bluuebunny/crossref_metadata_2025_split huggingface dataset:
Biodistribution of alpha‐lipoic acid in beta‐cyclodextrins: Analyzing ex vivo delivery to the posterior segment of the eye
Authors: Ta Phuong Linh , Just Lucia Bernat , Alambiaga‐Caravaca Adrián , Alarma Vicente Rodilla , Castellano Alicia López , Morell Francisco Bosch 
Published: January 2025

Aims/Purpose: α‐lipoic acid (ALA), a natural antioxidant, has shown significant value in delaying retinal damage progression. The purpose of this study was to quantify the amount of α‐lipoic acid in β‐ cyclodextrins (ALA‐βCD) complexation in various ocular tissues, especially in the posterior segment of the eye and the neuroretina, after administration from solution and ocular inserts containing the drug.Methods: ALA‐βCD was dissolved in phosphate saline solution (PBS) to obtain a 1 mg/mL solution. Inserts containing 1 mg/mL ALA‐βCD were prepared using eye‐compatible polymers: polyvinyl alcohol (PVA), polyvinylpyrrolidone (PVP), and hyaluronic acid (HA).Porcine eyes were obtained from an abattoir shortly after sacrifice and they were cleaned and placed on a Franz diffusion cell. The solution (250 μl) was administered every 2h and washed after 5 min with PBS. The inserts were placed in contact with either the cornea or the sclera. Both experiments were carried out for 8h at 37°C with humidity control. The eyes were then washed with PBS and stored at ‐80°C for 12 h wrapped in parafilm to maintain their morphology. The frozen eyes were surgically dissected to separate the different eye structures. The ALA from various structures/tissues was extracted by soaking them in acetonitrile: water solution (80:20, v/v) for 12h under constant stirring. The samples were then filtered, and the concentration of ALA determined by a validated HPLC method.Results: ALA was detected in all ocular tissues. The higher content of ALA found in the inserts was due to its longer contact time than the solution, and it increased bioadhesibility allowed greater biodistribution of ALA in the ocular tissues. Up to 1.5 % of ALA in the inserts reached the neuroretina, the target tissue for the treatment of retinopathies.Conclusions: The data show that in ex vivo, ALA can diffuse from the cornea and the sclera, reaching the posterior segment of the eye, and particularly the neuroretina. This data proves the way to carry out in vivo studies to assess the potential of topically administered ALA in protecting the eye from retinopathies.References
Alambiaga‐Caravaca AM, et al. Biodistribution of progesterone in the eye after topical ocular administration via drops or inserts. Int Jour of Pharma. 2023 Jan;630:122453.
Long‐term results of unilateral or bilateral injection of lenadogene nolparvovec gene therapy for leber hereditary optic neuropathy
Authors: Biousse Valérie , Yu‐Wai‐Man Patrick , Newman Nancy , Subramanian Prem , Moster Mark , Wang An‐Guor , Donahue Sean , Leroy Bart , Carelli Valerio , Vignal‐Clermont Catherine , Sadun Alfredo , Sergott Robert , Fernández Gema Rebolleda , Chwalisz Bart , Banik Rudrani , Taiel Magali , Sahel José‐Alain 
Published: January 2025

Aims/Purpose: To evaluate the efficacy and safety of intravitreal lenadogene nolparvovec gene therapy (LNGT) in patients with Leber hereditary optic neuropathy due to the m.11778G > A MT‐ND4 mutation for up to 5 years after administration.Methods: REFLECT is a randomized, double‐masked, placebo‐controlled phase 3 study. The first‐affected eye received LNGT; the other eye was randomly injected with LNGT or placebo. RESTORE is the 5‐year follow‐up study of the two phase 3 studies RESCUE and REVERSE, in which patients received an injection of LNGT in one eye and a sham injection in the other eye. REFLECT interim data at 4 years after LNGT and RESTORE final data at 5 years are presented.Results: In REFLECT, 48 patients were treated bilaterally and 50 unilaterally. The mean (standard deviation [SD ]) improvement in best‐corrected visual acuity (BCVA) from nadir to 4 years was ‐0.40 (0.32) (+20 ETDRS letters) and ‐0.34 (0.31) (+17 letters) LogMAR in the first and second‐affected eyes of bilaterally treated patients, and ‐0.38 (0.41) (+19 letters) and ‐0.27 (0.32) (+14 letters) LogMAR in the first and second‐affected eyes of unilaterally treated patients. Better BCVA improvement and higher responder rates were observed in patients treated bilaterally. In RESTORE, 62 unilaterally treated patients completed the study. At 5 years, mean (SD) change in BCVA from nadir was ‐0.44 (0.46) LogMAR (+22 ETDRS letters) for LNGT‐treated eyes and ‐0.39 (0.36) LogMAR (+20 ETDRS letters) for sham‐treated eyes. Overall, LNGT safety was favorable in REFLECT and RESTORE.Conclusions: The persistence of the LNGT effect and the favorable safety profile were confirmed 4 years after a unilateral or bilateral injection in REFLECT and 5 years after a unilateral injection in RESTORE. Bilateral LNGT provided additional benefit compared to unilateral LNGT.
Genome‐wide association study of anterior uveitis
Authors: Koskimäki Fredrika , Ahokas Oona , Consortium FinnGen , Team Estonian Biobank Research , Elnahas Abdelrahman , Reigo Anu , Reis Kadri , Esko Tõnu , Palta Priit , Leinonen Sanna , Kettunen Johannes , Liinamaa Johanna , Karjalainen Minna , Saarela Ville 
Published: January 2025

Aims/Purpose: The purpose of this study was to identify new genetic associations of anterior uveitis through genome‐wide association study (GWAS).Methods: We conducted a GWAS meta‐analysis combining data from the FinnGen, Estonian Biobank and UK Biobank with a total of 12 205 cases and 917 145 controls. A phenome‐wide association study was performed to investigate associations across phenotypes and traits. Genetic correlations of anterior uveitis were evaluated.Results: We detected six anterior uveitis associated genomic regions with genome‐wide significance (p < 5 × 10‐8). Three novel loci were identified: INAVA, NLRP3 and NOS2. Three previously reported associations at HLA region, ERAP1 and TNRC18 were detected. All of these loci had biologically relevant genes involved in immunity. We also replicated associations at two loci previously associated with acute anterior uveitis (IL23R and HDAC2‐AS2). Phenome‐wide association study indicated that lead SNPs at three of the anterior uveitis associated loci (ERAP1, INAVA and TNRC18) are associated with other immunity‐related phenotypes, including ankylosing spondylitis and inflammatory bowel disease. A moderate genetic correlation between anterior uveitis and inflammatory bowel disease was found in genetic correlation analysis (rg = 0.39, p = 8 × 10‐5).Conclusions: We identified six anterior uveitis associated loci including three novel loci with genome‐wide significance. Our findings deepen our understanding of the genetic basis of anterior uveitis and the genetic connections between anterior uveitis and immune related disorders, providing a foundation for further research and potential therapeutic interventions.
Prevalente of color vision anomalies among Brazilian industrial workers and the telemedicine role
Authors: Machado Roberto , Junior Pedro Ribeiro , Filho Mauro Guimarães , Negreiros Ariadne , Negreiros Marco 
Published: January 2025

Aims/Purpose: To evaluate the use of a color blindness test (Eyecare Color Vision Test®) applied through of telemedicine to assess the prevalence of color blindness, its subtypes and intensity of presentation in Brazilian industrial workers.Methods: An observational, cross‐sectional, and retrospective study was carried out. The study sample was a convenience sample, which included all patients from a company with headquarters in all Brazilian regions who underwent consultations for occupational purposes via telemedicine through Eyecare clinic between the months of October 2023 and January 2024. All patients underwent Eyecare Color Vision Test®, a validated virtual test based on the Ishihara Test that consists of 14 images with symbols and numbers. A score above 7 was considered normal for color vision defect.Results: 2197 workers from 5 regions of Brazil were evaluated through telemedicine. 91.81% were male, the mean age was 37 years, mean visual acuity for right eye was 0.24 (± 0.18) and for left eye was 0.19 (± 0.16). 50 patients, all male, showed changes in the Eyecare Color Vision Test® which resulted in a prevalence of color blindness of 2.28%. From patients with color blindness, 44% had protanomaly or deuteranomaly, 26% had deuteranopia, 18% had protanopia and 12% had an undiagnostic subtype.Conclusions: Our study was in line with international literature since we found a 2.28% prevalence of CVD in Brazilian industrial workers. Furthermore, we were able to demonstrate that telemedicine can be an important tool for democratizing access to eye health.References
Parikh D, Armstrong G, Liou V, Husain D. Advances in Telemedicine in Ophthalmology. Semin Ophthalmol. 2020 May 18;35(4):210–5; 30.
Sorkin N, Rosenblatt A, Cohen E, Ohana O, Stolovitch C, Dotan G. Comparison of Ishihara Booklet with Color Vision Smartphone Applications. Optometry and Vision Science. 2016 Jul;93(7):667–72.
Modified Nishida procedure for the treatment of complete cranial nerve palsies: A case series
Authors: Santos Miguel , Ferreira Rui , Fernandes Emanuel , Teixeira Filipa , Gama Rita 
Published: January 2025

Aims/Purpose: To describe the clinical characteristics and outcomes of a series of strabismus patients with horizontal recti palsies treated surgically with a Modified Nishida Procedure (MNP).Methods: A retrospective review of patients who underwent a MNP at Hospital de Santa Maria in Lisbon, Portugal, between November 2023 and February 2024 (n = 5). MNP is a no‐tenotomy, no‐splitting transposition of 1/3 of the muscle body of the vertical recti to the midpoint between itself and the affected horizontal rectus muscle. Inclusion criteria included diplopia due to Grade IV or V palsies of the lateral rectus (LR, n = 4) due to VI nerve palsy or of the medial rectus (MR, n = 1) due to III nerve palsy. A 3‐month post‐operative follow‐up was required. Surgical success was defined as post‐operative horizontal deviation ≤14 prism diopters (PD) and absence of horizontal diplopia in primary gaze.Results: Mean age was 60±13 years. Two patients had bilateral LR palsy with > 85PD esotropia (ET) and received bilateral MNP combined with 6mm MR recession, with additional MR botulinum toxin (BT) injection two weeks later. Two patients had unilateral LR palsy with 45 PD ET with previous 7mm MR recession: these received unilateral MNP. Surgical success was achieved in 3 of these 4 cases. The unsuccessful case had 40PD residual ET and diplopia at 4 months follow‐up. There were two cases of self‐limiting post‐operative ptosis and one case of a surgical complication where the whole vertical rectus body was transposed due to high muscle friability. The MR paralysis patient had 40PD exotropia and MNP was combined with 7mm LR recession. Surgical success was achieved in this case, and no intra‐ or post‐operative complications occurred. No cases of anterior segment ischemia were detected in this series.Conclusions: MNP is an effective surgical option as it greatly reduces the horizontal deviations and diplopia associated with severe cranial nerve palsies and has a reduced risk of complications.
Designing and testing anti‐scarring and anti‐inflammatory biomaterials for corneal implants: A promising alternative to human donors.
Authors: Abu‐Dieh Anas , Om Boda , Thathapudi Neethi , Kiyaseh Mozhgan , Roudbaraki Mostafa , Robert Marie‐Claude , Hébert Mélanie , Jabbour Samir , Harissi‐Dagher Mona , Griffith May 
Published: January 2025

Purpose: Corneal blindness is mainly treated by cornea transplantation. However, there is a shortage of cornea donors for surgeries in many countries. Even with accessible donors, patients suffering from severe pathologies causing inflammation may not benefit as they are at high risk for graft rejection. The Griffith laboratory is the first to use acellular human collagen implants to regenerate high‐risk corneas in a group of patients. For broader clinical applications, scalable collagen‐like peptide (CLP) synthetic hydrogels are being developed. It is important to identify design patterns to ensure the implants do not cause inflammation.Methods: The growth of stromal fibroblasts cultured on CLP hydrogels with and without RGD groups are compared, with collagen gels and tissue culture plastic as controls. Cellular growth and viability on the different substrates were compared using the AmarBlue assay. Next, TGF‐β was added to the media to stimulate fibroblast differentiation into myofibroblasts. The latter has been linked to corneal scarring. The proportion of resulting myofibroblasts was determined by immunostaining using anti‐smooth muscle actin (SMA) antibody. Stromal cells seeded onto the hydrogels were also stained against fibronectin to study its implication due to RGD. Furthermore, the CLP‐based hydrogel was tested in vivo on alkali burnt BALB/c mice to investigate their practical biocompatibility and efficacy.Results: α‐SMA expression was observed in cells grown on CLP‐RGD containing hydrogels but not on tissue culture plastic or CLP‐only control. There was a positive fibronectin expression by cells cultured on CLP‐RGD hydrogels, on 5% collagen hydrogels and on the issue culture control. The CLP‐RGD hydrogel is a smooth and soft gel with desirable water content. The in vivo test showed that there was no sign of inflammation or angiogenesis in the cornea after three months, which can prove the great biocompatibility of the prepared CLP‐based hydrogel.Conclusions: This project allowed for the testing of cell growth on RGD‐containing CLP hydrogels, which has not been done before. Early results suggest that RGD groups within CLPs induced myofibroblast differentiation and potential pro‐inflammatory responses.
Gene expression profiling of oxidative and anti‐oxidative genes in keratoconus patients
Authors: Sharma Shivam , Singh Lata , Kashyap Seema , Sen Seema , Sharma Namrata 
Published: January 2025

Aims/Purpose: Keratoconus (KC) is thinning of corneal stroma & irregular astigmatism, resulting in diminution of vision. Despite its prevalence, the underlying etiology is poorly understood. Emerging evidence suggests a dysregulation of oxidative balance and mitochondrial function in KC corneas. Therefore, our study conducted the gene expression profiling of oxidative stress‐based genes in KC patients.Methods: This was a prospective study for a period of two years. Fifty KC patients were recruited in this study. Demographic and clinical details were recorded. RNA was isolated from all the corneal samples and their cDNA was synthesized. mRNA expression levels of oxidative stress‐based genes (PRDX6, SCARA3, FOXC1, HMOX1, SOD2, GPX4, NRF2, NOX4) were measured by quantitative real‐time PCR (qRT‐PCR) in corneal tissues of KC patients and healthy controls. The relative gene expression was calculated using the ΔΔCt method.Results: The study included 50 keratoconus patients (mean age: 25.5 ± 12.34 years; 65% male) and 25 control subjects (mean age: 27.2 ± 11.26 years; 55% male). The severity of keratoconus among patients varied from moderate to advanced stages. In our study, qRT‐PCR analysis revealed significant differential expression of the oxidative and antioxidative genes in keratoconus tissues compared to the control samples. SCARA3, FOXC1, HMOX1, SOD2, GPX4, NRF2 were found downregulated, PRDX6 was upregulated in all the cases. NOX4 showed variable expression patterns with upregulation in 40% cases and downregulation in remaining 60% cases.Conclusions: The study included 50 keratoconus patients (mean age: 25.5 ± 12.34 years; 65% male) and 25 control subjects (mean age: 27.2 ± 11.26 years; 55% male). The severity of keratoconus among patients varied from moderate to advanced stages. In our study, qRT‐PCR analysis revealed significant differential expression of the oxidative and antioxidative genes in keratoconus tissues compared to the control samples. SCARA3, FOXC1, HMOX1, SOD2, GPX4, NRF2 were found downregulated, PRDX6 was upregulated in all the cases. NOX4 showed variable expression patterns with upregulation in 40% cases and downregulation in remaining 60% cases.Keywords: Cornea, Keratoconus, Oxidative stress, Real time PCR
Characterizing IPSC‐derived organoid models from the most prevalent retinal dystrophies
Authors: Navinés‐Ferrer Arnau , Gaudó Paula , Méndez‐Vendrell Pilar , Ruiz‐Nogales Sheila , Siles Laura , Pomares Esther 
Published: January 2025

Aims/Purpose: To establish novel retina cell models to investigate the mechanisms that lead to cell death in IRD.Methods: We generated induced pluripotent stems cells (iPSC) from a cohort of patients with some of the most prevalent IRDs: Retinitis Pigmentosa (RP), Stargardt Disease, Best Disease and Achromatopsia. We differentiated them into PR precursors, retinal organoids (RO) or retinal pigment epithelium cells (RPE) and analyzed the functional implications of each gene and pathogenic variant.Results: All cell models generated from 6 iPSC lines allowed for a better understanding of the molecular mechanisms of IRD. Specifically, in the Best Disease model, we determined using RPE cells that a particular dominant mutation in BEST1 is responsible for a defective closure of the bestrophin pentameric channel. The mutation responsible for RP in RHO shows rhodopsin accumulation and mislocalization, along with an increase of autophagy and ER stress. RO models with mutations in the genes PDE6A and PDE6C, causing respectively RP and Achromatopsia, suggest that expression levels of the pathogenic proteins are diminished. Finally, RPE and RO from two distinct Stargardt Disease patient lines show affectations in bisretinoid disposal, phagocytosis reduction and cell death. Interestingly, those results correlate with the severity of the phenotypes.Conclusions: We show that a wide range of mutations responsible for IRD can be studied using iPSC‐derived retinal models. This opens the door to a deeper understanding of retinal diseases and are key for the development of successful gene and cell therapies.ReferencesInherited retinal dystrophies (IRD) are a group of rare diseases where photoreceptor (PR) cell death leads to partial or total visual impairment. Over 300 genes have been determined to cause these dystrophies, but most of the molecular mechanisms underlying the start and development of the pathology are still waiting to be unraveled.
Progression of diabetic retinopathy during pregnancy: Retrospective study from Birmingham and Solihull
Authors: Khalifa Ahmad 
Published: January 2025

Aims/Purpose: To assess the progression of diabetic retinopathy (DR) in pregnant women with pre‐existing diabetes in the Birmingham and Solihull area and to evaluate adherence to recommended screening guidelines.Methods: A retrospective review was conducted over 12 months (01/09/2022‐31/08/2023) using data from the Diabetic Eye Screening Program (DESP) and hospital records (Medisoft, OCT, and retina images). The study included pregnant women with pre‐existing diabetes who received maternity services at University Hospitals Birmingham (UHB) and were referred to DESP. Patients with gestational diabetes were excluded. Data collected included demographics, DR screening attendance, progression rates, and clinical outcomes.Results: Out of 149 pregnant women with pre‐existing diabetes, 54 (36.2%) were not referred for initial screening by 12 weeks due to late presentation and delayed diabetes status confirmation. Of the total, 88 (59%) missed the 12‐week screening, 57 (40%) missed the 16‐20 week screening, and 67 (48%) missed the 28‐week screening. At 12 weeks, 27% were R0M0, 9% R1M0, 3% R1M1, and 1% R2M0/R2M1, with 8 referred to HES. At 16‐20 weeks, 43% were R0M0, 16% R1M0, 1% R3SM0, and 1% were unable to assess, with 2 referred to HES. By 28 weeks, 37% were R0M0, 12% R1M0, 1% R3SM1, and 2% were still being graded, with 1 referred to HES. The study highlighted significant cases, including one patient who progressed to severe NPDR and required bilateral PRP and Ozurdex treatment, and another who developed DMO treated with Ozurdex.Conclusions: Diabetic retinopathy progression during pregnancy remains a significant concern, with many patients missing critical screening appointments, leading to advanced DR stages and severe visual impairment. Despite adherence to screening guidelines, patient non‐compliance and late referrals hinder effective management. Improved patient education and follow‐up strategies are essential to enhance screening attendance and outcomes, thereby preventing severe DR progression during pregnancy. Further research is necessary to develop targeted interventions for better compliance and timely treatment.
Assessing retinal thickness and vascular structures in an Alzheimer's disease mouse model app NL‐F/NL‐F
Authors: Sanchez‐Puebla Lidia , López‐Cuenca Inés , Jiménez María González , Salobrar‐Garcia Elena , Matamoros José A. , Lozano María Pilar Rojas , Fernández‐Albarral José A. , Elvira‐Hurtado Lorena , Ramirez Ana Isabel , Salazar Juan Jose , Nieto‐Vaquero Carmen , Desviat María Isabel Cuartero , Moro María Ángeles , Saito Takashi , Saido Takaomi C. , Ramirez Jose Manuel , de Hoz Rosa 
Published: January 2025

Aims/Purpose: In Alzheimer's disease (AD), there are histopathological aspects that cannot be studied in patients, demanding the use of murine models of the disease. The APPNL‐F/NL‐F model reproduces the pathophysiology quite faithfully. The aim of the present study was to analyze the retinal vascular structures and retinal thickness in an AD model at different ages and compares these findings to age‐matched wild type (WT) controls.Methods: A diachronic study was conducted using spectral‐domain OCT angiography (SD‐OCTA) and AngioTool software to assess retinal vascular structures, alongside OCT for measuring inner and outer retina thickness. We include two study groups: the APPNL‐F/NL‐F AD model and WT controls at 6, 9, 12, 15, 17, and 20 months old. The analysis focused on the three vascular plexus and retinal thickness, using the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. We considered statistically significant a p‐value < 0.05.Results: Compared to WT, the APPNL‐F/NL‐F group exhibited both vascular and structural changes starting as early as 6 months, with these changes persisting and evolving at 15, 17, and 20 months. Significant vascular alterations, particularly in the superficial vascular complex (SVC), were noted. There was a marked decrease in vessel area and total vessel length in the SVC, as well as in the intermediate and deep capillary plexus. Additionally, the inner retina predominantly showed a thickness decrease, while the outer retina demonstrated an increased thickness at most time points compared to the control group.Conclusions: The study identifies early retinal vascular and structural changes in the APPNL‐F/NL‐F model that precede cognitive changes observed at later stages. These findings suggest that the retinal changes in this model more closely resemble those in human AD compared to other transgenic models, highlighting the potential of retinal assessments in early AD diagnosis.