bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cell‐type specific insights into the pathobiology of advanced diabetic retinopathy using single‐cell transcriptome analysis of the Akimba retina
Authors: Van Hove Inge , Porcu Michaël , De Groef Lies , Hu Tjing‐Tjing , Beets Karen , Van Bergen Tine , Boeckx Bram , Lambrechts Diether , Moons Lieve , Feyen Jean H.M. 
Published: December 2019

AbstractPurposeIn this study, single‐cell transcriptomics was applied to provide insight into cell‐type specific transcriptional dynamics in the neuronal, glial, vascular and inflammatory compartments of the Akimba retina. Investigation of the molecular characteristics and networks underlying the pathobiology of this diabetic retinopathy mouse model might lead to the identification of new pathophysiological or protective mechanisms.MethodsRetinas were isolated from 12‐week‐old Akimba (Ins2AkitaVEGF+/‐) and age‐matched wild type (WT) C57BL/6J mice and dissociated by collagenase treatment into single cell suspension. Single‐cell barcoded libraries were generated (10× Genomics) and sequenced on the Illumina HiSeq4000 platform. After data pre‐processing, principal component analysis‐based clustering was performed, and clusters were annotated based on marker genes. In addition, differential expressed genes between Akimba and WT retinal cells were further analyzed for statistically enriched pathways and categorized for biological function using STRING.ResultsOur results showed that neuronal cell death, especially of the rod photoreceptors, is accompanied by an immune response in the Akimba versus WT retina. This is demonstrated by the prominent increase in and activation of resident and invading immune cells and enrichment of e.g. complement, interferon and inflammasome signaling pathways. Transcriptional changes in macroglia point towards their attempt to rescue lost tissue via reactive gliosis, and towards a metabolic shift from glycolysis to oxidative phosphorylation. In addition, the Akimba retina is also characterized by an overall change in ribosome synthesis and translation, oxidative stress responses and metal dyshomeostasis.ConclusionOur data indicate substantial shifts in abundance of cell types in the Akimba retina, and cell‐specific changes that may lead to functional uncoupling of neuron‐glia interactions.
Visual outcomes of Descemet Membrane Endothelial Keratoplasty at a Single Surgeon United Kingdom Centre
Authors: Pekacka Aleksandra , Malik Hammad , Garella Manisha , Barsam Allon 
Published: December 2019

AbstractPurposeDescemet Membrane Endothelial Keratoplasty (DMEK) is a partial thickness corneal graft which involves replacing a recipient’s Descemet’s membrane and endothelium with healthy tissue. Main advantages include rapid visual recovery, fewer higher order aberrations and low rejection rate. However, DMEK is technically challenging and requires advanced surgical skills. The aim of the audit was to assess visual outcomes of DMEK performed at Luton and Dunstable University Hospital (L&D), United Kingdom.MethodsData was collected retrospectively from April 2015 to November 2018. 57 eyes were analysed (31 male, 26 female). Patient demographic data were collected, as well as indication for surgery and pre‐operative visual acuity. Post‐operative follow‐up visits were analysed, including assessment of visual acuity, complications and graft failure and rejection.ResultsPre‐operative visual acuity (Snellen chart) ranged from worse than 6/60 to 6/6. At an average of 6 months post operatively 87% of patients achieved 6/12 vision or better. At 1 year post procedure 59% of patients achieved 6/6 vision or better. At 2 years follow‐up 63% of patients achieved 6/6 vision or better. The most common DMEK related complications were steroid induced raised IOP (n = 9), partial graft detachment or dislocation (n = 8) and need for re‐bubbling (n = 7). 5 patients were listed for Descemet Stripping Automated Endothelial Keratoplasty (DSAEK).ConclusionsMost patients undergoing DMEK procedure in L&D Hospital achieve 6/12 vision or better from 6 months onwards. Outcomes at 6 months, 1 year and 2 years are in‐line with the guidelines set by the Royal College of Ophthalmologists and previously published data. These are re‐assuring findings which suggest that more advanced corneal techniques can be carried out at single surgeon sites. Future work should aim to collect long term data on outcomes.
Clinical efficacy of MC2‐03 (ciclosporin eye drop) in treatment of dry eye disease patients with severe keratitis randomized in the NORTHERN LIGHTS phase 2b trial
Authors: Praestegaard Morten , Gomez Frédéric , Teus Miguel A. , Horwath‐Winter Jutta , Heegaard Steffen 
Published: December 2019

AbstractPurposeAnti‐inflammatory treatment of moderate‐to‐severe dry eye disease (DED) remains a challenge with a need for eye drops showing better efficacy and tolerability. The effect of MC2‐03, a novel ciclosporin (CsA) eye drop using PAD™ Technology, was investigated in humans.MethodsThe NORTHERN LIGHTS trial is a 6 month phase 2b, multicenter, randomized, controlled, double‐masked trial evaluating MC2‐03 (0.03% and 0.06% CsA) administered once daily in 255 patients with moderate‐to‐severe DED with grade 3 and 4 corneal fluorescein staining (CFS) on the modified Oxford scale. The primary objective of the study was to evaluate safety and efficacy of two doses of MC2‐03 compared to vehicle and lubricant comparator. A total of 108 (42.4%) patients with severe keratitis (CFS 4) at Baseline were randomized.ResultsThe proportion of patients with severe keratitis (CFS 4) at Baseline achieving at least 2‐grade improvement in CFS at Month 6 was 63.0% for MC2‐03 0.03%, 41.4% for MC2‐03 0.06% versus 30.8% for both vehicle and lubricant comparator, showing statistical significant improvement for MC2‐03 0.03% compared to vehicle (p = 0.028) and to lubricant (p = 0.028). Further post‐hoc analysis demonstrated that the mean change in CFS from Baseline to Month 6 for MC2‐03 0.03% separated significantly from vehicle (0.8 CFS units, p = 0.012) and lubricant (0.7 CFS units, p = 0.020) with statistical significance already achieved at Month 3. Overall, the trial demonstrated favorable safety of MC2‐03.ConclusionA large unmet need exists for treating moderate‐to‐severe DED patients. The NORTHERN LIGHTS study confirms that MC2‐03 0.03% CsA is effective in treating severe keratitis in this patient group
Relationship between retinal thinning, disease duration and disability status in multiple sclerosis patients
Authors: Viladés Elisa , Orduna Elvira , Cordón Beatriz , Perez‐Velilla Javier , José Vicente Maria , Gil‐Arribas Laura , Fernandez‐Tirado Javier , Haro Erika , de Gopegui Erika Ruiz , Jesús Rodrigo‐Sanjuan Maria , Satué Maria , Garcia‐Martin Elena 
Published: December 2019

AbstractPurposeTo assess changes in the pattern of the neuro‐retina thinning during the evolution of multiple sclerosis (MS).Method64 eyes of healthy controls and 89 eyes of patients with MS without previous episode of optic neuritis were included in the study. Measurements were performed using the Posterior Pole Retinal Thickness Map protocol [shows the thickness of the retina throughout the posterior pole (volumetric examination of 30° × 25° OCT]) with the Heidelberg Spectralis optical coherence tomography (OCT) device. We analysed the 8 × 8 grid placed along the fovea symmetrically with the papilla, dividing patients with MS into 5 different groups at intervals of 5 years of disease duration and a group of patients with a few months of diagnosis.ResultsMS patients presented a significant thinning of the retinal nerve fibre layer (RNFL) and the ganglion cell layer (GCL). This thinning is visible and significant even in the first year after symptoms onset in RNFL and GCL. In addition, an inverse relationship between the thickness of these layers and the time of disease evolution was found, existing cells with a moderate‐strong relationship mainly in the GCL and RNFL. In contrast there is negative but poor correlation between retinal thinning of these 2 retinal layers and Expanded Disability Status Scale (EDSS).ConclusionAlthough there is no significant peripapillary damage in the first months of the disease, we can find a significant thinning in the RNFL and GCL around the macula. GCL seems to be the layer that presents a significant thinning earlier than the RNFL and stronger relationship with disease duration. On the other hand, EDSS does not seems to be so influent on retinal thinning than disease duration.
Do patients receiving laser treatment for sight threatening diabetic retinopathy and those under the care of a consultant led multidisciplinary diabetes specialist team have better HbA1c value than those that are not under a diabetes specialist?
Authors: Ahmed Syed , Shahid Syed , Parmar Sita , Kashani Shahram 
Published: December 2019

AbstractPurposeTo evaluate if patients with sight threatening diabetic retinopathy who undergo laser photocoagulation treatment and are under the care of a consultant‐led specialist diabetes team have a better HbA1c value than those that are not under a specialist diabetes team.MethodsRetrospective review of all patients who underwent pan laser photocoagulation (PRP) treatment or macular laser therapy between 1st January 2018 and 31st December 2018 were included in the study.ResultsWe identified 64 patients who underwent laser treatment for diabetic retinopathy in the 12‐month period, 21 female and 43 male. Of these, 36 patients (56%) had type‐2 diabetes, 12 patients (18%) had type‐1 diabetes and in 16 patients (25%), this was undocumented. In terms of type of laser therapy, 50 (78%) underwent PRP and 14 (22%) underwent macular laser. 33 patients (51%) who underwent laser treatment were under the care of a specialist diabetes team within 1 year of receiving treatment. The average HbA1c value of patients who were under a diabetes specialist was 80.9 mmol/mol (9.6%), versus those who were not under a diabetes specialist was 72.7 mmol/mol (8.8%).ConclusionOur study showed that amongst patients who underwent laser treatment for sight threatening diabetic retinopathy, majority underwent pan retinal photocoagulation for proliferative disease rather than macular laser for maculopathy. This observation is expected, as macular laser is less commonly practiced since the advent of anti‐VEGF therapy for diabetic maculopathy. Surprisingly, the HbA1c values on average were better in those who were not under a specialist diabetes team compared to those who were under the care of a specialist. Although this is unexpected, it may be explained by the fact that those under a diabetes team have poorer control of their blood sugars, and/or more advanced diabetes to begin with.
A case of bilateral acute angle closure glaucoma secondary to systemic decongestants
Authors: Jin Hui Goh Eunice , Neelam Kumari , Sangtam Tiakumzuk , Stanley Philip 
Published: December 2019

AbstractPurposeTo report a case of bilateral acute angle closure attack secondary to an oral decongestant and antihistamine use.MethodsA case report.ResultsA 42‐year‐old Chinese lady with no past medical or ocular history presented to the Emergency Department with a 2‐day history of headache, vomiting and bilateral eye redness. She had taken pseudoephedrine and chlorpheniramine the previous 5 days for cold symptoms. Best‐corrected visual acuity (BCVA) was 6/24 bilaterally. Her intraocular pressure (IOP) was 37 (right) and 39 (left) mmHg. On slit lamp examination, the corneas were hazy and edematous with mid‐dilated pupils. Gonioscopy revealed closed angles bilaterally. Glaukomflecken was noted on both lenses. A diagnosis of bilateral acute angle closure attack was made. She was immediately given intravenous acetazolamide and topical hypotensive drops (timolol 0.5%, brimonidine 0.1%, prednisolone acetate 1% and pilocarpine 2%) followed by oral acetazolamide and continuation of all the topical drops. 9 hours later, the BCVA had improved to 6/15 (right) and 6/9.5 (left). Her left cornea was clearer but right was still hazy. IOP was 32 (right) and 14 (left) mmHg. B‐scan ultrasound showed no choroidal thickening. Subsequently, a bilateral laser iridoplasty was performed followed by laser iridotomy. Her IOP normalized after the procedures to 8 mmHg in both eyes.ConclusionsSeveral systemic medications are known to precipitate angle closure glaucoma. It is important to counsel patients on risks and symptoms before initiating these seemingly benign medications for a common cold.
cGAS‐STING pathway activation in murine retina
Authors: Tang Miao , Pavlou Sofia , Chen Mei , Xu Heping 
Published: December 2019

AbstractPurposeThe intracellular DNA sensor, cGAS, initiates the host immune response by recognizing pathogen‐ or endogenous‐derived cytoplasmic DNA. After binding to DNA, activated cGAS‐STING pathway induces the transcription of the Type I interferon and other pro‐inflammatory genes. Mitochondrial dysfunction is known to be involved in various retinal degenerative and angiogenic diseases, including age‐related macular degeneration and diabetic retinopathy. As a consequence of mitochondrial stress, cytosolic escape of mitochondrial DNA has been reported to induce cGAS‐STING pathway activation. In this study, we characterized the expression of cGAS‐STING pathway in murine retina.MethodsThe expression of cGAS and STING in murine retina, microglia cells (BV2), primary RPE and B6‐RPE07, primary Müller glial and photoreceptor cells (661W) was examined by RT‐PCR and immunohistochemistry. The cells were transfected with exogenous dsDNA poly(dA:dT) (5ug/mL) for 8 hours. The expression of cGAS, STING, phosphorylated TBK1 (pTBK1) and IRF3 (pIRF3), type‐1 interferon, IL‐6 and TNFa was analysed by RT‐PCR and immunocytochemistry.ResultsBoth cGAS and STING were detected in the murine retina, microglia, Müller glial, photoreceptor and RPE cells. Following poly(dA:dT) treatment, the expression of cGAS and pTBK1 was increased in these cells. In addition, intranuclear translocation of pIRF3 was observed in poly(dA:dT)‐treated microglia, RPE, Müller glial and photoreceptor cells. In line with these observations, the mRNA expression of IFNa, IFNb, IL6 and TNFa was significantly increased (p < 0.05) in poly(dA:dT)‐treated cells.ConclusionsThe cGAS‐STING pathway is expressed in many cells within the retina, including microglia, Muller cells, photoreceptor and RPE cells. This pathway may play an important role in retinal innate immunity against endogenous or exogenous cytosolic DNA. Uncontrolled cGAS‐STING pathway may be involved in retinal degenerative diseases.
Synthesis and application of magnetic nanoparticles (MNPs) in siRNA delivery to the retina
Authors: Bassetto Marco , Sen Merve , Gonzalez Blanca Arango , Ueffing Marius , Poulhes Florent , Zelphati Olivier 
Published: December 2019

AbstractIntroductionSmall interfering RNA (siRNA) is an important RNA interference tool that has found significant application in ocular therapy. For this reason, there is a considerable demand of siRNA delivery platforms able to effectively transfect cells within the retina. Up to now several strategies have been investigated for this application such as lipids, nanoparticles and polymers but in all the cases invasive injections are the only administration routes explored. Moreover, a major limitation shared by all these delivery systems is the lack of active targeting toward the posterior segment of the eye that hampers high transfection efficiencies.PurposeWe aim to synthesize and formulate a new magnetic nanoparticles‐mediated delivery technology that shall allow safe and efficient siRNA delivery to the retina assisted by magnetic targeting.Methods(1) Cationic MNPs have been synthesized, characterized, and their ability to form complexes with siRNA has been demonstrated by Zeta Potential. (2) The in vitro MNPs mediated gene silencing have been tested on green fluorescent protein (GFP)‐stably transfected cells (661W & RPE). Also, gene silencing of the endogenous glyceraldehyde 3‐phosphate dehydrogenase (GAPDH) gene has been monitored. (3) Finally, the in vitro toxicity of the formulations has been determined in term of apoptosis, cell proliferation and protein production.ResultsMNPs were able to efficiently complex siRNA while maintain their size and charge. MNPs complexed with siRNA achieved high transfection efficiency and gene silencing of GFP as shown by fluorescence microscopy and flow cytometry. The knock‐down efficiency has been confirmed by targeting GAPDH by immunohistochemistry. Finally, proliferation, apoptosis and total protein content assays demonstrate the full biocompatibility of these gene delivery platforms.ConclusionsMagnetic nanoparticles are a promising platform for gene therapy in the context of ocular therapy and allow to achieve high transfection efficiencies in retinal cell lines.This project has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska‐Curie grant agreement No 722717.
Investigation of tear protein composition in healthy and dry eye subjects using trapped ion mobility spectrometry coupled with quadrupole time of flight
Authors: Kolman Ioannis , Kessal Karima , Chardonnet Solenne , Mélik Parsadaniantz Stéphane , Baudouin Christophe , Brignole‐Baudouin Françoise 
Published: December 2019

AbstractPurposeProteomic composition of tears is not yet fully characterized and has a great potential to be used as source for discovery of disease‐specific protein biomarkers. The present work is a preliminary evaluation of tear proteome using timsTOF Pro®, a new highly sensitive mass spectrometry technology.Material and MethodsThree tear samples from 3 healthy subjects (HS) and 2 from a dry eye (DE) patient were collected using plastic micropipettes and Schirmer’s strips respectively. After protein elution from the strips, all samples were treated under the same conditions. Proteins were reduced and alkylated then digested in solution with LysC and Trypsin prior to nanoLC‐MS/MS analysis (nanoElute and timsTOF Pro®, Bruker). Protein identification was performed with Xtandem.ResultsIn total, 1191 proteins were identified in both analytical groups with at least 1 specific peptide: 446 proteins in HS and 1034 proteins in the DE; 802 proteins were exclusively identified in DE (e.g. A2M, HPX, ALDH3A1, PKM, MYH14, ALDH3A1) while 157 were expressed only in controls (e.g. PLOD1, DNAJC3, GOLM1, RNASE4, SDF4, HYOU1). In DE cell structural associated proteins as well as proteins highly correlated with inflammatory and apoptotic processes were detected. Finally, among the proteins that are common to both groups 122 were upregulated in DE vs HS (e.g. ALB, TF, ENO1, ANXA1, GSTP1, S100A9) while 88 were downregulated (e.g. LTF, LCN1, LPO, CST4, LACRT, AZGP1). The upregulated proteins are associated with a blood‐lachrymal barrier failure, inflammatory & immune responses while the downregulated ones sign a lachrymal gland dysfunction.ConclusionsDifferences in the protein expression between HS and DE arise due to the pathological conditions but also due to the different sampling methods used. This preliminary study could offer a roadmap for designing further studies for the in‐depth characterization of the tear protein profile expression under physiological and pathological conditions.
Clinical impact of drug monitoring in non‐infectious uveitis treated with adalimumab
Authors: Mortelé Augustijn , Mortelé Marie , Potvin Arnaud , De Schryver Ilse 
Published: December 2019

AbstractPurposeTo assess the relationship between adalimumab (ADA) trough levels and clinical efficacy and to evaluate the importance of quantification of ADA serum in combination with clinical data of the patient.MethodsA retrospective study of patients with non‐infectious uveitis (NIU) treated with ADA for at least 6months who had ADA trough and antibody levels measured during maintenance therapy. Disease activity was evaluated by changes in best‐corrected visual acuity (BCVA), degree of anterior chamber cells, central macular thickness and imaging findings.ResultsTwenty‐four patients were included. The median age was 36 years and 50% were women. The most common diagnosis was idiopathic uveitis (50%), followed by sarcoidosis (17%) and Birdshot (8%). All patients received 40 mg adalimumab every other week and showed an initial clinical benefit. Mean follow‐up was 39.5 months. The median trough level of adalimumab was higher in patients in clinical remission (11.02 μg/mL) than in patients with active disease (4.22 μg/mL). Adalimumab cut‐off value was calculated to discriminate clinical remission from disease activity. A cut‐off drug level of 7.95 μg/mL yielded optimal sensitivity and specificity. Only 2 of 25 patients (8%) had undetectable adalimumab trough levels with antibodies against adalimumab which correlated with loss of clinical response. None of the responders had antibodies.ConclusionDespite the limited number of cases, our data suggest that in NIU clinical efficacy improves with increasing adalimumab serum levels. Clinical remission is more likely to occur in those patients who achieve an adalimumab trough level of at least 7.95 μg/mL The development of anti‐adalimumab‐antibodies was associated with undetectable trough adalimumab levels and worse uveitis outcome. Since there is variability in the range for its clinical applicability, controlled prospective studies are required to determine the optimal therapeutic window of ADA serum levels.