bluuebunny/crossref_metadata_2025_split huggingface dataset:
Current status & outcomes of the Welsh national cohort of patients with leber's hereditary optic neuropathy treated with idebenone
Authors: Sanders Francis W. B. , Votruba Marcela 
Published: January 2024

Aims/Purpose: To assess the real‐world effectiveness of idebenone in a heterogenous group of patients with LHON treated with idebenone in Wales. This provides insight into the national outcomes of.Methods: Patients were identified from the ophthalmic genetics service based at Cardiff Eye Unit. Clinical notes were reviewed and details were collated on: demographics of patients, genetic mutation ascribed to be causative of LHON, visual acuity from diagnosis through to March 2023. Visual acuity was analysed for clinically relevant recovery (CRR) defined as improvement from “off‐chart” to at least 5 letters “on‐chart” or “on‐chart” improvement of at least 10 letters.Results: 11 patients with LHON were identified as being treated with Idebenone 300 mg TDS. Currently 45.9 ± 20.3 years of age (range 22–73). 8 male and 3 female patients. 6 patients had the m11778G > A mutation and 4 patients had the m14484T>C. Disease duration at treatment onset ranged from 2 to 216 months with a mean of 35.8 months. Patients had a mean duration of treatment of 14 months (range 6–20). 2 eyes in one patient demonstrated CRR improving from a nadir of 6/60 and counting fingers acuity to 6/6 and 6/7.5 respectively. All other patients demonstrated no CRR at the time of data collection.Conclusions: Idebenone has mixed results in a heterogenous group of patients with LHON providing significant benefit for one patient out of a cohort of 12, meanwhile others demonstrated limited improvements, albeit prior to a full two‐year course of treatment. It remains to be seen what the long‐term outcomes will be with sustained treatment with idebenone.
Presentations patterns of acute onset binocular diplopia among paediatric population in the emergency department: Retrospective analysis and systematic review of the literature
Authors: Fustel Paula Boned , García Laura Fernández , Martí M. Ángeles Ruth Bort , González Honorio Barranco 
Published: January 2024

Aims/Purpose: This study aims to analyse the available evidence to identify the presentation patterns and underlying etiologies among paediatric patients presenting with acute onset binocular diplopia (AOBD) in the emergency department (ED).Methods: A longitudinal retrospective analysis of medical records from paediatric patients, younger than 21 years old, presenting with AOBD in a tertiary hospital's ED. All patients were followed until a final diagnosis was made. Emergent conditions (ECs) were defined as those reflecting significant neurologic abnormalities or requiring further investigations or interventions. In addition, a comprehensive systematic review of the literature was performed, which was conducted in accordance with the PRISMA guidelines. The search included 2 databases (PubMed and Google Scholar) and was completed on May 1st 2023.The search terms included (paediatric) AND (diplopia) AND (emergency).Results: During the 10‐years study period, of overall 745 patients admitted to ED with AOBD, 62 were children. Accounting for 8.36% of all the visits. Our population consisted of 27 females (43.54%) and 35 (56.45%) males. The mean age was 9.87 years (±4.83). 62 (retrospective analysis) and 590 patients (systematic review), met the inclusion criteria. The majority of the patients had non‐ECs, incidence between 60 and 80%. Among ECs, central nervous system tumours and demyelinating conditions were the most common diagnoses. Although not all the patients with ECs presented with associated sings (54%), most of the patients exhibiting associated signs were found to have an underlying EC.Conclusions: Most cases of diplopia in children admitted to the ED had non‐ECs underlying conditions. The literature indicates a statistically significant relationship between the presence of associated neurologic signs and ECs.
A simple method for preservation of embryonic rat brain tissue for primary neuron culture
Authors: Pehlivan Çiğdem , Kaleli Humeyra Nur , Sahin Afsun , Hasanreisoğlu Murat 
Published: January 2024

Aims/Purpose: In this study we aim to investigate the effect of short‐term storage of embryonic rat brain tissue in Hibernate‐E medium to be used in the isolation of primary neurons for in vitro biocompatibility and electrophysiology tests of retinal and optic nerve prosthesis. Functionally viable neuron cells will be an alternative method for regular dissection from tissue for further experiments.Methods: Hippocampal tissues from E15‐E17 embryos of Wistar Albino rat were dissecting for primary neuron culture. Half of the tissues were isolated on the same day and used as a control group for further experiments. The test group was stored in a Hibernate‐E medium for 1 week and the same isolation method was performed for the test group. For tissue preservation, half medium replacement with fresh Hibernate‐E medium on the 4th day was enhanced cell viability. Morphology, characterization and synapse formation were determined with immunoflorescence staining.Results: Comparison of neuronal survival between cultures prepared from stored hippocampi and freshly isolated hippocampi resulted in similar neuronal survival rates in both preparations with cell viability assays. Cell viability rate of hippocampus tissue isolated from rat embryo brain was demonstrated as 96% and cell viability rate of preserved tissue in Hibernate‐E Medium for 7 days was revealed as 90.22% by trypan blue cell viability test (n = 4). Morphological and immunocytochemical characterizations of stored and fresh hippocampal cultures were similar by observing beta‐III Tubulin neuron cytoskeleton biomarker.Conclusions: As a conclusion, our method has the potential to increase repeatability of primary neuron cultures within 1 week and reduce the number of isolation steps in research. In addition, it will provide a great convenience in the experimental timelines of the researchers and contribute to the reduction of the workload despite any obstacles during primary neuron culture.
Altered corneal structures in form‐deprived highly myopic chicks
Authors: Kang Byung Soo , Leung Tsz‐wing , Vyas Sonal , Ayerakwah Patience , Lin Jia Chun , Liang Yuanyuan , Stell William , Kee Chea‐su 
Published: January 2024

Aims/Purpose: Myopia is a leading cause of correctable and preventable vision loss worldwide, but the relationship between myopia development and growth of the anterior segment, particularly the cornea, has not been well established. This study aims to investigate whether experimental induction of myopia influences corneal structures in animals.Methods: Ten chicks were unilaterally form deprived by covering their right eyes with translucent diffusers at post‐hatching day 6 (P6). Refractive state, corneal shape, and ocular axial dimensions were measured at 4‐day intervals until P18 using a Hartinger refractometer, a custom‐made videokeratography system, and an A‐scan ultrasonographer, respectively. Parameters in treated vs control eyes were compared at the end of treatment. Repeated one‐way ANOVA was used for statistical analysis, and all parameters were expressed as mean ± SD.Results: At the end of treatment, form‐deprived eyes were myopic (−29.48 ± 8.26D vs. ‐0.61 ± 0.32D) and axially elongated (11.15 ± 0.55 mm vs. 9.51 ± 0.20 mm). At baseline (P6), treated and fellow contralateral eyes had similar corneal power (132.22 ± 6.37D vs. 132.64 ± 5.48D, p = 0.86) and thickness (167.93 ± 6.80 μm vs. 166.43 ± 7.27 μm, p = 0.63), but at P18 form‐deprived eyes had slower corneal flattening and thickening, resulting in significantly steeper (117.73 ± 5.03D vs. 113.22 ± 3.44D, p < 0.05) and thinner corneas (176.80 ± 7.52 μm vs. 192.35 ± 5.62 μm, p < 0.001) than fellow contralateral eyes. Repeated measures correlation analysis further indicated that axial elongation from P6 to P18 was significantly associated with corneal steepening (rrm = 0.77, p < 0.001) and thinning (rrm = −0.69, p < 0.001).Conclusions: This study provides insights into the impact of form deprivation myopia on corneal structures in juvenile animals. Specifically, the corneas of form‐deprived eyes were steeper and thinner because the natural corneal flattening and thickening processes were decelerated by treatment. Further studies are warranted to reveal the mechanisms responsible for this association between development of refractive error and corneal structure.
P3HT:ITIC polymer based photovoltaic biointerfaces for neural photostimulation
Authors: Kaleli Humeyra Nur , Karatum Onuralp , Pehlivan Çiğdem , Kesim Cem , Yıldız Erdost , Sahin Afsun , Nizamoğlu Sedat , Hasanreisoğlu Murat 
Published: January 2024

Aims/Purpose: Optoelectronic neural interfaces have diverse applications in comprehending neural network and treatment of neurodegenerative conditions especially in the field of the vision impairments. We aimed to use the non‐invasive, capacitive photocurrent generation stimulated by near‐infrared light in the biological environment integrating P3HT:ITIC devices to provide neuroprotective and neurodegenerative effects with reducing axonal damage through local repetitive photo‐stimulation.Methods: In this study, we performed neuron stimulation with the help of ITO/ZnO/P3HT:ITIC photoactive polymer implant placed on an indium tin oxide (ITO) glass. To evaluate the biocompatibility of the P3HT:ITIC devices, CTG cell viability and LDH leak assay were performed on primary nervous and visual system cells including Mio‐M1 and primary astrocytes. Cell specific biomarkers were examined by immunofluorescence staining to demonstrate short‐ and long‐term morphological changes and neural network improvements on both the biointerface and ITO control substrates.Results: We fabricated NIR‐responsive photovoltaic P3HT:ITIC biointerface with ZnO nanoparticles (NPs) as electron transport layer and P3HT:ITIC thin films as photoactive layer on ITO glass substrates. After evaluation of their stability, we showed that primary neurons, astrocytes and Müller glia cells on the biointerface have high cell viability, low cytotoxicity and preserved cellular network and morphology after 2 weeks of culture condition.Conclusions: Our study will provide novel solutions to existing problems in electrostimulation devices by exploring capabilities of wirelessly functional, biocompatible organic polymer‐based photoelectric devices with low cost of production. They have a potential in establishing a platform for the development of near infrared light‐controlled electrostimulation treatment, that can improve axonal healing in retina and optic nerve injuries.
Insights into human choroid melanocyte and stromal cells
Authors: Madigan Michele , Wu Chieh‐Lin (Stanley) , Cioanca V. , Conway Robert 
Published: January 2024

Aims/Purpose: The human choroid is a complex highly vascular pigmented tissue between Bruch's membrane and the sclera. Its dynamic nature is important for eye homeostasis and for in pathology including macular degeneration and myopia. The stroma comprises heterogeneous cell populations including fibroblasts, melanocytes, immune cells, smooth muscle cells and neurons within a loose collagenous extracellular matrix. We used RNA transcriptome and multimarker immunolabelling of human choroidal melanocytes and tissue to further characterize adult choroidal melanocytes.Methods: Human choroidal melanocytes were cultured (n = 6 postmortem donor eyes, <18 h delay, UNSW HREC), and used between passage (P) 2 to 5 for RNA transcriptome and multimarker immunofluorescence labelling and confocal microscopy. Sections and flatmounts from central choroid were also compared. Immunolabelling included melanocyte (Tyrosinase, TRYP1, DCT, MelanA) and stromal cell (S1004A, vimentin, α‐smooth muscle actin, CD45) markers.Results: Cultured melanocytes displayed mostly bipolar morphology with heterogeneous eumelanin density related to donor eye iris colour. Whole transcriptome findings showed enriched melanogenesis genes (high level TYR, PMEL, MITF, TYRP1; MLANA; low level DCT1, MC1R) but not genes reported for RPE (e.g. RPE65), pericytes (e.g. ACTA2) or fibroblasts (e.g. IGF2) confirming melanocyte culture quality. We also found expression for proposed Schwann cell precursors PLP1 and SOX10. Immunolabelling confirmed overall expression of melanogenesis proteins, and subpopulations expressing PLP1 and Sox10, in culture and in choroidal tissue.Conclusions: Melanocytes and stromal fibroblast are among the most numerous and complex heterogeneous populations within the choroid and our study provides further details on characteristics markers and topography. A possible role for Schwann cell precursors in renewing adult melanocyte populations is intriguing and continues to be investigated.
PGC‐1a inhibition promotes autophagy in induced pluripotent stem cell‐derived retinal pigment epithelial cells generated from age‐related macular degeneration patients
Authors: Hytti Maria , Kauppinen Anu , Skottman Heli , Blasiak Janusz , Kaarniranta Kai 
Published: January 2024

Aims/Purpose: Dysfunctional protein clearance, oxidative stress, mitochondrial damage, and chronic inflammation cause retinal pigment epithelial (RPE) cell damage and the development of age‐related macular degeneration (AMD). PGC‐1α can alleviate oxidative stress, is a key player in mitochondrial quality control and could be considered as a treatment target in AMD. Here, we assessed the effect of PGC‐1α inhibition on induced pluripotent stem cell (iPSC)‐derived RPE cells exposed to hydroquinone‐induced oxidative stress.Methods: iPSC‐derived RPE cells from two neovascular AMD patients or one healthy age‐matched control were cultured for 8 weeks on transwell cell culture inserts until mature. Cells were exposed to the PGC‐1α inhibitor SR‐18292 for 1 h before an exposure to hydroquinone for an additional 4 h. Lactate dehydrogenase (LDH) was measured from collected medium samples to assess cellular viability. Cells were lysed in 3x Laemmli sample buffer for analysis by western blotting or subjected to RNA extraction, followed by RT‐PCR analysis.Results: Hydroquinone caused a robust increase in LDH release to the medium, which was not modulated by PGC‐1α inhibition. In neovascular AMD‐derived iPSC‐RPE cells, hydroquinone caused an accumulation of p62 and LC3‐II, an effect that was reversed by SR‐18292 pre‐treatment. In control iPSC‐RPE cells, neither hydroquinone nor SR‐18292 affected autophagic markers p62 or LC3. RT‐PCR analysis showed an increase in p62 mRNA levels following hydroquinone exposure in both control‐ and AMD‐derived iPSC‐RPE cells while no change was observed in the RNA levels of LC3B or mTOR.Conclusions: Increased oxidative stress caused autophagy dysregulation in AMD‐derived iPSC‐RPE cells but not in healthy age‐matched control cells. Interestingly, PGC‐1α inhibition promoted autophagy and the clearance of p62, but further studies are necessary to explore the underlying pathways and the disease‐specific differences observed between healthy and disease‐derived RPE cells.
In situ distribution of markers for stemness, quiescence, proliferation and differentiation in the human cornea and limbus
Authors: Bisevac Jovana , Moe Morten Carstens , Petrovski Goran , Noer Agate 
Published: January 2024

Aims/Purpose: Identify the distribution of the most commonly used markers for stemness, quiescence, proliferation, and differentiation in limbal compartments such as human limbal epithelial crypts, posterior and anterior limbus, as well as the central and posterior cornea.Methods: Corneal‐limbal biopsies from cadaver human donors (n = 3) embedded in paraffin were proceeded for immunohistochemistry fluorescence and examined for stemness/progenitor markers (p63α, SOX9, ABCG2, N‐cadherin), proliferation markers (ki‐67), quiescence marker (CEBPD), differentiation markers (CX43, KRT3, KRT12, KRT13), and epithelial marker (E‐cadherin). Images were obtained by Zeiss Axio Observer. Fluorescent images were obtained using the Zeiss Axio Imager M1 fluorescence microscope (ZEISS, Oberkochen, Germany).Results: The stemness/progenitor markers p63α and SOX9 were found in basal and suprabasal cells of limbal epithelial crypts and limbal epithelium, whereas the ABCG2 and N‐cadherin were exclusive for limbal basal epithelium in all limbal structures. Proliferation marker Ki‐67 was most abundant in suprabasal layers of the limbus and rarely found in the posterior cornea, while absent in anterior cornea. Quiescence marker CEBPD was positive in the basal cells of both, limbus and cornea. Differentiation markers KRT3 and KRT12 were positive in the whole cornea and intermediate and superficial layers in anterior and posterior limbus, while rarely present in limbal epithelial crypts. However, CX43 was staining almost all suprabasal layers in the limbus as well as basal and suprabasal layers in the cornea. KRT13 was exclusive for superficial layer of the anterior and posterior limbus layers staining conjunctival cells.Conclusions: Here we identify the localization of the most common markers used to determine the stemness, quiescence, proliferation, and differentiation status to unravel the in situ distribution of these markers in the limbal epithelial crypts, posterior and anterior limbus, as well as the central and posterior cornea. The study accumulated new knowledge about the distribution of these markers and the corneal‐limbal organization.
ON–OFF electroretinogram analysis in patients with negative electroretinograms
Authors: Pojda‐Wilczek Dorota 
Published: January 2024

Aims/Purpose: In a healthy population, the flash full‐field electroretinography (ffERG) includes a negative a‐wave and a positive b‐wave. The amplitude of the b‐wave is larger than the a‐wave amplitude in normal patients. In dark‐adapted ERG, the b:a ratio is about 1.6–1.8. The term “negative electroretinogram” is used when the b‐wave amplitude is smaller (negative–negative) or relatively smaller (negative–positive) than the a‐wave amplitude.This study aims to describe the differences in the ERG of patients with a negative ERG caused by genetic and acquired diseases to help better narrowing down an accurate diagnosis.Methods: The retrospective study comprised 10 patients aged 5–43 years (4 female, 6 male). ffERG was done according to the ISCEV standards. ON–OFF ERG protocol was additionally used. RETeval portable device (LKC, USA) and sensor strip palpebral electrodes were used.Results: Negative ERG was found in patients with congenital stationary night blindness (X‐linked, autosomal dominant, autosomal recessive, Oguchi disease), fundus albipunctatus, X‐linked retinoschisis, vitamin A deficiency, vigabatrin toxicity, retinal inflammation. In ON–OFF protocol differences between the function of the ON and OFF bipolar cells in the various diseases are present and will be discussed.Conclusions: ffERG with ON–OFF protocol should be done in all patients with nyctalopia or inner retina diseases. Detailed analysis of ERG may help to establish the clinical diagnose of retinal disease and to narrow the area of genetic investigation.
Investigating focal macular electroretinogram function for fundus‐related perimetry application
Authors: Suzuki Naoto 
Published: January 2024

Aims/Purpose: This study aimed to investigate the utility of focal macular electroretinogram (ERG) function in fundus‐related perimetry (microperimetry) for assessing cryptogenic diseases such as macular dystrophy. The decline in visual sensitivity of the retina was measured using microperimetry, and the retinal layer causing this decline was identified using multifocal ERG.A focal macular ERG function was used for microperimetry instead of multifocal ERG.Methods: The developed apparatus comprised illumination and photographic optical systems separated by a mirror with a hole, a microperimetry optical system and an ERG optical system separated by a 45° cold mirror. It also consisted of an Edmund infrared camera EO‐50231, a lens, a halogen lamp, an objective lens, four double convex lenses, two aperture stops, a mirror, a 12.1‐inch high brightness (2000 cd/m2) monitor and an artificial eye. Its electrical measuring equipment included a differential amplifier, a high‐pass filter, a 50‐Hz notch filter and two non‐inverting amplifiers. Moreover, the equipment consisted of the National Instruments' I/O device USB‐6216, a shielded connector block, plate electrodes, an electromagnetic shield sheet and the LabVIEW 2018 software for data retrieval. To perform the focal macular ERG, a DynaScan 49‐inch ultrahigh brightness (3500 cd/m2) liquid crystal display (LCD) was prepared.Results: The ERG software could display three stimulus spot circles with diameters of 5°, 10° and 15° on the ultrahigh brightness LCD. Additionally, a function for adjusting the size of the stimulus spot circle was added as the diameter was changed from 1° to 15°. The focal macular ERG was able to measure a wave, b wave and photopic negative response (PhNR). It was found that certain small waves on the b wave were confirmed with high probability as oscillatory potentials (OPs), while one positive wave similar to the d wave was confirmed sometimes; however, the c wave was not confirmed.Conclusions: It can be concluded that when not only the a wave, b wave and PhNR but also the OPs and d wave are confirmed, the focal macular ERG function can identify the retinal layer causing visual alterations at specific points throughout the retina.
Texture analysis shows interocular retina asymmetries in women not existing in men
Authors: Bernardes Rui , Nunes Ana , Ferreira João , Guimarães Pedro , Serranho Pedro , Castelo‐Branco Miguel 
Published: January 2024

Aims/Purpose: Recent research has demonstrated that retinal texture is a valuable source of biomarkers for neurodegeneration. Previous studies have examined the layer thickness of the neuroretina in women and men as measured from optical coherence tomography (OCT) data. The effect of sex‐based retinal interocular differences remains relatively unexplored. This study looked into texture metrics from OCT data of healthy adult individuals to determine if interocular differences are related to sex.Methods: Grey‐level co‐occurrence matrix features were computed from mean‐value fundus images from the six layers of the neuroretina. These features were tested separately for group mean differences between the female and male participants' right and left eyes. A pairwise correlation analysis was first performed to exclude similar features. The non‐correlated features were tested for normality, and a paired‐sample t‐test or a signed rank test was applied accordingly to evaluate the group mean differences. Due to the many pairwise tests, three different pairwise correction methods were applied: Bonferroni, Benjamini–Hochberg, and the False Discovery Rate.Results: Initial uncorrected results showed that interocular retinal texture asymmetries were mainly present in women and with a larger effect size than in men. After correction, except for the highly conservative Bonferroni method, the results revealed that texture differences were only present in the female group, while the eyes of men were similar.Conclusions: Our work suggests that structural patterns in the right and left eyes manifest differently in females and males, raising the question of why such differences occur and how they might vary over the lifespan, both in healthy individuals and in patients diagnosed with neurodegenerative disorders. In addition, it further emphasizes the need for accurate control in studies that use both eyes.