bluuebunny/crossref_metadata_2025_split huggingface dataset:
Plasmalogens and cell‐cell communication between retinal glial cells
Authors: Bron A. , Mazzocco J. , Leclere L. , Fenech C. , Grall S. , Buteau B. , Gregoire S. , Creuzot‐Garcher C. , Leloup C. , Bretillon L. , Fioramonti X. , Acar N. 
Published: September 2017

PurposePlasmalogens are glycerophospholipids containing a vinyl‐ether bond at sn‐1 position of their glycerol backbone and polyunsaturated fatty acids (PUFAs) at sn‐2. We have previously shown that plasmalogens are involved in the regulation of perinatal retinal vascular development and particularly in astrocyte template formation (Saab et al, PLoSONE 2012 9(6):e101076). Since retinal Müller cells and astrocytes can communicate through calcium waves and connexin 43‐rich gap junctions, the aim of our study was to determine whether a reduction of plasmalogen levels affects communication between retinal glial cells.MethodsPrimary Müller cells and astrocyte were isolated from retinas of 9‐days old and cerebral cortex from 21‐days old Wistar rats, respectively. SiRNA against DHAPA‐AT ‐the key enzyme of plasmalogen biosynthesis‐ were used to decrease plasmalogen content of Müller cells before they were co‐cultured with naïve astrocytes. Calcium waves initiated in Müller cells by topical application of ATP were monitored by Fura‐2 calcium imaging. Expression levels of cellular proteins involved in calcium metabolism, including connexin 43, were evaluated by proteomics and Western‐blotting in reponse to Si RNA treatment.ResultsTreating Müller cells with SiRNA against DHAP‐AT led to a reduction of plasmalogen content of about 60% and to a remodelling of PUFA distribution in cell membranes. The expression of connexion 43 was reduced by more than 50% in Müller cells treated with SiRNA. This was associated with an alteration of calcium waves originating from Müller cells as well as a slowed propagation to neighbouring astrocytes.ConclusionsThese data suggest that membrane plasmalogens content influences cell‐to‐cell communication between retinal Müller cells and astrocytes. Altered coupling between these cells might be one of the factors influencing perinatal vascular development.
Modulation of the rod outer segment aerobic metabolism diminishes the production of radicals due to light absorption
Authors: Panfoli I. , Calzia D. , Degan P. , Caicci F. , Manni L. , Traverso C.E. 
Published: September 2017

PurposeOxidative stress is a primary risk factor for inflammatory and degenerative retinopathies. Irradiation with blue light of eye explants was shown to cause an oxidative stress, higher in the rod outer segment (OS) than in the inner limb, ultimately impairing the extra‐mitochondrial aerobic metabolism of the OS. Here, to establish a correlation between the energy metabolism and phototransduction, the aerobic metabolism of purified bovine rod OS was assayed in function of exposure to either ambient or dim light.MethodsIsolated bovine rod OS, purified by Fycoll/sucrose gradient were utilized. Production of Reactive Oxygen Intermediates (ROI) was evaluated by citofluorimetry, with dihydrorhodamine 123 (DHR) probe; ATP synthesis and oxygen consumption were assayed by luminometry or oximetry, respectively. When necessary, isolated OS were preincubated with 30 μM Resveratrol, for 15 min, or 5 mM Metformin, for 2 h.ResultsUpon exposure to ambient light for 1 h, a significant increase in oxygen consumption as well as ATP synthetic ability by rod OS was observed, along with a consistent ROI production, with respect to dim light, i.e. the physiological rod conditions. Pretreatment with resveratrol, inhibitor of F1Fo‐ATP synthase, or metformin, inhibitor of the respiratory complex I, significantly diminished the ROI production in vitro.ConclusionsData show for the first time the relationship between light and the rod OS metabolism. A production of ROI by the OS in vitro was also observed, positively correlating to light exposure. A beneficial effect of metformin and resveratrol was found, as modulators of ROI production, consistently with their inhibitory action on the complexes I and V of respiration, respectively. Data shed new light on the prevention of the cone loss secondary to rod damage due to oxidative stress.
Tube surgery in scarry eyes!
Authors: Ahmed F. 
Published: September 2017

SummaryThe use of glaucoma drainage devices (GDD) has been a vital advancement in the management of patients with refractory glaucoma. However, GDD implantation can be difficult‐ due to either the disease pathology or scarring from previous surgery.The aim of this presentation will be to show examples of implanting GDD in eyes in which conventional GDD surgery is difficult.The second part of the presentation will be looking at approaches on how to manage eyes with uncontrolled intra‐ocular pressure even after glaucoma drainage device implantation.
Ocular fluid analysis to pin down the cause of inflammation
Authors: Neri P. , Gorgoni F. , Pirani V. , Pelliccioni P. , Nicolai M. 
Published: September 2017

SummaryThe accuracy for the diagnosis of inflammatory eye diseases is a crucial step for an appropriate treatment strategy and their management in general. In most of the cases, non‐invasive techniques, such as fluorescein angiography, indocyanine green angiography and optical coherence tomography, can lead to a correct diagnosis. In addition, blood tests and neuro‐imaging can be strongly contributory. However, it has been estimated that in 8% of cases with uveitis, approximately, the clinical presentation can be atypical and, moreover, systemic medical evaluation might be non‐conclusive. In order to minimize such ambiguities, diagnostic sampling of ocular fluids can help in determining the etiology of the disease, and can provide sufficient evidences for the treatment management. The diagnostic tests for atypical or uncertain uveitis subsets include: anterior chamber tap, vitreous biopsy and chorioretinal biopsy. This lecture will focus on the indications, techniques, reliability and limitations of vitreous biopsy for ocular inflammatory or pseudo‐inflammatory diseases.
New biomaterials and ocular drug delivery
Authors: Sheardown H. , Muirhead B. , Zhang J. 
Published: September 2017

SummaryThe need for new methods of delivering pharmacologically active agents to the eye has never been greater with the growing incidence of ocular disorders. Polymeric drug delivery methods show great promise for enhancing drug residence time as well as convenience for the patient. This talk will focus on three novel polymer based drug delivery systems developed in our labs. A mucoadhesive micelle system has been developed using acceptable polymers and has been shown to enhance the on eye residence time and the delivery of cyclosporine A in the treatment of dry eye disease. A transparent, in situ gelling injectable system has been examined to enhance the delivery of various drugs for treating diseases of the back of the eye. Finally, a Vitamin E based system is injectable, gelling upon exposure to aqueous conditions will be described. The potential of these systems as well as their limitations will be discussed and next steps in their development with a goal of creating a clinically viable drug delivery system will be described.
Overview of conjunctival and eyelid tumours
Authors: Van Ginderdeuren R. 
Published: September 2017

SummaryIn this part of the course an overview will be given of the most common and most important conjunctiva and eyelid tumours (basal cell carcinoma, squamous cell carcinoma, sebaceous cell carcinoma, malignant melanoma). For each disease clinical‐pathologic correlations will be emphasized. Typical and atypical characteristics will be shown.In most cases the clinician finds the correct diagnosis, but even then it is important to investigate the section margins and the degree or details of the tumour. In rare cases a surprise in diagnosis is found and some important examples of these will be given, with also the useful consequences on the clinical follow‐up of these patients.Correct diagnosis can also be useful in non‐malignant processes and examples will be given.A short overview will be given of newer techniques and diagnostic possibilities.
A review of the nature & role of pre‐receptoral, wavelength‐selective, ocular filters in vertebrates
Authors: Douglas R. 
Published: September 2017

SummarySuch filters are widespread in all vertebrates groups, most notably fish. Several species have pigmented corneas, whose density may alter with illumination. Filters within lenses are common, occurring in animals that inhabit well‐lit environments as well as the deep‐sea. Pigmented humours are rare but have been reported in a few species. Various layers within the retina also contain pigments, including the primate macular pigment, that absorb short wavelength light and the inner segments of many animals, such as birds, contain coloured oil droplets.While many of these filters are various carotenoids, other substances such as mycosporine‐like amino acids, are common. The variety of filtering pigments indicates pigmentation has evolved independently on a number of occasions; a clear testament to its importance.Most pigments serve to reduce short wavelength light and have a variety of functions including; protection of the eye by removing the most damaging photons, acting as antioxidants, and improving image quality by reducing scatter. In deep‐sea fish they enhance the visibility of bioluminescence and in animals with oil droplets they refine the spectral properties of photoreceptors.
A review of motion photometry in the assessment of macular pigment distribution profiles obtained over two decades; applications and insights
Authors: Robson A. , Moreland J. 
Published: September 2017

SummaryThis presentation will review the use of a Moreland anomaloscope, modified for motion photometry, in the assessment of macular pigment (MP) over the last 20 years. Early studies examined the influence of MP on chromatic visual evoked potentials and highlighted the limitations of monitor‐based methods of MP quantification, involving the use of carotenoid solutions to simulate MP. Detailed examinations using motion photometry characterised a wide range of MP distribution profiles and revealed a lack of correlation between peak optical density at the fovea and computations of the total complement of MP within the central 15 degrees, corroborated using 2‐wavelength fundus autofluorescence measurements. Motion photometry assessments in individuals with widely different MP distribution profiles demonstrated a high degree of stability over periods of up to 19 years, pertinent to studies that aim to monitor MP in disease or modify MP through dietary supplementation.
A genome‐wide association study suggests that the NADPH Oxidase 4 (NOX4) gene is associated with severe diabetic retinopathy in a Scottish diabetic population
Authors: Meng W. , Hebert H. , Palmer C. 
Published: September 2017

SummaryDiabetic retinopathy is one of the devastating eye complications in patients with diabetes. The purpose of this study is to investigate the genetic contributors of severe diabetic retinopathy using a Scottish diabetic population through a genome‐wide association approach. In the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) datasets, cases of severe diabetic retinopathy were defined as type 2 diabetic patients who were ever graded as having severe background retinopathy (Level R3) or proliferative retinopathy (Level R4) in at least one eye according to the Scottish Diabetic Retinopathy Grading Scheme or who were once treated by laser photocoagulation. Controls were diabetic individuals whose longitudinal retinopathy screening records were either normal (Level R0) or only with mild background retinopathy (Level R1) in both eyes. 560 cases of type 2 diabetes with severe diabetic retinopathy and 4,106 controls were identified in the GoDARTS cohort. We revealed that rs3913535 in the NADPH Oxidase 4 (NOX4) gene reached a p value of 4.05 × 10−9. This genome‐wide association study of severe diabetic retinopathy suggests that the NOX4 gene might play a role in retinopathy.
A systematic review of the associations between dietary intake and diabetic retinopathy
Authors: Wong M. , Man R. , Gupta P. , Fenwick E. , Li L.J. , Lamoureux E. 
Published: September 2017

PurposeThe evidence linking diet with diabetic retinopathy (DR) is growing, but DR‐specific dietary guidelines are still lacking. We conducted a comprehensive systematic assessment of the association between dietary intake and DR, and determined key areas for further research.MethodsPubMed, Embase, Medline, and the Cochrane Central register of controlled trials were systematically searched for papers published between Jan 1967 and Jan 2017 according to standardized criteria. Interventional and observational studies, investigating nutrient intake, food and beverage consumption, and dietary patterns, were included. Data extraction was performed through a standardized extraction form, and study quality was evaluated using a modified Newcastle‐Ottawa scale for observational studies, and the Cochrane collaboration tool for interventional studies.ResultsOf 4265 titles initially identified, 31 studies (3 interventional, 9 cohort, 4 case‐control, 15 cross‐sectional) were retained. The evidence suggests the intake of dietary fibre, oily fish, and a Mediterranean diet to be protective of DR. Conversely, higher caloric intake was associated with higher DR risk. No significant associations of DR with carbohydrate, vitamin D and sodium intake were found. The association between DR and antioxidants, fatty acids, proteins, alcohol, and other popular beverages such as tea and coffee remains equivocal.ConclusionsDiet is a crucial aspect of DR management, with dietary components including dietary fibre, oily fish, and a Mediterranean diet being protective of DR, and a high caloric intake associated with greater DR risk. However, further cohort studies to untangle the effects of other key dietary components on DR, such as antioxidants, fatty acids, proteins, alcohol and popular beverages, are needed in order to better inform clinical guidelines.
Topical betamethasone sodium phosphate, tetracycline hydrochloride and nonsteroidal anti‐inflammatory drugs in the treatment of diabetic macular edema: a case report
Authors: D'Amico Ricci G. , Bouzios D. , Boscia F. , Pinna A. 
Published: September 2017

PurposeTo report a case of clinically significant diabetic macula edema (DME) cured only with topical Betamethasone Sodium Phosphate, Tetracycline Hydrochloride and nonsteroidal anti‐inflammatory drugs.MethodsA 44‐year‐old type I diabetic woman was referred to our Unit after a partial tarsorrhaphy procedure for exposure keratopathy in her left eye. OCT examination of her right eye revealed a clinically significant DME with important visual loss (Central Macular Thickness [CMT] 716 μm, Best Correct Visual Acuity [BCVA] 20/100 Snellen). The patient refused the suggested intravitreal therapy (Ranibizumab injections with PRN protocol). Topical treatment with Betamethasone Sodium Phosphate, Naphazoline Nitrate, Tetracycline Hydrochloride (Alfaflor®, Alfa Intest, Italy) and Diclofenac (Voltaren Oftabak®, Thea, France) eye‐drops 4 times/day was started.ResultsIn the following 10 months, right CMT decreased to 335 μm and right BCVA increased to 20/25 Snellen. However, OCT scans still showed some intraretinal cysts. Topical Diclofenac was then replaced with Bromfenac (Yellox®, Bausch & Lomb, Italy) eye‐drops 2 times/day. After 4 months’ treatment, right BCVA was 20/20 Snellen and OCT scans showed a normal CMT. This treatment was continued and there was no recurrence of DME in the next 11 months of follow‐up. No adverse events were noted.ConclusionsTopical Betamethasone Sodium Phosphate and Tetracycline Hydrochloride, together with nonsteroidal anti‐inflammatory eye‐drops, might be an effective alternative for the treatment of newly diagnosed DME in patients not suitable for intravitreal therapy. Future case‐control studies are necessary to confirm these results.
AD in the eye
Authors: Davis B. , Ravindra N. , Guo L. , Cordeiro M.F. 
Published: September 2017

SummaryAlzheimer's Disease (AD) is the most common form of dementia, however, diagnosis of this condition typically occurs late in the disease process and can only be confirmed post‐mortem. Late diagnosis of AD is problematic as considerable damage to the brain has already occurred by the time symptoms present. Timely diagnosis would therefore serve to create a window of opportunity for novel therapeutics designed to slow or prevent AD progression. The retina presents the only portion of the CNS that can presently be readily and non‐invasively imaged at the single cell resolution owing to the optically transparent nature of the eye. Visual defects have long been reported in AD patients and there are growing reports that histopathological changes in the brain can also be observed in the retina. This talk outlines recent developments in our understanding of potential retinal manifestations of AD with a view to using these findings to develop novel retinal based diagnostics.
Chronic exposure to TNFα impairs RPE barrier and immunosuppressive functions
Authors: Touhami S. , Beguier F. , Augustin S. , Reichman S. , Goureau O. , Nandrot E. , Guillonneau X. , Bodaghi B. , Sennlaub F. 
Published: September 2017

PurposeThe retinal pigment epithelium (RPE) is a monolayer of pigmented cells with important roles in the outer blood‐retinal barrier and subretinal immune suppression. Failure of RPE functions and inflammation have both been hypothesized to play a role in the pathophysiology of age related macular degeneration (AMD). We here investigated the long‐term effects of TNFα on RPE morphology and function in vitro.MethodsPrimary porcine RPE cells were cultivated until confluence, then recombinant TNFα was added daily in the culture medium (at 0.8, 4, 20 or 100 ng/ml=C1,C2,C3 and C4) for 10 days. RPE cell morphology and gene expression, barrier, phagocytosis and immunosuppressive functions were assessed.ResultsCell morphology and gene expression:TNFα (i) decreased cell number (3653.6,3428,3227,2791 and 2020 cells/mm2 respectively for control,C1,C2,C3 and C4, all p < 0.01); (ii) increased cell size (+5.3,+12.6,+13.9 and +9.5% of control for C1,C2,C3 and C4, all p < 0.05); (iii) increased the % of multinucleated cells (5.7,7.7,9.4,9.9 and 15.9% of multinucleated cells for control,C1,C2,C3 and C4, all p < 0.05); (iv) and decreased OTX2 (a major RPE gene) expression (‐11.1, ‐19.7, ‐52 and ‐82.9% of control for C1,C2,C3 and C4, all p < 0.05). Barrier function: Stimulation by TNFα (i) disturbed Zonula Occludens 1 cellular distribution and actin F distribution and (ii) significantly decreased RPE transepithelial resistance in a dose‐dependent manner (‐70, ‐88.5 and ‐90.8% of control for C2,C3 and C4, p < 0.05). Immunossupressive function: 10 day pre‐stimulation with ‐TNFα significantly decreased RPE capacity to induce monocyte death after 24 h of co‐culture (p < 0.05).ConclusionsChronic exposure to TNFα deteriorates major RPE functions that are essential to visual function and might play a key role in the pathophysiology of AMD.
Imaging endpoints in clinical trials
Authors: Garhofer G. 
Published: September 2017

SummaryClinical drug trials usually rely on primary endpoints that are well‐described direct measures of patient benefit or are closely related to clinical outcomes such as visual field testing. However, there is a lack of short‐term, easy to measure, highly reproducible endpoints predictive for visual acuity outcomes that would qualify as sufficiently predictive variables for patients′ benefit in clinical trials. This of special importance for the follow up of slowly developing diseases, which requires long‐term studies with large sample sizes. The rapid progression in the development of in‐vivo imaging techniques offers now new and exiting possibilities to assess human anatomic or physiologic information in unprecedented high resolution. Thus, the use of these new imaging techniques such as optical coherence tomography as possible endpoints in clinical phase III trials has been widely and controversially discussed. This talk aims to summarize the potential and limitations of modern imaging techniques to serve as surrogate parameters to substitute for clinical endpoints in ocular drug development.
Ultrawidefield OCT
Authors: KOLB J.P. , Klee J. , Klein T. , Kufner C. , Wieser W. , Neubauer A. , Huber R. 
Published: September 2017

SummaryRetinal wide‐field imaging plays an increasingly important role for the diagnosis of various types or pathologies, some of which start or prevalently appear in the periphery. Despite the great value of wide field fundus cameras and scanning laser ophthalmoscopes for diagnosis and documentation, these devices only acquire 2‐dimensional data in form of en face projections. However, cross‐sectional imaging with optical coherence tomography (OCT) can provide a wealth of additional information. To cover a wide area of the retina of 100° or more of viewing angle, 5 – 10 million OCT scans are required. Current commercially available OCT technology is not able to capture such large data sets and the acquisition time would be prohibitively long.We recently developed retinal Megahertz OCT (MHz‐OCT), an OCT system that can acquire more than 1 million depth scans per second. It can achieve the high speed by using a new type of swept laser source: the Fourier Domain Mode Locked (FDML) laser. This high speed enables us to acquire a densely sampled 3‐dimensional OCT data set in the non‐mydriatic eye, covering an area of up to 100° angle on the human retina. Technology development and diagnostic potential of such devices will be discussed.
Rostock Cornea Module 2.0 – a versatile extension for anterior segment imaging
Authors: Stachs O. , Sperlich K. , Bohn S. , Stolz H. , Guthoff R. 
Published: September 2017

PurposeIn vivo corneal confocal laser scanning microscopy became a valuable tool for studying corneal morphology in health and disease. Enabling the optical dissection of the corneal architecture, this technique offers non‐invasive in vivo imaging at a cellular level being important for current research. Presently there is only one device available without undergoing technological changes in the last years. We are presenting new Rostock Cornea Module developments for anterior segment imaging using up to date confocal scanning laser technology.MethodsWe redesigned the RCM in a modular way. It is possible to use different microscope objectives for user defined requirements as well as to choose between contact and non‐contact application. Since the focal adjustment inside the cornea is often fiddly, we incorporated a fast piezo stage for closed‐loop focus control and adjustment. Further topics addressed: modular setup, extended field of view, reduction of eye movement and compression artifacts as well as software based noise reduction technologies.ResultsWe tested the new RCM in combination with a Spectralis platform, offering a resolution of 1536 by 1536 pixel. Performing contact measurements, we get similar results compared to the well‐known RCM‐HRT combination, but with a higher resolution and wider field of view. In non‐contact measurements, the reflection on the cornea surface is very prominent and limits imaging of epithelial structures. We could achieve high resolution stromal imaging of e.g. keratocytes nuclei and stromal nerves.ConclusionsThe RCM 2.0 concept is a versatile extension for visualization corneal structures at a cellular level enabling instant focal plane shifts. Further improvements, wavelength adaption and dedicated customizations are subject of current research.