bluuebunny/crossref_metadata_2025_split huggingface dataset:
Understanding structural changes in keratoconus: Anterior scleral and choroidal thickness analysis using swept source optical coherence tomography
Authors: Hassairi Asma , Ahmed Chebil , Mehdi Oueslati , Limaiem Rim 
Published: January 2025

Aims/Purpose: The study aims to investigate the anterior scleral thickness (AST) profile and choroidal thickness (CT) variations in keratoconus (KC) patients compared to healthy controls, with the objective of providing a comprehensive understanding of ocular structural changes in KC.Methods: A cross‐sectional case‐control study was conducted, involving 46 eyes: 23 KC eyes and 23 age‐ and axial‐length‐matched healthy eyes. Anterior scleral thickness (AST) was evaluated at three scleral eccentricities (1, 3, and 6 mm from the scleral spur) across four scleral zones (nasal, temporal, superior, and inferior) using the anterior segment module of the Triton SS OCT (Topcon, Tokyo, Japan). Additionally, choroidal thickness profiles in KC patients were derived from SS‐OCT scans. Comparative analyses were conducted to assess thickness variations within and between groups.Results: In KC eyes, AST exhibited significant variations across several meridians, particularly over the temporal and inferior meridians, in comparison to healthy eyes. Although AST profiles did not differ significantly between groups, differences in inferior‐superior thickness asymmetry were observed, particularly in subclinical KC eyes. Choroidal thickness in KC patients was notably greater compared to healthy controls and displayed a declining trend with age.Conclusions: Keratoconus eyes manifest substantial anterior scleral thickness variations across eccentricities, indicating structural alterations in the paracentral sclera. While AST profiles did not reveal significant differences between KC and healthy eyes, observed asymmetry disparities in thickness imply vertical meridian scleral changes in KC, warranting further exploration. Additionally, the increased choroidal thickness in KC patients, coupled with its age‐related decrease, suggests potential implications for understanding KC pathogenesis.
Effect of insulin eye drops for refractory persistent corneal epithelial defects
Authors: Valyi Zsuzsanna , Relvas Lia Judice De Menezes , Makhoul Maxime , Willermain François 
Published: January 2025

Aims/Purpose: The aim of this study is to investigate the effect of insulin eye drops on corneal wound healing in persistent epithelial defects (PEDs) resistant to standard treatmentMethods: This retrospective monocentric study is based on a clinical chart review of patients with PEDs treated with insulin eyedrops between April 2022 and December 2023. All patients had received priorly the current standard therapy for PEDs ranging from bandage contact lenses and punctum plugs to autologous serum and amniotic membrane grafts without any clinical response. The effect of topical insulin treatment was evaluated by the rate and time of corneal reepithelization and recurrence. Side effects and clinical factors that may influence the outcome of the treatment were also analyzed.Results: In total 54 eyes of 50 patients were included in this study. Previous and unsuccessful standard PED treatment time ranged days between 216.1 ± 49.9 days. Reepithelization with insulin eyedrops occurred in 49 eyes (90.8%) after 22.4 13.6 days. Complete wound closure was observed in 31 eyes (57.5%) and partial reepithelization in 18 eyes (33.3%). Five eyes (9.2%) showed no improvement at all. Among those eyes with a complete reepithelization 11 (35.5%) had a recurrence after stopping the treatment. Insulin drops were less effective in patients with PEDs of inflammatory or auto‐immune origin, and those treated with corticosteroids and amniotic membrane grafts. No side effects were observed.Conclusions: Insulin eye drops for PEDs seem to be a safe and effective treatment option. Further prospective clinical studies are needed to confirm these promising results.
Surgical detachment of irido‐ and lenticulocorneal adhesions in Peters anomaly
Authors: Kotola Elsa‐Leea , Turunen Joni A. , Lindahl Päivi , Krootila Kari , Majander Anna 
Published: January 2025

Aims/Purpose: To report anatomical and visual acuity outcome of surgical detachment of iridocorneal or lenticulocorneal adhesions in pediatric patients with Peters anomaly.Methods: An observational study of pediatric patients with Peters anomaly treated with surgical detachment of iridocorneal or lenticulocorneal adhesions between 2011 and 2024 at the Helsinki University Hospital. Ocular and extraocular diagnoses, age, sex, best corrected visual acuity (BCVA), intraocular pressure, ocular surgeries, surgical complications, family history, genetics and anterior segment optical coherence tomography data were collected from the medical records.Results: Fourteen eyes from nine patients underwent the surgery. The median age at the time of surgery was 14 months (range 5‐56) and the median follow‐up period was 156 months (range 6‐166). Of the treated eyes, 12 had iridocorneal adhesions, while two eyes also had lenticulocorneal adhesions. No surgical complications were reported. Anterior segment anatomy and corneal clarity were stable or improved during the follow‐up. Among the fourteen eyes, three eyes achieved a BCVA better than 0.3 (Snellen decimal), while none had a BCVA worse than 0.05. BCVA was not available for three treated eyes due to the patients' young age. The following additional ocular conditions were recorded: microphthalmia, cataract, glaucoma, retinal degeneration, nystagmus, corectopia and strabismus. Four eyes underwent further ocular surgeries, such as cataract surgery with intraocular lens implantation, anterior vitrectomy, pupilloplasty, and temporal iridectomy. Five patients had systemic findings. Pathogenic variants in the PITX3 and RARB genes were detected in three patients and one patient, respectively.Conclusions: This study demonstrates that surgical detachment of irido‐ and even lenticulocorneal adhesions in Peters anomaly is safe and results stable anatomical and visual acuity outcome over the period of critical visual development.
Extraction and quantification of human tear proteins sampled by schirmer test strips. A validated and standardized method
Authors: Porru Emanuele , Ciavarella Carmen , Comito Rossana , Astolfi Gloria , Violante Francesco , Versura Piera 
Published: January 2025

Aims/Purpose: The identification of biomarkers in tears help in diagnosis and management of ocular diseases, and beyond [1]. We aimed to develop and validate a method for extracting and quantifying proteins from human tears collected using Schirmer test strips, which are typically discarded after clinical use.Methods: Tears from 18 healthy volunteers were collected by aspiration with a micropipette and by paper strips after use for Schirmer test (5 minutes at closed eyes). Aspirated tears were centrifuged and stored at ‐80°C until processing. Tears from strips were eluted using a developed extraction buffer (ABC 100mM, Chaps X‐100 0.25%), and both samples were analyzed using the Agilent 2100 Bioanalyzer. The conversion of the wetted portion (mm) into volume tears (μL) was accurately assessed. The method's accuracy, precision, and sensitivity were estimated, and it was further validated using mass spectrometry.Results: The elution buffer enabled high recovery values for proteins such as albumin, lysozyme, zinc‐alpha2‐glycoprotein (ZAG), lipocalin A, transferrin, and lactoferrin, as compared to the results from the aspirated tears. The method demonstrated high accuracy (bias% < 10%), precision (CV% < 10%), and sensitivity, with a matrix effect of less than 5% for the studied proteins. The recovery rates were greater than 90% for lysozyme and albumin, and greater than 80% for ZAG, lipocalin, transferrin, and lactoferrin. Validation using mass spectrometry confirmed the reliability of protein identifications and quantifications.Conclusions: The developed protocol is simple, cost‐effective, and achieves significant protein recovery, making it suitable for routine clinical analyses in the clinical setting. The method's validation through mass spectrometry highlights its robustness and applicability for identifying and quantifying tear proteins.Reference
Rentka, Aniko, et al. "Evaluation of commonly used tear sampling methods and their relevance in subsequent biochemical analysis." Annals of Clinical Biochemistry 54.5 (2017): 521‐529.
Comparative efficacy of receptor tyrosine kinase inhibitors in a mouse model of alkali burn‐induced corneal neovascularization
Authors: Gladkauskas Titas , Rundgren Ida , Cristea Ileana , Rødahl Eyvind , Bredrup Cecilie 
Published: January 2025

Aims/Purpose: This study evaluates the efficacy of topical dasatinib and axitinib for treating experimentally induced corneal neovascularization (CNV) in a mouse alkali burn model, comparing these treatments to established therapies like dexamethasone and bevacizumab. The study aims to determine which treatment provides superior efficacy in inhibiting CNV in this model.Methods: Thirty‐six C57BL/6; 129Sv mice underwent a standardized alkali burn to induce CNV in both eyes using a paper disc soaked in 1M NaOH. The mice were randomly assigned to one of six treatment groups: saline (0.9% sodium chloride), DMSO (5%), dexamethasone (0.1%), bevacizumab (0.5%), dasatinib (0.5%), or axitinib (0.5%). Treatments were applied topically three times daily. CNV assessments, including corneal neovascularization area (CNA), vessel length index (VLI), and limbus vasculature thickness, were conducted post‐mortem using corneal flat‐mounts stained with CD31 antibody for immunohistochemistry.Results: Dexamethasone proved the most effective in inhibiting alkali burn‐induced CNA (p < 0.0001), with bevacizumab showing comparable efficacy (p < 0.001). Axitinib also effectively reduced CNA (p < 0.001) and VLI (p < 0.01). In contrast, dasatinib did not significantly reduce CNA (p = 0.74) or VLI (p = 0.98).Conclusions: While dexamethasone was most effective, both bevacizumab and axitinib successfully reduced CNA, with axitinib additionally decreasing VLI. Axitinib has a broad‐spectrum inhibition of vascular endothelial growth factor receptors 1, 2, and 3 (VEGFR1, VEGFR2, VEGFR3), and platelet‐derived growth factor receptor β (PDGFRβ). This may offer superior benefits compared to narrower‐spectrum TKIs like dasatinib, which primarily target PDGFRβ and fibroblast growth factor receptor (FGFR). The results highlight the effectiveness of targeting the VEGF‐VEGFR pathway for managing corneal neovascularization, presenting a viable option for patients who are sensitive to steroids.
Engineering multicellular organoid for corneal niche modelling and regenerative therapies
Authors: Gulzar Ayesha , Goktan Isilay , Yalcin Esra , Sahin Afsun , Kizilel Seda 
Published: January 2025

Purpose: The corneal niche is composed of various cell types, including limbal stem cells (LSCs), corneal epithelial cells (CECs), and neuronal cells. LSCs are pivotal for corneal epithelial regeneration, CECs maintain the corneal transparency, and neuronal cells contribute to sensory and trophic functions. Despite advances in corneal research, the interplay among these cell types within the corneal niche remains insufficiently understood. This study aims to engineer organoids combining LSCs, CECs, and neuronal cells to create a robust model for studying the corneal niche and to explore their transplantation potential.Methods: LSCs, CECs, and SHSY‐5Y neuronal cells were separately seeded in their growth mediums. After reaching confluency, cells were trypsinized and co‐cultured to form multicellular organoids using the hanging drop technique [1]. Various parameters including cell number, cell‐cell ratio and incubation time were optimized for organoid formation. The organoids were characterized for their cellular composition, structural integrity, and viability using immunohistochemical staining and confocal microscopy. Functional assays, including cell proliferation and differentiation markers, were performed to assess their regenerative potential.Results: To determine the optimal conditions for organoid formation, we experimented with different ratios of LSCs, CECs, and SHSY‐5Y cells, specifically 1: 1: 1, 2: 2: 1, 4: 2: 1, and 8: 2: 1. The results showed that the engineered organoids formed under all four ratios exhibited a well‐organized structure with high viability for a week. Functional assays including Ki67 and CD44 revealed active proliferation and differentiation, indicating the regenerative potential of the spheroids.Conclusions: This study underscores the potential use of tri‐coculture organoid as a promising therapeutic strategy for limbal stem cells deficiency and a valuable tool for investigating the complex cellular interactions within the corneal environment.Reference
M. Birgul Akolpoglu, Yasemin Inceoglu, Seda Kizilel, An all‐aqueous approach for physical immobilization of PEG‐lipid microgels on organoid surfaces. Colloids and Surfaces B: Biointerfaces, Volume 186, 2020, 110708, ISSN 0927‐7765, https://doi.org/10.1016/j.colsurfb.2019.110708.
Efficacy and tolerability of a new riboflavin‐based dye compared to double staining with fluorescein and lissamine green in the evaluation of corneal‐conjunctival epithelial defects: Preliminary data
Authors: Troisi Mario , Caruso Ciro , Troisi Salvatore , Bellucci Carlo , Costagliola Ciro 
Published: January 2025

Aims/Purpose: To evaluate the diagnostic sensitivity and tolerability of a new 0.5% riboflavin vital dye (Remark®, Servimed Ind. SpA, Rome, IT), on corneal and conjunctival epithelial defects, compared to standard stains (fluorescein and lissamine green).Methods: 56 eyes of 28 patients (15M, 13F; mean age 51.3 ± 9) with bilateral ocular surface epithelial defects were evaluated. In one eye of each patient selected randomly, after the application in the conjunctival fornix of Lissamine Green Ophthalmic strip (GreenGloTM, Stag Medical, Raleigh, NC) moistened with an eye drop of fluorescein 0.5% solution (Fluorofta®, Fidia Farmaceutici S.p.A., Abano Terme, IT), SLE was carried out using cobalt blue filter to evaluate corneal staining and white filter for the conjunctiva. Grading was assessed according to NEI score. After 30 minutes and washing with 5 drops of saline instilled every 10 minutes, a similar evaluation was carried out with cobalt blue light and yellow filter in the eyepiece after instillation of Remark® (Group A). The same evaluation was performed in the fellow eyes by reversing the sequence of dyes (Group B). A symptom score questionnaire was obtained for each group.Results: The average corneal NEI score was 3.32 (Gr. A) and 3.12 (Gr. B) for double staining, 3.38 (Gr. A) and 3.22 (Gr. B) for Remark®; average conjunctival score was 5.12 (Gr. A)/4.88 (Gr. B) for double staining and 5.04 (Gr. A)/4.76 (Gr.B) for Remark®. The differences between the two staining methods were not statistically significant in both groups (p > 0.05). In no case an intolerance to the products used has been recorded.Conclusions: The new riboflavin‐based dye was effective in detecting both corneal and conjunctival defects, without statistically significant differences compared to double staining, and with a good tolerability. The study highlights the potential of this new dye overcoming the limit of the need of 2 different dyes, reducing costs and evaluation time.
In‐situ printing of GelMa‐based hydrogels for cornea regeneration
Authors: Goodarzi Hamid , Om Boda , Griffith May , Boutopoulos Christos 
Published: January 2025

Aims/Purpose: Corneal perforation is a medical emergency that can lead to blindness. Treatment options encompass cyanoacrylate or fibrin glue, both linked to side effects, including cytotoxicity. Gelatin methacryloyl‐based biomaterials offer an alternative to these adhesives [1, 2]. Achieving optical clarity and smooth surface integrity is crucial for the restoration of vision in treated corneal wounds.Methods: Currently, the delivery of corneal biomaterials utilizes standard syringe systems, which lack the accuracy to reconstruct the cornea's shape. Therefore, the use of a laser bioprinting technology, developed in the Boutopoulos lab [3], for achieving precise in‐situ corneal wound repair was examined. We used a photocrosslinkable ink comprising Gelatin Methacryloyl (GelMa), hydroxyethyl acrylate (HEA), and Lithium phenyl‐2,4,6‐trimethylbenzoylphosphinate (LAP) as a photoinitiator.Results: Printability was optimized by generating nanoliter‐volume individual droplets using 230 μJ laser energy, a flow rate 20 microliter per minute, and a temperature of 37°C. Rheology, optical characterization, and bursting pressure measurements assessed its potential to seal corneal perforations. Results indicated a hydrogel storage modulus of 1.31 ± 0.31 KPa for printed LiQD cornea and a bursting pressure of 38 ± 6 mmHg when used to seal full thickness cornea perforation in cadaveric pig eyes. Optical clarity akin to the native cornea was observed (%light transmission: 93.12 ± 1.02 printed vs 92.61 ± 1.50). The OCT results showed that the LIST technique could potentially fill the corneal wounds and reconstruct the natural curvature of the wounded cornea.Conclusions: In conclusion, a precise printing system for delivering adhesive corneal regenerative biomaterials to wounds was developed and characterized.References
Sharifi, S., et al., 2021. 6(11): p. 3947‐3961.
Barroso, I.A., et al., 2022. 9(2).
Ebrahimi Orimi, H., et al., Sci Rep, 2020. 10(1): p. 9730.
Comparison of refractive parameters provided by a new open field aberrometer and the subjective refraction
Authors: Puche Ana Belen Plaza , Martínez‐Abad Antonio , Cantó‐Cerdán Mario , Yebana Pilar , José‐Martínez Marina , Rodriguez Alejandra , Alio Jorge 
Published: January 2025

Aims/Purpose: To compare and evaluate the agreement of the refractive parameters provided by a new open field aberrometer (OFA‐Osiris CSO®) and those obtained by the subjective refraction.Methods: It is an observational, prospective, and transversal study composed by subjects younger than 40 years‐old without ocular pathologies neither accommodation disfunction. All subjects underwent an exhaustive optometric evaluation including the subjective refraction and an ocular aberrometry with OFA‐Osiris device. The sphere, cylinder and axis were obtained from both methods being converted to polar notation using M, J0 and J45 vectors for an accurate refractive management. The refractive data provided by ocular aberrometry were extracted at 4 and 5mm of pupil diameter. The Wilcoxon sum tank test was applied for the comparison between methods and the Bland‐Altman plots were used for the agreement analysis.Results: A total of 183 subjects of a mean age of 24.85 ± 5.19 years‐old were included. Selecting a pupil diameter of 5 mm with ocular aberrometry, the refractive measurements did not present statistical differences with the subjective method obtaining a mean M of ‐1.58 ± 2.26D and ‐1.59 ± 2.31D respectively (p: 0.228), a mean J0 of 0.03 ± 0.27D and 0.01 ± 0.26 Drespectively (p: 0.280), and a mean J45 of 0.01 ± 0.24D and 0.01 ± 0.26D respectively (p: 0.259). However, considering an aberrometric pupil diameter of 4 mm, the M vector was significantly different to the obtained by subjective refraction (‐1.49 ± 2.33D and ‐1.59 ± 2.31d respectively, p < 0.001) not presenting difference in terms of astigmatism. Bland‐Altman plots revealed limits of agreements higher than 1 diopter to refractive parameters.Conclusions: The aberrometric refraction provided by a new open field aberrometer presented good agreement with the subjective refraction, especially considering a pupil diameter of 5mm. However, it may present clinical differences between both techniques, therefore the subjective refraction must be considered as the gold standard for the refractive evaluation.
Correlation between multifocal electroretinogram and autofluorescense in patients with ABCA4 retinopathy
Authors: Álvarez Marta Arias , Sopeña‐Pinilla Maria , Fernández‐Espinosa Guisela , Garza Inés Vicente , Orduna‐Hospital Elvira , Boned‐Murillo Ana , Díaz‐Barreda Mª. Dolores , Mena Diego Rodríguez , Pinilla Isabel 
Published: January 2025

Aims/Purpose: Stargardt disease is the most common hereditary retinal dystrophy (HRD) affecting primarily the cones, typically associated with an autosomal recessive inheritance pattern, mainly due to mutations in the ABCA4 gene.New diagnostic techniques have been introduced such as OCT, OCTA, and autofluorescence (AF). In this context, multifocal electroretinogram (mfERG) has gained importance as a diagnostic tool.The aim of this study is to correlate the structural findings obtained through AF with the functional changes detected by mfERG in patients with ABCA4 retinopathy.Methods: Twenty‐two eyes from patients diagnosed with Stargardt disease, confirmed by genotyping with double mutation in ABCA4, were included. The most frequent mutation was ABCA4 c.3386G > T (p.Arg1129Leu). One patient had the mutation in homozygosity, and the others in heterozygosity. The participants were evaluated using the Roland RETIscan system for mfERG, following the standardized guidelines of the International Society for Clinical Electrophysiology of Vision (ISCEV). The N1‐P1 electrical density and P1 implicit time were measured and analyzed in 5 concentric rings centered on the fovea. Additionally, a structural study was conducted using AF.Results: The average visual acuity (VA) was 0.49 ± 0.31 (range 0.05‐0.8). The average age was 37.22 ± 19.64 years (range 10‐78). AF showed central hypofluorescence in all patients, with 5 presenting a patchy pattern. Eight patients had flecks within the arcades, of which 3 had minimal central flecks.Patients with larger central hypofluorescent areas showed lower electrical density in the central rings. Those with flecks in the central 30° had functional alterations in ring 4 and, in some cases, in ring 5.Conclusions: A decrease in electrical densities in the central rings was observed, correlating with larger areas of hypofluorescence on AF. The presence of flecks in the arcades correlated with a decrease in electrical density in the more peripheral rings.
Neurovascular coupling response: A follow‐up study
Authors: Jordão João , Rodrigues Sérgio , Domingues Joana , Serranho Pedro , Guimarães Pedro , Bernardes Rui 
Published: January 2025

Aims/Purpose: This work aims to assess the consistency of the neurovascular coupling (NVC) response of a healthy subject group at two visits 5 months apart.Methods: Fundus images (4x4 degrees) of the macular region (3 baseline acquisitions and 3 acquisitions each preceded by flicker stimulation) of 13 healthy adults (one eye each, age (m+/‐sd): 33.08+/‐11.4 yrs.) were acquired with the rtx1 AO camera (ImagineEyes, Orsay, France). The rtx1 was configured for a 20 second, 15Hz, and 4 μW.cm^(‐2) flicker stimulation over a 29x20 degrees area of the imaged eye fundus. Acquisitions for each subject were repeated 159+/‐17 (m+/‐sd) days later.The lumen of retinal arterioles within the macular region was determined using custom‐developed software for the automatic segmentation of lumen‐wall interfaces. An experienced technician visually assessed all segmentations to reject subpar results. Lumen diameters were calculated from the distance between the lumen‐wall interfaces as measured perpendicular to the vessel axis along a vessel segment. NVC responses were calculated per eye as the relative difference (%) of the lumen diameter after stimulation to the respective baseline.Results: A total of 22 out of 156 images (14%) were rejected and excluded from further analysis. NVC responses ranged from 0.21% to 8.28% (3.36+/‐2.75 % (m+/‐sd)) for the first visit and from ‐0.24% to 9.13% (3.03+/‐2.54 %) for the follow‐up. Response differences between time points ranged from ‐6.15% (8.28% to 2.13%) to 4.21% (0.98% to 5.19%), with an average (sd) of 0.34(3.03) % for the group. A paired sample Wilcoxon test between time points is not statistically significant (p = 0.650), supporting that the responses are consistent between time points.Conclusions: The obtained results show a consistent NVC response for a 5‐month interval.