bluuebunny/crossref_metadata_2025 huggingface dataset:
Macular surgery in myopic eyes
Authors: Ilyuk Oksana
Published: December 2022

Purpose: Despite the variety of different techniques for large macular holes (LMH) closure, this task is still challenging, especially in patients with myopia. We compared closure rates of LMH achieved by conventional internal limiting membrane (ILM) peeling and inverted ILM flap.

Methods: Material and Methods. We represent single‐surgeon series of 42 consecutive treatment‐naive patients (pts) with LMH and myopia, for 21 pts retinal detachment (RD) was confirmed either before or during surgery. Initially we performed conventional ILM peeling (CP) – 17 pts, 8 with RD; starting from 2017 all patients were operated with inverted ILM flap (IF) technique – 25 pts, 13 with RD.

Results: Results. Conventional ILM peeling allowed us to attain LMH closures in 3 of 8 pts with RD (33%) and 4 of 9 pts without RD only. Again, we achieved closures of LMH in all patients (with and without RD), operated with IF technique. In 1 patient operated with inverted ILM flap technique we observed gliotic changes along the line of overlapping, but without significant loss of vision.

Conclusions: Conclusion. Inverted ILM flap technique serves as a novel exceptionally effective approach for LMH closure in myopic patients. We found no influence of retinal detachment on the effectiveness of IF technique.
Prediction of causative genes in inherited retinal disorders from spectral‐domain optical coherence tomography utilizing deep learning techniques
Authors: Fujinami‐Yokokawa Yu
Published: December 2022

Technological advancement has markedly increased the medical information required for clinical management. Processing medical information automatically and comprehensively through the application of artificial intelligence (AI) is becoming essential to improve the quality of medical data management and reduce medical expenses.

Deep learning techniques have been successfully applied in medical fields, especially in analysing clinical images for the predicted diagnosis of common ocular disorders, such as diabetic retinopathy and age‐related macular degeneration. In contrast, due to limited clinical resources, AI‐oriented bioinformatic engineering has not yet been applied in a clinic for orphan diseases, such as inherited retinal disease (IRD), although IRD is the most prevalent cause of blindness.

Therefore, the purpose of the current study was to investigate the utility of deep learning in a nationwide cohort of patients with IRD, which enables to explore the typical phenotypes of IRD based on unique findings from clinical images and predict the genetic diagnosis.

Clinical and genetic data with IRD were reviewed. Three categories of genetic diagnosis were selected based on the high prevalence of their causative genes: Stargardt disease (ABCA4), retinitis pigmentosa (EYS), and occult macular dystrophy (RP1L1). Optical coherence tomographic (OCT) images were cropped in a standardized manner with a macro algorithm. Algorithms for pipeline analyses, based on TensorFlow Inception V‐3 were determined with learning parameters through evaluation with a randomized 4‐fold cross‐validation method, given the accuracy of concordance (aimed >80%) between the genetic diagnosis and the machine diagnosis (ABCA4, EYS, RP1L1, and normal).

A total of 178 images from 75 subjects were examined. The mean training accuracy was 98.5%, ranging from 90.6 to 100.0. The mean overall test accuracy was 90.9% (82.0–97.6).

This study highlighted a novel application of deep neural networks in the prediction of the causative gene in IRD retinopathies from SD‐OCT, with a high prediction accuracy. The obtained study results have been registered in the database to support clinical/genetic diagnosis. These achievements will extensively promote the improvement of medical care quality by providing accurate real‐time diagnoses, reducing cost by avoiding unnecessary referrals and testing, enriching the education of non‐specialists, and realizing an application of personalized medicine.
In silico interpretation of variants identifies novel causes of inherited eye disease in the 100 000 genomes project
Authors: Arno Gavin
Published: December 2022

Inherited retinal dystrophy (IRD) describes a widely heterogeneous spectrum of disorders with over 270 genes implicated to date across all inheritance patterns and an estimated prevalence of around 1 in 2000 people. Genetic testing for IRD had evolved dramatically since the discovery of the first pathogenic variant in 1990: the advent of massively parallel sequencing means that the more than half of patients are now able to receive a molecular diagnosis although there is still significant missing heritability (up to ~40% of patients). Novel genes, non‐coding variants, structural variants/copy number variants, novel gene/disease associations, non‐Mendelian inheritance and non‐genetic disease are some of the mechanisms thought to account for the missing heritability of rare disease. This presentation will focus on non‐coding variant analysis.

Whole genome sequencing (WGS) enables the capture and interrogation of all variants covering up to approximately 95% of the genome, and advances in genomic analysis technology, genome and variant databases, bioinformatics and in silico tools mean that nowadays variant prioritization pipelines are able to filter the huge variant numbers leaving only a handful of candidate pathogenic coding variants per patient.

For the missing heritability in patients whose phenotype cannot be fully explained by this approach, however, non‐coding variant analysis is more challenging. Many more variants exist outside of coding exons and our understanding of their effect on transcripts and proteins is limited. Functional assays, especially for retina specific genes may be complex and difficult to establish, so accurate variant effect predictions are critical to enable molecular geneticists and clinical laboratories to maximize their ability to provide a definitive molecular diagnosis.

This presentation will focus on the analysis of non‐coding variants in IRD genes in a cohort of patients who underwent WGS in the UK's 100 000 genomes project. Key to this study, patients were identified for study following multidisciplinary team discussion to highlight the most likely gene to be implicated in their disease. Identification of candidate non‐coding variants, filtering and prioritization were performed to identify the most compelling variant, followed by molecular investigation and confirmation of the predicted effect. Exemplar case studies will demonstrate the power of this analysis pipeline and accuracy of in silico predictions.
Genetics of keratoconus; how realistic is gene therapy?
Authors: Anogeianakis George
Published: December 2022

Keratoconus (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

In 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

The 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

The 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

Here 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

Nerve 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

Corneal 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

Trabeculectomy 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

Aims 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.

Abstract

Corneal 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

British 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

Roman 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

The 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

Unlike 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

A 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

Introduction: 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

Purpose: 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.
Congenital myopia
Authors: Robert Matthieu
Published: December 2022

Introduction: Acquired myopia – usually known as “myopia” – because of its a very high and growing prevalence, is increasingly discussed in the scientific literature. It shares hardly any feature with congenital myopia, which is a completely distinct entity.

Objective: To describe the clinical and pathophysiological characteristics, and management challenges, of congenital myopia.

Methods: Literature review using Pubmed and Google Scholar and chosen clinical case series.

Results: While temporary and moderate myopia in newborns, especially premature ones, can be considered physiological, congenital high myopia is rare and mostly monogenic. It is almost always characterized by an excessive growth of the globe in utero, leading to a high or very high myopia from birth, quite stable over time after birth. It results from collagenopathies in the vast majority of cases (most often Stickler syndrome); more rarely to proteoglycanopathies or lamininopathies. Rarely, it can result from congenital lens ectopia. In both cases, management is debated and mainly relies on small series of cases. The rate of visual and oculomotor complications is particularly high.

Conclusions: Congenital myopia are a challenge for both clinicians and geneticists; recent progress has been achieved in these fields.
Congenital and childhood toxoplasmosis
Authors: Kozyreff Alexandra
Published: December 2022

Toxoplasmic retinochoroiditis is a world‐wide disease and the most frequent infectious posterior uveitis resulting in vision loss with considerable consequences for the patient. Genetic and environmental factors may influence the course of the disease but the prenatal and postnatal antibiotic treatment of the infected neonates and the follow‐up of these children may substantially influence and improve their vision prognosis.

The actualized recommendations will be discussed in this presentation.
The 9 months and beyond dilemma: Glaucoma and pregnancy
Authors: Stalmans Ingeborg
Published: December 2022

Pregnancy comes with various challenges for glaucoma patients.

First of all, alterations and fluctuations in intra‐ocular pressure may occur not only during pregnancy but also during delivery. The clinical impact of these IOP changes in pregnant women with glaucoma will be discussed.

Secondly, medical therapy needs to be scrutinized and if necessary adjusted to avoid toxic effects to the fetus. Also during lactation, this aspect must be taken into account. The different classes of glaucoma medications will be discussed in this aspect and finally a potential therapeutic strategy for pregnant and lactating women will be proposed.

Also, the role of lasertrabeculoplasty and surgery will be highlighted and practical guidance will be given for these specific situations.

Lastly, the general recommendations from the Guidelines of the European Glaucoma Society for the management of women with glaucoma during pregnancy and lactation will be summarized.
Old is the new young: A paradox for glaucoma patients
Authors: Oddone Francesco
Published: December 2022

Older/mature glaucoma patients are increasingly active these days and it is a myth that glaucoma patients are all passive and sedentary. Glaucoma does not only occur in the elderly, but even those glaucoma patients who are mature are working longer and staying more active. So perceptions of the ‘normal’ glaucoma patient need to be adjusted. Quality of life is increasingly important as older patients still feel young inside and want to enjoy their daily lives and interests and treatment must therefore be effective, but also tolerable so that patients' QoL is not limited by side effects. These patients have high expectations, but at the same time, this older population has a higher incidence of ocular and systemic comorbidities which can pose challenges. For instance, to start with ocular comorbidities it is well known that glaucoma patients have a higher risk of suffering from ocular surface disease and that the prevalence of ocular surface disease increases with increasing age. In this context therapeutic choices should be focused at lowering the intraocular pressure while preserving as much as possible the health of ocular surface for example by using preservative‐free medications to minimize ocular side‐effects. We know from published studies and from clinical experience that ocular surface disease shows improvements after switching from preserved to preservative free topical medications. Since glaucoma prevalence increases with age the prevalence of age‐related ocular comorbidities increases as well such as in the case of macular degeneration with additional deterioration of vision and increased impact on quality of life.

Important to keep in mind that also systemic comorbidities that may particularly impact older patients, and the effect this might have on treatment (e.g. impairment in fine motor skills that can impact their ability of self‐administering the drops).

Additionally, more mature patients may experience increased prevalence of systemic comorbidities such as cardiovascular or pulmonary ones limiting the therapeutic choices. More challenges to diagnosing and monitoring the disease might be posed by increased difficulties in performing psychophysical tests such as visual field testing.

In this scenario it has to be highlighted the importance of communication to assess patients' level of comprehension and ability to cooperate with treatment and monitoring schedule.
Vitrectomy with ILM peeling and subretinal injections of BSS in diabetic macular oedema in one eye vs. intravitreal anti‐VEGF injections in the second eye – A swept source OCT angiography study
Authors: Nawrocka Zofia Anna , Nawrocka Zofia , Nawrocki Jerzy
Published: December 2022

Purpose: The aim of this study was to compare the results of vitrectomy performed in patients' worse eyes with diabetic macular oedema to the results of continuous anti‐VEGF treatment performed in patients' fellow eyes.

Methods: A retrospective interventional study of patients with diabetic macular edema in both eyes. The better eye was always qualified for aflibercept injections (group 1), and the worse eye was scheduled for vitrectomy (group 2). The follow‐up lasted 12 months. The following parameters were measured: visual acuity (V), central retinal thickness (CRT), maximum retinal thickness (MRT), central choroidal thickness (CCT), superficial (sFAZ) and deep fovea avascular zone (dFAZ), and vessel density at the level of superficial (sVD) and deep (dVD) retinal vessels.

Results: None of the analysed factors differed between groups with statistical significance at any timepoint. The time of recovery of vision was identical in both eyes (F = 0.91, p = 0.449). The final sFAZ was significantly smaller for group 2 (median 196 μm), than for group one (median 375 μm; U = 101.0; p = 0.022; r = 0.44).

Conclusion: Both techniques resulted in similar improvements in visual acuity and decreases in CRT after one year. sFAZ decreased in all eyes, with a higher extent after vitrectomy.
Intraocular drug delivery methods: Conventional versus modern approaches
Authors: Lytvynchuk Lyubomyr
Published: December 2022

Intravitreal injection (IVI) belongs to a standard and most used drug delivery technique for the treatment of exudative age‐related macular degeneration (AMD) and other ocular diseases associated with increase of VEGF concentration in the vitreous cavity and retinal layers. Moreover, this technique is used to inject antibiotics, steroids, antiviral, antifungal and cytostatic agents during the treatment of eye infection and eye injury. The risk of serious vision‐threatening complications after IVI, including aseptic and septic intraocular inflammation, is very low. However, the number of patients who require the IVI grows together with the absolute number of serious injection‐associated complications. Regarding the rate of endophthalmitis, various possible contamination mechanisms have been considered, including contamination of the surface of the eye, contamination of the needles or therapeutic substances, etc. Nevertheless, an accurate mechanism of these contaminations as well as the ways to prevent them remains unclear. It was suggested, that one of the possible causes of the post‐IVI inflammation is the use of hypodermic needles with the sharp tip, which cuts out potentially contaminated cellular material and brings it inside the eye together with the drug. Modern studies are focused on the enhancement of the safety of the IVI technique by developing less traumatic injection needles. Drug companies are developing the new drugs, which action is more prolonged in order to reduce the number of required injections. Additionally, the new alternative drug delivery systems have been proposed and already tested in the clinical condition. Development of novel intraocular drug delivery techniques with their implication into the everyday practice will improve the safety profile of the treatment methods.
No dye, no glory: Fluorescein and indocyanine green angiography in uveitis
Authors: Salas Ester Carreño
Published: December 2022

The advantages of the new imaging techniques such as optical coherence tomography (OCT) and OCT‐angiography (OCT‐A) have decreased the use of fluorescein angiography (FA) and indocyanine green angiography (ICG) in the diagnosis and management of uveitis. The aim of this talk is to highlight the need of using FA and ICG (including wide field and ultra‐wide field devices) in the diagnosis and follow‐up of uveitis patients.
The magic of time: Imaging analysis in uveitis
Authors: Agarwal Aniruddha
Published: December 2022

In the recent times, there has been a significant interest in the quantification of retinochoroidal vasculature in ocular inflammatory diseases. Using various imaging modalities such as optical coherence tomography (OCT) and OCT angiography (OCTA), non‐invasive ultra‐structural imaging of the retinochoroidal vasculature is now possible. Various authors have attempted to quantify the alterations in retinochoroidal vasculature in various uveitic conditions, including anterior and posterior/panuveitis. Using third‐party software, it is possible to perform quantification in an automated manner using predesigned pipelines with optimum thresholding strategies and image binarization techniques. The quantification must be performed after careful consideration of the retinochoroidal anatomy to avoid incorrect interpretation of the data. In this talk, the speaker will highlight the various techniques of quantification of retinochoroidal vasculature, paying specific attention to the correct ways of pre‐processing and application of image processing algorithms to obtain the most accurate results.
Management and prognosis of vitreous haemorrhage
Authors: Xirou Tina
Published: December 2022

Vitreous haemorrhage is one of the most common causes of sudden deterioration in vision with an incidence of seven cases per 100 000 and it is affecting most often only one eye.

The most common causes for nontraumatic, spontaneous vitreous haemorrhage include diabetic retinopathy, retinal tear/detachment, vitreoretinal traction resulting from posterior vitreous detachment, retinal venous occlusive disease, ruptured retinal macroaneurysm, and exudative age‐related macular degeneration In the setting of severe vitreous haemorrhage and no visualization of the fundus and without a history of underlying cause the diagnosis may be challenging. B‐scan is the most useful diagnostic tool but ultrasound has limitations both in sensitivity and specificity for excluding retinal tear and detachment, as well as operator dependent variability. General ophthalmologists tend to follow up patients, waiting the haemorrhage to clear or to have some indication for the underlying pathology. This waiting time could compromise the final visual outcome of a vitreous haemorrhage related to retinal breaks or affect the quality of life of patients. With the safety profile of modern small gauge vitreoretinal surgery we would suggest an early referral of all cases to vitreoretinal surgeons as delayed diagnosis and management could implicate consequences affecting the final visual result.
Management and diagnosis of subretinal and suprachoroidal haemorrhage
Authors: Kontou Evgenia
Published: December 2022

Subretinal and suprachoroidal haemorrhage, particularly when central macula is involved, represent challenging clinical entities since their natural course, if left untreated, often leads to severe, progressive and irreversible vision loss, due to photoreceptor and retinal pigment epithelium (RPE) damage. Significant variation in prognosis and treatment of different types of haemorrhage dictates the need to establish the level of haemorrhage, which is primarily based on fundus appearance, as haemorrhage in different levels tends to present with a distinct configuration. Additional modalities, such as ultra‐sonography, optical coherence tomography, fluorescein angiography and focal electroretinography, contribute to diagnosis the clinical evaluation.

Despite the wide range of techniques described for managing both subretinal and suprachoroidal haemorrhage, there is still no consensus among vitreoretinal surgeons on optimal approach. Pneumatic displacement with or without the intraretinal use of tissue plasminogen activator (t‐PA), pars plana vitrectomy with subretinal t‐PA and gas tamponade, pars plana vitrectomy and retinectomy for clot extraction and co‐treatment with anti‐vascular endothelial growths factors (anti‐VEGFs) and pars plana vitrectomy with choroidal blood drainage, have all been described as effective management approaches. Over the last few years, a trend towards a more timely and less invasive approach has emerged. However, the preferred technique is often determined by the level, the extent and duration of haemorrhage as well as surgeon preference.
From biomimetic in vitro culture towards functional transplantation of hPSC‐RPE
Authors: Skottman Heli
Published: December 2022

Human pluripotent stem cell‐derived retinal pigment epithelium (hPSC‐RPE) transplantation is currently under evaluation as treatment for macular degeneration. In our studies, we have shown that the culture substrate affects hPSC‐RPE properties in vitro, and our results also suggest that the choice of coating proteins may have implications to the functional properties of these cells also after important cryostorage cell banking. Importantly, transplanted cells must tolerate cellular stress caused by various sources such as retinal inflammation and regain their functions rapidly after the transplantation. In our studies, we have shown that the maturation level of the cultured hPSC‐RPE cells influence for example their calcium signalling properties and for the ability to tolerate cellular stress. With our collaborators, we have also studied the role of ion channels and their involvement in diverse physiological functions of hPSC‐RPEs. Last but not least, we have transplanted hPSC‐RPE as cell sheets in a novel immunosuppressed non‐human primate (NHP) model with a disrupted ocular immune privilege to study safety and submacular graft integration. In transplantations, microscope‐integrated intraoperative optical coherence tomography (miOCT)‐guided surgery, postoperative follow‐up incorporated scanning laser ophthalmoscopy, spectral domain (SD‐) OCT, and full‐field electroretinography (ERG) were used as outcome measures in addition to the histology performed after a 28‐day follow‐up. As a result, miOCT revealed foveal disruption and ERG showed amplitude and peak time preservation in cases with favourable surgical outcomes. Histology confirmed photoreceptor preservation above the grafts and in vivo phagocytosis by hPSC‐RPE, albeit evidence of cytoplasmic redistribution of opsin in photoreceptors and glia hypertrophy. The established immunosuppression protocol efficiently suppressed retinal T cell infiltration and microglia activation. As a conclusion, our results suggest the important role of biomimetic in vitro culture for the hPSC‐RPE maturation and for the functional transplantation outcome.
Developing autologous cell therapy for macular degeneration: From bench‐to‐bedside
Authors: Bharti Kapil , Investigator Senior
Published: December 2022

Induced pluripotent stem cells (iPSCs) can provide autologous and allogeneic replacement tissues, potentially for all degenerative diseases. Autologous tissues have the advantage of not requiring immune‐suppressive drugs that have deleterious side‐effects. The safety and feasibility of autologous iPSC‐based therapies has not been established. Here, we developed an autologous iPSC‐based therapy for age‐related macular degeneration (AMD), a blinding eye disease that affects over 30 million people world‐wide. AMD is caused by the progressive degeneration of retinal pigment epithelium (RPE), a monolayer tissue that maintains photoreceptor function and survival. We tissue engineered a clinical‐grade iPSC‐RPE‐patch on a biodegradable scaffold using autologous cells from AMD patients. Preclinical investigational new drug (IND)‐enabling studies performed on iRPE‐patch derived from multiple AMD patients demonstrated reproducible manufacturing, validating our manufacturing process – a key requirement for an autologous phase I trial. Functional validation of clinical‐grade iRPE‐patches allowed determination of tissue barrier resistance, purity of RPE cells, and RPE cell shape metrics as key critical quality attributes now used as clinical product release criteria. Preclinical animal studies performed in immune‐compromised rats confirmed safety of the auto‐iRPE‐patch and efficacy studies performed in a porcine laser‐induced RPE injury model that mimics AMD‐like eye conditions demonstrated integration and functionality of RPE patches. A phase I/IIa IND‐application for an auto‐iRPE‐patch to treat AMD was recently cleared by the FDA. This Phase I/IIa clinical trial will test safety, feasibility, and integration of an auto‐iRPE‐patch in twelve advanced AMD patients. The trial is currently being run as a single site study at the NIH and targets patient enrollment in two cohorts – with visual acuity between 20/100 to 20/500 and between 20/80 to 20/500.