bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intracorneal ring segments for KC and iatrogenic keratectasia
Authors: Daas Loay , Hamon L. , Flockerzi E. , Seitz B. 
Published: December 2022

AbstractICRS are polymethylmethacrylate (PMMA) implants developed to be inserted in the corneal stroma aiming to remodel the ectatic corneal curvature. In 2000, ICRS have been introduced for the implantation in KC treatment. Since then, several authors have demonstrated the efficacy of this surgical procedure for improving the refractive and topographic results of KC patients. Moreover, the method has been extended to a larger spectrum of corneal ectasia, such as pellucid marginal degeneration (PMD) and iatrogenic ectasia after laser in situ keratomileusis (LASIK). Our aim was to evaluate the functional results, i.e. how uncorrected and corrected distance visual acuity can be improved by implantation of ICRS. Progression of ectasia seems to be retarded. However, consistent follow‐up visits at close intervals are necessary to identify complications at an early stage. The complications after ICRS implantation are rare due to strict patient selection and modern surgical techniques.
Role of AS‐OCT in DALK and PKP for KC
Authors: Wylegala Edward 
Published: December 2022

AbstractOCT has been a diagnostic device in corneal diseases for many years. Non‐contact examination enables obtaining morphological and morphometric data useful in clinical practice. For example, a patient with keratoconus is a diagnostic tool in surgical procedures such as keratoplasty, intracorneal ring implants, and corneal collagen cross‐linking (CXL). The presentation will show the practical aspects of using AS OCT diagnostics in patients with a cone qualified for deep lamellar keratoplasty and penetrating keratoplasty. The use of intraoperative OCT in surgical treatment supported by excimer and femtosecond lasers will also be presented.
Insights into corneal re‐vascularization and vascular remodelling in the eye
Authors: Lagali Neil 
Published: December 2022

AbstractWhile corneal neovascularization is a well‐known, sight‐threatening condition presenting a risk for corneal transplant rejection and failure, corneal revascularization has received much less attention. Although ocular revascularization is well studied in the context of regrowth of choroidal vessels following regular anti‐angiogenic injections for age‐related macular degeneration, the corneal context is less well documented. Here, the differences between initial and subsequent episodes of corneal neovascularization are explored, as well as the underlying changes at the mechanistic, structural and biochemical levels, through basic studies in the murine cornea. Repeat neovascularization is found to be more aggressive than the vessel ingrowth in an initial phase, pointing towards a memory effect in the corneal tissue. Furthermore, these regrown vessels are more resistant to treatment than initial vessels, which can have implications for the long‐term treatment and rebound of corneal vessels and prognosis for graft survival. We also highlight several factors that may be driving this aggressive revascularization response, with an eye towards future interventions aimed at preventing revascularization following initial treatments for corneal neovascularization.
Nerves, vessels and inflammation at the ocular surface
Authors: Ferrari Giulio 
Published: December 2022

AbstractCorneal nerves are essential in the maintenance of ocular surface homeostasis. The role of peripheral nerves in promoting the onset of corneal inflammation, instead, is only recently starting to emerge. The extremely dense sensory innervation, and complete absence of vessels, in the normal cornea, makes it an ideal target of neuroinflammation.Previous work from us demonstrated that acute nerve disruption is followed by corneal neovascularization and inflammation. We hypothesized that neuropeptide Substance P is a key modulator of corneal neuroinflammation. Indeed, our data show that neuropeptide Substance P is a key promoter of inflammation and neovascularization in pre‐clinical models of corneal burns, neovascularization, stem cell deficiency and ocular graft versus host disease. Further, we demonstrate that this effect is mediated by the Neurokinin 1 receptor, which is the principal receptor for Substance P. Moreover, we show that highly prevalent human corneal diseases/trauma are associated with increased Substance P expression in the tear fluid. This has significant clinical implication because medications are available to selectively block Neurokinin 1 receptor. Indeed, topical application of Neurokinin 1 receptor antagonists inhibits leukocyte infiltration, and ameliorate multiple clinical signs of inflammation in animal models of ocular surface inflammation.These data have allowed us to initiate a clinical trial for compassionate use of neurokinin 1 receptor antagonists for the treatment of recalcitrant ocular surface inflammation.
Colour vision changes in patients with pressure differences across the lamina cribrosa
Authors: Barbur John , Wong Sui 
Published: December 2022

AbstractThe retinal nerve fibre layer (RNFL) thickness parameters describe the integrity of retinal ganglion cells (RGC) and their axons and can be affected in pathological processes involving the optic nerve. Glaucoma and papilledema are two conditions where RGCs and hence RNFL, are damaged due to the pressure differences across the lamina cribrosa. The latter separates the intraocular and intracranial pressure compartments. In glaucoma, the intraocular pressure (IOP) is elevated and in papilledema, the intracranial pressure is elevated. When intracranial pressure is managed, papilledema patients can recover without significant loss of RGC. Conversely irreversible RGC loss can occur in severe cases.Subtle, functional changes that are often not detected clinically can remain following recovery. The detection of such changes require sensitive functional tests and a knowledge of normal age limits for the stimulus attribute investigated.Results of preliminary studies designed to assess how colour vision and rod and cone mediated flicker sensitivity recover in papilledema will be reported for a number of patients. Following recovery, the results often reveal binocular summation effects, even when the differences between the two eyes remain significant. Patients classed clinically as fully recovered continue to show small differences between the two eyes, even when the measured binocular thresholds are within the expected age limits.In summary, the preliminary findings from this investigation show how various attributes of vision are affected during the early stages of the disease and after treatment and recovery from late stage of severe papilledema with loss of RGCs.
Colour vision impairments in ophthalmological and neurological disorders
Authors: Castelo‐Branco Miguel 
Published: December 2022

AbstractThe value of colour vision assessment in the understanding of ophthalmological and neurological disorders impairments cannot be underestimated. Here we discuss impairment of parallel retinocortical pathways in early stages of Parkinson's disease. The debate on the relative contribution of retinal vs. cortical mechanisms is also addressed concerning Multiple Sclerosis and Alzheimer's Disease.We discuss evidence on the hypothesis that the retina mirrors the brain in terms of pathology and in which neurological conditions this might apply. The converse situation of retrograde degeneration in the case of multiple sclerosis is also addressed.Cortical changes secondary to retinal disease, such as glaucoma and diabetic retinopathy may also bias colour perception. Finally, we discuss the potential role of colour vision measures as disease related biomarkers that can be used for diagnostic, prognostic and treatment effects assessment.
Basics of artificial intelligence
Authors: Wong Damon 
Published: December 2022

AbstractArtificial intelligence (AI) is increasingly being used in different fields, including ophthalmology. Recent studies have demonstrated that AI‐based techniques have started to approach near‐human levels of performance, and has led to much interest and excitement. Yet, excitement about AI has also been accompanied by sometimes unrealistic expectations. This talk will provide an overview on the basics of AI, including a brief history on its development and the different types of AI, including machine‐learning and deep‐learning. Fundamental principles of deep‐learning will be introduced, and key differences between traditional image processing techniques and deep‐learning will also be discussed, together with limitations and potential pitfalls of the technology. The talk will also provide a glimpse into recent and emerging trends in this rapidly evolving field.
Artificial intelligence for diabetic retinopathy screening
Authors: Grzybowski Andrzej 
Published: December 2022

AbstractDiabetes constitutes a significant problem for global health and wellbeing. The number of people living with diabetes raised from 108 million in 1980 to 422 million in 2014. By 2035, 592 million people will have diabetes, with the largest rise in low‐ and middle‐income regions. Diabetic retinopathy (DR) is one of the major complications of diabetes, estimated to be the leading cause of blindness among working‐age adults globally. The increasing worldwide population, coupled with increasing prevalence of diabetes and increased incidence of diabetic retinopathy all lead to increasing number of patients with ocular complications of diabetes. Only a few countries were able to successfully establish and continue diabetic retinopathy screening on national level, most prominently – United Kingdom and Singapore. The NHS Diabetic Eye Screening Programme, a continuation of an English screening programme set up in 2006, reported in 2014 that DR is no longer the leading cause of certifiable blindness in England and Wales for the first time in 50 years. The advent of deep‐learning based DR detection revealed a significant improvement in the accuracy of the newly developed or improved systems. It requires a careful balance between sensitivity and specificity, imaging modality, gradeability of the images, all of which will need to be weighed against the potential cost. Deep learning DR detection has been found to be cost‐effective in developed countries, like Singapore and United Kingdom. However, the feasibility of implementing AI DR screening in countries without a robust teleophthalmology screening programme setup beforehand and other resource‐limited settings should still be evidenced. IDx‐DR is the first autonomous diagnostic software and one of the very first AI‐based software's in medicine to receive Federal Drug and Administration (FDA) approval. Eyeart was approved by FDA for the similar purpose in 2020. In European Union, there are more than 10 different AI‐based devices for DR screening registered, however in different classes, I and IIa. There are also significant shortcomings in current studies of AI in DR, including that great majority of them are sponsored or dependent on the respective algorithm's' company. Independent studies, particularly comparisons or studies establishing objective criteria through which the respective algorithms could be compared are rare.
AI‐based software for cardiovascular disease assessment
Authors: Arnould Louis 
Published: December 2022

AbstractThe healthcare burden of cardiovascular disease remains a priority. Understanding their underlying mechanisms and improving identification of people with higher systemic vascular risk profile with non‐invasive examinations seem to be crucial. In Ophthalmology, retinal imaging is simple, non‐invasive and it can provide in vivo insight of the retinal microcirculation. For more than 10 years, research teams have been working on software developed to allow automatic analysis of the retinal vascular network from different imaging technique (fundus photographs, oct‐angiography or adaptive optics…) and to provide a description of the geometric characteristics of its arterial and venous components. At the same time, research teams have explored the pathophysiological association between macro vascular and micro vascular alterations. Thus, retinal microcirculation could be considered as a witness of the systemic cardiovascular status. New approach with retinal images dataset and artificial intelligence algorithms recently strengthened the interest of retinal microvascular biomarker. Deep learning and machine learning algorithms provided very thorough description of the retinal vascular network. Moreover, they were able to assess strong associations between retinal features and calcium heart score or biological age for example. Thus, the interest of retinal biomarker in terms of screening, monitoring or prediction of cardiovascular disease is very promising.
In vivo confocal microscopy demonstrates longitudinal bilateral changes of corneal immune cells and nerves in herpetic keratitis
Authors: Hamrah Pedram 
Published: December 2022

AbstractPurpose: To analyse bilateral corneal immune cell and nerve alterations in patients with unilateral herpes zoster ophthalmicus (HZO) by laser in vivo confocal microscopy (IVCM) and their correlation with corneal sensation and clinical findings.Materials and methods: This is a prospective, cross‐sectional, controlled, single‐center study. Twenty‐four eyes of 24 HZO patients and their contralateral clinically unaffected eyes and normal controls (n = 24) were included. Laser IVCM (Heidelberg Retina Tomograph/Rostock Cornea Module), corneal esthesiometry (Cochet‐Bonnet) were performed. Changes in corneal dendritiform cell (DC) density and morphology, number and length of subbasal nerve fibres and their correlation to corneal sensation, pain, lesion location, disease duration, and number of episodes were analysed.Results: HZO‐affected and contralateral eyes showed a significant increase in DC influx of the central cornea as compared to controls (147.4 ± 33.9, 120.1 ± 21.2, and 23.0 ± 3.6 cells/mm2; p < 0.0001). In HZO eyes DCs were larger in area (319.4 ± 59.8 μm2; p < 0.001) and number of dendrites (3.5 ± 0.4 n/cell; p = 0.01) as compared to controls (52.2 ± 11.7, and 2.3 ± 0.5). DC density and size showed moderate negative correlation with total nerve length (R = −0.43 and R = −0.57, respectively; all p < 0.001). A higher frequency of nerve beading and activated DCs close to nerve fibres were detected specifically in pain patients.Conclusions: Chronic unilateral HZO causes significant bilateral increase in corneal DC density and decrease of the corneal subbasal nerves as compared to controls. Negative correlation was observed for DC density and size to nerve parameters, suggesting interplay between the immune and nervous systems. Patients with chronic pain also showed increased nerve beading and activated DCs.
Implication of Müller glia in glaucoma
Authors: Vecino Elena , Pereiro Xandra , Ruzafa Noelia 
Published: December 2022

AbstractGlaucoma is a neurodegenerative disease and the leading cause of irreversible blindness in the world, whose main risk factor is increased intraocular pressure. When visual problems are first detected in patients with glaucoma, already half of the retinal ganglion cells (RGCs), the neurons that send visual information from the eye to the brain, have died principally in the peripheral retina. The timeframe of cell death is prolonged, lasting even decades after an initial diagnosis. Müller glia (MG) are the main macroglial cell in the retina, play prominent roles regulating normal and pathological physiology and react to neuronal injury in glaucoma. The change to a reactive phenotype of MG initiates signalling cascades that may serve a neuroprotective role, but may also proceed to promote damaging effects on RGCs. However, the underlying mechanisms and signalling pathways that specifically promote protective versus destructive roles of reactive glial cells are mostly unclear.Our main hypothesis is that MGs exert an important role in the death of RGCs in glaucoma with the MGs in the periphery being the most sensitive to intraocular pressure, promoting the death of RGCs. Preventing MG response to elevated pressure, MG can neuroprotect RGCs in early stages of glaucoma.We have proved in vitro, that in control condition MG secret neuroprotective factors, and under elevated pressure MG are the responsible for the RGCs death, being less sensitive to the elevated hydrostatic pressure (EHP) the MG present in the central retina. Moreover, stretch‐activated nonselective TRPV4 cation channels present in MG are differently activated by the pressure depending of their location within the retina. Proteomic analysis from the conditioned media (CM) of MG revealed different protein expression levels being more pronounced in the CM from MG from peripheral retina in EHP. Proteins identified correspond mainly to functions such as: apoptosis, oxidative stress, inflammation and angiogenesis.We conclude that the different sensibility of the RGCs to pressure in glaucoma could be related with the different activation of the neighbours MG.
Macular surgery in myopic eyes
Authors: Ilyuk Oksana 
Published: December 2022

AbstractPurpose: 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

AbstractTechnological 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

AbstractInherited 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.