bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deep learning model to identify angle dysgenesis on ASOCT images
Authors: Dhakonia Shweta Birla 
Published: December 2022

AbstractAnterior segment spectral domain–optical coherence tomography (ASOCT) is increasingly used in glaucoma patients, primarily to investigate the anterior chamber angle and visualize the trabecular meshwork (TM) and Schlemm's Canal (SC) in‐vivo. The anatomical variability of the drainage angle, TM and SC morphology makes it difficult to distinguish normal from abnormal. Therefore, the interpretation of ASOCT images requires expertise and a deep understanding of the complexity involved in the developmental anomalies of the outflow pathways. While the ASOCT scans can successfully capture the gross changes, they may fail to identify angle dysgenesis in cases where altered extracellular matrix anomalies are subtle enough to get unnoticed by the human eyes of an expert. Deep learning (DL) has demonstrated convincing results and potential in classifying ophthalmic diseases. The integration of high‐resolution ASOCT images trained DL algorithms can further enhance the translational potential of DL‐based classification for angle dysgenesis. Apart from the gross changes in the iridocorneal angle region, the perturbations in TM layers due to associated gene mutations are also captured on ASOCT scans and may be identified by DL algorithms. We have developed DL models, which can identify obscure features of angle dysgenesis in ASOCT scans (ADoA) and validated its performance in eyes with primary open angle glaucoma. Eight hundred ASOCT B‐scans were included, and each image was cropped to extract the iridio‐corneal angle (ICA) area and a TM area to form two datasets. Finally, the total number of images after augmentations in each dataset increased to 8160, divided into training and testing sets for model building. To avoid overfitting, incorporate variability and increase the size of the datasets, 23 different types of augmentation techniques were performed on each image using the CloDSA tool, a freely available package.Three deep learning models were developed for a consensus‐based outcome to identify ADoA objectively. The models performed well on the internal as well as external validation datasets. The model performance on the multiple independent datasets highlights the translational relevance of image‐based diagnostic alternatives in clinical settings, as it has the potential to be deployed for screening patients and their family members for detection of angle dysgenesis in vivo.
The ABC of AI
Authors: Stalmans Ingeborg 
Published: December 2022

AbstractArtificial Intelligence (AI) is a booming field, and is extensively present in our daily life. But at the same time AI is often perceived a mysterious and therefore even threatening. A better understanding of the principles of AI may unveil the mysteries of this technology and allow to reveal its potential to aid our lives, and in particular facilitate and move forward the medical field. In this presentation, the principles of AI, the different methods as well as the applications in various field (going from daily life to application in ophthalmology) will be discussed.
Promises and hazards of artificial intelligence
Authors: Grzybowski Andrzej 
Published: December 2022

AbstractArtificial intelligence (AI)‐based technologies employing deep‐learning (DL) approaches have proven effective in supporting decisions in many medical specialties, including radiology, cardiology, oncology, dermatology, ophthalmology, and others. For example, AI/DL algorithms have been shown to reduce waiting times, improve medication adherence, customize insulin dosages, and help interpret magnetic resonance images. The number of AI life‐science papers listed in PubMed increased from 596 in 2010 to 12 422 in 2019. The number of papers on the use of AI in the field of ophthalmology also has increased dramatically. Moreover, human cognitive capacity to effectively manage information is often exceeded by the quantity of data generated, and unlike humans, who have bad days and emotions, and who get tired, with subsequent decreases in performance and accuracy, AI works 24/7 without vacations or complaints. AI/DL algorithms have been used to detect diseases based on image analysis, with fundus photos and optical coherence tomography (OCT) scans analysed for retinal diseases, chest radiographs assessed for lung diseases, and skin photos analysed for skin disorders. Retinal photos have also been used to identify risk factors related to cardiovascular disorders, including blood pressure, smoking, and body mass index.One of many challenges in the field of AI is determining what constitutes evidence of impact and benefit for AI medical devices and who should assess the evidence. The majority of AI studies are conducted in experimental conditions and based on preselected data. They might provide inadequate insight into the use of AI applications in heterogeneous, real‐world care settings. One of the potential hazards of the clinical use of algorithms identified was the risk of applying an algorithm trained on a particular demographic group to a population that differs in factors such as ethnicity, age, and sex. Moreover, many studies of algorithms developed with AI have excluded low‐quality images, treating them as ungradable images, and patients with comorbid eye diseases, making them less reflective of real‐world conditions. The future development of ophthalmology depends on better and possibly unlimited access to the medical data stored within electronic health records. However, this access cannot be allowed to compromise of privacy of this very sensitive data. There is a need for effective regulations that will set a balance between individual protection and the common good.A recent report from the National Academy of Medicine highlights some important challenges in the further development of AI applications in health care. The authors advocate the use of openly accessible, standardized, population‐representative data; addressing explicit and implicit biases related to AI; developing and deploying appropriate training and educational programs for health workers to support health‐care AI; and balancing innovation and safety through the use of regulation and legislation to promote trust.
How to make glaucoma screening cost‐effective?
Authors: Abegão Pinto Luis 
Published: December 2022

AbstractGlaucoma screening has not been recommended as part of any Scientific Society Guideline, due mostly to low prevalence in overall population, high cost and a high rate of false positives.Hospital‐based healthcare systems, based on within‐department referrals present a new opportunity for screening. A human‐lead secondary screening has thus been implemented in CHLUN, Lisbon Portugal since 2019, with positive results.A retrospective review of 12‐month sample was conducted. Patient charts were reviewed through a retinography‐based AI. Comparison of the human‐based model (which used ancillary examinations, including OCT, Perimetry, Retinography and Paquimetry) and the AI‐assisted diagnosis was done in terms of diagnosis and associated direct and indirect costs.Based on this single site results, AI‐based analysis of retinographies can prove to be tool for ophthalmologists considering referral for a Glaucoma Clinic.
Mesenchimal stem cells for ocular surface disease
Authors: Calonge Margarita 
Published: December 2022

AbstractCorneal damage due to different circumstances such as chemical injuries, cicatrizing immune‐based keratoconjunctivitis, severe dry eye disease (graft vs host disease mainly), sequelae of infections, repeated ocular surgeries or congenital disorders (such as congenital aniridia) affects the integrity of the corneal epithelium, being an important cause of visual impairment and blindness that affects millions of people worldwide Mesenchymal stem cells (MSC) and its derivatives represent a readily available, non‐immunogenic source of stem cell that has a great amount of regenerative and anti‐inflammatory properties. For these reasons, MSC have emerged as very attractive candidates for cell‐based therapies in numerous and diverse clinical applications including the treatment of ocular surface diseases such as limbal stem cell deficiency, dry eye disease, or even as a potential therapy to improve corneal allograft survival. Although part of the current preclinical evidence has already been successfully translated into the clinical evidence field, work must continue to overcome all the scientific and the technical challenges that still need to be solved. This presentation summarizes the main preclinical and clinical evidence that encouragingly supports MSC‐based therapies as safe and effective treatments for the regeneration of the ocular surface.
Micellar solutions of Pluronic F127 for ocular drug delivery
Authors: Klahan Butsabarat , O'Reilly Niall , Chauhan Anuj , Sigurdsson Hakon Hrafn , Mering Satu , Fitzhenry Laurence 
Published: December 2022

AbstractThe goal of this research was to prepare drug‐encapsulated polymeric micelles for delivery to the posterior segment of the eye. Solutions of surface active PF127 at the critical micellar concentration (CMC) were prepared in deionized water (DI water) and phosphate buffer (PBS). The CMC of PF127 solution in DI water and PBS solution were found to 0.21 ± 0.04 and 0.16 ± 0.05% (w/v), respectively. In addition, the micellization of the PF127 was observed around 25 and 21°C in DI water and PBS solution, respectively by DSC analysis. The hydrodynamic diameter of the PF127 micelles were found to range between 3 and 4 nm with polydispersity indices ranging between 0.35 ± 0.22 and 0.96 ± 1.52.Curcumin (CUR), a natural dietary compound having an anti‐VEGF properties, was successfully loaded into PF127 copolymers by the thin‐film hydration method. The CUR‐loaded PF127 micelles were confirmed by several characterization techniques including DLS and HPLC. A detailed study of the effect of experimental conditions on both the particle size and drug encapsulation efficiency (%EE) of the CUR micelles was also carried out. CUR‐loaded PF127 micelles with small particle sizes (around 15 nm, PDI = 0.19 ± 0.13) and %EE around 10% were observed at high centrifugation speed. Also, increasing the copolymer‐to‐drug ratio resulted in higher %EE (>90%). Additionally, the CUR‐loaded PF127 micelles were easy to reconstitute in water by manual shaking after lyophilization. These results suggest that PF127 micelles are a promising carrier for delivery of CUR to the eye. Future work will study in more detail about the physicochemical properties and the ability of these micelles to transport CUR across ocular barriers in ex vivo and in vivo trials.
ex vivo model of spontaneous neuroretinal degeneration for evaluating neuroprotection
Authors: Fernandez‐Bueno Ivàn 
Published: December 2022

AbstractEx vivo neuroretina models are considered adequate tools for improving the knowledge of retinal physiology and pathobiology. Neuroretina explant cultures closely resemble in vivo conditions, thus, preserving complex in vivo neuronal connections and retaining the functionality of non‐neuronal cells of the retina. Furthermore, immunohistochemistry, electrophysiology and molecular biology techniques can be applied over retinal explant cultures.Although several cell culture‐based techniques have been developed to investigate retinal function, such as retinal cells primary cultures, co‐cultures with retinal pigment epithelium (RPE) cells, or 3D aggregates cultures, ex vivo models provide a better alternative to animal experimentation and are inexpensive and easy to develop. Limitations of these ex vivo systems include the absence of choroidal and retinal blood flow, the lack of vitreous and RPE, and the axotomy of the ganglion cells, which considerably limit the evaluation of the inner retina modifications. However, these limitations are also critical for the retina to degenerate spontaneously and progressively as the culture progresses.Neuroretina culture systems began to develop in the 1920 s, using chicken embryos' retinas and posteriorly mammalian retinas. In 1954, Trowell developed the membrane culture method, in which the retina was placed with the vitreous surface in contact with a supporting porous membrane and maintained at an air‐medium interface. In 1989, Caffé et al. cultured the neuroretina with the photoreceptors layer facing downward over porous membrane, the technique that is currently considered the gold standard. Since then, ex vivo mammal neuroretina cultures from rats, mice, hamsters, guinea pigs, rabbits, cats, dogs, pigs, cows or primate, have been used to describe the differentiation processes of post‐natal retinas; to provide valuable insights into retinal diseases processes; to test potential therapeutic substances; to examine the role of growth factors over retinal cells' dynamics; to assess nanostructured scaffolds and their potential cytotoxicity, and to evaluate potential advanced therapies.Although mammal neuroretina is an excellent alternative to the dependency on post‐mortem human eyes, ex vivo human neuroretina cultures have also been characterized. They have improved the current knowledge about photoreceptors, ganglion cells, glial cells and microglia dynamics. Furthermore, human tissues are theoretically better suited for translational research than animal cells and perhaps even animal models, which exponentially increases the usefulness of the neuroretina cultures, and the extrapolation of the results obtained, marking a promising future for the screening and evaluation of potential neuroprotectors.
An overview of functional, psychophysical and structural techniques to study murid models in vision science
Authors: Navarro Santiago Milla 
Published: December 2022

AbstractThe retina is a highly specialized tissue, made up of various cell types that are structured and organized to form a complex neural network. However, the retina is also highly susceptible to various types of pathophysiological alterations, which can lead to the loss of the different cellular elements and thus to the loss of a large part of the retina's visual functions.Over time, different types of behavioural, functional or electrophysiological tests have been developed that have allowed us to study the different visual capacities of the retina in murine models of retinal neurodegeneration, without the need to sacrifice the animals or induce serious damage from invasive recording.Behavioural testing has proven to be a powerful tool for the study of alterations in retinal visual pathways. These techniques allow a simple but effective analysis of the visual capabilities of experimental animal models with retinal degenerative processes. Physiological aspects such as light sensitivity or the degree of visual acuity of these animal models can be quickly and effectively analysed by applying different types of tests such as the Light/Dark Transition Test or the Optomotor Test, respectively. Likewise, behavioural techniques also allow us to study other biological aspects such as the circadian activity of the animal models, which would allow us to study alterations that also affect the retinal pathways that do not participate in the image formation process. In addition, the simplicity of some of these tests allows the combination of several parameters that allow us to simultaneously study several visual abilities equally.Likewise, other non‐invasive functional tests, such as the Pupillary Light Reflex study, allow us to determine the degree to which retinal neurodegenerative disorders affect other closely related signalling pathways, such as the afferent and efferent pathways responsible for the pupillary reflex.Finally, electroretinographic recording techniques are an invaluable tool for studying the functionality of the various retinal cell populations. By applying specific light stimuli, it is possible to record the specific response of certain cellular elements, studying how various pathophysiological alterations of the retina affect its functionality. Variations of these techniques have even made it possible to study the activity of cells in the primary visual cortex.With the development of new fields of study, such as optopharmacology, the knowledge and correct choice of visual characterization techniques is essential to study the efficacy of these new ophthalmological approaches.
Development of a new vitreous tamponade for the treatment of rhegmatogenous retinal detachment
Authors: Valldeperas Xavier 
Published: December 2022

AbstractWe are developing a new endotamponade for the management of rhegmatogenous retinal detachment (RD). It will be reabsorbable and its efficacy will not be dependent on head posture, being equally effective for superior and inferior RD. This solution will be totally biocompatible and it will not need major changes in the usual pars plana vitrectomy surgical process.
VCN‐01: from the preclinic to a phase I trial for refractory retinoblastoma patients
Authors: Catala Jaume 
Published: December 2022

AbstractWhy do we propose an oncolytic adenovirus for the treatment of retinoblastoma?Physiopathology:
Conventional chemotherapy‐independent
Highly selective RB1 route (only infects E2F‐1‐high cells)
Convenient local administration & low systemic spread
Clinical availability of a GMP‐grade virus already evaluated by the AEMPS (Spanish Drug Agency)
Security data available from adult treatment of refractory solid tumours

Clinical translation to EudraCT: 2016–001060‐11
VCN‐01 is active for the treatment of chemo‐resistant retinoblastoma
The distribution of the infective virus is restricted to the eye in mice and rabbits
VCN‐01 intravitreal injection is both feasible and safe in rabbits

Phase I Safety and Activity trial of the Oncolitic Adenovirus VCN‐01 for Patients With Refractory Retinoblastoma
Single Site,
Open Label With Dose Escalation
To evaluate safety and Activity of intravitreal VCN‐01in Patients With Refractory Retinoblastoma

Inclusion criteria
Unilateral somatic mutation RBL
Germinal mutation RBL active in only one eye (fellow eye non‐affected or enucleated)
Rellapsed or refractory to systemic, intra‐arterial or intra‐vitreal chemotherapy
Age: 1–12 yo

Exclusion criteria
Indication for immediate enucleation of the affected eye:
glaucoma
rubeosis iridis
anterior chamber disease

Conclusion.Phase I trial EudraCT: 2016–001060‐11 to include Patients with Reactivated or refractory RBL.
value of the retina in the diagnosis of Alzheimer's disease
Authors: Salobrar‐Garcia Elena 
Published: December 2022

AbstractVision, which is a process that requires the involvement of a large number of neurons, is often impaired during Alzheimer's disease (AD). Over the past few decades, research has shown that several visual functions and structures are compromised during AD and can also be used to differentiate affected individuals from those who show normal aging. Retina is a projection from the central nervous system and shares many features with the brain. Classically, the damage in AD was thought to be restricted mainly to the brain. However, in the last years it has been demonstrated in retinas of AD human postmortem specimens, the presence of Aβ plaques and pTau deposition, being more abundant in the superior region of the retina matching with greater neuronal degeneration. Also, it has been suggested that Aβ plaques in the retina may anticipate those in the brain. In addition, recently it has also been possible to observe in vivo Aβ plaques in human retinas, with imaging techniques and ingesting curcumin as a marker of Aβ deposits. Recently, using in vivo hyperspectral imaging techniques in the retina, it has been reported that Aβ load in the brain can be predicted. These findings provide histopathological evidence that the visual system may be altered much earlier in the AD disease process than previously thought, and thus support the use of visual biomarkers in the early detection of the disease. Current in vivo imaging techniques such as OCT are allowing ophthalmologists to detect and quantify data consistent with the histopathological findings described in the retinas of AD patients. In early AD, OCT has demonstrated a thickening of the macular region and a subsequent thinning of the peripapillary area of the retina in more advanced stages of the disease. New analytic methods have shown in AD patients that thinned regions are interspersed with thickened ones in all retinal layers, except inner nuclear and outer segments. This causes roughness to appear on retinal layer thickness maps, finding that Fractal Dimension (FD) of retinal layers is greater in the AD patients, being roughness of retinal layers, assessed by the FD of their thickness maps, a possible early retinal biomarker of AD.In the other hand, recent data suggest the vascular involvement of the retina in AD patients. Vascular changes in the retina are thought to share similar pathogenic mechanisms with cerebral vasculature. OCT and OCT angiography (OCTA) has demonstrated a thinning of the choroidal thickness in early AD and decrease of the foveal avascular zone in patients with moderate AD.All these observations support the value of the retina as a biomarker of AD that will allow us, with the development of new research, to discover new retinal biomarkers that will help us to improve the diagnosis and follow‐up of this growing pathology.
Binocular, accommodative and oculomotor alterations in multiple sclerosis
Authors: Piñero David P. , Gil‐Casas Amparo , Molina‐Martín Ainhoa 
Published: December 2022

AbstractMultiple sclerosis (MS) is an acquired demyelinating and inflammatory neurodegenerative disease affecting the central nervous system (CNS). Clinical and subclinical ocular disturbances occur in almost all patients with MS. Among them, oculomotor, accommodative and binocular alterations have been reported in MS. Our research group has conducted a complete analysis of the visual and oculomotor function in several researches with MS patients conducted in the last 4 years, obtaining a characterization of some visual aspects of the patient with MS. Concerning the binocular function, several alterations have been detected in MS patients, with divergence at near distance and stereopsis the most affected parameters. Likewise, MS patients with previous optic neuritis present worse binocular vision. Symptomatology compatible with convergence insufficiency measured with the CISS (Convergence Insufficiency Symptom Survey) is frequently reported by MS patients, but not supported by signs that show clear trend to esophoria at near. This discrepancy between the signs and symptoms could be due to the peculiarities of the CISS questionnaire, including items that are also related to the cognitive function and other ocular abnormalities.Oculomotor alterations have been reported also in patients with multiple sclerosis (MS), especially saccadic dysfunctions. The indirect analysis of horizontal saccades with the Developmental Eye Movement (DEM) and King‐Devick tests shows that are affected by MS, with more level of alteration if there has been a previous episode of optic neuritis. Similar findings have been also reported by other authors using objective eye tracking or video‐oculographic systems. Specifically, the most reported saccadic alterations in advanced MS and clinically isolated syndrome (CIS) are saccadic dysmetry (41.7%) and impaired smooth pursuit (42.3%), which relates to prolonged saccadic latency, no matter if they have suffered or not optic neuritis or internuclear ophthalmoplegia (INO). An increase in saccadic latency has been even found in children with MS. Saccadic initiation time (SI time) and average inter‐saccadic intervals (ISI) are also higher in patients with MS. Furthermore, the first cause of acquired pendular nystagmus is MS.Finally, macular sensitivity measured by microperimetry has been found to be altered in MS patients, especially in eyes with previous optic neuritis. Likewise, a fixational instability characterized also my microperimetry is present in MS patients with optic neuritis, with more increase of the vertical axis of the fixation area than of the horizontal. The ratio of the disease also affects the patient fixation pattern.