bluuebunny/crossref_metadata_2025_split huggingface dataset:
Visualizing morphological features of diseases of the corneal endothelium
Authors: Dallinga Marchien , van der Krogt J. M. A. , van der Meulen I. J. E. , Murphy C. C. , van Buul J. D. 
Published: January 2025

Aims/Purpose: To study several corneal endothelial diseases in order to find a set of morphological characteristics for each disease.Methods: Human cornea samples were collected from patients receiving a corneal transplant that involved the endothelium. Samples were fixed and immunofluorescently stained using antibodies against the nucleus, actin cytoskeleton, Beta‐catenin and the ZO‐1 junctional protein. Images were analyzed and variation in cell size and percentage of hexagonal cells were compared to in vivo specular microscopy to validate the staining methods. Images were then further analyzed to find new characteristics for the different diseases.Results: Samples were collected from patients with healthy endothelial cells, Fuchs’ endothelial corneal disease, Pseudophakic bullous keratopathy, rejection of a previous corneal graft, failed corneal graft, inflammatory corneal melt and congenital hereditary endothelial dystrophy. A set of parameters for each disease was established which included newly described features such as leukocyte transendothelial migration, morphology of the interdigitations on the basal surface of the cells and the presence of multinucleated cells.Conclusion: We have established morphological parameters for several diseases affecting the corneal endothelium. These can be used for further studies into the pathological mechanisms of each disease and possibly in the development of future therapies.
Topical sevoflurane role as antiseptic on normal conjunctival flora in a rabbit model
Authors: Encalada Denisse Michelle Espinosa , Cejudo Raquel Maroto , Rodríguez Óscar Esparcia , Sango Mónica Gómez Juárez , Pretel Fernando Andrés , Valenciano Carlos Cava 
Published: January 2025

Aims/Purpose: To assess the antiseptic properties of Sevoflurane (SF) when topically applied to the ocular surface in an animal model, and to compare the results with that of 5% Povidone Iodine (PY), a commonly used ophthalmic antiseptic.Methods: This randomized clinical trial involved 24 eyes from 12 New Zealand white rabbits, which were divided into two groups: SF (n = 12) and PY (n = 12), based on the substance administered. Prior to the application of any agent, baseline samples were collected from the conjunctival sac of each eye to determine the normal conjunctival flora. Subsequently, a single dose of 0.1 mL of either SF or PY was administered according to the group allocation. Conjunctival sac samples were then taken at 5 and 30 minutes post‐application. The collected samples were subjected to microbiological analysis.Results: At the commencement of the study, Moraxella cuniculi was identified as the predominant species, with a statistically significant higher colony‐forming units per milliliter (CFU/mL) compared to other species (p < 0.001). In the SF group, there was a statistically significant reduction in CFU/mL for both Moraxella cuniculi and Staphylococcus aureus following treatment. Conversely, in the PY group, a significant reduction was observed only for Moraxella cuniculi. Comparative analysis between the SF and PY groups revealed no statistically significant differences in the reduction of CFU/mL for Moraxella cuniculi at any time point during the study (p > 0.05).Conclusions: Topical application of SF effectively reduces the CFU/mL of predominant germs on the ocular surface of albino rabbits, yielding results comparable to those achieved with PY.
The analysis of miR‐133b and miR‐122 in cord blood for eye drop preparations. The differential contribution of platelet‐rich‐plasma and serum
Authors: Ciavarella Carmen , Bergantin Elisa , Buzzi Marina , Versura Piera 
Published: January 2025

Aims/Purpose: Cord blood (CB) –derived eye drops are safe and effective in many ophthalmological diseases, primarily persistent keratopathy related to severe dry eye disease. MicroRNA (miRNA) fine tune multiple messenger RNAs (mRNAs) and modulate several pathological pathways. This study was aimed at comparing platelet‐rich plasma (PRP) and serum (S) from CB, for expression of miR‐133b and miR‐122, negative regulators of inflammation and neuropathic pain respectively.Methods: PRP and S prepared from the same CB donor (n = 6) were processed for miRNA extraction, subjected to miRNA specific Reverse‐Transcription and Pre‐amplification. MiRNA analysis was performed by Real Time PCR and Digital Droplet PCR, (ddPCR) comparing the two approaches in terms of yield and data comparability. Small nuclear RNA U6 and RNU44 were used as housekeeping genes.Results: PRP samples displayed higher yield in terms of RNA amount and purity than serum (mean RNA concentration: 30 ng/ul vs 8 ng/ul, respectively). The snU6 was more stable among all samples and was selected as housekeeping gene. miR‐133b was 26% lower in S than in PRP, whereas miR‐122 did not show significant differences between CB and S. ddPCR data were comparable with Real Time analysis, displaying higher sensibility also in samples with lower RNA yield.Conclusions: According to our data, CB preparations contain miRNA involved in the modulation of inflammatory process and pain in ocular surface diseases. PRP and S share similar expression levels of miR‐122, whereas miR‐133b is higher in PRP, indicating that PRP is more powerful in terms of anti‐inflammatory function than S, whereas both CB preparations contribute to ameliorating pain in ocular surface diseases. Further investigations are addressed at increasing the CB sample number to dissect the miRNA: mRNA network and validate the miRNA analysis by ddPCR, for a more accurate quantification in view of the therapeutic applications of CB preparations.
Building a framework for public and patient involvement in dry eye disease research. A case study
Authors: Ames Tess , Reynolds Alison , Matthews Evan , Golestenah Dorsa , Sarfraz Muhammad , Gooney Martina , Kinsella Sharon , Logan Ann , Lynch John , McLoughlin Peter , O'Donovan Orla , O'Reilly Niall , Rani Sweta , Filipe Helena Prior , Fitzhenry Laurence 
Published: January 2025

Aims/Purpose: This study aims to improve bidirectional communication strategies between patients/public, preclinical researchers, and clinical experts to address the lack of effective public and patient involvement (PPI) in preclinical vision research, aiming to refocus research on actual patient needs.Methods: An international team conducted multiple PPI activities, including a critical review on PPI in preclinical ocular research1, World‐café workshops, patient interviews, structured surveys, and round‐table discussions. Dry Eye Disease's wide clinical presentation and impact on daily life were explored. Patient experiences were shared to better understand their needs, increase research value, awareness, and advocacy.Results: Activities highlighted the need for incorporating PPI in ocular research at the preclinical stage. Recurrent themes were identified across patients and researchers. From 20 patient interviews and 50 surveys, 82% responded that they received most information from clinical spaces and were unaware of current research.2 Patients did not know how to become involved in PPI. In a PPI Training Course, 19 preclinical researchers agreed on the need for clearer PPI guidelines and training.Conclusions: PPI activities emphasized DED's severe impact on QoL and the need for new treatments. Round‐table discussions fostered connections and deeper understanding of DED, shifting researchers' focus to unmet patient needs. Further integration of PPI into preclinical research will benefit both researchers and patients. This multimodal PPI approach can benchmark incorporating patient perspectives in preclinical ocular research. Next steps – with patients, create a tool kit for communications skills development for pre‐clinical researchers.References
Ames T, Matthews E, Reynolds A et al. How patient/public involvement impacts the research journey – an overview of the visual impairment research field, Open Res Europe 2023, 3: 135. https://doi.org/10.12688/openreseurope.16057.1.
Ames T, Matthews E, Reynolds A et al. ARVO. 2024. Dry Eye Disease as a case study to understand the public and patient involvement gap in lab‐based preclinical vision research using interdisciplinary approaches [Poster].
Computational and experimental mechanical characterization of a novel corneal implant for the treatment of keratoconus
Authors: Ragonese Graziana Maria , Carbonaro Dario , Zambon Sara , Villa Elena , Grosso Edoardo , Kakanga Moses , Lepore Emiliano , Gallo Diego 
Published: January 2025

Aims/Purpose: Current treatment options of keratoconus have several limitations. These limitations have been addressed by developing a novel nitinol GROSSO® implant, that restores the physiological curvature of the cornea by virtue of a dome‐shaped design. Its minimally invasive implantation requires accurate assessment of the mechanical properties, investigated here both experimentally and computationally.Methods: Bending of two opposite edges of the implant is necessary for its implantation in the intracorneal pocket. Bending was conducted experimentally at 37°C using a DMA Q800 (TA Instruments) with a thermal chamber and a cell load of 18 N to obtain force‐displacement curves. A computational model of the real implant was reconstructed from microcomputed tomographic acquisitions (Phoenix v|tomo|x m, resolution: 1μm). The mechanical behaviour of the implant was modelled by implementing a superelastic constitutive law with material parameters obtained from experimental tensile tests of the nitinol, which also determined the plastic permanent deformation value. Finite element analysis of the bending simulation was performed in Abaqus (Dassault Systèmes Simulia Corp.) to obtain the bending force (BF) and assess the absence of permanent deformation.Results: A good agreement between the experimental (0.09 N) and computational tests (0.08 N) in terms of BF was observed. The computational simulation highlighted that the maximum principal strain value during bending was 10.8%, i.e. below the limit strain for plasticity of 12%.Conclusions: The GROSSO® implant can be safely bent during implantation with minimal effort, as the force applied does not exceed 0.1 N. The ongoing validation of the computational model will enable a cost‐effective prediction of macro‐scale mechanical properties and compliance with relevant standards and regulatory requirements. Additional critical scenarios and the remodeling effect imposed by the implant on corneal tissue will be the subject of future investigations.
Anterior segment optical coherence tomography assisted analysis of characteristics of graft dehiscence after descemet membrane endothelial keratoplasty for failed penetrating keratoplasty
Authors: Mestanoglu Mert , Vishwakarma Pratima , Welge‐Lüßen Veronika , Schlereth Simona , Cursiefen Claus , Bachmann Björn 
Published: January 2025

Aims/Purpose: To analyze anterior segment optical coherence tomography (AS‐OCT) parameters of graft dehiscence after Descemet membrane endothelial keratoplasty (DMEK) performed due to graft failure post penetrating keratoplasty (PK).Methods: All cases with available AS‐OCT images after DMEK performed due to previously failed PK graft were retrospectively analyzed. In total 142 dehiscences after DMEK in 75 eyes could be identified. The size, depth, location of dehiscence and its correlation between presence of graft‐host interface (IF) override and presence of step at the IF was assessed.Results: Majority of the patients were male (58.7%) and average age at presentation was 67 ± 13.6 years. Multiple areas of dehiscence were noted in 49.3% of eyes. Rebubbling was required once in 72% and multiple times in 24% cases. Dehiscence was noted to cross over the IF in 53.5%. Steps at the IF was noted in 41.5%, and 22.5% of the dehiscences with step crossed the IF. No significant difference was noted when median depth and size of the dehiscences crossing over the IF were compared with those not crossing over the IF (p = 0.268 and p = 0.206, respectively). Comparison between the median depth and size of the dehiscences crossing over the IF with presence and absence of step showed no significant difference (p = 0.23 and p = 0.196, respectively). Also, presence and/or size of step at the IF did not have a significant effect on depth, size and incidence of dehiscence.Conclusions: In our study, dehiscence of DMEK grafts occurred in close vicinity to the PK graft‐host interface. However, size and depth of the dehiscence were not affected by crossing of the dehiscence over the graft‐host junction interface. Also, presence of step and its size did not seem to affect the depth, size and incidence of the dehiscence. Our evaluation suggests that the edge of the DMEK graft should have a distance to the PK interface, independent of the regularity of the PK graft‐host junction.
Success rate of primary cultures of corneal endothelial cells from donors over 50 years old
Authors: He Zhiguo , Aouimeur Inès , Sagnial Tomy , Louise Parveau , Perrache Chantal , Thuret Jean‐Yves , Gain Philippe , Thuret Gilles 
Published: January 2025

Aims/Purpose: Due to the global shortage of corneal donors, alternatives such as cell injection therapy and tissue‐engineered endothelial keratoplasty are being developed. These methods require mass production of corneal endothelial cells (CECs), which is challenging, especially with corneas from "regular" donors (aged around 70 on average in Europe). Notably, the first clinical successes reported by Kinoshita et al. used corneas from donors under 29, which are rare. This study aims at investigating the success rate and specific challenges of primary cultures of CECs from older donors.Methods: An analysis was conducted on the primary culture of CECs from 127 organ‐cultured (OC) corneas. The average donor age was 74 ± 13 years (range 50‐96), with a postmortem (PM) duration of 15 ± 7 hours (range 1‐27), initial endothelial cell density (ECD) of 2280 ± 567 cells/mm2 (range 1060‐3536), and an OC time of 29 ± 21 days (range 1‐90). Cell cultures were classified as successful or failed based on cell morphology and ECD. A successful culture was defined by typical CEC morphology and ECD ≥ 2000 cells/mm2 at the third cell passage or later.Results: Successful cell cultures were achieved from 13 corneas (10.2%). The characteristics of these 13 corneas were: average age 74 ± 15 years (range 52‐96), PM duration 14 ± 7 hours (range 1‐24), initial ECD 2416 ± 523 cells/mm2 (range 1287‐3248), and OC time 23 ± 17 days (range 4‐56). No significant differences in these characteristics were found between successful and failed cultures. Among the failed cultures, 63.9% had lower ECD, 26.2% exhibited endothelial to mesenchymal transition (EndMT), and 9.9% displayed both failure features. Different wells from the same cornea sometimes showed different cell features.Conclusions: Primary culture of CECs from older donors is feasible but has a low success rate (10%). No correlations were found between the success of cultures and corneal characteristics, suggesting the influence of random, poorly understood factors likely related to the culture method. Optimizing the culture method is essential to improve the success rate and facilitate industrial application.
Morphometric histological description of fuchs endothelial dystrophy guttae
Authors: Jonas Rahul , Howaldt Antonia , Matthaei Mario , Schlereth Simona , Bachmann Björn , Cursiefen Claus 
Published: January 2025

Aims: Morphometric histological description of Fuchs corneal endothelial dystrophy guttae as well as anterior banded and posterior layer of Descemet's membraneMethods: After routine DMEK procedures, 47 consecutive explants were taken for histopathological examination as part of clinical routine from 38 patients. 6μm thick sections were cut and stained with PAS and HE. The morphometric analysis was done using a Leica DM‐2500 microscope. Guttae were counted in a line measuring 400μm randomly selected in the middle of the tissue. The largest guttae with the best cross section was used to measure height and width at the base, the middle and the top. The anterior banded layer (ABL) and the posterior (banded and non‐banded as one) layer (PL) were measured below that gutta. The endothelial cells closest to that gutta were measured to get the height and width. Measurements were done using Discus Software (Ingenieursbüro Hilgen). Statistical analysis was done using linear regression on SPSS (Version 29.0 IBM).Results: The mean amount of guttae in the 400μm section was 11.76 ± 4.8. The mean thickness of ABL was 2.92 ± 0.96μm and of PL 8.59 ± 2.7μm. The guttae measured in height 8.68 ± 2.99μm, in width (base) 14.55 ± 4.22μm, in width (middle) 13.13 ± 4.54μm and in width (top) 14.72 ± 4.69μm. The endothelial cells measured in height 3.28 ± 0.98μm and in width 8.02 ± 2.8μm. The width (middle) of the guttae correlated with the width (base) (p < 0.001), width (top) (p < 0.001) and the width of the endothelial cells (p = 0.041). The PL correlated with the height of the guttae (p = 0.028), which also correlated with the height of the endothelial cells (p = 0.044). The width (top) correlated, additionally to the width (middle), with the width of the endothelial cells (p = 0.031). The PL did not correlate with the age of the patients. Most of the correlations kept their statistical significance after Bonferroni correction.Conclusions: The thicker the PL was, the higher were the guttae (r2 = 0.14). The wider the width (base) was, the wider the width (top) (r2 = 0.209) and width (middle) (r2 = 0.455) was. Considering the observed variability in corneal guttae shape and dimensions even at the same corneal location at, there might be differences in the pathophysiological processes warranting further analysis.
Evaluation of neurophysiological findings by portable full‐field electroretinogram in long‐term type 1 diabetics without diabetic retinopathy
Authors: Álvarez Marta Arias , Sopeña‐Pinilla Maria , Fernández‐Espinosa Guisela , Tomas‐Grasa Cristina , Orduna‐Hospital Elvira , Mena Diego Rodríguez , Pinilla Isabel 
Published: January 2025

Aims/Purpose: Diabetic retinopathy (DR), a common complication of Diabetes Mellitus (DM), is the primary cause of irreversible blindness among the working‐age population, particularly affecting those with type 1 diabetes (DM1). This condition poses a global health challenge. DR is acknowledged as a neurovascular disease, initially causing neurodegeneration in the cells of the inner retina and glial cells, which leads to both structural and functional changes. The study aimed to identify early functional changes in long‐standing DM1 patients without DR using a portable full‐field electroretinogram (ERG) to enhance management and preserve vision.Methods: This prospective study included 23 DM1 patients with over 20 years of disease progression without DR, along with a control group of similar ages. Participants underwent clinical history assessment, ophthalmologic examination, and neurophysiologic evaluation using the mydriasis free RETeval portable system, applying the DR evaluation protocol without mydriasis.Results: The average age of DM1 participants was 48.00 ± 9.77 years, and 51.69 ± 4.75 years for the control group. The average duration of DM1 was 28.69 ± 6.6 years. Among DM1 patients, significant findings included a reduction in the rod response amplitude, an increase in a‐wave implicit time (IT), and a decrease in b‐wave amplitude in the mixed response to 280 Td.s. Additionally, there was an increase in IT and a decrease in the amplitude of OP2 and OP3, as well as an increased IT and decreased amplitude of the response to 16 Td.s at 28.3 Hz. These results were consistent with those obtained using conventional ERG and were statistically significant (p < 0.05).Conclusions: Long‐standing DM1 patients without DR primarily exhibit ERG alterations under scotopic conditions, especially in oscillatory potentials, when evaluated with the portable ERG system. This emphasizes the importance of using this system for the early detection and monitoring of DR.
Evaluation of cone‐mediated dark adaptation using a smartphone app (MOBILE_DA) in healthy subjects
Authors: Gavilán Beatriz Sánchez , Marin Maria Cinta Puell , Pundlik Shrinivas 
Published: January 2025

Purpose: There is evidence of the role of dark adaptation (DA) as a functional biomarker in age‐related macular degeneration (AMD) where foveal cones are impacted during the initial stages of AMD. In this study we determine the repeatability of smartphone application (MOBILE DA) to evaluate the cone‐mediated dark adaptation (DA) in healthy young adults.Methods: Testing was done by placing a smartphone in front of the subject in a dark room. The App presented a 1.5° flashing stimulus at 3° eccentricity using an adaptive staircase. A 14800 lux white bulb was used for bleaching before testing. In two different sessions 1 week apart, the cone‐mediated dark adaptation was measured in 40 healthy subjects aged 21.4 ± 3.4 with good visual acuity (VA). Cone‐mediated DA recovery threshold was measured for 5 min. Threshold recovery functions were fitted to an exponential decay model to determine the time constant (τ, minutes) of cone sensitivity recovery and final cone luminance threshold (LTf). Repeatability was estimated by the Bland‐Altman method, whereby the mean difference (MD) and the 95% limits agreement were determinate as the coefficient of repeatability (COR).Results: Mean time constant () values was 1.28 ± 0.43 minutes in session 1 and 1.28 ± 5.4 for the session 2 and for the final luminance threshold the mean values were ‐2.12 ± 0.23 log cd/m2 for the session 1 and ‐2.13 ± 0.28 for the session 2. Mean differences in time constant measurements and LTf between session 1 and 2 were not significant. COR value for was 1minute and COR value for LTf was 0.33 log cd/m2.Conclusions: The MOBILE‐DA offered repeatable measurements. The APP was able to detect rapid changes in light sensitivity that occur during cone‐mediated dark adaptation indicating the clinical potential of using mobile device based DA measurements.