bluuebunny/crossref_metadata_2025_split huggingface dataset:
Haemorrhage due to intraocular tumours
Authors: Papastefanou Vasilios 
Published: December 2022

AbstractDiffuse intraocular haemorrhage poses challenges for the clinician. These involve the multitude of clinical aetiologies and the variability in the treatment pathways or plan employed towards its treatment. A particular challenge involves its association with the presence of intraocular tumours. Haemorrhage is a rare manifestation in both pigmented and non‐pigmented tumours manifesting as an initial presentation or as part of the natural course of an untreated intraocular tumour. On some instances, the mere visibility and proper assessment of an intraocular tumour might be impeded with a challenging differential diagnosis.In addition, haemorrhage can be baffling for the ocular oncologist as it might develop in treated tumours and in relation to radiation related events. The latter could affect tumour presentation post treatment and lead to treatment dilemmas.This talk addresses the aetiology, pathophysiologic mechanisms, imaging and clinical features involved with the development of haemorrhage in this clinical setting taking into account the particular features of pigmented and non‐pigmented tumour paradigms.
Effect of MIGS on corneal endothelium
Authors: Gugleta Konstantin 
Published: December 2022

AbstractCorneal endothelium is one the meeting points between glaucoma and corneal pathologies. Endothelial cells maintain corneal transparency by dehydrating the cornea, by pumping fluid from the corneal stroma back into the aqueous humour. Loss of these cells leads to fluid accumulation and corneal opacification. Loss of endothelial cells was indeed also observed with trabeculectomy, but it evolved in one of the major issues in the “big tube” glaucoma surgery. Rapid development of new glaucoma surgery techniques in the last decade re‐opened the question in the context of microinvasive suprachoroidal and Schlemm canal techniques. The more classic subconjunctival surgical drainage pathway has observed changes lately as well: collagen gel stent XEN and PreserFlo Microshunt were relatively recently introduced. With these still relatively new techniques, the research focus in the initial stages was placed on intraocular pressure reducing efficacy and general safety. However, in the meantime also research results also on the topic of endothelial cell density following these interventions have been published, and this talk will try to summarize the current knowledge in this area.
Post‐keratoplasty glaucoma; diagnosis and treatment
Authors: Wylegala Edward 
Published: December 2022

AbstractPost‐keratoplasty glaucoma is one of the most detective complications. The increase in pressure after keratoplasty destroys the ganglion cells and damages the corneal endothelial cells. The presentation was prepared based on the author's experience with nearly three thousand corneal transplants. The incidence of post‐transplant glaucoma ranges from 10 to 50%, with an average of 35%. Difficulties and variations related to measuring intraocular pressure, visual fields, and OCT will be discussed. Finally, an overview of the options for classical and laser surgical treatment will be presented.
Stem cells versus keratoprostheses
Authors: Zarei‐Ghanavati Mehran 
Published: December 2022

AbstractRoutine penetrating keratoplasty will not survive well in some circumstances, including harsh ocular surface environment, stem cell deficiency and chronic ocular inflammation. Fortunately, there have been advances to restore vision in these conditions in two directions: artificial keratoplasty and limbal stem cell transplantation. The recipient eye should have an intact lid mechanism and good tear film for stem cell transplantations. There may also be a need for future lamellar or penetrating keratoplasty with a chance for graft rejection. Treatment of unilateral limbal stem cell deficiency is relatively simple with three surgical options: Conjunctival Limbal Autograft (CLAU), Cultivated Limbal Epithelial Transplantation (CLET) and Simple Limbal Epithelial Transplantation (SLET). However, most patients have bilateral diseases like Stevens‐Johnson syndrome (SJS), aniridia and mucous membrane pemphigoid (MMP). In this scenario, an allogenic source for limbal stem cells is needed.Moreover, systemic immunosuppressive will be required to decrease the chance of rejection. Another option is Cultured Oral Mucosal Epithelial Transplantation (COMET) which usually provides less optimal visual acuity. The last option is keratoprosthesis (KPro). Many KPro devices have come and gone through, and two clear winners have emerged:
Boston Keratoprosthesis KPro type I
Osteo‐odonto‐keratoprosthesis, also known as the ‘OOKP’

OOKP is suitable for patients with severe dry eye and permanent lid damage. These patients should be excluded from any type of stem cell transplantation due to the inevitable chance of failure. However, Boston KPro type I may be considered as an alternative option for stem cell transplantation. Recent meta‐analysis for comparison of Keratolimbal Allograft (KLAL) and Boston KPro I in eyes affected by chemical burn has shown quite similar outcomes. Though, it should be mentioned that there are many limitations in included studies that make it difficult to reach an accurate conclusion. KPro has the advantages of shorter rehabilitation time and no need for systemic immunosuppression.Nevertheless, there is more chance of complications or loss of visual potential with KPro. Corneal surgeons should, in fact, be familiar with both options of KPro and stem cell transplantation to guide their patients towards the correct choice of treatment. The learning curve of such surgical techniques is steep. An extended follow‐up time is necessary to evaluate the safety of any method.
United Kingdom OOKP outcomes
Authors: Avadhanam Venkata S. 
Published: December 2022

AbstractThe osteo‐odonto‐keratoprosthesis (OOKP) is the only option for sight restoration in patients with end‐stage ocular surface blindness in eyes with severe dryness and eyelid anomalies or defective blink. OOKP is performed as a multistage procedure, which involves buccal mucosal grafting over the eye, OOKP device construction and its impanation into the eye in sequential steps. A retrospective study was conducted at Sussex eye hospital, Brighton, and the long‐term outcomes of the OOKP cases are presented here. In total 64 patients were included, and 74 laminae were implanted, which included 60 tooth autografts, 11 tooth allografts and 3 tibial grafts. Stevens‐Johnson syndrome was the most common indication accounting for 43% (n = 7) of the cases. Glaucoma was the most common complication noted in 86% (n = 57) of the cases. Laminar resorption was noted in 67% of the laminae. At 10 years of follow‐up, 59% of the eyes had a vision better than 6/12 and 82% had a vision better than 6/60. Autograft laminae showed a survival probability of 91% over 18 years. In summary, OOKP provides excellent visual recovery and longevity of the device over the long term; nevertheless, it requires close monitoring and timely interventions to treat any complications.
Leading and managing a keratoprosthesis service
Authors: Liu Christopher 
Published: December 2022

AbstractKeratoprostheses are last resort procedures and are inherently unstable. A multidisciplinary team needs to be in place, available 24/7/365 through a coordinator, with the team led by the main keratoprosthesis surgeon. There should be a telephone number and email address which are manned day and night year round. Attention should be paid to colocation of subspecialty team members who will have different timetables. Vitreoretinal expertise, including endoscopic vitrectomy expertise, and operating theatre time should be instantly available for infection and macular on retinal detachments. The extended team may include eye surgeons (corneal, adnexal, glaucoma, vitreoretinal), maxilla‐facial surgeons, anaesthetists, radiologists, fellows, and a coordinator supported by named nurses in theatres, ward and outpatients. Attention should be paid to make keratoprosthesis services more robust by having more than one key person for key roles to cover leave and sickness and orderly succession planning.
Glaucoma gene mutations and their association with angle dysgenesis
Authors: Gupta Viney 
Published: December 2022

AbstractAngle dysgenesis is associated with developmental immaturity of the outflow pathways regulated by genes, which can only be ascertained with the help of histopathological studies. Mutations in some of the commonly associated genes with glaucoma, namely CYP1B1,FOXC1 PITX2, and TEK have been shown to be associated with developmental abnormalities in the outflow pathways in experimental studies. The severity of angle dysgenesis has been correlated on histopathology with certain CYP1B1 gene mutations in patients with Primary congenital glaucoma (PCG). Though MYOC mutations are known to be associated with Juvenile onset open angle glaucoma (JOAG) and even with PCG, no studies have shown the involvement of MYOC mutations in causing angle dysgenesis. There is only one histopathological report of a JOAG patient with MYOC Tyr453His mutation, where no apparent changes of the Trabecular meshwork(TM) or Sclemm's canal were noted though intense MYOC immune‐reactivity was observed at the TM. Histopathological studies for angle dysgenesis in human glaucomatous eyes are difficult to perform and are inherently associated with tissue handling artefacts. While grossly identifiable features of Ange dysgenesis on ASOCT (ADoA) have been described before, many subtle changes may also be present on ASOCT scans which are challenging to detect or precisely quantify by human observers.We studied the ASOCT scans of patients with open angle glaucoma diagnosed between 10 to 40 years of age, who had undergone Whole Exome Sequencing (WES) followed by a bioinformatics analysis and were found to harbour a mutation (that was pathogenic) in a known glaucoma gens. We used Deep learning (DL) models to detect ADoA.We detected MYOC mutations in 15 patients, 10 had CYP1B1, 2 had FOXC1 and 2 had LTBP2 mutation. Among these patients, angle dysgenesis on ASOCT was observed as predicted by the DL models, among all patients with known gene mutations. Overall, our DL Model was predictive of angle dysgenesis in 81% scans among MYOC positive patients, 89% CYP1B1 patients, 85% FOXC1 and 96% among those with LTBP2 mutation on an average.Our findings demonstrated that different gene mutations affect different parts of the proximal outflow pathways. While CYP1B1 and LTBP2 was found to affect primarily the SC morphology, the MYOC and FOXC1 were found to be associated with morphological variations in the TM, since the SC in the latter was normally developed.
On a quest for solutions
Authors: Hemelings Ruben 
Published: December 2022

AbstractA plethora of classification models, and especially convolutional neural networks (CNN), have been proposed for the detection of glaucoma from fundus images. Often trained with data from a single glaucoma clinic, they report impressive performance on internal test sets, but (I) lack in objective insights into the decision making process, and (II) rarely generalize well to external sets.Opening the black‐box: need for explainable AIData‐driven, feature‐agnostic CNN models have shown to outperform classical machine learning approaches that rely on manually curated image features. But this comes at the expense of explainability, a concept introduced to delineate the insights into the decision process of the algorithm. Explainable AI is particularly relevant in the field of medicine, as regularity bodies require understandable decisions, in order to gain trust from both clinicians and patients. The largest area of research in explainable AI proposes the framework of saliency or heat maps, i.e. visualizations of image regions that are deemed the most important to the trained model. However, these techniques are facing increased scrutiny over the years, as some studies indicated that most saliency mapping methods perform no better than random baselines.In our recent work, we used various fundus image cropping policies to investigate the salient regions for glaucoma detection. Our findings provide the first irrefutable evidence that deep learning can detect glaucoma from colour fundus image regions outside the ONH.Generalizability and domain shiftsThe ability to generalize, generalizability, to unseen data is of crucial importance in building clinically useful deep learning models. This can be defined on two levels. First, a model is deemed useful when it performs well on unseen data from the same domain as the training data. More concretely, this would mean that a model trained on glaucoma data from one glaucoma center works well on a holdout set of images from the same clinic. Next to internal testing, it is critical to have models that scale well to imaging data from external sources, such as a glaucoma clinic from a different city. This transition introduces a domain shift, an event where the data distribution changes. This shift can be as small as an undetectable different image colour histogram due to other lighting conditions at the external center.Typically, domain shifts are more marked between ophthalmic centers. The usual suspects include the following non‐exhaustive list: change in camera manufacturer, disease prevalence, and demographic characteristics such as ethnicity and age. A tool that would be suited for glaucoma screening should be able to adapt to a much lower glaucoma prevalence, when initially trained on a data set obtained from a referral center. We demonstrate that a deep learning approach backed by regression loss seems more robust to data shifts than a traditional binary classification system for glaucoma screening from fundus images. Excellent results were obtained on 12 different data sets, with close to 150 000 images evaluated.
Visual field‐based AI in glaucoma
Authors: Schmetterer Leopold 
Published: December 2022

AbstractArtificial intelligence (AI) has recently evoked tremendous excitement for research in the field of Ophthalmology and glaucoma. One of the areas where AI could come into play relates to the prediction of visual field progression. Currently linear trend‐based analysis is the most widely used method for assessing visual field progression. In the recent years a variety of deep learning based approaches have been proposed to better predict visual field progression. Techniques including archetypal analysis, Gaussian mixture model with expectation maximization and Visual Geometry Group standard deep Convolutional Neural Network (CNN) will be discussed. AI has also been used to study mapping of structure to function in glaucoma. This is of importance because it may be used to reduce the variability of visual field data. Hence it may increase our ability to study functional progression by combining perimetry and OCT data. Moreover, the structure/function relationship has been shown to be an independent risk factor for glaucoma progression.
Current status of limbal transplants for the treatment of limbal stem cell deficiencies
Authors: Barraquer Rafael I. 
Published: December 2022

AbstractThe possible treatments for limbal stem cell (LSC) deficiencies include a wide spectrum spanning from general support measures (medical, lubricants and plasma derivatives), resection techniques, the different options for supplying LSC (limbal transplants, expanded cell transplants, SLET, heterotopic mucosal transplants), all the way to keratoplasty and keratoprosthesis. This presentation will review the current status of limbal transplants for LSC deficiencies, including autologous and homologous kerato‐limbal and conjunctivo‐limbal grafts, with an update on the indications, techniques, results and postoperative management.
Corneal stromal regeneration
Authors: Alió Jorge L. 
Published: December 2022

AbstractCorneal grafting is one of the most common forms of human tissue transplantation. The corneal stroma is responsible for many characteristics of the cornea. For these reasons, an important volume of research has been made to replicate the corneal stroma in the laboratory to find an alternative to classical corneal transplantation techniques. There is an increasing interest today in cell therapy of the corneal stroma using induced pluripotent stem cells or mesenchymal stem cells since these cells have shown to be capable of producing new collagen within the host stroma and even to improve its transparency. The first clinical experiment on corneal stroma regeneration in advanced keratoconus cases has been reported and included. Fourteen patients were randomized and enrolled into 3 experimental groups: (1) patients underwent implantation of autologous adipose‐derived adult stem cells alone, (2) patients received decellularized donor corneal stroma laminas, and (3) patients received implantation of recellularized donor laminas with adipose‐derived adult stem cells. Clinical improvement was detected with all cases in their visual, pachymetric, and topographic parameters of the operated corneas.
Intracameral injection of cross‐linking hydrogel polymer as an animal model of IOP increase
Authors: Di Pierdomenico Johnny , Henderson D. C. M. , Smith C. A. , Hooper M. L. , Chauhan B. C. 
Published: December 2022

AbstractGlaucoma is a multifactorial neurodegenerative disease that leads to the progressive loss of retinal ganglion cells (RGCs) and their axons resulting in visual field damage and retinal and optic nerve head changes. Progression is generally slow but, in some patients, can lead to a ‘catastrophic’ reduction of visual function and in advanced cases may lead to blindness. Glaucoma is, in fact, the leading cause of irreversible blindness worldwide.Finding a model of retinal ganglion cell (RGC) loss or experimental glaucoma which accurately mimics human disease has been a challenge for researchers. There have been many attempts to produce a model of studying RGC pathophysiology or death longitudinally to study pharmacological treatments or neuroprotective interventions. There are many methods, both acute and chronic, that have been used to induce retinal ganglion cell death. Some methods made a direct injury to the optic nerve which causes rapid RGC death, while others are models try to increase the IOP with mechanical damage or injection of different agents into the anterior chamber to block aqueous humour outflow.Several models of chronic glaucoma, primarily in non‐human primates and rodents, in which IOP is elevated has been described. However, most of these animal models due to the opacification of the ocular medias as a result of the inflammation or intraocular pression increase only allow to perform a single time point for many different time ex vivo analysis of the RGCs. So, longitudinal changes in the number of RGCs in the same animal can only be performed in vivo. This is an important way to remove the between‐subject variability, but any aging effects will be compounded to those due to disease progression.A novel glaucoma model using a cross‐linking polymer result in a consistent and sustained elevation of IOP with preservation of optical media clarity for long term.This model is based on in situ temperature sensitive cross‐linking of a mixture of two components (hyaluronic acid functionalized with vinyl sulfone (HA‐VS) and thiol groups (HA‐SH)). When the mixture is injected into the anterior chamber, the higher temperature of aqueous humour compared to air causes the gel to solidify within the anterior chamber angle thereby blocking aqueous outflow through the trabecular meshwork and increasing the IOP. Furthermore, the hydrogel is localized to the anterior chamber angle with no noticeable media opacities, thereby allowing repeated in vivo imaging.It has been shown that the increased IOP and the optical media clarity produced in this animal model of glaucoma allows for in vivo study with the Confocal Scanning Laser Ophthalmoscope of the density and structural loss of RGCs, as well as functional loss of RGCs with electroretinography for more than 4 weeks after the hydrogel injection.
Mitochondrial transport along RGC axons: Strategies to restore energy homeostasis and visual function
Authors: Di Polo Adriana 
Published: December 2022

AbstractDeficits in mitochondria anterograde axonal transport is a common feature of neurodegenerative diseases including glaucoma. Whether aberrant expression of components in the transport machinery impinge directly on metabolic stress, neuronal death, and circuit dysfunction, is currently unknown. We used multiphoton microscope live imaging to monitor mitochondrial transport along the axons of retinal ganglion cells (RGC), the neurons that die in glaucoma. We found that high intraocular pressure, the most important risk factor to develop the disease, impairs anterograde movement of mitochondria along RGC axons leading to mitochondria depletion and energy decline. Molecular profiling of motor and adaptor proteins revealed loss of Disrupted in schizophrenia (Disc1) expression in glaucomatous RGC. Adeno‐associated virus (AAV)‐based Disc1 gene delivery rescued anterograde transport and replenished mitochondria in proximal and distal axonal segments. Delivery of a genetically encoded ATP sensor combined with longitudinal live imaging revealed that Disc1 supplementation increased ATP production in stressed neurons. Strikingly, Disc1 gene therapy promoted neuronal survival, reversed abnormal RGC calcium dynamics, and restored light‐evoked retinal responses and visual behaviour. Our study provides proof‐of‐principle that enhancing mitochondrial anterograde transport is an effective strategy to alleviate metabolic stress and glaucomatous neurodegeneration.
The role of autophagy in disease
Authors: Boya Patricia 
Published: December 2022

AbstractDefective proteostasis is one of the hallmarks neurodegenerative diseases. Of the different components of the proteostasis network, we are interested in autophagy and its changes with age. We have previously shown that, out of the different autophagic pathways that co‐exist in all mammalian cells, macroautophagy is the first that declines with age in the retina, A crosstalk between macroautophagy and chaperone mediated autophagy (CMA) has been described whereby, in aged mice retinas, the decrease in macroautophagy correlates with increased CMA. Our working hypothesis is that in aged and degenerated retinal cells increase CMA to compensate for macroautophagy loss, in an attempt to maintain cell viability. Here, I will present our latest data showing how CMA upregulation can protect photoreceptor cells in retinitis pigmentosa models.