bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genetics of keratoconus; how realistic is gene therapy?
Authors: Anogeianakis George 
Published: December 2022

AbstractKeratoconus (KC) is a complex, non‐inflammatory eye condition that impairs the focusing ability of the eye by progressively thinning and distorting the cornea. Its causes remain elusive, as it is a genetically heterogeneous, multifactorial degenerative disorder. KC follows an autosomal (either recessive or dominant) pattern of inheritance and is associated with genes which interact with environmental, genetic and/or other factors.At present, the only fairly reliable treatment that slows down the progression of KC is cornea collagen cross‐linking. In extreme cases a corneal transplant may be required. This fact alone makes gene therapy for KC, a promising therapeutic approach. Such hopes are bolstered by the biophysical properties of the corneal tissues which include the corneal immune privilege, the transparency of the corneal tissue together with its and ex vivo stability, and the uncomplicated operative approach to the eye anterior chamber. In addition, recent advances in vectors, along with the ability to modulate the corneal milieu in order to ensure a relatively long survival of the target gene and allow its successful translation, further bolster the hopes for successfully treating KC via gene therapy.Over the last two decades, however, genome‐wide association studies and studies on SNP and genetic loci identification have identified more than 50 genomic loci that are implicated in both the dysregulation of the corneal collagen matrix formation and maintenance or the cell differentiation pathways that sustain corneal integrity. Among the most prominent genes involved in KC are the VSX1 gene, which is involved, among others, in posterior polymorphous corneal dystrophy; the SOD1 gene which determines the effects of reactive oxygen species; the ZNF469 gene which is also involved in the Brittle Cornea Syndrome; the TGF8 pathway which is involved in the regulation of the extracellular matrix composition; the TGFI gene which plays a role in cell‐collagen interactions. The roles of the MicroRNAs (especially that of the miRNA 184) and of mitochondrial DNA must, also, be stressed. Recently, we bibliographically identified and documented 18 different KC symptoms and clinical signs and cross referenced them to 24 different genes/genetic loci. It turns out that each of these symptoms is associated with from between 3 and 14 identified KC genes. We similarly identified 49 diseases and/or syndromes that involve at least some of the KC‐implicated genes and cross‐referenced them to these 24 genes. Again, it turns out that each one of the 49 diseases/syndromes is associated with from between 1 and 23 KC‐implicated genes.The complex interrelations among the different biophysical and biochemical processes involved in KC, the multitude of related genomic loci, and the large number of comorbidities, collectively, they cast gene therapy in an unfavourable light as a realistic treatment option for KC., On the other hand, the possible identification of a pivotal role for only a handful of genes, may open the path for gene therapy in KC.
Retina‐brain structure functional correlations in health and neurological disorders
Authors: Castelo‐Branco Miguel 
Published: December 2022

AbstractIn spite of the appeal of using retinal markers as potential windows to study brain neurodevelopment and aging in health and disease, many challenges remain. Here we address the relative role of multimodal techniques in basic, translational and clinical research, in a set of neurodevelopmental and neurodegenerative disorders differentially affecting parallel visual pathways, from the retina to the cortex. It is important in this context also to take into account into which extent the retina is a mirror of the healthy aging brain across the lifespan.We then address the debate whether the nature of visual impairments in neurodegenerative and chronic disorders stem from the brain, the retina or both. This discussion is addressed from the structural (including connectivity), functional and neurochemical points of view.Finally, we also discuss the impact of acquired and genetic disorders of retinal origin on cortical structure and function, as well as the issue whether retinal phenotypes can be uncovered in disorders so far believed to have a specific cortical foundation.
Machine learning approaches using OCT
Authors: Bernardes Rui 
Published: December 2022

AbstractThe use of the retina as a window into the brain has been widely debated but is now gaining additional momentum with new insights into retinal changes based on new data processing techniques leading to the development of new biomarkers of retinal changes and their association with neurodegenerative disorders.With all the advantages of allowing the non‐invasive imaging of the CNS and the fact that ocular disorders share characteristics of other CNS diseases, this symposium will cover retina‐brain relationships in health and neurological disorders, in humans and animal models of disease, the use of texture biomarkers, and the use of machine learning and AI in this field.
Gut microbiome in retina health
Authors: Scuderi Gianluca 
Published: December 2022

AbstractThe term microbiome defines a complex ecosystem of microbial species colonizing our body, including their genome and the environment in which they live. Recent studies support the existence of a gut‐retina axis involved in the pathogenesis of several chronic progressive ocular diseases, including age‐related macular disorders. Understanding the role of the microbiome in ocular disorders may be crucial in driving the disease prevention and treatment approach. The presentation aims to offer an overview of the importance of the gut microbiome in relation to ocular health. More in detail, the gut microbiome will be characterized in terms of composition and functions. The role of gut microbiome dysbiosis will be discussed to understand the clinical and prognostic implications in the development or progression of retinal diseases. Moreover, the relationship between gut microbiome composition and retinal health will be examined in light of the recent evidence on the gut‐retina axis.
The anatomy of corneal nerves
Authors: Lagali Neil 
Published: December 2022

AbstractHere we review the latest findings elucidating the anatomy and organization of the corneal nerves, with a focus on the nature of the subbasal nerve plexus in humans, in both health and disease. The subbasal nerves are an important landmark for the study of corneal innervation, as these are the source of epithelial nerves and thus a surrogate marker for the health of the epithelium and the cornea. Across a range of disease states, these nerves are perturbed or lost due to degeneration, with specific patterns of corneal nerve change and loss being apparent. We will further review the latest techniques used to visualize and quantify the corneal nerves in humans, and examine the benefits and potential pitfalls of using in vivo confocal microscopy for the examination, quantification and assessment of corneal nerves in the clinic, for both eye disease and a range of systemic diseases.
Mast cells and their role in corneal neuroinflammation
Authors: Chauhan Sunil 
Published: December 2022

AbstractNerve damage following injury has been associated with impaired wound healing. We have previously shown that corneal injury leads to increased activation of ocular surface mast cells. Here, we investigated whether mast cells interact with corneal nerves and contribute to nerve degeneration and neuroinflammation by utilizing trigeminal ganglion‐mast cells (TG‐MCs) co‐culture system and a murine model of corneal injury. Corneas, harvested 6 hours post‐injury and immunostained with β‐tubulin III and avidin, demonstrated that ocular surface mast cells infiltrate into the injured cornea in close proximity to the damaged corneal nerves. Moreover, the corneal injury resulted in significant activation of TG mast cells and inflammation, as indicated by increased levels of tryptase, CD11b, and SubP (p < 0.01) in the lysates of ipsilateral trigeminal ganglions harvested 6 hours post‐injury compared to those from naïve mice.Furthermore, our in vitro data show that mast cells significantly promote neurite degeneration, as indicated by shorter lengths of neurites (p < 0.001) and upregulation of nerve activation markers SubP and CGRP by TGs (p < 0.01) co‐cultured with MCs, compared to TGs cultured alone. Lastly, pharmacological inhibition of ocular surface mast cell activation using cromolyn resulted in a significant decline in injury‐induced hyperalgesia, as shown by decreased eye wipes in cromolyn‐treated groups compared to the control group (p = 0.005). The current investigation on the neuro‐immune axis of mast cells and corneal nerves provides novel insights into the function of ocular surface mast cells in exacerbating nerve degeneration and promoting inflammation in the trigeminal ganglion.
Nerves, substance P and ocular surface inflammation
Authors: Ferrari Giulio 
Published: December 2022

AbstractCorneal nerves are instrumental to maintain cornea integrity through regulation of key physiological functions such as epithelial wound healing, tear secretion, blink reflex. Corneal nerve injury/stimulation is a common consequence of most ocular surface diseases/surgeries. Nerve disruption initiates a process named neurogenic inflammation which leads to edema, pain, and recruitment and activation of leukocytes. Interestingly, leukocyte influx in the cornea can further damage nerves by releasing inflammatory mediators‐including neuropeptides. The clinical outcome of neuroinflammation can be beneficial or detrimental to corneal integrity. On one side, it allows proper wound healing. On the other, prolonged and/or deranged neuroinflammation can permanently disrupt corneal integrity and impair vision. Substance P (SP), a peptide secreted by sensory nerves, is abundantly expressed I the cornea. SP exerts multiple biological activities, including promotion of cell migration, leukocyte activation and diapedesis, angiogenesis and pain, among others, which make it an ideal mediator of neuroinflammation in the cornea. Accumulating evidence suggests that modulation of SP activity is a promising therapeutic approach to treat signs (i.e. inflammation) and symptoms (i.e. pain) of highly prevalent diseases of the ocular surface.
Trabeculectomy complications and management
Authors: Diamond Jeremy P. 
Published: December 2022

AbstractTrabeculectomy complications can broadly be categorized by when they occur: per‐operative, early post‐operative or late post‐operative.Mr Diamond will discuss how to manage common per‐operative complications including conjunctival button‐holes and post‐operative complications including under and over‐drainage, hyphaema, shallow or flat anterior chamber, bleb leak, bleb dysesthesia and failure.
The VISICORT project: Lessons learned from solid organ transplantation
Authors: Griffin Matthew 
Published: December 2022

AbstractAims of the Presentation: (a) To summarize the rationale and research strategies for the VISICORT project. (b) To compare and contrast research approaches to understanding adverse immune responses to corneal and solid organ allo‐transplants.AbstractCorneal allo‐transplantation has been utilized for over 100 years to restore and improve vision in patients suffering from opacifying diseases of the cornea. Its development preceded that of solid organ transplantation and its worldwide frequency continues to exceed that of commonly‐transplanted organs including kidney, heart, liver and lung. The scope and success rates for corneal transplantation have evolved over time as a result of technical innovations, clinical practice developments and advances in eye banking. However, the impact of immunological complications, in particular acute rejection, on the long‐term functional survival of high‐risk corneal allografts has remained significant and the evidence base for specific immunosuppressive regimens to prevent rejection is limited. Strikingly, the large amount of elegant pre‐clinical research into the immunological response to corneal allografts has not been complemented by extensive studies of adverse immune responses in human recipients. Against this background, the VISICORT project was initiated in 2014 to bring together corneal transplant experts and investigators with expertise in solid organ transplantation, immunological profiling, proteomic analysis, regenerative therapies and biobanking to collaboratively address the challenge of better understanding adverse immune responses in human corneal transplantation.In this presentation, I will first summarize the strategies and designs for cross‐sectional and longitudinal clinical cohort studies of corneal allo‐transplant recipients at 5 European academic centres with collection of extensive clinical data and biological specimens including donor and recipient cornea, aqueous humour, tears, whole blood, serum, plasma and peripheral blood mononuclear cells. I will also describe the development of bespoke resources and protocols for the coordination of patient enrolment, data gathering and biospecimen processing, storage and transfer to a central biobank which underpinned the results to be described by other presenters in this session. Finally, I will discuss the extent to which the fields of corneal and solid organ transplantation have engaged in collaborative investigation prior to and during the course of the VISICORT project and reflect on the potential for such cross‐discipline research to advance towards the shared goal of preventing harmful allo‐immune responses and promoting donor‐specific tolerance.
Mr Ernest Maddox and his work
Authors: Ghazi‐Nouri Seyed 
Published: December 2022

AbstractBritish ophthalmologist Ernest Edmund Maddox (1860–1933) who made a great contribution in the field of refraction and strabismus. He was an inventor of several instruments: Maddox rod, Maddox wing test, double prism and cataract needles to name a few. He effectively created the field of Orthoptics and his daughter, Mary, was the first Orthoptist working in the UK.In this presentation the life and works of Ernest Maddox will be discussed.
Hispanic collyria seals in the Roman empire
Authors: Perez‐Cambrodì Rafael J. 
Published: December 2022

AbstractRoman seals associated with collyria (Latin expression for eye drops /washes and lotions for eye maintenance) provide valuable information about eye care in the antiquity. These small, usually stone‐made pieces bore engravings with the names of eye doctors and also the collyria used to treat eye diseases. The collyria seals have been found all over the Roman Empire and Celtic territories in particular and were usually associated with military camps. Thus, it seems that they were rather specific for doctors working in the Roman army.In Hispania (Iberian Peninsula), only three collyria seals have been found. These findings inform about eye care in this ancient Roman province as well as about of the life of the time. The main aim of this communication is to take a look at the morphological characteristics, the utilities and social significance of the collyria seals and seeks to give an insight through the ophthalmological practice in the Roman Empire.
The retinex of colour vision impairment
Authors: Plant Gordon T. 
Published: December 2022

AbstractThe concept of the “Retinex” was introduced by Edwin Land in 1962. The aim of his theory of colour vision was to highlight the observations on colour perception that were at odds with the simple “Newtonian” concept that the colours that humans perceive when viewing narrow band light are directly related to perceived colours in the environment. There are, however, two particular observations which are at odds with this simple interpretation of the colours seen in the “spectrum” of light. One was emphasized by Gӧethe in his colour theory: namely that there are a range of named colours that are influenced by the luminance contrast (e.g. brown which is a darkened orange) or closeness of the colour to white. This was explored by Chevreul, Munsell and others who developed systems of colour based on the three dimensions: hue (colour category), saturation (closeness to white) and value (brightness). The second was the observation studied extensively by Land: namely that colours remain constant across a certain range despite a change in the spectral content of the illuminant. Thus despite a change in the pattern of cone excitation the colour appearance does not change. Land also emphasized that this phenomenon is influenced by other colours in the scene and introduced the study of natural scenes with natural illumination rather than narrow band light in the laboratory.So in this context Land decided to refer to the “Retinex” as it was clear that the various processes were taking place both at the retinal and cortical levels. I am adopting this term in my talk because clinical studies provide an opportunity to study the influence of damage at all levels in the visual pathway on colour perception. Beginning with congenital colour anomalies affecting the cone opsins all the way to damage to extra‐striate visual cortex clinical studies, such as those presented in this symposium, alterations in colour vision provide an insight into how damage at various levels in the “Retinex” influence colour perception.
The role of microbiome in uveitis in experimental mice model
Authors: Heissigerova Jarmila , Dusek Otakar , Fajstova Alena , Klimova Aneta , Brichova Michaela , Svozilkova Petra , Kverka Miloslav 
Published: December 2022

AbstractUnlike the individual's genetic makeup, gut microbiota can be influenced, and thus used in the disease therapy or even prevention. We have shown that absence or reduction of microbiota modifies the inflammatory response in the murine model of experimental autoimmune uveoretinitis (EAU). Our further purpose of the project was to test influence of probiotics on intensity of intraocular inflammation in EAU. Uveitis was induced in C57BL/6J mice by interphotoreceptor retinoid binding protein in complete Freund's adjuvant and with pertussis toxin. The grade of uveitis was assessed in vivo by using otoscope connected to camera and post mortem on haematoxylin and eosin stained tissues. Bacteria Escherichia coli were administered orally three times a week and saline solution was administered to control group. Different regimens of administration were tested. Interestingly, mice administered with probiotics reached statistically significant lower grade of uveitis in comparison to the control group in clinical and histological evaluation. This may have valuable implications for the control of sight‐threatening uveitis in patients.Supported by research project AZV MZ CR 17‐31248A.Key words: microbiome, probiotics, Escherichia coli, experimental autoimmune uveitis, EAU.
Home monitoring
Authors: Tatham Andrew 
Published: December 2022

AbstractA wide range of relatively cheap wearable digital devices are now available that enable self‐monitoring of parameters such as heart rate, blood pressure, physical activity, and sleep patterns. Although these devices are often marketed at healthy people, new technologies that permit home monitoring may also have the potential to improve the detection and management of chronic diseases including glaucoma. If patients were able to measure their intraocular pressure or perform perimetry at home, many more measurements could be obtained, with the potential to improve our ability to differentiate true change from test re‐test variability. Home monitoring may also improve our ability to determine efficacy of treatment and enhance patient engagement. This presentation explores whether home monitoring of glaucoma is feasible.
Clinical spectrum of neuro‐ophthalmological manifestations associated in MOG antibodies in children
Authors: Robert Matthieu 
Published: December 2022

AbstractIntroduction: The discovery of the role of MOG antibodies over the last decade has tremendously modified our comprehension of inflammatory disorders of the central nervous system (CNS), especially in children.Objective: To describe the clinical spectrum of neuro‐ophthalmological manifestations associated in MOG antibodies in children.Methods: Literature review using Pubmed and Google Scholar and chosen clinical case series.Results: Three long known clinical entities affecting the optic nerve in children have been recently proven to be largely associated with MOG antibodies: optic neuritis in the context of acute disseminated encephalomyelitis (ADEM); monophasic optic neuritis; chronic relapsing inflammatory optic neuropathy (CRION). ADEM is a child's specificity. CRION often starts during late childhood. These entities can occur after one another in a same child.Conclusions: The absence of overlap between multiple sclerosis, aquaporine 4 antibodies (associated with neuromyelitis optica only) and MOG antibodies, allows for a new, clearer delineation of inflammatory disorders of the CNS in children, closer to the precise classical clinical descriptions than to the semi‐recent criteria‐based “spectra”.
Genetic coding of lens fibre cell differentiation
Authors: Cvekl Ales 
Published: December 2022

AbstractPurpose: The DNA genetic code operates at multiple levels, including cis‐regulatory code of promoters and enhancers regulating transcription, cis‐regulatory code of 5′‐ and 3′‐UTRs in spliced mRNAs to control their localization and stability and 3D‐organization of chromatin within the nucleus.Methods: To study chromatin landscape dynamics during lens differentiation, ATAC‐ and RNA‐seq experiments were conducted using epithelia and fibres from E14.5 and newborn (P0.5) mouse lenses. Whole genome bisulfite sequencing (WGBS) was performed to map DNA methylation and integrate the data with corresponding ATAC‐ and RNA‐seq data sets. ChIP‐seq data were generated for transcription factor CTCF and histone H3.3 in microdissected newborn lenses. ChIP‐seq data on Pax6 and RNA polymerase II landscapes in whole newborn lenses were used for comparisons. A census of the most abundant RNA‐binding proteins (RBPs) in the lens was generated using mouse proteomic data. Immunoflourescence analyses were employed to visualize selected RBPs in the mouse lens.Results: Open chromatin and DNA methylation changes were defined through identification of differentially accessible regions (DARs), unmethylated/low methylated regions (UMRs/LMRs) coupled with differential gene expression during lens differentiation. Pax6 proteins were found both in open and closed chromatin domains, including both closed and methylated regions. As expected, histone H3 variant H3.3 is present all across crystallin and other highly expressed lens genes/loci. Novel abundant RNA‐binding proteins in lens include Carhsp1, Ddx5, Ddx39b, Fxr1, Pabpc1, Rbm24, Rbm38, Ybx1 and Ybx3.Conclusions: A combination of different –omics is a powerful approach to examine molecular mechanisms governing lens differentiation. Current studies reveal additional levels of genetic code complexity and stimulate follow up mechanistic studies of the individual cellular and molecular processes of lens morphogenesis and their underlying GRNs and identification of cataract‐causing mutation in non‐coding regulatory sequences. Ongoing studies are aimed to generate Hi‐C data to probe 3D‐organization of lens chromatin using microdissected newborn lenses.