bluuebunny/crossref_metadata_2025 huggingface dataset:
Glaucoma Surgery‐ How to manage the failing trabeculectomy
Authors: Crawley Laura
Published: December 2019

In this session we will explore the short and longer term strategies for maximizing filtering bleb surgery success. This will include pre, intra and post operative management tips. We will explore the common and unusual reasons for bleb failure and ask the question is there a place for redo trabeculectomy in the modern era of glaucoma drainage devices.
How does aging influence tear fluid proteomics
Authors: Nättinen Janika
Published: December 2019

The prevalence of many ophthalmic diseases increases with age. While the clinical characteristics and pathophysiological mechanisms of these diseases are relatively well‐known or extensively studied, the underlying biological systems of normal aging in the ocular surface remain unclear. In order to examine the effects of aging on tear fluid proteomics and ocular surface, tear microcapillary samples were collected preoperatively from 115 subjects and analysed using NanoLC‐TripleTOF mass spectrometer. Bioinformatics analysis revealed several inflammation and immune response‐related proteins, which correlated significantly with increased age. Our results display the effects of normal aging in the ocular surface and identify a group of age‐dependent proteins. Knowledge of the proteins, pathways and upstream regulators discovered in our study can be later implemented in the research of dry eye and other ocular surface diseases, which are associated with increased age.
Diagnosis of haematological diseases with monoclonal gammopathy
Authors: Mikala Gabor
Published: December 2019

Despite the complexity of lymphoproliferative disorders, the presence of monoclonal immunoglobulins has been providing diagnostic guidance to the haematologist for more than a century. Clinicians may be alerted for the possible presence of serum monoclonal immunoglobulins produced in excess by increased erythrocyte sedimentation rate. Thereafter the diagnosis of monoclonal gammopathy could be proven by serum protein electrophoresis followed by immunofixation to properly identify the M‐protein. In a quarter of the cases, no intact monoclonal immunoglobulin could be detected in the sera, however, free light chains produced in excess may be identified using specialized immunoassays, so called free light chain analysis.

Idiopathic monoclonal gammopathy of unknown significance (MGUS) may be present in 1% of the population above age 50 and up to 10% for individuals over 80 years of age. Due to the high frequency of MGUS, between 50‐65% of all monoclonal proteins detected fall into this category and most asymptomatic patients remain undetected for many years. MGUS patients have a 1% per year chance for transformation into malignant monoclonal gammopathies. Presently, it is accepted that most multiple myeloma and amyloidosis patients have their disease developed by transformation from preexisting MGUS. Additionally, some nonmalignant hematological disease also frequently exhibit monoclonal immunoglobulin synthesis, most notably Gaucher’s disease.

From the field of neoplastic hematological diseases, smouldering and symptomatic multiple myeloma as well as Waldenström’s macroglobulinaemia almost always exhibit significant amounts of serum M‐protein and/or monoclonal free light chain excess. In case of solitary plasmocytoma, primary AL amyloidosis, cryoglobulinaemia and plasma cell leukemia, the correlation with gammopathy is less strict. Monoclonal gammopathy is less common in different types of non‐Hodgkin lymphoma. Within lymphomas lymphoplasmocytic lymphoma and marginal zone lymphoma more commonly secrete monoclonal immunoglobulins, while other B‐cell lymphomas have 14% cumulative chance for specific gammopathy. In the case of B‐cell chronic lymphocytic leukemia (the most common leukemia), intact monoclonal gammopathy has a 2% appearance, while abnormal free light chains may be detected in a third of the cases. Sporadically monoclonal gammopathy may be detected in chronic myelomonocytic leukemia, refractory anaemia, large granular cell leukemia and angioimmunoblastic lymphoma. Notably, in many of these diseases, the amount of secreted monoclonal immunoglobulin and/or free light chains correlate with the tumor burden and could be used for disease monitoring, especially in indolent hematological neoplasias.
Small graft, simultaneous amniotic membrane transplantation, temporary lateral tarsorrhaphy and autologous serum improves outcome of penetrating keratoplasty in congenital aniridia with aniridia associated keratopathy
Authors: Fries Fabian
Published: December 2019

Purpose

Congenital aniridia is a challenge not only for the corneal surgeon. Persisting epithelial defects, suture loosening, and an increased risk of graft rejection are typical postoperative complications in high risk keratoplasty such as in congenital aniridia.

Methods

Between 2012 and 2018, 20 keratoplasties were performed in 13 patients with congenital aniridia at our Department. Visual acuity and intraocular pressure before and after keratoplasty, corneal graft size, suture technique (interrupted or double running), use of amniotic membrane transplantation and serum eye drops, size of bandage contact lens as well as morphological and functional status during follow‐up were analysed retrospectively.

Results

Six keratoplasties were performed using continuous double running suture, 14 using interrupted sutures. Amnion membrane transplantation as a patch with a 17 mm bandage contact lens was applied 18 times to promote postoperative corneal wound healing. In 10 cases, a simultaneous temporary lateral tarsorrhaphy was performed to support corneal wound closure. All patients received systemic immunosuppression. Visual acuity improved in 14 eyes at 6 months follow‐up, in 6 eyes visual acuity remained stable, no eye showed a decrease in visual acuity.

Conclusions

Keratoplasty in congenital aniridia must be considered a high risk keratoplasty. A modified keratoplasty scheme combining a small corneal graft size, interrupted sutures, simultaneous AMT Patch, large bandage contact lens, temporary lateral tarsorrhaphy, postoperative autologous serum eye drops, and systemic immunosuppression seems to be appropriate to reduce the postoperative complication rate in these most difficult eyes.
Human induced pluripotent stem cell‐derived retinal pigment epithelial cell model of Sorsby fundus dystrophy
Authors: Hongisto Heidi
Published: December 2019

Sorsby fundus dystrophy (SFD) is a rare degenerative disease of the macular retina, caused by mutations in the tissue inhibitor of matrix metalloproteinase‐3 (TIMP3) gene. SFD leads to bilateral loss of central vision and shows significant clinical overlap with the more common age‐related macular degeneration, suggesting shared underlying mechanisms. In SFD the mutant TIMP‐3 deposits under the retinal pigment epithelium (RPE), leading to pathological sub‐RPE thickening, but the initiating pathology is poorly understood. We have established patient specific human induced pluripotent stem cell (hiPSC) lines from three SFD patients carrying Ser204Cys mutation in TIMP3 gene, and three healthy controls. The hiPSC lines were extensively characterized and differentiated to RPE. SFD‐iPSC‐RPE showed no difference in RPE properties such as morphology, gene or protein expression, phagocytosis capacity or growth factor secretion compared to control‐hiPSC‐RPE. SFD‐iPSC‐RPE showed lowered epithelial resistance, and transmission electron microscopy indicated basal laminar changes and deposits under the SFD‐iPSC‐RPE. Quantitative proteomics analyses indicated upregulation of retinal degeneration associated pathways and accumulation of related proteins including apolipoprotein E. Western blotting verified clear accumulation of the TIMP3 protein in the SFD‐iPSC‐RPE cultures. Overall, the SFD‐iPSC‐RPE cell models recapitulate the disease phenotype in vitro for the study of disease mechanisms.
History of concepts of myopia pathogenesis and treatment
Authors: Grzybowski Andrzej
Published: December 2019

In the last 60 years, there has been a marked increase in the prevalence of high myopia in developed countries in East and Southeast Asia, and there are signs of similar, but less dramatic increases, in North America and Europe. In some parts of the world, 70‐90% of children completing high schools are myopic, and as many as 20% may be highly myopic. It is accepted now that myopia results from excessive axial elongation of the eye, which appears to be environmentally driven. The present methods of myopia control are based on the use of topical atropine and increased outdoor activity. Interestingly, the early observations on similar concepts and the first reports of atropine treatment date back to the 19th century. This is evidenced by papers of Ware (1813), Cohn (1864), and Tscherning (1883). Dobrowolsky published the first case series case series of myopia improvement after atropine therapy in German in 1868.
High resolution imaging of radiation retinopathy
Authors: Paques Michel
Published: December 2019

We explored by fundus photographs, OCT and adaptive optics ophthalmoscopy (AOO) the vessels of eyes after proton beam therapy for uveal melanoma in 10 eyes. We observed strong fluctuations of diameters in both arteries and veins, without significant changes in vascular wall thickness suggesting that vasoconstriction was involved in this process. Reduction of lumen diameter could be focal or diffuse, and could lead in some cases to branch retinal vein occlusion unrelated to arteriovenous crossings. The ensuing collateral circulation could lead to the development of TelCaps (capillary macroaneurysms), successfully treated by targeted laser in one case. Many areas of capillary closure followed a vascular perfusion or drainage scheme, suggesting that vasoconstriction played a role in the complex pattern of radiation retinopathy. This may provide the basis for therapeutic trials based on the modulation of vasomotricity.
Autoinflammatory uveitis
Authors: Chaques‐Alepuz Vicente
Published: December 2019

Autoinflammatory syndromes are a new group of distinct hereditable disorders characterized by episodes of seemingly unprovoked inflammation (most commonly in skin, joints, gut, and eye), the absence of a high titer of auto‐antibodies or auto‐reactive T cells, and an inborn error of innate immunity.

Ocular involvement is frequent in the monogenic autoinflammatory disorders and generally occurs as spontaneously recurring inflammatory events at different ocular sites caused by aberrant release of proinflammatory cytokines, mainly IL‐1β.

Innate and adaptive immune systems have evolved together to protect the host by quickly responding to danger signals, eliminating pathogens and creating immunological memory as well as immunological tolerance to self. Loss of control mechanisms and/or regulation of either the adaptive or the innate immune system lead to autoimmunity and autoinflammation respectively.

We present the clinical case of a family with three members affected with the same form of uveitis, that we have considered as presumed autoinflammatory uveitis.

As from this case we discuss about pathogenesis and therapy of autoinflammatory diseases and uveitis.
Tear proteome in uveitis
Authors: Roger Eidet Jon
Published: December 2019

Purpose

Uveitis represents the fourth commonest cause of legal blindness in adult patients. Analysis of tear fluid proteins in acute anterior uveitis (AAU) patients could represent a novel diagnostic modality. This study aimed at detecting potential tear fluid biomarkers in patients with AAU and bacterial keratitis (BK).

Methods

Fourteen patients with unilateral AAU, seven patients with bacterial keratitis (BK) and 14 healthy age‐ and sex‐matched control subjects were included. Tear fluid samples were obtained by inserting two Schirmer’s test strips behind the lower eyelid of each eye for five minutes without anesthesia. Proteins were then identified by liquid chromatography tandem mass spectrometry. Pooled tear fluid samples from healthy controls were compared with samples from AAU and BK patients, respectively. Ingenuity Pathway Analysis (IPA) was used to explore biological function.

Results

A relative protein level was obtained for 235 proteins in AAU patients and 198 proteins in BK patients, while using healthy control subjects as reference. In AAU patients, nine proteins were at least two‐fold up‐regulated, whereas in BK patients, 12 proteins were up‐regulated more than two‐fold. None of the top ten upregulated proteins in AAU and BK overlapped. The top canonical pathway identified by IPA was ‘Acute Phase Response Signaling’ in AAU and ‘LXR/RXR activation’ in BK. Top upstream activated regulators included peroxisome proliferator activated receptor delta in AAU and interleukin 6 in BK.

Conclusions

Tear fluid protein analysis represents a promising diagnostic modality for ocular inflammatory diseases and demonstrate differentially expressed proteins in acute anterior uveitis and bacterial keratitis.
Harnessing the power of OCT imaging in clinic by smart data analysis and presentation
Authors: Yap Timothy
Published: December 2019

The limiting factor in the success of imaging is the end‐user’s interpretation of it. Therefore, the manner in which the raw data is analysed and presented is crucial in leading the clinician to make the correct management decisions for each individual patient. With such a variety of OCT biomarkers and graphical representations available from a single scan, the results can often be time consuming for the clinician to analyse, underused due to lack of training or education, and often conflicting in terms of results. We aim to offer a summary of what we have available to us today in terms of the different ways OCT data is analysed and presented, and the clinical information that can be gleaned from these. Following this, we will explore novel ways in which OCT data can be most effectively presented in clinic and how this may help us make better, more efficient clinical decisions in order to improve the care for patients and meet the growing demands for glaucoma care.
Strategies to improve corneal endothelial graft outcomes
Authors: Levis Hannah
Published: December 2019

Our research is focused on the development of strategies to improve corneal endothelial graft survival. We are interested in improving the current treatments by optimising endothelial graft preparation techniques, shipping and delivery protocols. We are also interested in combining cultured endothelial cells with novel biomaterials to create tissue engineered biosynthetic grafts suitable for transplantation and have developed a useful ex vivo corneal model to test these grafts before future in vivo experiments.
Abnormalities of vision and colour vision in Parkinson's disease
Authors: Weil Rimona
Published: December 2019

Often thought of as a movement disorder, Parkinson's disease has prominent non‐motor symptoms. Vision is frequently affected, with deficits in acuity, contrast sensitivity and higher order visual processes, as well as retinal changes. These visual deficits may be predictive of dementia in Parkinson's disease. There is now pressure to define accurate markers that predict dementia, to help stratify clinical trials of disease modifying therapies in Parkinson's’ disease.

We have collected visual, cognitive and retinal (OCT) data in 112 patients with Parkinson's and 35 age‐matched controls. We assessed risk of dementia using validated risk algorithms. We show that higher risk of dementia is associated with poorer performance in visual tests including in colour vision. We also show that retinal thinning in the ganglion cell and inner plexiform layers is linked with higher risk of dementia.

Our findings suggest that visual measures and retinal structure may be useful to predict dementia in Parkinson's disease.
Limbal stem cell transplantation and keratoprosthesis
Authors: Moussa Sarah
Published: December 2019

Limbal stem deficiency (LSCD) is a severe ocular disease which may lead to vision impairment or corneal blindness. Beside conservative options like topical and systemical medical therapy, chronic stage treatment options include conjunctival replacement procedures and limbal autografting. If limbal cell transplanation in form of either cultivated limbal epithelial transplantation (CLET), simple limbal epithelial transplantation (SLET) or conjunctival limbal autograft (CLAU) and corneal transplantation are not successful a Keratoprosthesis in form of a Boston Keratoprosthesis or a Osteo‐odonto‐ Keratoprosthesis might be the last chance for these patients. In the following presentation indication and surgical options in LSCD will be discussed.
Intravitreal chemotherapy. indications and results
Authors: Matet Alexandre
Published: December 2019

Current methods and protocols of intravitreal chemotherapy for intraocular lymphoma will be exposed. The benefits in terms of functional and anatomical outcome, as well as potential complications will be discussed.
OCT in peripheral chorioretinal tumors and pseudo‐tumors
Authors: Zografos Leonidas
Published: December 2019

Differential diagnosis of peripheral tumors and pseudo‐tumors may be challenging in selected cases. Peripheral OCT allows the location of the tumors in various chorioretinal layers and the recognition of internal reflectivity of the tumors. In addition, the presence and extent of the serous retinal detachment is documented in order to observe the evolution in the time. Peripheral OCT contributes in addition to the definition of tumor borders and assists the treatment planning for radiation therapy. The use of peripheral OCT is a valuable diagnostic modality for the diagnosis and management of peripheral tumors and pseudo‐tumors.
Bioengineered corneal stroma: from laboratory to clinical adoption
Authors: Rafat Mehrdad
Published: December 2019

Blindness caused by corneal stromal disease and injuries affects millions worldwide, with the greatest burden in low‐ to middle‐income countries with inadequate donation and tissue banking infrastructure to meet the demand for sight‐restoring corneal transplantation. We bioengineered a regenerative cell‐free corneal scaffold from medical‐grade type I collagen and developed a minimally‐invasive implantation method avoiding the need for surgical suturing or long‐term immunosuppression. Applying good manufacturing practices and third‐party certified biocompatibility, toxicity, sterility and long‐term shelf life studies, sterile corneal scaffolds were tested in preclinical animal models and in a first clinical case series. Scaffolds integrated with recipient tissue and supported host cell ingrowth without inflammation or scarring. 22 subjects with advanced keratoconus were implanted with the bioengineered scaffold without complications. During 6–12 months of follow‐up, no rejection, inflammation, vascularization or adverse event occurred. Visual acuity, spherical refractive error, keratometry, corneal thickness and volume all improved significantly in the cohorts. Initially contact lens‐intolerant patients were tolerant postoperatively and are eligible for refractive surgery to optimize visual acuity. Results indicate bioengineered scaffold implantation can restore vision in patients with advanced stromal disease, avoiding more invasive procedures and the need for donor tissue.
Analysis of current colour assessment protocols for the cabin crew
Authors: Ozpinar Ayse
Published: December 2019

Colour vision (CV) requirements for cabin crewmembers are set in accordance with the regulations of the European Aviation Safety Agency (EASA).They are required to identify correctly 9 of the first 15 plates of the Ishihara (IH)24‐plates.The aim of this study was to assess the severity of CV loss of applicants in relation to certification outcome based on the EASA cabin crew protocol. 126 applicants (78 deutans, 46 protans and 2 normal trichromats) were tested.The IH, CAD(Colour Assessment and Diagnosis) and anomaloscope were carried out to the specification required for Class I certification. 72% (56/78) of deutans passed the IH, but only 37% (17 /46) of protans passed.For all subjects 40% (51/126) passed both the IH and CAD.8% (7 protans and 3 deutans) of subjects failed IH and passed the CAD.19% (23 deutans and 1 protan) passed the IH and failed the CAD and 7 of these subjects had severe CV loss on the CAD and unusual anomaloscope results. The IH is used widely in aviation, and the number of errors is often used as a measure of the severity of CV loss. This study shows that the number of errors is not a good indicator of the applicant’s severity of CV loss. When the current EASA protocol for cabin crewmembers based on IH is applied, severe colour deficient subjects can pass and less severe subjects fail. A revision of the current colour assessment protocol for the cabin crew is needed to produce justifiable minimum CV requirements using colour assessment tests that are less variable.
The role of Wnt/β‐catenin signaling pathway in lens and retina development
Authors: Kozmik Zbynek
Published: December 2019

Wnt/β‐catenin signaling pathway functions by regulating the amount of the transcriptional co‐activator β‐catenin that controls key developmental gene expression programs. However, β‐catenin is known to have a dual function in cells. Apart from its key role as a nuclear effector of Wnt/β‐catenin signaling pathway (transcriptional function), β‐catenin is an integral structural component of cadherin‐based adherens junctions (cytoskeletal function). The essential role of β‐catenin during development is demonstrated by the finding that β‐catenin knockout mice fail to develop beyond embryonic day E6.5. Tissue‐specific deletion of β‐catenin gene in lens and neural retina resulted in a number of ocular phenotypes such as formation of ectopic lenses, failure to form lens vesicle, altered fiber cell differentiation and disruption of typical laminated structure of neural retina. In order to distinguish the phenotypes resulting from cytoskeletal or transcriptional function of β‐catenin we used mouse strain, in which the endogenous β‐catenin is replaced by mutant form of the protein, retaining cytoskeletal but lacking transcriptional function. We found that mice deficient for transcriptionally competent β‐catenin manifest abnormal development of lens epithelium and ciliary marginal zone of the neural retina. Our data unequivocally identify specific roles of canonical Wnt signaling for lens and neural retina development.
Histological aspects of limbal stem cell transplantation
Authors: Gießl Andreas
Published: December 2019

Maintenance and regeneration of the corneal epithelium relies on unipotent progenitor cells at the corneoscleral limbus, which are regulated by extrinsic factors from their local microenvironment, the stem cell niche. The postulated limbal niche is an anatomically protected site of intimate epithelial‐mesenchymal interaction and is highly vascularised, innervated, pigmented due to intraepithelial melanocytes. In addition, the limbal niche is infiltrated with immune cells, and supported by a specialized extracellular matrix as well as subepithelial mesenchymal cells emitting soluble signals. For ex vivo expansion and transplantation, limbal stem cells are unfavourably removed from their niche. This lecture outlines our current understanding and novel findings regarding the structural and molecular composition of the limbal niche including specific matrix components, cell‐matrix‐ and cell‐cell adhesion molecules, and niche cell populations, which are involved in stem cell regulation through multiple signalling pathways. This lecture also provides an overview of current tissue‐engineering approaches for corneal surface regeneration that aim at incorporating specific niche components, such as matrix proteins, growth and signalling factors, or putative niche cells, into the culture systems in order to support maintenance of stemness and to improve the therapeutic use of limbal stem cell transplantation.
Outcome of DMEK with prestripped grafts
Authors: Maier Philip
Published: December 2019

DMEK has become the standard procedure for patients with Fuchs endothelial dystrophy. However, graft preparation seems to be more difficult than graft preparation for DSAEK. Therefore, more and more surgeons ask their eye bank for prestripped tissue for DMEK that can directly be used by the surgeon. In our hands clinical results following DMEK using surgeon stripped tissue were better than after DMEK using precut tissue. Yet, data from the literature show that using prestripped tissue compared to surgeon stripped tissue for DMEK can lead to equal clinical results. However, the kind of storage following preparation seems to be an important factor. In the talk we discuss advantages and disadvantages of prestripped tissue compared to surgeon stripped tissue used for DMEK with respect to the preparation and storage techniques.
ANCA‐associated optic neuropathy
Authors: Kawasaki Aki
Published: December 2019

Antineutrophil autoantibodies (ANCAs) directed against either antiproteinase3 (anti‐PR3) or myeloperoxidase (anti‐MPO) are associated with a small vessel vasculitis in which the characteristic feature is a focal necrotizing damage of capillaries, venules and arterioles. The ANCA‐associated vasculitic syndromes are; granulomatosis with polyangiitis (formerly know as Wegener’s granulomatosis), microscopic polyangiitis, Churg‐Strauss syndrome and idiopathic necrotizing crescentic glomerulonephritis. Ocular and orbital manifestations may be a presenting manifestation of Wegener’s granulomatosis, in particular optic perineuritis. This presentation will review ANCA‐associated optic perineuritis and how it is distinguished from idiopathic optic perineuritis.
Post‐keratoplasty glaucoma; current state of diagnosis and treatment
Authors: Ratnarajan Gokulan
Published: December 2019

In this talk the examination and investigation used in the diagnosis of Post‐keratoplasty glaucoma will be considered, as well as potential challenges. The treatment options will be evaluated including traditional glaucoma surgery as well as newer treatment options such as sub‐conjunctival mircoshunts such as the Innfocus Microshunt and Xen Implant. Potential intra‐operative and post‐operative complications will be discussed as well as tips to minimise these.
CLET – Cultivated Limbal Epithelium Transplantation
Authors: Dobrowolski Dariusz
Published: December 2019

Injury and inflammatory factors disturb the homeostasis of corneal epithelium renewal. The idea for restoring the physiologic condition is therefore not only to provide the proper cell population within a zone of damage, but also to ensure stable conditions of the surrounding microenvironment. Transplantation methods based on either allogeneic grafts or autologous corneal epithelial stem cells are recognized as effective methods of treating the limbal stem cells insufficiency. Treating the disease, we try to create optimal conditions for development and maintenance of the function of stem cells. Autologous approach, in recent years, has become an minimally invasive and the most efficient technique of treatment. Long‐term observations of such patients allow to present conclusions regarding presurgical as well as postsurgical management.
Clinical translation of eye drops and complex drug products
Authors: Kompella Uday B.
Published: December 2019

Eye drops constitute majority of ophthalmic drug products, with solutions, suspensions, ointments, and emulsions being the top formulations. While solutions are considered simple formulations, with biowaiver granted for qualitatively and quantitatively similar generic formulations, others are complex formulations, whose generic products are difficult to develop and translate. In particular, manufacturing processes as well as the grades of inactive ingredients used can affect drug product attributes and bioavailability. Thus, bioequivalence of complex generics is less certain. The US FDA issued some draft guidance documents to ease approval of complex generic drug products. One purpose of this presentation is to discuss the difficulties in clinical translation of complex generic eye drop products. In recent years, there has been significant effort in developing eye drops for back of the eye drug delivery, using either pure drug formulations or carrier‐drug composite formulations (e.g., polymeric nanoparticles), with little or no success to date. The second purpose of this presentation is to discuss translational gaps in advancing eye drops for back of the eye drug delivery and to further discuss the difficulties in manufacturing and stabilizing composite nanoparticle formulations for eye drop applications.
Non‐OPA1 genetic causes of dominant optic atrophies
Authors: Wissinger Bernd
Published: December 2019

Dominant optic atrophy (DOA) is one of the most common forms of inherited optic nerve disease. The prevalence of DOA has been estimated to range from 1:16 000–1:50 000 in different populations. Clinical expression of DOA is highly variable and reduced penetrance is rather common which may hamper to establish the proper mode of inheritance. Dominant optic atrophy is a genetically heterogeneous condition with mutations in the OPA1 gene being by far the most common cause of DOA. Yet the knowledge about other genetic causes of DOA is still limited and sometimes equivocally. In recent years it became apparent that ‐ in term of its genetic basis ‐ DOA is just part of a continuous spectrum of syndromic neurodegenerative disease in many of which optic atrophy is only one clinical feature. Notably, the vast majority of the involved genes encode for proteins which are imported into mitochondria and exert diverse biological functions therein. In this presentation, I will give an overview on the current knowledge of non‐OPA1 genetic causes of dominant optic atrophies and the potential molecular mechanisms underlying the clinical outcome as DOA or syndromic neurodegenerative disease.
Biotherapies and ocular surface
Authors: Doan Serge
Published: December 2019

The pathophysiology of ocular surface diseases is better understood today. Several targets have been identified for their treatment, and currently available biotherapies are already used in clinical practice for selected cases.

In severe allergic diseases:

Omalizumab (Xolair®) is a systemic anti‐IgE treatment that suppresses the allergic response. It has been successfully used in vernal and atopic keratoconjunctivitis

Dupilumab (Dupixent®) is an anti‐IL4/IL13 systemic therapy indicated for severe atopic dermatitis. It has been used in atopic keratoconjunctivitis patients. It also has frequent ocular side effects such as conjunctivitis and blepharitis

In severe dry eye:

Lifitegrast (Xiidra®) is a LFA1 receptor inhibitor eye drop that prevents inflammatory cells to bind to the adhesion molecule ICAM 1. It has been approved in the US for the treatment of dry eye. The effects on symptoms seem to be superior to those of topical cyclosporine.

In mucous membrane pemphigoid:

Rituximab (Mabthera®) is a systemic anti CD20 antibody that targets B and pre‐B lymphocytes. It has shown very interesting results in severe cases.
Maximizing the outcomes of Simulation Based Training
Authors: Filipe Helena
Published: December 2019

Whilst offering multiple opportunities to practice procedural, cognitive and behavioral skills in a protected learning environment, simulation based training (SBT) is widely valued by surgeons at all levels, from medical students to the practicing specialist. Faculty should be expert in specific content as well as in specific simulation educational strategies. SBT effectiveness will not be maximized unless well planned, implemented and evaluated, trends being to build integrated simulation curricula. Simulation centers should work as rich multifaceted educational platforms involving a network of educators, experts in skills, learners and researchers. Translating educational theory into SBT practice will enable to measure the offset outcomes and thus self regulate the simulation center program. We will explore how to design, implement and evaluate a simulation session. We will specifically: (1) Define 6 steps to develop a curriculum; (2) Describe 3 segments of a simulation session; (3) Explain 3 types of assessment; (4) Identify 3 components of giving feedback; (5) List the 7 steps to evaluate an SBE program.
Adnexal complications after irradiation
Authors: Mouriaux Frederic
Published: December 2019

Orbital and eyelids side effects have been reported after irradiation. There exists a spectrum of radiation tolerance among normal ocular tissues. For example, whereas orbital bones, muscle, and fat can tolerate relatively high doses, and contrary the eyelids and lacrimal system are more radiosensitive. Moreover, children can develop severe complication after irradiation even several years later. It is not possible to determine an exact dose‐response relationship for ophthalmic side effects. This is because multiple factors (e.g., patient age, the condition of tissues, concurrent ophthalmic and systemic disease, dose, dose rate, medications) can affect the incidence and severity of radiation side effects
EyeClin – Customized Clinical Patient Management System dedicated to Rare Eye Diseases
Authors: Leroux Dorothée
Published: December 2019

The Clinical Patient Management System (CPMS) is a virtual clinic software provided by the European Commission aiming at improving the diagnostic process and treatment of patients with rare disorders within the ad‐hoc European Reference Network (ERN). Rare patient cases can be discussed online in respect to all the security requirements by a ‘virtual’ advisory board of medical specialists across different European member states using this secure IT platform. Thanks to this virtual clinic every patient across Europe could have access to the best recommendation of highly specialized experts wherever they are in European Union. Moreover, to fit the ERN‐EYE needs, the system has been customized by ERN‐EYE to enable entry of different ocular examinations and imaging and thus to ease the standardization of data entry and consequently ease the review by the experts. This talk will present EyeClin, its use and explain its specific features.
Approaches for quantification of OCT Angiography data
Authors: Schmetterer Leopold
Published: December 2019

Optical coherence tomography angiography (OCTA) is a functional extension of OCT that allows for the non‐invasive visualization of the ocular microvasculature. The technique is used for the visualization of neovascularization in the choroid, retina and cornea. In addition, several investigators have tried to quantify OCTA data. This is not an easy task because the decorrelation signal in OCTA does not linearly scale with blood velocity. In the retinal microvasculature the most frequently used parameter is vessel density. This requires post‐image processing methods including Modified Bayesian Residual Transform (MBRT) based filters, Hessian filters, Gabor filters and Gaussian filters. In the choroid the most frequently used approach is related to quantification of choriocapillaris flow voids. Again, a variety of different algorithms were proposed to quantify such flow voids providing different results and variable reproducibility. The present talk will summarize different techniques and also provide an outlook on quantification of widefield OCTA images.
RPE tissue engineering based on human pluripotent stem cells for cell therapy
Authors: Ben M'Barek Karim
Published: December 2019

In developed countries, retinal degenerative diseases affecting the Retinal Pigment Epithelium (RPE), including Age‐related Macular Degeneration and inherited retinal diseases such as Retinitis Pigmentosa (RP), are the predominant causes of human blindness. Despite the scientific advances achieved in the last years, there is no cure for the majority of patients. In this context, cell therapy based on human pluripotent stem cells is an attractive therapeutic alternative to replace dead or defective RPE cells. Different formulations were proposed: either as a cell suspension or as an engineered tissue. We will discuss the preclinical data obtained with these two strategies. In particular, we will present the preclinical development of our own RPE tissue therapy. This cell therapy consists in RPE cells derived from clinical grade human embryonic stem cells disposed on a biocompatible substrate allowing the formation of a 3D functional sheet, suitable for transplantation. Functionality and safety were evaluated in rodents and the surgical approach in non‐human primates. This therapy is currently evaluated in a phase I/II clinical trial targeting RP patients with mutations in RPE genes.
Potential mechanisms to reverse BRVO related retinal ischemia
Authors: Pournaras Constantin
Published: December 2019

During the evolution of ischemic microangiopathies, impairment of structure and function of the retinal neural tissue and endothelium, affect the interaction of these metabolic pathways, leading to a disturbed blood flow regulation. The resulting ischemia, tissue hypoxia and alterations in the blood barrier trigger the formation of macular edema and neovascularization. Close interaction between nitric oxide (NO), lactate, arachidonic acid metabolites, released by the neuronal and glial cells during neural activity and energy‐generating reactions of the retina strive to optimize blood flow according to the metabolic needs of the tissue. Efficient control of the multiple pathways, such as retinal blood flow, tissue oxygenation and metabolic substrate support, aiming at restoring retinal cell metabolic interactions, may be effective in preventing damage occurring during the evolution of ischemic microangiopathies.
siRNA in neuroretinal disease: from dream to reality
Authors: Levin Leonard A.
Published: December 2019

Small interfering ribonucleic acid (siRNA) molecules are used for gene silencing by activating a degradation pathway for transcribed mRNA molecules after they are transcribed. By complementing a highly specific sequence of the mRNA, the siRNA prevent translation of the mRNA into the targeted protein. They have long been the subject of translational research as treatments for various diseases, but only recently has the expectation come closer to realization. This talk will discuss the development of improved siRNA therapies and review their use in the laboratory and some recent and currently active clinical trials.
Definitions: Machine learning, deep leerning and AI understanding
Authors: Pourjavan Sayeh
Published: December 2019

Aim: AI is the use of algorithms and software to mimic human cognitive function. AI is the ability for computer algorithms to approximate conclusions without direct human input. A brief description of big data and the 4V’s of big data and its use in healthcare will be given during this lecture. This lecture aims to explain the basic definition in artificial intelligence techniques which have been found useful in the medial applications. The three categories of AI devices, mainly the classical machine learning techniques, the deep learning techniques and the natural language processing (NLP) methods will be reviewed.
OCT and OCT‐A based management of vaso‐occlusive retinal disorders. Present indications for the use of fluorescent angiography
Authors: Pournaras Constantin
Published: December 2019

OCT angiography images, improved the detail observation regarding macular capillaries status and became a novel imaging technique for the diagnosis and treatment of the retinal ischemic microangiopathies. OCT angiography offer the ability to visualize the flow in various capillaries layers of the retina and the freedom and safety of not having to use an injected dye. The deeper capillaries layer selective involvement, in cases of ischemic microangiopathies, was precisely defined. Additional information concerning the health of vessels barrier assessing the vessels leakage and the wide field imaging view allowing the assessment of the peripheral retinal filling defects are obtained by the use of the fluorescein angiography.
Bridge research to industry: Thea Open Innovation
Authors: Muriaux Emmanuel
Published: December 2019

Laboratoires Théa has decided to create a new entity called Théa Open Innovation which aims to identify, assess and value start‐ups, University and research teams' best innovative solutions to help develop new treatments for eye diseases.

By putting license agreements and/or participations in place, Théa Open Innovation brings:

its expertise in ophthalmology development and the necessary funding to these partners to achieve proof of concept in humans

and Laboratoires Théa's ability to drive the regulatory phases of product development and commercialization.

Small & medium sized companies, innovative start‐ups, researchers or academics can team up with Théa Open Innovation to deliver the solutions of tomorrow to patients and practitioners.

Managed by Henri and Jean‐Frédéric Chibret, Laboratoires Théa is a major player in ophthalmology, with a presence in 70 countries around the world, more than 25 subsidiaries, and a turnover of over 500 M€.
How to manage the failing tube
Authors: Ahmed Faisal , ahmed Faisal
Published: December 2019

The use of traditional glaucoma drainage devices (GDD) plays a vital role in the management of patients with refractory glaucoma. In a recent US survey the number of GDD implants had increased from 7,788 in 2003 to 12,021 in 2012. However, GDD implantation can be difficult‐ due to either the disease pathology or scarring from previous surgery. This presentation will discuss options for when the GDD has not been able to sufficiently reduce the intra‐ocular pressure or completely failed. A management step ladder will be looked at to review, medical, surgical and laser options in high risk recalcitrant glaucoma patients.
Axon transport as a target for promoting RGC survival and optic nerve regeneration
Authors: Eva Richard
Published: December 2019

Adult CNS neurons have a weak intrinsic capacity for regeneration after injury, but the underlying cellular mechanisms preventing regeneration are not completely understood. Increasing intrinsic growth ability is a critical part of enabling injured optic nerve axons to regenerate. The work presented here is part of a large body of research into understanding the role of membrane protein trafficking and transport in the control of regenerative ability. We have found that as CNS neurons mature, there is a developmental decline in the axonal transport of integrins (cell surface adhesion and guidance molecules) and their endosomal transporters, Rab11 positive recycling endosomes. This is controlled by a molecular switch called ARF6. Switching off ARF6 in mature CNS axons leads to an increase in the anterograde axonal transport of integrins and Rab11 endosomes, leading to a restoration of the regenerative capacity that is lost as axons mature. We have been targeting these mechanisms to stimulate axon regeneration in the optic nerve, and neuroprotection of retinal ganglion neurons during raised IOP. Here we present novel data from two new lines of investigation into facilitating CNS axonal transport, neuroprotection and regeneration, focusing on signaling pathways and organelle motility. Firstly, by investigating signaling upstream of ARF6, we have identified an isoform of PI3 Kinase which we have used to stimulate axon transport, neuroprotection and regeneration; both after laser axotomy in vitro and after optic nerve crush. Secondly, we present exciting new data from studies into a trafficking molecule which resides in the endoplasmic reticulum (ER) and demonstrate that this can be targeted to enable robust optic nerve regeneration and neuroprotection in the retina. These findings confirm integrins and Rab11 as critical facilitators of optic nerve regeneration whilst establishing an important new role for the axonal ER in this process.
Fueling axonal regeneration: dendritic energy to the rescue?
Authors: Moons Lieve
Published: December 2019

Up to now neuroregenerative research mainly focused on improving axonal regrowth, leaving the dendrites, which form an essential component of the neuronal circuit, largely unstudied. Nevertheless, subtle changes in the dendritic arbors of neurons are one of the first stages of various neurodegenerative diseases, leading to dysfunctional neuronal networks and ultimately cellular death. Maintaining dendrites is therefore considered an essential neuroprotective strategy. Here, we postulate the intriguing hypothesis, that dendritic shrinkage is an important stimulant to boost axonal regeneration, and thus that preserving dendrites might not be the ideal therapeutic method to regain a full functional network upon CNS damage. Indeed, our study in zebrafish, a versatile animal model with robust regenerative capacity, recently unraveled that dendritic retraction is evoked prior to axonal regrowth after optic nerve crush (ONC) injury, and that the retinal ganglion cell (RGC) dendrites regenerate after axonal repair. This orderly sequence of neurite outgrowth is a recapitulation of development, where axogenesis also precedes dendritogenesis. Strikingly, inhibiting RGC dendritic pruning upon damage perturbed axonal regeneration in zebrafish. This constraining effect of dendrites on axonal regrowth has sporadically been proposed in literature. In line with this, we observed an increased loss of RGC dendrites and reduced dendritic arbor complexity in the mouse retina when axonal regeneration was induced by inflammatory stimulation. All together, these data point towards a conserved neuronal remodeling mechanism, where dendritic pruning upon neuronal injury supports axonal regeneration. We now hypothesize that a reprogramming and relocation of the neuronal energy production machinery towards the axon is needed for regeneration, a process in which the shrinking dendrites might play a key role. To test this idea, a combination of state‐of‐the‐art in vitro and in vivo research approaches are being pursued. We are characterizing, in the axonal versus dendritic cell compartment, the subcellular and molecular players modulating energy production and enabling axonal regrowth of injured CNS neurons. Overall, our findings could generate pivotal insights into how re‐directing intra‐neuronal energy channelling may promote neuronal repair in the mammalian CNS.
OCT‐ Angiography in pediatric diseases: New insights
Authors: Atilla Huban
Published: December 2019

With the advances in technology, new devices and instruments provide detailed information about the morphology and histology of the eye especially retina and retinal vessels. In children with hereditary or congenital retinal and optic nerve pathologies, the new advances help us to diagnose, treat and follow patients. Optical Coherence Tomography Angiography (OCTA), a new diagnostic modality without need of dye injection and complications of contrast agent will provide information about vascular system of retina and choroid. OCTA provide information about capillaries around the optic disc and and macular area noninvasively. Optic nerve and retinal vessels can be evaluated structurally and functionally with the blood flow and also retinal microvasculature can be analyzed qualitatively and quantitatively with measurement of flow index and vessel density. Nerve fiber and ganglion cells changes that can be detected with OCT, can be further evaluated with OCTA for associated vascular drop out or reduced retinal perfusion areas.