bluuebunny/crossref_metadata_2025_split huggingface dataset:
Induced to cure: Engineering iPS cell derived RPE scaffolds to treat degenerative eye diseases
Authors: Bharti K. 
Published: September 2015

SummaryThe recent success with embryonic stem (ES) cell derived retinal pigment epithelium (RPE) has provided hope for a cure for degenerative eye diseases. Induced pluripotent stem (iPS) cells are an autologous source of stem cells potentially with fewer immune‐challenges as compared to ES cells. Using a developmentally guided differentiation protocol we have developed fully polarized RPE tissue from iPS cells. The RPE monolayer along with its secreted ECM and a degradable scaffold form a tissue that mimics the native tissue in structural and functional properties. This RPE tissue performs several key RPE functions like phagocytosis of photoreceptor outer segments, ability to transport water from apical to basal side, and the ability to secrete cytokines in a polarized fashion. Currently, we are testing the safety and the efficacy of this tissue in animal models. We have begun Phase I Investigational New Drug (IND) enabling studies with the goal to transplant autologous iPS cell derived RPE in patients in advanced Geographic Atrophy stage of age‐related macular degeneration (AMD), one of the leading blinding diseases in the US. Our work will provide a potential personalized cell therapy for AMD patients.
Relation of oxygen saturation to stage of diabetic retinopathy
Authors: Sin M. , Chrapek O. , Sinova I. , Stanakova L. , Rehak J. 
Published: September 2015

SummaryAimTo assess whether oxygen saturation of the retinal vessels is related to degree of diabetic retinopathy.MethodsA prospective study included 114 eyes of 76 patients with diagnosed diabetes and 57 eyes of 29 non diabetic patiens. The diabetic patients were divided into groups according to severity of the retinopathy.ResultsIn healthy controls mean arterial saturation was 96.5 ± 2.6%, mean vein saturation was 62.3 ± 7.4% and A‐V difference was 34.3 ± 7.2%. In diabetic patients with no retinopathy mean arterial saturation was 96.5 ± 3.2%, mean vein saturation was 66.3 ± 6.3% and A‐V difference was 30.2 ± 4.9%. In patients with mild diabetic retinopathy mean arterial saturation was 96.7 ± 4.6%, mean vein saturation was 67.9 ± 7.2% and and A‐V difference was 28.8 ± 8.2%. In patients with moderate nonproliferative retinopathy mean arterial saturation was 97.8 ± 4.6%. mean vein saturation was 69.9 ± 6.7% and A‐V difference 27.9% ± 5.8%. In patients with severe non‐proliferative and proliferative retinopathy mean arterial saturation was 100.5 ± 5.6%, mean vein saturation was 74 ± 7.2% and A‐V difference was 26.5 ± 7.8%.ConclusionWe confirmed an increase in oxygen saturation in both retinal artery and vein in relation to degree of diabetic retinopathy.
Novel techniques in corneal regeneration and bioscaffold engineering
Authors: Lagali N. , Rafat M. , Xeroudaki M. , Koulikovska M. , Fagerholm P. 
Published: September 2015

SummaryRestoration of corneal transparency and a functioning epithelium and stroma may involve multiple procedures that are limited by availability of donor tissue and an inability of host tissue to self‐regenerate. We present a tissue‐engineered collagen‐based hydrogel bioscaffolds for regenerating a transparent stroma and providing the additional possibility of carrying and delivering corneal stem cells to the stroma or epithelium. We present in vitro results of bioscaffold compatibility with epithelial and stem cells, and techniques for the optimal implantation of scaffolds using femtosecond laser surgery. Using models of in vivo bioscaffold implantation in the rabbit, we evaluate transparency, stability, and controlled degradation characteristics of the scaffolds. Tissue engineering provides the opportunity to tune the size, thickness, transparency, homogeneity and degradation rate for specific applications. For example, the bioscaffold may be used to substantially thicken the stroma or allow non‐invasive in vivo tracking of its controlled degradation as it releases therapeutic cells. In vitro and in vivo results with bioscaffolds are presented that provide the basis for further preclinical and clinical development.
The link with the EBO: the glaucoma subspecialty diploma
Authors: Sunaric Megevand G. 
Published: September 2015

SummaryThe EBO has gained worldwide respect for its efforts on harmonizing education and training in general ophthalmology within Europe. The comprehensive EBO Diploma examination, awards successful candidates the title of the Fellow of the European Board of Ophthalmology (FEBO), and is the most evident result of such efforts. More recently the EBO has established a Subspecialty European Board of Ophthalmology Diploma Examination (FEBOS) with the goal to increase standards of knowledge and care in various subspecialties. The first of these subspecialty examinations to be introduced is in the field of glaucoma and is developed in close collaboration with the European Glaucoma Society (EGS). The FEBOS‐Glaucoma examination and diploma represent a logical continuation of the efforts in providing sustainable education and glaucoma care within Europe led by the EGS.The goals, the organisation and requirements to sit the subspecialty exam as well as the first experience with the FEBO‐Glaucoma exam and Diploma will be presented.
Pharmacokinetics of anti‐VEGF and steroid agents in vitrectomized eyes with diabetic macular edema
Authors: Papastefanou V. 
Published: September 2015

SummaryAnti‐VEGF and steroid agents for diabetic macular edema (DME) in a vitrectomized eye is fraught with difficulties, bearing in mind the numerous confounding factors in DME. The pharmacokinetic parameters are affected as the vitreous cavity milieu is altered and the vitreous consistency is not reformed post vitrectomy (PPV). Pharmacokinetic data are largely based on experimental animal models.VEGF clearance is increased in the vitrectomized eye compared to the non‐vitrectomized eye, but there is little direct evidence that the protein expression profile in the vitreous cavity is altered after vitrectomy. Whilst some studies have demonstrated longer intravitreal retention for Bevacizumab compared to Ranibizumab and reduced half‐life for both agents after PPV, other studies have found no changes. There is a characteristic lack of pharmacokinetic data for anti‐VEGF agents in human vitrectomized eyes.The vitreous half‐life of triamcinolone acetonide (TA) after intravitreal injection was reduced in vitrectomized eyes in both animal models and human eyes. No pharmacokinetic differences between vitrectomized and non‐vitrectomized eyes are noted in animal eyes following the injection of the Dexamethasone implant (Ozurdex, Allergan).
Choroidal blood flow and thickness measurements
Authors: Schmidl D. 
Published: September 2015

SummaryMost of the ocular blood supply goes into the choroidal circulation. Intensive research has been directed towards choroidal structure and function in health and disease. Indeed, choroidal blood flow and its regulation has been found to be altered in several ocular diseases, such as age‐related macular degeneration. Several techniques for the assessment of choroidal blood flow have been developed including laser Doppler flowmetry, laser speckle flowgraphy, laser interferometric measurement of fundus pulsation amplitude or pneumotonometric measurement of pulsatile ocular blood flow. All these techniques have significant limitations and currently no gold standard method for the assessment of choroidal blood flow exists.With the introduction of enhanced depth imaging optical coherence tomography (OCT) systems, it is now possible to image choroidal thickness in vivo. Alterations in choroidal thickness have been observed in several ocular diseases. The correlation between functional and structural choroidal parameters is, however, weak. Further research is required to better understand the results obtained in patients with ocular pathologies and to investigate whether choroidal thickness is a good biomarker for choroidal disease.
Scleral lenses in the management of exposure/neurotrophic keratopathy in patients with cranial nerve palsy
Authors: Schornack M. 
Published: September 2015

SummaryScleral lenses are increasingly being recognized as a viable option for management of exposure keratopathy. Unlike more aggressive surgical interventions, the lenses can provide complete protection of the ocular surface without compromising visual clarity or restricting visual field. Preservation of corneal epithelial integrity is of utmost importance when lid function is compromised or absent. The fluid reservoir between the posterior surface of a scleral lens and the anterior corneal surface provides continuous hydration of the corneal epithelium and allows for healing of any epithelial defects. Furthermore, the lens itself protects fragile epithelial tissue from shear forces arising from lid movement over the cornea during the blink. Preservation of visual function is also important for these patients. Those who suffer from decreased vision due to irregularity of a desiccated ocular surface frequently note improvement in visual function with scleral lens wear, because the lens provides a smooth optical surface and neutralizes any corneal irregularity. This presentation will review and summarize visual and ocular outcomes of scleral lens therapy for management of exposure keratopathy at the Mayo Clinic.
Understanding the molecular genetic causes of inherited corneal disorders
Authors: Davidson A. 
Published: September 2015

SummaryInherited corneal diseases comprise a group of clinically and genetically heterogeneous disorders that can lead to bilateral severely impaired vision and/or blindness. Advances in next generation sequencing (NGS) technologies have revolutionised clinical genetics over the past five years. The application of NGS, in combination with genome wide association studies, to the field of inherited corneal disorders has provided significant insights into the genetics of corneal diseases and their underlying aetiology. An overview of our current understanding of the genetics of monogenic corneal dystrophies, as well as the contribution of genetic factors to complex conditions such as keratoconus and Fuchs endothelial corneal dystrophy (FECD), will be provided. Examples from our laboratory exploiting NGS platforms, in combination with careful phenotyping of patient sub‐groups, to identify novel genetic causes and mechanisms of inherited corneal disorders such as; posterior polymorphous corneal dystrophy, epithelial recurrent erosion dystrophy, and X‐linked megalocornea, will be highlighted. Furthermore the impact of these findings on clinical care and their potential to provide translational outcomes will be discussed.
Mutation in the Ercc2 gene of the mouse causes cataracts
Authors: Graw J. , Kunze S. , Dalke C. , Fuchs H. , Klaften M. , Sabrautzki S. , Hrabe de Angelis M. 
Published: September 2015

SummaryCataracts have been associated with many mutations. In a large‐scale high‐throughput ENU mutagenesis screen we analyzed the offspring of paternally treated C3HeB/FeJ mice for obvious ocular dysmorphologies.We identified a mutant suffering from rough coat and small eyes only in homozygotes; homozygous females turned out to be sterile. The mutation was mapped to chromosome 7 between the markers 116J6.1 and D7Mit294. The critical interval (8.6 Mb) contains 3 candidate genes (Apoe, Six5, Opa3); none of them showed a mutation. Using exome sequencing, we identified a c.2209T>C mutation in the Xpd/Ercc2 gene leading to a Ser737Pro exchange.During embryonic development, the mutant eyes did not show major changes. Postnatal histological analyses demonstrated small cortical vacuoles; later, cortical cataracts developed. Since XPD/ERCC2 is involved in DNA repair, we checked also for the presence of the repair‐associated histone γH2AX in the lens. During the time, when primary lens fiber cell nuclei are degraded, γH2AX was strongly expressed in the cell nuclei; later, it demarcates clearly the border of the lens cortex to the organelle‐free zone.These findings demonstrate the importance of XPD/ERCC2 for lens fiber cell differentiation.
Mutations in Connexin‐encoding genes
Authors: Beyer E. , Berthoud V. 
Published: September 2015

SummaryGap junctions formed of connexin46 (Cx46) and connexin50 (Cx50) facilitate lens function and survival. Mutations of the connexin‐encoding genes (GJA3 and GJA8) have been linked to inherited cataracts. We expressed these mutants in vitro to elucidate abnormalities that contribute to cataractogenesis. Most of the mutants reduce intercellular communication due to alterations of channel function or impaired connexin synthesis/assembly/stability. One unusual mutant (Cx50P88S) forms cytoplasmic accumulations that may act as light scattering particles. Another unusual mutant (Cx50G46V) exhibits increased hemichannel function that may cause cell injury and death. We have studied mice expressing two different connexin mutants (Cx50D47A and Cx46 fs380) that mimic cataract‐linked human mutations. Both mouse lines develop cataracts (although with different time courses) and have reduced connexin levels (mutant and co‐expressed wild type) likely due to protein degradation. Our studies suggest that reduction of intercellular communication is a common feature that contributes to connexin mutant‐linked cataractogenesis, but individual mutants cause additional abnormalities that contribute to differences in phenotypes.
Ocular autonomic dysfunction in glaucoma
Authors: Vandewalle E. 
Published: September 2015

SummaryThe retina relies primarily upon autoregulation of the retinal vasculature in cases of increased metabolic demand or reduced ocular perfusion pressure. The choroidal blood vessels are highly innervated by the autonomic nervous system, but are separated too far from the retina to respond to the local accumulation of vaso‐active metabolites. It could therefore be hypothesized that conditions interfering with either the autoregulation or the autonomic nervous regulation could render the retina at a higher risk of ischemic damage. Glaucoma has been associated with disturbances in both types of regulation. Retinal oximetry is capable of providing reproducible in vivo, non‐invasive measurements of the retinal vessel oxygen saturation and with the advent of enhanced depth imaging optical coherence tomography (EDI‐OCT), allowing a detailed non‐invasive evaluation of the choroid in‐vivo, renewed interest in the role of the choroid in the pathogenesis of glaucoma has grown.
Longterm restoration of ocular surface function with scleral lenses
Authors: Carrasquillo K.G. 
Published: September 2015

SummaryThe ocular surface ecosystem is altered when any of its components becomes compromised. In order to have a stable and healthy ocular surface, there has to be good lid function, healthy and functioning lacrimal and accessory glands, healthy and functional limbal stem cells to allow corneal regeneration and prevention of corneal conjunctivalization, a healthy tear film, and adequate sensory innervation. Without these, the ocular surface, in particular the cornea is vulnerable to severe desiccation, vascularization, opacification, conjunctivalization, chronic epithelial breakdowns, chronic exposure, amongst other sequela; ultimately resulting in compromised vision, severe forms of pain, and light sensitivity. Scleral lenses play an important role in restoring the ocular surface function of compromised ocular surfaces, even when other topical or surgical approaches have failed. Not only are they a viable option, but they are able to provide long‐term support of the ocular surface. We report on various cases where long‐term restoration of ocular surface function was achieved with the use of prosthetic replacement of the ocular surface ecosystem (PROSE) treatment and use of BostonSight® PROSE devices.
What are the general requirements for candidates to sit the exam
Authors: Midena E. 
Published: September 2015

SummaryThe European Board of Ophthalmology (EBO) has recently decided to promote, at the European level, a subspecialty diploma in some selected areas of Ophthalmology. The first subspecialty diploma is related to Glaucoma. The guidelines for this kind of diploma have been developed with the European Glaucoma Society, because the aim of EBO is to have the already existing European subspecialty Societies (European Glaucoma Society, Euroepan Society of Cataract and Refractive Surgery, EURETINA, …) as the driver of the EBO Subspeciality examination. The characteristics of the examination, and any information related to the curriculum and major requirements to sit the exam will be presented.
Partial thickness Macular holes and pharmaceutical treatment of FTMH
Authors: Pournaras J.A.C. 
Published: September 2015

SummaryThe pathophysiology of full thickness macular hole and lamellar macular hole are different and will be discussed. Oct characteristics will be repeated according to new classification. Taking in account the natural history, indication of treatment will be detailled according to each stage of those diseases. Recently, ocriplasmin has been introduced as an alternative treatment to vitrectomy. Favorable Prognostic factors have been recognized as age inferior to 65 years old, full thickness macular hole < 400 microns, the absence of epiretinal membrane, vitreous adhesion < 1500 microns and phakic status. While management of full thickness macular hole shows good visual prognosis for the patients, the visual result of lamelar macular hole is not so obvious.
Macular surgical diseases in myopia
Authors: Pournaras J.A.C. 
Published: September 2015

SummaryMacular surgical diseases in myopia are consecutive to vitreoretinal interface disorders associated to stretching forces due to staphyloma on the other side. OCT have largely contributed to the recognition and the understanding of vitreoretinal interface disorders occuring in myopic condition: epiretinal membrane alone or associated to foveoschisis, lamellar or full thickness macular hole and posterior retinal detachment. Surgical management by vitrectomy associated or not to ILM peeling will be discussed according to myopic disorders. Main surgical complications are macular hole formation and foveal atrophy. Fovea‐sparing internal limiting membrane peeling for myopic traction maculopathy may represent an alternative option to avoid these complications. Scleral buckling surgery associated to vitrectomy may represent an other option under investigation.
Ocular tests and interpretation
Authors: Marques‐Neves C. 
Published: September 2015

SummaryThe eye is a richly enervated organ, with a dual supply from both the sympathetic and parasympathetic nervous system. The inputs from these two branches of the autonomic nervous system (ANS) are responsible for a vast number of ocular physiological responses, ranging from pupillary reflexes to accommodation and aqueous humor turnover. Accordingly, any dysfunction in one (or both) of these inputs can have a significant impact on the overall organ physiology and are likely involved in a number of diseases – such as glaucoma.Accordingly, several ophthalmological tests using specific systemic and ocular stimuli have been developed to determine the integrity and relative contribution from each of these two ANS inputs. Validated normative databases allow for a proper diagnosis of an ANS dysfunction and can provide a valuable input in the diagnostic and treatment algorithm in a number of ocular conditions.However, interpretation of these signals is usually complex and thus are not regularly used in the clinical setting. The purpose of this talk is to give an insight into the logistics and complexity of these ANS ocular tests and – more importantly – to provide the tools for its interpretation by a clinical researcher.
Imaging and Biopsies
Authors: Van Ginderdeuren R. 
Published: September 2015

Imaging is necessary before taking a biopsy for diagnostic purposes, to delineate the extension, find the correct location and plan the most adequate procedure for the biopsy. In case of suspicion for conjunctival/palpebral lymphoma a CT scan is performed to exclude bilaterality and delineate the exact proportions. For orbital/lachrymal gland tumors with differential diagnosis of lymphoma a CT/MRI shows the exact location and dimensions of the tumor. In case of a tumor with easy access a large biopsy is preferred over fine needle aspiration biopsies. Special precaution is necessary not to crush the specimen to prevent artefacts of the fragile lymphoma cells The biopsy is divided in a fresh portion for frozen sections and for genetic analysis; the bulk of the tumor is fixed in formalin for the standard stainings Retinal/choroidal lymphomas can be diagnosed by fundus examination, OCT, ultrasound and fluoangiography. Biopsies require special surgical skills and adapted laboratory techniques because of the paucity of cells. Steroids must be discontinued for at least 10 days. A vitreal above a scleral approach is preferred because of the possibility to obtain also a retinal sample.
Healthcare delivery, not just about the doctor and the patient
Authors: Mazy R. 
Published: September 2015

SummaryIn this paper we explore the evolution of a classic hospital in a static building to a patient‐focused “concept” of healthcare delivery system where the healthcare provider can exercises high quality medicine with the necessary structural and organizational support. An organizational support for each individual(ist) healthcare provider who wants to perform “independently” the excellence in his work and be patronage and protected by its organization. As Wegener described “doctors are not manageable” but they should be supported and encouraged. Lean implementation, teamwork, promoting healthcare pathways, enriching the resources for all professionals to prevent Burn‐out are some of the aspect of a modern supportive organization to improve the quality of care AND the quality of life for the healthcare provider. Promoting the excellence and the professionals in order to increase the financial resources is one of the “jobs” of the manager of the hospital in his extensive list of To Do's.
Development pathway
Authors: Cordeiro M.F. 
Published: September 2015

SummaryOne of the biggest hurdles in ophthalmology, particularly glaucoma, in recent years has been the successful translation of laboratory advances to the clinic. This is not unique to glaucoma – such a problem has been well‐described in different spheres of medicine. In fact, a search in PubMed on this subject reveals over 1000 references. A major identifiable bottleneck is the developmental pathway and the adherence to regulatory requirements. Regulatory issues and common problems will be provided, using examples that are well‐documented in the field of glaucoma.
Scheimpflug analysis in an epidemiological study
Authors: Wegener A. 
Published: September 2015

SummaryRadiation cataract enhances age‐related scattering increase. Radiation induces formation of subcapsular and cortical cataracts. Light scattering changes in lens layers evidences radiation damage to lens proteins. Scheimpflug imaging today offers standardized recording procedures minimizing the operator influence. The initial disadvantage of Scheimpflug imaging of only a few optical sections, has been overcome by the number of images recorded by the Pentacam® (25/50 images/eye). Densitometric and biometric image analysis needs a 3D data localization in the lens. This type of image analysis has been proven suitable for nuclear and cortical cataracts. Subcapsular cataracts pose more problems because of their 2D extension. Scheimpflug imaging with 50 images per eye partly compensates this, but retroillumination imaging can be superior in this case. OCT has been developed for imaging of the retina, but is now also used for the anterior eye segment. However, in radiation cataract and epidemiological studies, this technique is not useful, because optical coherence tomography detects coherence shifts at interfaces not particle related light scattering. It detects clearly shaped cataracts, but not changes in lens light scattering.