bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mesenchymal stromal cell therapy to modulate corneal allograft rejection: From bench to bedside
Authors: Ritter Thomas 
Published: December 2022

AbstractCornea transplantation has been a target for mesenchymal stromal cell (MSC) therapy for several years with a number of publications highlighting the therapeutic potential and mechanism of action of these cells. It is widely known that MSC possess potent anti‐inflammatory capabilities and are able to modulate the activity of a wide array of immune cells including T cells, B cells, dendritic cells and macrophages. This modulation occurs through both cell–cell contact and the paracrine release of soluble factors such as nitric oxide and prostaglandin E2.Although the mechanism of MSC‐mediated immunomodulation following intravenous administration (i.v.) remains to be fully elucidated, it is evident that the lung (where the majority of MSCs become trapped and are subsequently cleared within 24 hours) plays an important role. Our group and others have reported that MSCs enrich innate immune regulatory cells in the lung following i.v. administration.Previous results from our laboratory have demonstrated the efficacy of pre‐transplant infusion of allogeneic (allo) but not autologous (auto) MSC in a fully allogeneic, MHC‐mismatched rat model of cornea transplantation. This suggests that in our previous work the expression of allo‐antigen by allo‐MSCs provides a priming stimulus that enhances their immune modulatory effects while auto‐MSCs administered to an immunologically compatible non‐inflamed (pre‐transplantation) host did not receive the required priming stimulus. We hypothesized that pre‐emptive priming (“licensing”) of auto‐MSC could overcome the lack of efficacy in preventing cornea transplantation rejection by better promoting regulatory innate and adaptive immune cells. We demonstrate that auto‐MSCs administered post‐operatively promote rejection free graft survival upon licensing with a cocktail of pro‐ or anti‐inflammatory cytokines. Interestingly, while the different licensing strategies promote corneal allograft survival in rodents overall, the mechanisms of action appear to be different how these licensed MSC operate in vivo. Finally, the potential of extracellular vesicles secreted from licensed MSC as potential cell‐free therapy will also be discussed.This work contributes to the growing body of literature highlighting the fact that MSC require a pre‐activation stimulus in order to be therapeutically active and the importance of.regulatory cells in mediating MSCs immunomodulatory function.Funding received for this work.This work was supported by Science Foundation Ireland (12/IA/1624), by a grant from the European Commission [FP7 Collaborative Health Project VISICORT (grant number 602470), www.visicort.eu], by infrastructural funds from the European Regional Development Fund and by the European Union's Horizon 2020 research and innovation programme under grant agreement no. 814439.Keywords: corneal transplantation, mesenchymal stromal cells, licensing, cytokines, immunomodulation, regulatory cells.
Loss of colour vision in patients at risk of developing diabetes
Authors: Rodriguez‐Carmona Marisa , Bastaki Qais , Barbur John L. 
Published: December 2022

AbstractRecent studies carried out in diabetic patients with no more than moderate maculopathy revealed that over 70% had significant losses of both Yellow/Blue (YB) and Red/Green (RG) colour vision (https://doi.org/10.1111/j.1755-3768.2012.F073.x). The purpose of this study was to investigate whether clinically ‘normal’ subjects, identified as being at ‘risk’ of developing diabetes show significant changes in rod‐ and cone‐mediated rapid flicker sensitivity as well as RG and YB colour vision.Three groups of subjects were recruited; a normal subject group (n = 40), a ‘high‐risk’ group (n = 150) and subjects diagnosed with diabetes (n = 23). The inclusion criteria for ‘high‐risk’ group required 3 or more recognized risk factors for diabetes (e.g., age > 45, HbA1C >5.7, high blood pressure, smoking history, high BMI, family history of diabetes, FPG levels >100 mg/dL). All subjects had full ophthalmic assessment and their RG and YB colour vision, Functional Contrast Sensitivity (FCS), Visual Acuity (VA) and Rod‐ and Cone‐mediated flicker sensitivity were measured using AVOT tests (https://researchcentres.city.ac.uk/applied-vision/avot).Consistent with previous findings, the diabetic group show significant loss of both RG and YB colour vision. Our findings show that these subjects also exhibit higher thresholds for rod and cone mediated vision. In addition, the ‘high‐risk’ group who are clinically classified as ‘normal’, also show significant loss of colour vision and rod and cone sensitivity. The latter group, do not, however, show significant differences in either VA or FCS. These findings suggest that accurate assessment of colour vision and rod‐ and cone‐ mediated rapid flicker sensitivity qualify as important risk factors in prediabetic screening.
Potential challenges in AI application in the clinical setting
Authors: Schmetterer Leopold 
Published: December 2022

AbstractArtificial intelligence (AI) solutions have attracted much interests in ophthalmology. Whereas multiple papers have been published the translation to clinical ophthalmology is challenging. The present talk will summarize five key elements that hamper translation. 1. Applicability of AI solutions to external real world datasets. Convolutional neural networks (CNNs) may fail if they were trained on datasets that do not match the target population in terms of ethnicity, age, disease severity and/or diagnostic criteria. 2. Burden of false negatives and false positives. Although the Area under the Curve (AUC) for detection of disease is often high, the application of the CNN still results in many false positives due to the low prevalence. In addition, false security is feigned in false negatives. 3. Inadequate facilities. Whereas CNNs have often been proposed for screening, the screening facilities are frequently not in place. Establishing a screening facility is expensive and requires support from health care providers. 4. Inadequate image quality. Even the best CNN does not perform well if image quality is insufficient. Continuous training and quality control is an expensive task for achieving optimal results. 5. Human interaction studies. Little is known to which degree AI based solutions will be accepted by health care providers and by patients.
Unilateral corneal insult also alters sensory nerve activity in the contralateral eye
Authors: Acosta M. Carmen 
Published: December 2022

AbstractWhen the ocular surface of one eye is inflamed or injured, its corneal sensory nerve activity is modified, which in turn evokes ocular discomfort, irritation, and pain sensations referred to the affected eye. Some patients with unilateral ocular inflammation, infection, or surgery also report discomfort and pain in the contralateral eye. Are these sensations experienced at the fellow eye due to alterations of its sensory nerve activity?To test this hypothesis, we recorded in vitro the activity of corneal mechanonociceptor, polymodal nociceptor and cold thermoreceptor nerves of both eyes of guinea pigs previously subjected unilaterally to three different experimental inflammatory and lesion conditions: UV‐induced photokeratitis, microkeratome corneal surgery, and chronic tear deficiency caused by removal of the main lacrimal gland. Recordings from the eyes of naïve animals were used as control.Compared with the naïve guinea pigs, animals subjected to unilateral UV‐induced mild corneal inflammation, showed inhibition of the spontaneous and stimulus‐evoked activity of cold thermoreceptors, and increased activity (sensitization) of nociceptors affecting both the ipsilateral and the contralateral eye. Unilateral microkeratome surgery affected the activity of nociceptors mostly, inducing sensitization in both eyes. Chronic eye dryness by removal of the main lacrimal gland increased cold thermoreceptor activity in both eyes. These results show that after unilateral eye damage, corneal sensory nerve activity is altered in both eyes, although to a lesser degree in the contralateral eye.This is the first direct demonstration that unilateral corneal nerve insult, and especially ocular surface inflammation, functionally affects the activity of the different types of corneal sensory nerves in both the ipsilateral and contralateral eyes. The mechanisms underlying the changes of contralateral sensory nerve activity remain to be determined, although available data support the involvement of the immune system. The present results have two main implications: (a) contralateral eyes cannot be considered as a control in experimental designs of both preclinical and clinical studies; and, (b) clinicians must consider the convenience of treating both eyes of patients with unilateral ocular conditions to avoid pain and secondary undesirable effects in the fellow eye.
Contralateral inflammatory effects on the trigeminal ganglion after unilateral corneal lesion
Authors: Ferrari Giulio 
Published: December 2022

AbstractThe purpose of this study was to test whether a corneal injury can stimulate inflammation in the trigeminal ganglion (TG) located (i) on the same side, or (ii) on the opposite site of a cornea alkali burn.Following monolateral administration of a corneal alkali burn, we performed in vivo magnetic resonance imaging (MRI) of the brain before and after ultrasmall superparamagnetic iron oxide nanoparticle (USPIO) contrast to track macrophages. Trigeminal ganglia were stained for Prussian Blue and inflammatory cell markers. Moreover, the tissue levels of pro‐inflammatory cytokines Interleukin‐1β, TNF‐α, and VEGF were quantified on days 1, 4, and 8, and 4 days after corneal topical anti‐inflammatory treatment with 0.2% dexamethasone. The expression of Substance P and its receptor NK‐1R was measured in the TG on day 4.Corneal alkali burn induced leukocyte infiltration, including T cells, in the right TG at 4 and 8 days. In vivo MRI showed an increased contrast uptake in the right TG, which peaked at day 8. Prussian Blue(+) USPIO(+) macrophages were observed in the right TG and exhibited an M2 phenotype. The M2‐macrophage infiltration was preponderant in the TG after damage. The proinflammatory cytokines Substance P and NK‐1R were significantly increased in both the TGs. The expression of IL‐1β and VEGF‐A was significantly reduced in the right TG with dexamethasone treatment.Our data support: (i) bilateral onset of inflammation in the TG following ocular surface damage; (ii) involvement of the neuropeptide Substance P in the propagation of inflammation from the cornea to the TG through corneal nerves.
Shedding light on myopia by studying complete congenital stationary night blindness
Authors: Zeitz Christina , Roger Jerome E. , Michiels Christelle , Sánchez‐Farías Nuria , Varin Juliette , Frederiksen Helen , Wilmet Baptiste , Gimenez Marie‐Laure , Bouzidi Nassima , Blond Frederic , Guilllonneau Xavier , Léveillard Thierry , Sahel José‐Alain , Picaud Serge , Audo Isabelle 
Published: December 2022

AbstractPurpose: Myopia is the most common eye disorder, caused by heterogeneous genetic and environmental factors. Rare inherited retinal disorders are often associated with high myopia. Genes implicated in myopia encode proteins involved in eye morphogenesis, extracellular matrix organization, visual perception, circadian rhythms, and retinal signalling. Differentially expressed genes (DEGs) identified in animal models mimicking myopia are helpful in suggesting candidate genes implicated in human myopia. Complete congenital stationary night blindness (cCSNB) in humans and animal models represents an ON‐bipolar cell signal transmission defect and is also associated with high myopia. The purpose of this work was to identify the molecular cause of myopia present in cCSNB.Methods: A whole transcriptome sequencing (RNA‐seq) approach was performed using retina from three mouse lines with cCSNB, Gpr179−/−, Lrit3−/− and Grm6−/− and the expression data compared to data of age‐matched wild‐type littermates (n = 5). DEGs with fold changes of at least 1.2, p‐values of ≤0.01, an expression value of at least 5 transcripts per million reads and appearing in at least two cCSNB mouse lines were investigated in detail. A meta‐analysis was performed by (a) comparing our data with published transcriptome data from purified retinal cells and single cell RNA‐Seq data, (b) pathway analyses, (c) myopia databases and publications concerning their role in normal vision. Several of the DEGs were validated by RT‐qPCR experiments and analysed by western blot and immunolocalization studies.Results: More than 50 DEGs were found in at least two cCSNB mouse lines. Expression of those was found in different retinal cell types. The difference in expression was independent of the number of nuclei present in wild‐type and mutant inner retina. Pathway analysis revealed that mitogen‐activated protein kinase pathways, synaptic signalling, G protein‐coupled receptor ligand binding pathways, and proteins implicated in eye, endoderm and connective tissue development were affected in cCSNB. More than half of the genes were already associated with myopia.Conclusions: Our study reveals DEGs in all retinal cell types of cCSNB models, previously associated with myopia and novel candidates. These studies combined with pathway analyses provide the basis for the development of pharmacological and optical myopia therapies.
Ocular blood flow and myopia
Authors: Świątczak Barbara 
Published: December 2022

AbstractPurpose: It has previously been found that imposing positive defocus changes axial length and choroidal thickness after only 30 minutes. In the present study, we investigated whether these changes may result from an altered choroidal blood flow.Methods: Eighteen young adult subjects watched a movie from a large screen (65 inch) in a dark room at 2 m distance. A fifteen‐minute wash‐out period was followed by 30 minutes of watching the movie with a monocular positive defocus (+2.5D). Changes in axial length and ocular blood flow were measured before and after the defocus, by using low‐coherent interferometer (LS 900, Haag‐Streit, Switzerland) and a laser speckle flowgraphy (LSFG) RetFlow unit (Nidek Co., LTD, Japan), respectively. Three regions were analysed: (1) the macular area, where choroidal blood flow can be measured, (2) the optic nerve head (ONH), and (3) retinal vessel segments.Results: Changes in choroidal blood flow were significantly and negatively correlated with changes in axial length that followed positive defocus in exposed eyes (R = −0.67, p < 0.01). The absolute values of changes in choroidal blood flow in the defocused eyes were significantly larger than in the fellow control eyes. ONH and retinal blood flow were not associated with the induced changes in axial length.Conclusions: Positive defocus selectively alters choroidal, but not retinal or ONH blood flow in young human subjects after short‐term visual exposure. The results suggest that blood flow modulation is involved in the mechanism of choroidal responses to optical defocus.
Insights into myopia gleaned from retinal electrophysiology
Authors: Mahroo Omar A. , Jiang Xiaofan , Xu Zihe , Hammond Christopher J. , Hysi Pirro G. 
Published: December 2022

AbstractThe prevalence of myopia is increasing dramatically. Retinal signalling controls eye growth and a retinal myopia‐signalling cascade has been postulated. One of the strongest genetic associations with myopia susceptibility is a locus near the GJD2 gene which codes for a protein forming gap junctions in the retina. We explored whether any parameters of retinal electrophysiology were associated with presence of the risk allele. Full‐field scotopic and photopic electroretinogram (ERG) recording was performed in over 200 healthy volunteers from the TwinsUK cohort. Responses were elicited by stimuli conforming to international standard protocols and additional experimental protocols aimed at isolating rod and cone system responses. The majority of participants had been genotyped previously for their identity at the relevant locus. A mixed linear model was employed with ERG parameters (amplitudes and peak times) as outcomes and allelic dosage at the relevant locus as a predictor, adjusting for age, sex and inter‐individual relatedness. ERG recordings and genotype data were available for the majority of participants (95% female; mean (SD) age 64.2 (9.7) years). Light adapted single‐flash a‐waves and b‐waves associated significantly with allelic identity at the locus of interest. None of the standard dark‐adapted ERG parameters associated significantly with genotype at this locus. Further investigation of responses to experimental protocols, and those obtained from patients with loss of ON or both ON and OFF bipolar cell responses, suggested changes specific to the cone‐driven OFF pathway. The findings suggest associations between photopic cone‐driven retinal electrophysiological signalling and one of the genetic polymorphisms most strongly linked to myopia. Higher environmental light levels are known to be protective in myopia, and our results support the hypothesis that changes in light‐adapted cone system signalling might play a role in myopia development.
Genetics of myopia: Gene finding and beyond
Authors: Haarman A. E. G. , Tedja M. S. ,   The Erasmus MC Myopia Research Group,   Consortium of Refractive Error, Myopia (CREAM), Verhoeven V. J. M. , Klaver C. C. W. 
Published: December 2022

AbstractThe knowledge on the genetic background of refractive error and myopia has expanded dramatically in the past few years. To date, over 500 genetic loci have been identified for refractive error and myopia, and risk variants mostly carry low risk but are highly prevalent in the general population. Several genes for secondary syndromic myopia overlap with those for common myopia. Polygenic risk scores show overrepresentation of high myopia in the higher deciles of risk. However, also patients with low scores can develop myopia and vice versa. Annotated genes have a wide variety of functions, and all retinal layers appear to be sites of expression. The current genetic findings offer a world of new molecules involved in myopiagenesis. As the missing heritability is still large, further genetic advances including large‐scale, in‐depth genetic studies using complementary big data analytics, consideration of gene–environment effects by thorough measurement of environmental exposures, and focus on subgroups with extreme phenotypes and high familial occurrence are needed. Functional characterization of associated variants is simultaneously needed to bridge the knowledge gap between sequence variance and consequence for eye growth.
A new inverted meniscus IOL to improve peripheral vision
Authors: Artal Pablo 
Published: December 2022

AbstractThe optical quality of the images formed by the eye in the retina imposes a physical limit to our vision. For decades, the eye's optics has been mainly studied on axis, typically at the fovea where the eye has its maximum spatial resolution. However, beyond the fovea, the quality of the eye in the periphery of the retina presents special characteristics. It was discovered that the crystalline lens have a protective effect for the peripheral optics that was missed after cataract surgery when intraocular lenses were implanted. In this talk, I will revise the state of the art of this area with special emphasis in the results of my lab including the design and clinical result of a new intraocular lens with an inverted meniscus shape to improve peripheral optics in pseudophakic patients.
Customized asphericity for increased depth of focus
Authors: Yago Ines 
Published: December 2022

AbstractIn this presentation, I will revise the visual performance at different distances of a binocular combination of two models of a new inverted meniscus intraocular lens (IOL), Art40 and Art70 (ArtIOLs, Voptica SL, Murcia, Spain) which induce different amounts of negative spherical aberration to increase the depth of focus. This combination significantly extended the depth of focus up to at least 40 cm improving visual performance at intermediate distance in comparison with trifocal LIOs. This resulted in spectacle independence for the patients without the compromise of halos or disphotopsias.
Options and considerations for the correction of presbyopia in the absence of cataract
Authors: Reinstein Dan Z. 
Published: December 2022

AbstractPRESBYOND Laser Blended Vision is a treatment option for presbyopic patients that combines micro‐anisometropia with increased depth of field through non‐linear aspheric ablation profiles. This technique substantially improves visual outcomes in comparison with the conventional monovision approach. Trials show that PRESBYOND is effective in presbyopic patients with refractive errors between +5.75 and −9.00 D, including emmetropic presbyopes. With the safety advantages of modern femtosecond LASIK, retention of functional stereo acuity, contrast sensitivity and quality of vision, the rapid bilateral surgical procedure and a recovery time of a few hours, patient satisfaction is extremely high. In patients with no visually significant cataract, performing a corneal treatment avoids the increased risks associated with intraocular surgery, particularly risks that are relatively higher in younger presbyopic patients such as retinal detachment.
Innovative approaches to measuring intraocular pressure
Authors: Royo Maria Jesús Muniesa 
Published: December 2022

AbstractAlthough different factors have been implicated in the development and progression of glaucoma, intraocular pressure (IOP) remains the main modifiable risk factor. Goldmann applanation tonometer (GAT) considers the “gold standard” for measuring IOP. The main deficiency of GAT, however, is the static nature of its measurements and that it is dependent on corneal biomechanics, central corneal thickness as well as scleral stiffness. The single measurement of IOP for the management of glaucoma provides limited information since it does not take into account the natural fluctuation of IOP, individual ranges, IOP peaks or variations throughout the day. Although the role of IOP fluctuations in glaucoma progression is not clearly defined, there is consensus on the importance of understanding the circadian profiles of IOP in glaucoma patients. Given the limitations of GAT for the actual measurement of IOP, different tonometers have been designed with the aim of advancing in self‐tonometry as Icare HOME, or obtaining independent measurements of corneal biomechanics, as Ocular Response Analyser (ORA), Pascal dynamic contour tonometer or the Corvis ST tonometer. Research to monitor IOP is based on three different strategies: (1) self‐tonometry; (2) permanent monitoring of the IOP; and (3) the temporary monitoring of the IOP. Currently, the sensors in contact lenses allow the IOP profiles to be recorded semi‐continuously for 24 hours with a minimally invasive technique, independent of the patient's position and the activity performed, opening new perspectives in the knowledge and management of glaucoma.