma were not interconnected and the lamellae in the middle stroma were undulated (or cone shaped) not parallel. In the stroma just above the INTACS insertion, lamellae were completely disorganized and running randomly in the large electron lucent spaces. The CF in this region were small in size and had very large spacing among them.Conclusions: The epithelium, lamellae and CFs were degenerated in the post INTACS inserted cornea. We believe that insertion of the INTACS disturbed the lamellar organization and uniform distribution of the CFs. This non‐uniform distribution of the CFs increased over time resulting in the impairment of vision. Further research is required to study the gradual changes in the corneal architecture after the insertion of INTACS.
Ultrastructure of long fibers of the peripheral posterior cornea and immunogold localization of BIG‐H3 and alpha‐elastin proteins
Authors: Akhtar Saeed , Kirat Omar , Alkanaan Aljohara , Almubrad Turki 
Published: January 2025

Aims/Purpose: This study was conducted to investigate the ultrastructure of the long fibres present at the posterior peripheral cornea and expression of the proteins associated with these fibres.Methods: Five anonymous‐donor human corneoscleral rims (leftover after corneal transplants) were used in the study. Five pieces (1.5‐mm) from each ring were cut and were fixed in 4% paraformaldehyde + 0.5% glutaraldehyde in 0.1‐M phosphate buffer for transmission electron microscopy (TEM). The tissues were embedded in LR White resin and polymerized under UV light at 4°C for 48 hrs to investigate the ultrastructure and for immunogold localization of BIG‐H3 and α‐elastin proteins with immunogold technique. Semi‐thin and ultrathin sections were cut using RMC PowerTome ultra cut microtome and observed under Olympus BX53 and JOEL JEM‐1400 (HC) respectively. The long fibres were observed in the posterior peripheral cornea at a radial distance of approximately 900μ from the endpoint of Descemet's membrane (DM). Images were captured using a Quemesa 14 Mega and Xarosa 20 Mega Pixel Bottom Mount CCD Camera.Results: A large number of long fibres with electron dense bands and sheath material were observed above the DM. These fibres contained electron dense fibrillar material and some of the fibers contained collagen fibrils with a banding pattern. The long fibres were strongly labelled with BIG‐H3 antibody but not with α‐elastin antibody. The BIG‐H3 antibody also labelled the microfilaments in the sclera. The α‐elastin antibody strongly stained the central elastic core of the elastic fibres in the sclera.Conclusions: The long fibres enclosed the collagen fibrils and were strongly labelled with BIG‐H3 protein. The fibres were not labelled with elastin antibody whereas elastic fibres in the sclera were strongly labelled. The presence of the collagen fibrils within the long fibres suggests that the long fibres may be formed by the aggregation of the collagen fibrils and BIG‐H3 protein. These long fibres were not elastic fibers.
Characterization of cold thermosensitive trigeminal neurons that innervate the cornea
Authors: Diaz‐Tahoces Ariadna , Aleixandre‐Carrera Fernando , Velasco Enrique , Acosta M. Carmen , Gallar Juana 
Published: January 2025

Aims/Purpose: To electrophysiologically characterize the populations of thermosensitive trigeminal neurons that innervate the cornea based on their response to cooling.Methods: The activity of trigeminal ganglion neurons was recorded in anesthetized Wistar rats using epoxylite‐insulated W microelectrodes inserted at specific stereotaxic coordinates. Saline drops at different temperatures were instilled on the cornea to change corneal temperature, which was constantly recorded with a high‐speed thermal probe. Spontaneous activity without intended stimulation (background activity, BA) and the peak frequency evoked by cold saline instillation (PA) were recorded and analyzed in 22 corneal cold thermosensitive neurons. Parametric or non‐parametric statistical tests were used as needed.Results: Based on their BA, hierarchical clustering segregated the recorded cold thermoreceptor neurons into two groups: High Background (HB; those with BA equal or higher than 5 imp·s‐1) and Low Background (LB; those with BA lower than 5 imp·s‐1). HB cold thermosensitive neurons robustly increased their firing frequency when detecting mild cold stimuli (), being PA proportionally to ΔT (p < 0.05). For corneal ΔT between ‐1° and ‐14°C, PA of HB was maximal regardless of the stimulus intensity. In LB neurons, PA response increased proportionally to the cold stimulus intensity for ΔT between 0‐1° and ‐14°C, and the response to ΔT ‐3°C was significantly different from basal firing.Conclusions: Two subpopulations of corneal cold sensory neurons have been identified in the ophthalmic branch of the trigeminal ganglion. These neurons, which have high background activity, are sensitive to cold temperatures and can detect small changes in corneal temperature. We propose that these neurons detect the temperature drop between blinks and, in turn, trigger the so‐called spontaneous blink.(Supported by PID2020‐115934RB‐I00 from DOI: MCIN/AEI/10.13039/50110001103, Spain, and CIPROM/2021/48 from Generalitat Valenciana, Spain).
Anti‐inflammatory effects of thealoz duo eye drops on the ocular surface of dry eye patients
Authors: Fomo Kristian Nzogang , Perumal Natarajan , Hadji Majd , Yang Jie , Wolters Dominik , Pfeiffer Norbert , Grus Franz 
Published: January 2025

Aims/Purpose: Dry eye syndrome (DES) is a complex pathological condition of the ocular surface characterized by a disturbance of tear film due to lack of tears or excessive tear evaporation. Topical application of medicated eye drops has been shown to be an effective treatment for this disease. In a previous study, Thealoz® Duo eye drops (Laboratoires Thea, France) were demonstrated to significantly enhance vision‐related functions and to inhibit inflammation in patients with DES. The objective of this study was to provide further insight into the efficacy of Thealoz® Duo eye drops by analyzing the expression profiles of marker proteins in the tears of dry eye patients using microarray technology.Methods: A total of 58 candidates were divided into two groups: those with dry eye (DES, N = 35) and those with healthy eyes (CTRL, N = 23). Thealoz® Duo (hyaluronic acid 0.15% and trehalose 3%) was administered only to the DES patients. Tear samples were collected from each individual in both groups at three distinct time points: prior to treatment (day 0, designated T1), on day 28 ± 4 (T2) and on day 56 ± 4 (T3) following the administration of Thealoz® Duo. Thereafter, all samples underwent analysis of the expression of targeted proteins (e.g., APOA1, S100A8, TNFa, FBP1, IL2, IL8, IL17A, IL1RN, SERPINA1 and MMP9) using microarray technology.Results: The data analysis revealed a significant increase in all maker proteins in DES vs. CTRL at T1 (p < 0.05). Furthermore, the data demonstrated that the application of Thealoz® Duo resulted in a decrease in the expression of inflammatory markers in DES vs. CTRL at T2 and T3.Conclusions: The present findings provide further evidence supporting the potential of Thealoz® Duo to improve the visual outcomes by mitigating the inflammation on the ocular surface in patients with DES.
Revisiting fuchs endothelial corneal dystrophy clinical classification using innovative high‐resolution, far‐red, reflexion free retroillumination
Authors: Thuret Gilles , Dorado‐Cortez Oliver , Poinard Sylvain , Ain Anthony , Vaitinadapoule Hanielle , Trone Marie‐Caroline , Lepine Thierry , Gain Philippe 
Published: January 2025

Purpose: Fuchs endothelial corneal dystrophy (FEDC) is by far the most common corneal endothelial diseases in Western countries, and 50% of keratoplasties are carried out to treat endothelial diseases. New treatments are also emerging (Descemetorhexis only, rock‐inhibitors, mTor‐inhibitors, FGF‐1). It will therefore soon be vital to be able to determine the stage of each patient in a simple and reliable way, in order to personalize treatment. Visual acuity, retroillumination, specular microscopy and thickness mapping are the 4 pillars of the examination. However, current retro‐illumination images are of insufficient quality. Aim: to present the first series of FECD observed using new‐generation retroillumination.Methods: We developed a prototype retroilluminator by modifying a slit lamp with the aim of obtaining high‐resolution images, without parasitic reflection and without dazzling the patient. We then prospectively photographed 200 FECD patients. The images were then classified by 3 independent observers according to the modified Krachmer classification, which is the most widely used in the literature: it distinguishes patients according to the number of Guttae, the size of the area of confluent Guttae and the presence of oedema.Results: The prototype produced clear, glare‐free images in over 95% of cases. Persistent reflections were observed exclusively in pseudophakic patients. The high resolution made it possible to observe all the Guttae and to challenge Krachmer's grade 2 classification (more than 12 non‐confluent drops), which included a major diversity of patients, some of whom had thousands of non‐confluent Guttae. We also highlighted for the first time to our knowledge 2 new elements: the high frequency of radial alignment of Guttae, often over 360°, and the presence of Guttae in the periphery of the endothelium, suggesting that a cell migration anomaly is involved.Conclusions: Innovative retroillumination images challenge Krachmer's classification by providing exceptional precision. They will make it easier to distinguish between sub‐groups of patients with different visual repercussions and evolutionary profiles. Easy to use, this new device should help to improve both our understanding of FECD and its routine management.