bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinical and morphological parallels in the assessment of the lamina cribrosa of sclera as a risk factor and potential target in promotion for survival of optic nerve axons
Authors: Huseva Yuliya 
Published: January 2025

Purpose: To study the lamina cribrosa (LC) of sclera in people of different age.Methods: Longitudinal sections of trepanned fragments of 31 enucleated eyeballs of deceased donors aged from 27 to 81 years stained by Masson trichrome were studied histologically and immunohistochemically with an antibody to glial fibrillary acidic protein (GFAP). The results were compared with optical coherence tomography (OCT) of the optic disc (OD) of 32 eyes of patients aged 34–74 years. Four age groups were identified. The optic nerve (ON) prelaminar and retrolaminar parts and LC of sclera were assessed. The data was statistically approved, the Pearson, Spearman correlation coefficients, the Kruskal‐Wallis and Mann‐Whitney tests were calculated.Results: Three patterns of LC were identified based on connective and glial tissue ratio: mixed predominated in all age groups; elastic was more common until 44 years (45.5%); collagenous was typical for group III over the age of 60 (40%) and after 75 years (50%). The perivascular proliferation of collagen fibres was mostly after 75 years (group IV), correlated with deformation of LC anterior surface resulting in a decrease in LC elasticity in groups III and IV, increased frequency of axonal deviation in group III (40%) and IV (50%) and a ‘slowing down’ myelination of ON axons (35.5%). The age‐related tendency to LC superficial location, disorganisation of its structure and deformation of its anterior surface in all groups was revealed. The prelaminar zone showed a decreased number of fibroblast processes in groups II and III compared to group I. All ON zones demonstrated immunoreactivity to GFAP, predominantly in the prelaminar determining its susceptibility to ischaemia. Distribution and morphology of GFAP‐positive cells demonstrated that the structure of astrocytes decreased with age.Conclusions: Age‐related morphological features of the LC beyond 60 years are considered to be risk factors for ischaemia and blockade of axonal transport. The effect of age on LC should be taken into account when predicting the results of treatment of optic neuropathies. The variability of cells in LC opens up new prospects for developing protection and regeneration of ON, in particular, influencing the process of LC remodelling.
Generation of an isogenic control from an induced pluripotent stem cell line of a patient with dominant optic atrophy harbouring the genetic variant C.1024 A>G (P.K342E) in the OPA1 gene
Authors: Jabardo Raquel González , López Marta García , Anda Natalia Robles , Vicente Lydia Jimenez , Monreal Helena Dorado , de Arriba Pablo Rueda , Gallardo Maria Esther 
Published: January 2025

Aims/Purpose: Dominant Optic Atrophy (DOA) is an inherited optic neuropathy commonly caused by OPA1 gene mutations, affecting mitochondrial function. The main symptom of patients is vision loss, but the syndromic form of DOA, DOA‐plus, presents with additional manifestations such as deafness and myopathy, among others. The visual impairment occurring in DOA is caused by the degeneration of Retina Ganglion Cells (RGCs), specialized neurons that convey visual information from the retina to the brain. Currently, there is a lack of an effective treatment for DOA patients, which highlights the importance of developing a proper experimental model. Induced Pluripotent Stem Cells (iPSCs) technology could be a promising approach to generate a model of DOA, useful not only for studying mechanisms of disease and therapeutic strategies, but also to confirm if a genetic variant is pathogenic. Our final aim is to determine if a genetic variant in OPA1 gene is pathogenic in a patient with DOA‐plus by the generation of an isogenic human RGC model.Methods: An iPSC line, OPA1.15, carrying the variant NM_015560.3: c.1024 A>G (p.K342E) in OPA1 gene, obtained from a patient with DOA‐plus was created. Subsequently, a battery of assays was performed to confirm the pluripotency and good quality of the OPA1.15 iPSC line. In this work, as a first step for the creation of the RGC model, the generation of an isogenic control from OPA1.15 with the CRISPR/Cas9 system has been developed.Results: A bona fide iPSC line from a patient with DOA‐plus has been created. Using this line, an isogenic control was generated with the genome editing tool CRISPR/Cas9.Conclusions: The iPSC line OPA1.15 and its matched isogenic control will be very useful to generate a RGC model to delve into the pathogenicity of this variant.
Optic nerve damage model: A preliminary study to determine injury duration and degree of gliosis
Authors: Kaleli Humeyra Nur , Kesim Cem , Hasanreisoğlu Murat 
Published: January 2025

Aims/Purpose: The aim of this study was to investigate the effects of varying durations of optic nerve compression on retinal function and morphology in an adult DA/HanR rat with optic nerve crush model.Methods: In the study, adult DA/HanR rats (4‐8 mo) were divided into 5 experimental groups. Lateral canthotomy and lateral bulbar conjunctiva incision were performed to reach the area. The optic nerve was held 2‐3 mm posterior to the globe with the help of calibrated forceps and compressed for four different periods of time: 10 seconds, 15 seconds, 30 seconds and 2 minutes. During the injury, retinal fundus observation of rats was checked with a 90‐diopter fundus lens. To evaluate changes in vision after optic nerve damage, in vivo electrophysiological tests (VEP, EEG and ERG) with daylight stimulator, a light intensity of 500 μW/cm2, was studied. Changes in optic nerve and retina morphology after injury were evaluated by hematoxylin‐eosin (H&E), TUNEL assay, immunofluorescence staining of gliosis and retina cell markers.Results: It was observed that the response to light was reduced in both the retina (ERG) and visual cortex (VEP‐EEG) in the damaged eyes compared to the control group. Retina cell survival showed decrease in injured groups by TUNEL assay. In immunofluorescence staining, an increase in the severity of gliosis with activation of the microglia and Müller cells in the retina and optic nerve depending on the duration of damage was shown by the expressions of GFAP, Glutamine Synthetase and Vimentin. It was observed that the expression of the neural marker NeuN and the photoreceptor marker Rhodopsin decreased upon injury.Conclusions: Our study provided preliminary results to further optic nerve regeneration studies to select optimum time points for improve axonal healing in retina and optic nerve injuries.Funding Information: This work is supported by the Scientific and Technological Research Council of Turkey (TÜBİTAK) under Grant ARDEB‐121S762
Comparison of synchrotron‐based ftir spectra in lens epithelial‐ and idiopathic epiretinal membrane‐ cells
Authors: Josifovska Natasha , Ducic Tanja , Andjelic Sofija , Petrovski Goran 
Published: January 2025

Purpose: To determine the synchrotron radiation‐based FTIR microspectroscopy spectrum of lens capsules (LCs) from cataract surgery and that of idiopathic epiretinal membranes (iERMs) towards finding a possible causal relationship between lens fragments falling onto the posterior segment during phacoemulsification procedure and development of iERMs.Methods: LCs from cataract surgery and iERMs were collected from 5 patients. FTIR measurements were performed at the MIRAS beamline of the ALBA Synchrotron, Barcelona, Spain, and the complete bio‐macromolecular spectral information at cellular level (proteins, lipids, and nucleic acids) in the lens epithelium of LCs from cataract surgery and iERMs were evaluated and compared.Results: The FTIR spectra revealed several bands corresponding to the vibration of various groups associated with proteins, lipids, and nucleic acids, demonstrating the complex biochemical composition of the LCs and iERMs. Overall, the spectra of the LCs and iERMs were very similar, showing slight differences in the spectral region of the proteins, particularly in the Amide I, then in the carbonyl groups, and phosphate groups of DNA. Additionally, the lipid region showed differences in the spectral ratio between the LCs and iERMs, characterized by CH2 and CH3 bands.Conclusions: The FTIR spectra of lens epithelial cells on LCs and cells within the iERMs appeared similar, with slight differences in some spectral regions. It is possible that the lens fragments falling onto the retina during cataract surgery could contribute to the pathogenesis of iERMs.
Artificial intelligence‐powered glaucoma screening: Demographic and clinical comparison between screening attendees and non‐attendees
Authors: Lobo Vasco , Lima‐Cabrita Afonso , Monteiro Bernardo , Whitfield Rafael , Theriaga Sofia , Marques Rodrigo , Ourique Matilde , Barão Rafael , Pazos Marta , Stalmans Ingeborg , Abegão‐Pinto Luís 
Published: January 2025

Aims/Purpose: Investigate demographic and socio‐economic differences between individuals who accepted and declined participation in a glaucoma screening program in Sete Rios Health Center, Lisbon, and identify factors potentially responsible for decrease in screening adherence.Methods: Subset analysis of ongoing prospective study (Clinicaltrial.gov: NCT05875090). Diabetic and healthy patients between 55 and 65 years were invited to an AI‐powered glaucoma screening by both telephone and letter. Demographic, socio‐economic and clinical data were collected through both surveys to the patients and through medical records.Results: 545 subjects (out of 690) were reachable by telephone. 80.0% of those (n = 436) accepted scheduling and roughly 4 out of 5 (72.5%, n = 316) attended the screening visit. Additional 27 people attended screening having received the letter only. Telephone contact revealed overall effectiveness of 45.7% (overall effectiveness of 47.8%). Both screening attendees (S group, n = 343) and non‐attendees (NS group, n = 357) showed homogeneity in age, sex and family history of glaucoma. NS group had a higher percentage of people with more than 12 years of education compared to the S group (42.0% vs 30.5%, p = 0.036). Notably, managers were the professional group which exhibited the highest avoidance rate (47.7%), whereas conversely armed forces occupations showed no refusals. The prevalence of diabetes was significantly higher in the NS group (49.3% vs 32.2%, p = 0.004). Most non‐participants (50.6%) cited prior ophthalmology consultation as their reason for their refusal. Only 15.6% actively refused the screening.Conclusions: These findings shed light on potential barriers to participation and underscore the importance of tailored approaches to engage diverse populations in preventive eye care initiatives.
Preoperative fluorometholone in glaucoma surgery: 1 year clinical and anatomical outcomes with in vivo confocal microscopy (IVCM)
Authors: Tomaselli Davide , Monsellato Gianluca , Calzi Gaia Li , Fantaguzzi Francesca , Lizzio Umberto , Sacchi Matteo , Nucci Paolo 
Published: January 2025

Aims/Purpose: To report preliminary data on the preoperative application of topical Fluorometholone in patients requiring glaucoma surgery due to primary open‐angle glaucoma (POAG), evaluating clinical and anatomical outcomes with in vivo confocal microscopy (IVCM) at 1 year follow‐up.Methods: We conducted a prospective study involving 54 eyes with POAG requiring glaucoma surgery: Trabeculectomy or Minimally Invasive Bleb Surgery (MIBS) (XEN® and PreserFlo®). The sample was randomized: the treatment group (25 eyes) received Fluorometholone 1mg/ml QID for 1 month pre‐surgery, while the control group (29 eyes) did not. IVCM of the conjunctiva was performed at baseline, after 1 month of treatment, and 1 year post‐surgery. Preoperative parameters included goblet cell density (GCD) and dendritic cell density (DCD) as inflammatory markers, while postoperative parameters were density and mean area of intraepithelial cysts (MMD and MMA) as indices of bleb function. Pre and post‐surgery stromal meshwork reflectivity (SMR) served as an indirect marker of stromal collagen.Results: Preoperative Fluorometholone led to significantly decreased in DCD (p < 0.001) compared to baseline and in DCD (p < 0.001) and SMR (p = 0.014) compared to the control group. At 1 year, there were no significant differences between the two groups in mean IOP, medications, needling procedures, and failure rates. IVCM analysis showed increased MMD in the treatment group compared to the control group (p = 0.028). In the separate analysis, the MIBS treatment subgroup group had lower IOP (p = 0.046) and less medication use (p = 0.032), but this was not observed in the trabeculectomy treatment subgroup. MMD increased in both the MIBS (p = 0.037) and trabeculectomy (p = 0.024) treatment subgroups.Conclusions: Preoperative Fluorometholone reduced ocular inflammation, improving bleb function at 1 year as detected by IVCM. However, its impact on overall bleb functionality remains unclear, with a clinically detectable improvement only in the MIBS group. Larger studies with longer follow‐up are necessary to fully understand the implications of preoperative Fluorometholone on long‐term surgical outcomes across different types of glaucoma surgeries.
Soft matter 3D printed drug‐loaded subconjunctival inserts for post‐surgical anti‐inflammatory drug delivery
Authors: Alambiaga‐Caravaca Adrián , Bernat‐Just Lucia , Luembe Esther Nginyu , Hibbitts Alan 
Published: January 2025

Aims/Purpose: The aim of this study is to develop 3D printed drug‐loaded subconjunctival inserts to reduceinflammation post‐trabeculectomy by delivering antifibrotic therapies in a controlled and targetedmanner.Methods: Different gelatin derivatives were functionalized with methacrylate anhydride to create printable hydrogels. Methacrylation was confirmed by FT‐IR and quantified by 1H NMR, identifying optimal functionalization methods. Various water‐soluble co‐polymers, were incorporated to enhance the mechanical properties, stability, and biocompatibility of the hydrogels as well as a photo‐initiator. The stability of the formulations was assessed by immersing them in PBS at 37°C for up to three months. Extrusion and printability tests were conducted to select the best‐performing blends, which were then used to print different models under UV light exposure to cross‐link the blends and control drug release based on surface contact.Results: The incorporation of polymers improved the stability of the gelatin hydrogels, with controlled degradation possible between 2 and 12 weeks depending on polymer blend. Extrusion and printability tests identified lead candidates. Optimal candidates exhibited controlled drug release over a three‐month period, meeting the therapeutic goal for post‐surgical inflammation management.Conclusions: The development of 3D printed drug‐loaded subconjunctival inserts shows promise in providing targeted antifibrotic therapy post‐trabeculectomy. The optimized hydrogels exhibit improved stability and controlled drug release, potentially enhancing post‐operative outcomes and reducing intraocular pressure effectively. Further studies are warranted to evaluate the ex vivo biodistribution, the in vitro performance in cell culture and long‐term benefits of these customized drug delivery systems.References
Barroso IA, Man K, Robison TE, Cox SC, Ghag AK. Photocurable GelMA Adhesives for Corneal Perforations. Bioengieering. 2022, 9, 53.
Towards visual field reliability with machine learning
Authors: Wong Damon , Chua Jacqueline , Jonas Jost , Schmetterer Leopold 
Published: January 2025

Aims/Purpose: To evaluate the reliability of visual field mean deviation slope with explainable artificial intelligenceMethods: 6,869 visual field reports (Humphrey Visual Field, Carl Zeiss) from a study of 645 participants with glaucoma were acquired using a 24‐2 SITA FAST protocol. An additional 704 visual field reports from 54 glaucoma patients with the same visual field protocol was also retrospectively acquired from the clinic. The visual field data was organized into 5‐visit segments and visual field mean deviation (MD) slope was calculated for each segment. 3‐visit MD slopes from corresponding segments aligned with the first visit of each 5‐visit segment were also obtained. A gradient‐boosted machine learning model was developed to predict if the difference between the 3‐visit and 5‐visit slopes was within 1 dB/year. 2,883 segments from the study cohort were used for model development. Area under the receiver operating curve was used to evaluate the model prediction performance, which was compared with a logistic regression baseline operating on the slope values. Model explainability was evaluated using Shapley additive explanations (SHAP).Results: The models were evaluated on 815 segments from the study cohort and 449 from the clinical cohort. Of these, 221 from the study cohort (27%) and 204 (45%) from the clinical cohort were found to have MD slope differences within 1 dB/yr between the 3‐visit and 5‐visit segments. The machine learning model achieved AUCs of 0.89 and 0.88 on the study and clinical cohorts, compared to 0.87 and 0.85 respectively with logistic regression. SHAP analysis found that the key determinants of the model were the magnitudes of the slope values, followed by inter‐visit intervals.Conclusions: The machine learning model better predicted visual field slope reliability compared to logistic regression. MD slope values and inter‐visit intervals were found to be important factors in VF reliability analysis.
Correlation between dyslipidaemia and glaucoma risk: insights from a population‐based glaucoma screening (NCT 05875090)
Authors: Whitfield Rafael , Lima‐Cabrita Afonso , Lobo Vasco , Monteiro Bernardo , Marques Rodrigo , Ourique Matilde , Leal Inês , Barão Rafael , Pazos Marta , Stalmans Ingeborg Stalmans , Abegão‐Pinto Luís 
Published: January 2025

Aims/Purpose: Glaucoma, a leading cause of irreversible blindness globally, is often associated with elevated intraocular pressure (IOP). However, other risk factors may play a role, particular vascular related parameters. This investigation aimed to explore the association between glaucoma and dyslipidaemia (DL) in participants in a primary care screening pilot. NCT 05875090Methods: analysis at screening visit comparing the odds of a positive referral between participants with and without DL. Secondary outcomes were medication with statins. Positive referral was defined by IOP≥24mmHg or AI≥0.73. Descriptive and bivariate analyses were used to compare the glaucoma proportions and IOP/AI means between groups. Significance was set at p < 0.05 with 95% confidence intervals (CI).Results: Data from 839 participants (54% male, 62 ± 4 years) across 11 functional units were analysed. Many had low educational attainment (69%), diabetes (81,1%), hypertension (63,4%), and DL (66,2%). Among participants with DL, 7,38% had glaucoma positive outcome at screening. No difference in glaucoma odds was found between DL and non‐DL patients (OR 0.782; CI 0.400‐1.528), nor between DL patients medicated with statins compared to those non‐medicated (OR 2.083; CI 0.597‐7.276). Interestingly, DL may be associated with a positive referral due to high IOP (but not disc damage) when compared to non‐DL subjects (OR 0.404; CI 0.155‐1.055; p = 0.09), but further analyses with larger samples are needed.Conclusions: Analysing the association between dyslipidaemia and glaucoma revealed a significant prevalence of DL, with 7,38% meeting positive referral criteria. While the study suggests a potential difference in glaucoma based on IOP between individuals with and without DL, this finding lacks statistical significance. Further analyses, including consideration of confounders and biases, are necessary for confirmation. Continued research and clinical observation are vital for a deeper understanding of this association.
Efficacy of orthokeratology on peripheral refraction in youth: A comprehensive meta‐analysis
Authors: Queirós António , Silva‐Pinheiro Inês , Fernandes Paulo 
Published: January 2025

Aims/Purpose: This study aims to determine the impact of orthokeratology lenses on relative peripheral defocus (RPD) in children and adolescents through a systematic review and meta‐analysis.Methods: A thorough literature search was conducted using PubMed and Web‐of‐Science databases, focusing on randomized controlled trials (RCTs) and cohort studies investigating the effects of orthokeratology on peripheral refraction. The search employed the keywords "peripheral refraction" AND "orthokeratology." The inclusion criteria required studies to report spherical equivalent (M) peripheral refraction at 25° and/or 30°, including standard deviation or standard error of the mean, and present data graphically or in tables for horizontal meridian measurements before and after orthokeratology treatment. Relative peripheral refraction (RPR) was computed. From an initial pool of 133 studies, 124 were excluded for various reasons, resulting in a final sample of 9 studies. Four studies included data up to 12 months, while five provided data for less than three months, allowing separate analyses before pooling for an overall effect.Results: The 9 studies included 3 RCTs and 6 cohort studies with 239 participants aged 6 to 30 years. The pre‐treatment refractive error was M=‐2.48 ± 0.29D, with follow‐up periods ranging from 14 days to 1 year. All studies indicated a myopic shift at 30° Nasal (‐2.13 ± 1.05 D) and 30° Temporal (‐2.40 ± 0.47 D), averaging ‐2.27 ± 0.83D. The meta‐analysis yielded an overall myopic defocus effect size of M=‐2.29 (95% CI ‐1.94 to ‐2.64, Z=12.84, p < 0.001) using a random effects model due to observed heterogeneity (I2=63%; p < 0.001). Myopic blur induction was greater at 1 year (M=‐2.64, 95% CI ‐2.42 to ‐2.85, Z=24.52, p < 0.001; I2=0%; p = 0.84) compared to treatments under 3 months (M=‐1.98, 95% CI ‐1.94 to ‐2.64, Z=7.37, p < 0.001; I2=63%; p < 0.001).Conclusions: The results suggest a more consistent effect with longer treatment durations, highlighting the necessity for extended follow‐up periods to achieve a reliable effect size estimate. Orthokeratology effectively induces myopic defocus at 30° eccentricity in children and adolescents over both short and long‐term treatments.