bluuebunny/crossref_metadata_2025_split huggingface dataset:
Retinal degeneration development in Cnga1 deficient mouse
Authors: Veronica Amarie Oana 
Published: December 2019

AbstractRetinitis pigmentosa (RP; OMIM 268,000) is a group of retina degenerative diseases with chronic, progressive degeneration of retinal pigmented epithelium and photoreceptors, with about 2.5 million people affected worldwide. Being highly genetic heterogeneous, RP exhibits various clinical phenotypes. Cyclic nucleotide gated (CNG) channel is involved in the visual photo‐transduction upon hyperpolarizing the rod photoreceptor. CNG family comprises six homologous members in mammals, A‐type subunits (CNGA1–4) and B‐type subunits (CNGB1 and CNGB3). Here we report the first Cnga1 mouse model identified from the library if previous ENU‐mutagenesis screens, which shows retinal degeneration in mice starting with 4 week of age. Additionally, using the ACmaster we observed changes in the axial length of the eye, the anterior chamber and lens thickness, all being reduced.
Changes in biomechanical properties of keratoconic corneas following intracorneal ring segment (ICRS) implantation
Authors: Daas Loay 
Published: December 2019

AbstractPurposeStudies using Corvis ST (CST, Oculus; Wetzlar, Germany) and Ocular Response Analyser (ORA, Reichert, Depew, NY, USA) have reported significant differences between keratoconic and healthy corneas. Implantation of intracorneal ring segments (ICRS) using a femtosecond laser represents a reliable surgical option to widen the spectrum of the stage‐related therapy of keratoconus in patients with contact lens intolerance, post‐LASIK‐keratectasia or pellucid marginal degeneration (PMD). Our aim was to evaluate the ability of the Corvis ST and Ocular Response Analyser to detect the possible stiffening effect after Intacs SK (Addition Technology, Inc.) implantation in patients with keratoconus.Patients and MethodsBetween January 2018 and January 2019, ICRS were implanted in 31 eyes of 27 patients (age 31.9 ± 10.2 years) with clear central cornea. The patients had to fulfill the corneal diagnostic tests required for femtosecond laser‐assisted Intacs SK implantation in 80% depth. The following CST/ORA parameters were recorded: deformation amplitude Ratio (DA Ratio), stiffness parameter at applanation 1 (SP A1), Corvis biomechanical index (CBI), tomographic biomechanical index (TBI), Keratoconus Match Index (KMI), corneal hysteresis (CH) and corneal resistance factor (CRF) preoperatively and 6 months after the ICRS implantation.ResultsDA Ratio (5.43 ± 1.0 vs 5.52 ± 1.1, p = 0.4), SP A1 (58.76 ± 17.5 vs 59.11 ± 17.8, p = 0.4) CBI (0.96 ± 0.1 vs 0.97 ± 0.1, p = 0.3), TBI (0.98 ± 0.0 vs 0.99 ± 0.1, p = 0.3) and KMI (−0.03 ± 0.3 vs −0.17 ± 0.2, p = 0.1) did not change significantly between both time‐points. However, CH (7.96 ± 1.2 vs 7.05 ± 0.9) and CRF (6.33 ± 1.2 vs 5.35 ± 1.2) decreased significantly from preoperative to postoperative measurement time‐point (p = 0.03 for both).ConclusionBoth devices ORA and CST are supposed to analyse the dynamic behavior of the cornea during its temporary deformation by an air puff. The lack of significant changes in the standard parameters of the CST reflects the inability of this device to document the stiffening effect of ICRS in keratoconus patients. In contrast, the standard ORA parameters CH and CRF, but not the KMI, showed a significant decrease 6 month postoperatively. The meaning of those findings in relation to the progression of a keratoconus the disease has to be evaluated further.
Ocular gene therapies in clinical practice: Viral vectors and non‐viral alternatives
Authors: Behar‐Cohen Francine 
Published: December 2019

AbstractOcular gene therapy has entered into the clinical practice. While viral vectors are today the best option to replace/correct genes, the optimal method to deliver these treatments to the retinal pigment epithelial (RPE) cells and / or to the photoreceptor cells, non‐viral gene delivery approaches offer the promise of sustained fine‐tuned expression of secreted therapeutic proteins that can be adapted to the evolving stage of the disease course and that can address more common non‐genetic retinal diseases like age‐related macular degeneration (AMD). Current gene therapy strategies for ocular diseases will be reviewed here with a focus on clinical stage products.Conflict of interest: Patent, consultancy and founder of Eyevensys.
The reproducibility crisis
Authors: Behar‐Cohen Francine 
Published: December 2019

AbstractThe reproducibility of research made in academic laboratories is crucial and a major concern for the scientific community, the payers, and the society, which are all expecting that results from academic research translate to concrete applications. It is estimated that more than 50% of money spend by the US government for preclinical research is lost in unreproducible results. More than 70% of scientists have tried and failed to reproduce another scientist's experiment and more 50% have failed to reproduce their own research. More than 80% of scientists consider that we are facing a reproducibility crisis. The reasons for such a crisis will be presented and propositions made to reduce this problem.
GSK3/CRMP2 signaling confers PTEN knockout mediated axonal regeneration
Authors: Fischer Dietmar 
Published: December 2019

AbstractKnockout of phosphatase and tensin homolog (PTEN‐/‐) is neuroprotective and promotes axon regeneration in mature neurons. Elevation and maintenance of mTOR activity in injured neurons have been proposed as the main underlying mechanism. Here we demonstrate that PTEN‐/‐ also abrogates the inhibitory activity of GSK3 on collapsin response mediator protein 2 (CRMP2) in retinal ganglion cell (RGC) axons. Moreover, maintenance of GSK3 activity in GSK3S/A knockin mice significantly compromised PTEN‐/‐‐mediated optic nerve regeneration as well as the activity of CRMP2, and to a lesser extent, mTOR. These GSK3S/A mediated negative effects on regeneration were rescued by viral expression of constitutively active CRMP2T/A, despite decreased mTOR activation. GSK3S/A knockin or CRMP2 inhibition also decreased PTEN‐/‐ mediated neurite growth of RGCs in culture and disinhibition towards CNS myelin. Thus, the GSK3/CRMP2 pathway is essential for PTEN‐/‐ mediated axon regeneration. These new mechanistic insights may help to find novel strategies to promote axon regeneration
Corneal transparency restoration by gene therapy
Authors: Mohan Rajiv R. 
Published: December 2019

AbstractLoss of corneal transparency after trauma, injury or infection results in blindness. Compromised wound healing because of excessive production of myofibroblasts has been identified a major mechanism for the loss of corneal transparency. We tested a hypothesis that de‐differentiation of corneal myofibroblast into precursor corneal stromal fibroblast by silencing of MyoD (basic helix‐loop‐helix) gene will restore corneal transparency by inhibiting alpha smooth muscle actin (αSMA) transcriptional machinery responsible for myofibroblast production. To test the hypothesis, donor human corneas, human corneal stromal fibroblasts (CSFs) and myofibroblasts (CMFs), MyoD/scrambled‐RNAi plasmids, nanoparticles, immunofluorescence, western blotting, qPCR, 2D/3D confocal microscopy, and slot blots were used. The fibrotic human corneas showed significantly greater MyoD expression compared to the normal human cornea (p < 0.05). Likewise, CMFs showed markedly increased MyoD compared to the CSFs in vitro (p < 0.01). The MyoD‐RNAi or scrambled‐RNAi delivery into CSFs and CMFs did not alter their appearance, viability, or proliferation in normal culture conditions. MyoD‐RNAi delivery into CMFs led to phenotype similar to CSFs in a time‐dependent manner. Furthermore, MyoD‐RNAi silencing in CMFs demonstrated significantly deceased αSMA mRNA and protein levels in a time‐dependent manner (p < 0.001). MyoD gene silencing is a novel approach for the restoration of corneal transparency by promoting de‐differentiation of opaque corneal myofibroblasts to transparent corneal keratocytes.
OCT‐RNF and GCC in hereditary glaucoma
Authors: Vitovska Oksana , Kurilina Olena 
Published: December 2019

AbstractGlaucoma takes the leading place as the cause of blindness in Ukraine (19.3%).The level of incidence is higher among urban population (coefficient > 1.2), and among disabled person (coefficient > 2.2) in 70.4% of regions. Relative risk of glaucoma was high in male (RR = 1.49, p < 0.01); increasing with age (RR = 1.18) and reaches maximum rate in the age over 70 yo (RR = 7.11, p < 0.01).It was determined that hereditary factor is more manifested among female (RR = 10.90, p < 0.001), vs male (RR = 5.69, p < 0.05). Blood group is associated with glaucoma: male – B (III) (RR = 1.67) and AB (IV) (RR = 1.44); female – AB (IV) (RR = 1.78) and A (II) (RR = 1.65).PurposeTo investigate characteristics and patterns of progressive macular GCC layer thinning in patients with a family history of the disease.Material72 eyes of 36 patients with hereditary pre‐perimetric stage of glaucoma. Follow up was up to 3 years.MethodsMacular Ganglion cell complex (GCC) and ganglion cell inner plexiform layer (GCIPL) and VF were performed every 6 month. Spatial characteristics of progressive GCIPL thinning was evaluated by the thickness changes and pattern – by comparing the baseline and final GCIPL thickness change map.ResultsIt was determined VF and GCIPL progression at the 28 eyes (38.8%). The deterioration of GCIPL thickness started earlier (8.3 ± 7.8 months) than in VF (31.5 ± 9.1 months).ConclusionOCT is promising method of early glaucoma detection. Progression of GCIPL thinning occurred before VF progression.
Diagnostic clues in keratoconus. Scheimpflug is better?
Authors: Kovács Illés 
Published: December 2019

AbstractAlthough the identification of early forms of keratoconus during refractive screening would probably be the most appropriate method to prevent postoperative ectasia, the detection of this preclinical stage often pose challenges to clinicians. Moreover, for any tomographic or topographic parameter a significant overlap exists between keratoconus suspects and normal eyes resulting in lower sensitivity and specificity in identifying corneas with mild ectasia compared to detecting keratoconus. In this lecture, we describe the topographic and tomographic characteristics of preclinical keratoconus in paralell with the comparison of the accuracy of different paramateres in discriminating normal corneas from eyes with early keratoconus.
Assessing colour vision in the clinic: when is it useful and could we do better
Authors: Plant Gordon 
Published: December 2019

AbstractMost Ophthalmology and Neurology clinics have a few tests of colour vision available: Ishihara plates and tests for colour desaturation are the most commonly used. In this presentation I will explore how the clinician can get more from the Ishihara plates with an understanding of how they are constructed. I will also discuss the more elaborate tests such as the Farnsworth Munsell 100 Hue test and explain when these can be useful in diagnosis and management of patients.
Corneal recurrent erosions dystrophies in Sweden
Authors: Byström Berit 
Published: December 2019

AbstractCorneal dystrophies are a heterogeneous group of genetic disorders. We aimed to identify genetic cause of a dominantly inherited Epithelial Recurrent Erosion Dystrophy (ERED)‐like disease common in Northern Sweden. Examinations and interviews were performed at the Ophthalmology Clinics of the University Hospital of Umeå and Skellefteå Hospital. A total of 20 patients from Västerbotten were extensively examined and blood samples for genetic analysis collected. Four unrelated families were subject to genealogical studies. Known genes causative of corneal dystrophies were excluded by array‐based allele specific primer extension. Haplotype assessment was done by array genotyping and identification of potentially causative genomic variants by whole exome sequencing (WES). The dystrophy common in Västerbotten has three phases; recurrent erosions during childhood, alleviated symptoms in the higher teens and finally, after the age 40, decreased visual acuity. Haplotype analysis and WES revealed a novel mutation, c.2816C>T, p.T939I, in the COL17A1 gene coding collagen type XVII alpha1. It appeared to be a founder mutation that segregated with disease in a genealogically expanded pedigree dating back 200 years to a common ancestor, Theodor. Notably, the patients called the disease ‘Theodor's eyes’, but Theodor being unknown to them. Furthermore, COL17A1 expression in cornea was demonstrated by RT‐PCR and immunohistochemistry. We identified COL17A1 mutation as a cause of ERED, revealing a novel corneal disease in Sweden, and highlighting the necessity of COL17A1 screening in corneal dystrophies with erosions and no known genetic defect. Our genealogical analysis identified a common ancestor, Theodor, living 200 years ago.
Longitudinal data of static and dynamic retinal vessel parameters
Authors: Heitmar Rebekka 
Published: December 2019

AbstractThis presentation will provide a brief overview of the literature and will present some case data on longitudinal studies assessing static and dynamic retinal vessel parameters. To date, there is a vast amount of data published highlighting the clinical potential of static retinal vessel measurements. Structural retinal vessel changes such as arteriolar narrowing and venular dilation have been suggested to be useful for cardiovascular risk prediction and monitoring disease progression in diabetic patients. However, while there is a standardised analysis approach there is still a lack of long‐term data to date. In addition to the lack of long‐term data, static analysis provides only a snapshot image of the retinal superficial vasculature and does not provide any insight into the vessel dynamics. Vessel pulsatility, dilation and constriction due to stimulation by flicker light or other interventions however allows for a better understanding of the functional aspects. Current publications indicate alterations in vessel pulsatility and reactivity (dilation and constriction) in patients suffering from systemic and ocular vascular conditions.
Which irradiation technique for which ocular tumor
Authors: Thariat Juliette 
Published: December 2019

AbstractIn ocular oncology, the choice of the radiotherapy modality depends on tumor location (with respect to surface) and extent, tumor radioresistance (a biological characteristic that determines the dose needed to eradicate the tumor), and radiosensitivity (which translates in toxicities) of nearby critical structures. Radiotherapy has increasingly been used over years as a conservative approach to avoid enucleation. The aim of radiotherapy is to cure the tumor while minimizing toxicities and preserving visual function. Definitive high‐dose proton therapy or brachytherapy (with plaques loaded with radioactive elements) are appropriate techniques for uveal melanomas; 5‐year local control rates are in the order of 95%. Malignant tumors of the bulbar conjunctiva can be treated with a combination of no‐touch surgery, topical chemotherapies and intermediate‐dose proton therapy or brachytherapy. Conjunctival mucosal‐associated lymphoid tissue lymphoma can be treated with definitive low‐dose external beam X‐ray radiotherapy. Conventional external beam X‐ray radiotherapy is often sufficient for choroidal metastases to achieve tumor control and restore vision at doses that are little toxic to ocular structures. Palpebral carcinomas.
Autoimmunity and glaucoma
Authors: Grus Franz 
Published: December 2019

AbstractSeveral clinical studies were able to demonstrate alterations in the abundances of various autoantibodies in individuals with glaucoma. Interestingly, these changes in serum antibody profiles of glaucoma patients are stable among different study populations and differ between the different glaucoma subtypes. Thereby, not only antibodies with a higher concentration but also such with a lower level in glaucoma patients in comparison to healthy individuals have been observed. Of particular interest here are the low abundant antibodies present in glaucoma patients since they display neuroprotective properties in vitro and in glaucoma animal model, and could hold a hitherto unused therapeutic potential. Although glaucoma is not considered a classical autoimmune disease, these changes in antibody profiles hold an enormous diagnostic potential based on autoimmune biomarkers and could additionally open up new therapeutic options.
Ex vivo bovine retinal models to study intravitreal mobility and inner limiting membrane penetration of nanomedicines
Authors: Remaut Katrien 
Published: December 2019

AbstractSeveral viral and non‐viral nanoparticles aim to deliver therapeutics such as proteins or nucleic acids to the back of the eye, to halt or slow down retinal cell death. To reach the retinal cell types, intravitreal or subretinal injections are performed. Intravitreal (IVT) injection delivers the therapeutics into the vitreous, from where they need to diffuse to the back of the eye and cross the Inner Limiting Membrane (ILM) to reach the retinal cells. IVT injected therapeutics and nanoparticles might suffer, however, from a limited mobility and penetration through the vitreoretinal (VR) interface (e.g. vitreous and ILM), hampering their efficiency. We recently developed two ex vivo bovine eye models that are suitable to study the barrier role of the vitreoretinal interface. The IVT Mobility Model allows to measure the mobility of fluorescent nanoparticles in intact vitreous on a single‐particle level by tracking their movement by fluorescent Single Particle Tracking. In the VR explant Model, penetration over the ILM is studied in a bovine ex vivo retinal explant with the vitreous still attached. In regular ex vivo explants, the removal of vitreous distorts the ILM, making the explant unsuited for penetration studies. With the VR explant, however, the crossing of IVT injected material over the intact ILM and the penetration depth into retinal cell layers can be determined. Both models were applied to study the potential of intravitreal injected mRNA lipoplexes, where we found good mobility in the vitreous but limited crossing of the ILM after IVT injection. This most likely explains the low in vivo expression obtained after IVT injection of mRNA nanoparticles in mice, while expression was found in vivo after subretinal injection.
Placebo response in phase 2 and 3 trials of systemic and biological therapies for atopic dermatitis—a systematic review and meta‐analysis
Authors: Andreasen T.H. , Christensen M.O. , Halling A.‐S. , Egeberg A. , Thyssen J.P. 
Published: December 2019

AbstractA growing number of clinical trials of biological and systemic therapies have been conducted within adult atopic dermatitis (AD). No study has yet examined and meta‐analysed the pooled placebo response in AD. We performed a systematic review and meta‐analysis to examine the placebo response in clinical trials evaluating the effect of systemic and biological therapies in adult AD and compared it to results from clinical trials in psoriasis. Two screeners independently searched the databases ClinicalTrials.gov, Embase, Pubmed and Web of Science. A total of 2058 articles were identified, of which 78 were full‐text reviewed. Overall, 25 trials were included in the qualitative analysis, of which 24 were further included in the quantitative analysis. At 12‐week follow‐up, EASI50, EASI75 and EASI90 placebo responses were 39.9% [95% confidence interval (CI), 36.7–43.2], 20.9% (95% CI, 18.2–23.8) and 9.0% (95% CI, 6.7–11.6), respectively. At week 12, the pooled proportion of placebo‐treated AD patients that obtained EASI50, EASI75 and EASI90 was significantly higher than the pooled proportion of placebo‐treated psoriasis patients obtaining PASI50, PASI75 and PASI90 (P < 0.05). Our findings emphasize the fluctuating nature of AD and show that correct and consistent use of topical treatments strongly reduces disease severity.
Neurodevelopmental profile of siblings with Angelman syndrome due to pathogenic UBE3A variants
Authors: Sadhwani A. , Willen J. M. , Miller H. , Barbieri‐Welge R. , Horowitz L. T. , Noll L. M. , Peters S. , Hundley R. , Bird L. M. , Tan W. H. 
Published: December 2019

AbstractBackgroundAngelman syndrome (AS) is a neurodevelopmental disorder caused by a lack of expression of the maternally inherited UBE3A gene on chromosome 15. Individuals with AS due to a UBE3A mutation are more likely to have siblings who also have AS compared with those with AS due to other cytogenetic/molecular mechanisms, but it is unknown whether the developmental outcome of siblings who have AS is similar.MethodsThrough an ongoing AS Natural History Study, we identified seven pairs of siblings with AS due to a UBE3A mutation. We compared the neurodevelopment of the first‐born and second‐born siblings with AS participants who have a UBE3A mutation and have either typically developing siblings or no siblings.ResultsSecond‐born AS participants due to a UBE3A mutation were more likely to be diagnosed at an earlier age. With the exception of higher expressive language scores among the second‐born participants, no other differences were observed in the developmental and adaptive functioning skills across the different groups.ConclusionsThe presence of an older sibling with the same neurodevelopmental disorder is associated with an earlier age of diagnosis and may be associated with an improvement in expressive language skills; the developmental outcome of siblings with AS due to a UBE3A mutation is otherwise comparable.
Development of the empowerment scale for family caregivers of community‐dwelling people with dementia in Japan
Authors: Sakanashi Sayori , Fujita Kimie 
Published: December 2019

AbstractAimThis study aimed to develop the empowerment scale for family caregivers of community‐dwelling people with dementia (PWD) in Japan (EFCD) and to validate the scale.MethodsThe questionnaires were mailed to 820 family caregivers of PWD. The first version of the EFCD based on interviews with family caregivers and elderly care specialists and content validity results was tested. Participants also completed the Revised Scale for Caregiving Self‐Efficacy and the General Health Questionnaire. For the EFCD development procedure, construct validity was evaluated by item analysis and exploratory factor analysis. Criterion validity was tested using Spearman's correlations between scores of the three scales. Reliability was evaluated using Cronbach's alpha, intraclass correlation coefficients (ICC), and Bland and Altman analysis. The final model was verified by confirmatory factor analysis.ResultsData from 304 family caregivers were analyzed. Exploratory factor analysis identified a 16‐item, four‐factor structure for the final version of the EFCD, as follows: (a) Excellent Practice in Dementia Care; (b) Understanding the Essence of Dementia Care; (c) Caring for Oneself as well as for the Person with Dementia; and (d) Having Peers with Shared Support Activities. Reliability and validity of the scale was established using the methods described.ConclusionsThe developed EFCD is a reliable and valid measure that provides a simple assessment of empowerment among family caregivers of PWD.