bluuebunny/crossref_metadata_2025_split huggingface dataset:
Deficiency in the expression of Vps13C is associated with altered retinal and lens development in mice
Authors: Amarie O. , Rathkolb B. , Fuchs H. , Gailus‐Durner V. , Hrabě de Angelis M. , Graw J. 
Published: September 2017

SummaryWhile performing genotyping screening in the German Mouse Clinic we identified the Vps13C mouse mutant with eye phenotype where the homozygous mutant mice show signs of neurodegeneration, indicated by a reduction in the total retinal thickness, additionally the retinal blood vessels showed a pattern with structural alteration. Eye histology revealed the display of lipid‐like droplets in the retinal layers and in the anterior lens matrix. VPS 13C is a member of the VPS13 family of vacuolar protein sorting‐associated proteins highly conserved throughout eukaryotic evolution. While mutations in VPS13A and VPS13B cause the genetic diseases chorea‐acanthocytosis (ChAc) and Cohen syndrome, respectively, VSP13C is reported to be associated with Parkinsons disease and late onset Alzheimer's disease (LOAD). Moreover VPS13C has recently been found to be involved in the protein degradation through the ubiquitin being closely associated with lipid droplets and lysosomes. Human diseases are caused by the dysregulated accumulation of ubiquitinated protein aggregates, including neurodegenerative disorders. We believe Vps13c could open novel avenues for uncovering new treatments of metabolic and neurodegenerative disorders.
Human case
Authors: Hamel C. , Bocquet B. , Manes G. , Meunier I. 
Published: September 2017

SummaryWe will present two cases of early onset, possibly congenital, retinal dystrophies, in children, who do not have Leber congenital amaurosis. Visual acuity is decreased, and the fundus shows serpentine like images, most visible in infrared. OCT evidences abnormal retinal structure. ERG has been performed. Molecular genetics is undergoing.
Role of taurine in cone death
Authors: Picaud S. , Trouillet A. , Hadj‐Saïd W. , Dubus E. , García‐Ayuso D. , Sahel J. , El‐Amraoui A. , Petit C. 
Published: September 2017

SummaryCone photoreceptors degenerate in a number of retinal diseases leading thereby to blindness or low vision as in age‐related macular degeneration or retinal dystrophies. However, mechanisms leading to cone photoreceptor death remain enigmatic. In the 70s, taurine depletion was shown to lead to complete photoreceptor degeneration. We have investigated the relative cone/rod sensitivity to taurine depletion and the effect of taurine supplementation on cone degeneration in a model of Usher syndrome type 1. Using a taurine transporter blocker, we have shown that taurine depletion induces a cone degeneration prior to the rod loss. This cone degeneration affect both blue and green cones throughout the retina. To investigate whether taurine could provide an interesting neuroprotective agent in retinal diseases, we supplemented a mouse model of Usher syndrome type 1 with taurine. This taurine supplementation prevented the cone photoreceptor degeneration and the associated retinal gliosis. These studies demonstrate that taurine is an essential antioxidant for cone photoreceptor survival. Its supplementation could slow down the degenerative process of cone photoreceptors as in our in animal models of Usher syndrome type 1.
The role of p62/SQSTM1 in IL‐1β‐mediated cytokine production in retinal pigment epithelial cells
Authors: Kauppinen A. , Korhonen E. , Piippo N. , Hytti M. , Kaarniranta K. 
Published: September 2017

Purposep62/SQSTM1 is a selective autophagy substrate being added to ubiquitinated proteins directed to lysosomal degradation. Its levels increase inside the retinal pigment epithelial (RPE) cells when proteasomal activity and autophagic clearance decline during aging. p62/SQSTM1 can also contribute to the activation of pro‐inflammatory nuclear factor kappa B (NF‐κB) or mitogen‐activated protein kinase (MAPK) pathways. According to our previous studies, reduced intracellular clearance promotes the NLRP3 inflammasome‐mediated release of IL‐1β, which subsequently stimulates RPE cells to produce other pro‐inflammatory mediators, such as IL‐8. In the present study, we have investigated, whether increased levels of p62/SQSTM1 play a role in the IL‐1β‐induced response.MethodsUpregulation of p62/SQSTM1 was induced by bafilomycin A1 or the over‐expression vector, or prevented by p62/SQSTM1‐specific small interfering RNA (siRNA) transfection. Thereafter, the cells were exposed to IL‐1β. The release of IL‐6 and IL‐8 were detected using the enzyme‐linked immunosorbent assay (ELISA) method. In addition, the autophagy markers p62/SQSTM1 and LC3 were determined using the western blot technique.ResultsIL‐1β resulted in low IL‐6 and high IL‐8 production in human RPE cells. p62/SQSTM1 and its absence were verified but they did not affect the cytokine profiles.ConclusionsOur data suggest that p62/SQSTM1 does not play a role in the IL‐1β‐induced production of pro‐inflammatory cytokines in human RPE cells.
National diabetic retina screening programme: identifying non‐diabetic eye disease
Authors: Murphy R. , Keegan D. 
Published: September 2017

PurposeThe Irish Diabetic RetinaScreen Service offers Nationwide screening to all diabetics over the age of 12. It is internationally unique given the integrated nature of its screening and treatment arms. It is now well established, demonstrating impressive uptake with considerable clinical impact. The aim of this study is to explore the significant and increasing number of referrals from the Diabetic RetinaScreen Service with non‐diabetic eye disease. We determine the individual contributions of pathology sub‐groups and their respective outcomes.MethodsWe retrospectively examined a 12‐month referral assessment database from the Mater Misericordiae University Hospital treatment center from January 2016 to 2017. Non‐diabetic eye disease referrals were identified and analysed with respect to their frequency of referral and outcome.ResultsOne thousand nine hundred and ninety‐three patients seen in the MMUH during the 12‐month period were included in the study. Diabetic eye disease referrals comprised 1250/1993 (63%) referrals, with 743/1993 (37%) referred for assessment of non‐diabetic eye disease. Substantial pathology sub‐groups included retinal artery and vein occlusions; Arterial emboli; Cataract; Glaucoma; Age Related Macular Degeneration; and Pigmented retinal lesions. We discuss the relative contribution from each pathology and the subsequent assessment outcomes.ConclusionsSeveral non‐diabetic, sight threatening ocular pathologies, which are often asymptomatic in their early course, are being identified and referred for appropriate treatment. The referral volume is increasing. Quantifying this promotes a more informed discussion on increased service demands, helping predict its practical and financial impact, and influencing strategies on future service provisions.
Macular changes in patients with multiple sclerosis – A texture analysis of optical coherence tomography data
Authors: Bernardes R. , Silva G. , Batista S. , Sousa L. , Castelo Branco M. 
Published: September 2017

PurposeIn this work, a novel approach is used to assess macular changes in patients diagnosed with multiple sclerosis. The vast majority of the studies, if not all, do use the capacity of the optical coherence tomography (OCT) to detect changes along the optical path to identify the different retinal layers and the detection of these to measure the thickness of the retina and the different layers. In particular, the measurement of the retinal nerve fibre layer (NFL) has played a fundamental role in related studies. In this work, we computed a fundus image for the NLF, the ganglion cell layer (GCL), the inner plexiform layer, the inner nuclear layer, the outer plexiform layer and the out nuclear layer and analysed the texture of these fundus images to find their relative differences to the healthy control group.MethodsA total of 152 eye scans, from 38 healthy controls (age (m/sd): 36.3/9.2 years) and 39 multiple sclerosis patients (age (m/sd): 38.8/7.3 years) were performed by the Cirrus HD‐OCT (Carl Zeiss Meditec, Dublin, CA, USA) and exported to be segmented by the OCT Explorer (Retinal Image Analysis Lab, Iowa Institute for Biomedical Imaging, Iowa City, IA, USA). The segmentation was further analysed and corrected when necessary.ResultsEach of these images was analysed using first and second order statistics. A support vector machine (SVM) classification process was used to assess the capacity to discriminate between healthy controls and patients to find that the layer presenting the highest difference between the control and the patient group is, surprisingly, the GCL, with over 10% in classification accuracy compared to the NFL layer.ConclusionsThis finding points to the need for further analysis of retinal changes beyond that of the thickness measurement and only in the nerve fiber layer.
Ophthalmoscopic and video OCT methods to detect spontaneous venous pulsation in individuals with apparently normal intracranial pressure: the rebirth of the SVP?
Authors: Jenkins K.S. , Layton C.J. , Adams M.K.M. 
Published: September 2017

PurposeTo compare the efficiency of high magnification binocular indirect ophthalmoscopy and direct ophthalmoscopy in detecting the spontaneous venous pulsation (SVP) at the optic nerve head, and to demonstrate the utility of video optical coherence in detecting the phenomenon in patients with normal intracranial pressure.MethodsThe SVP of the right eye of 54 consecutive clinic patients presenting without neuro‐ophthalmic symptoms and with BMIs under 30 were dilated and examined by one ophthalmologist using a 66D handheld Volk lens, then examined by a second blinded ophthalmologist using direct ophthalmoscopy. Immediately the patient was assessed by a third blinded ophthalmologist via vOCT for the presence or absence of SVP.ResultsThe population included 20 males and 34 females and were corrected for VA (M 0.127 LogMAR, SD 0.22, SE 0.036), IOP(M 16.5 SD 4.02 SE 0.558), phakia, age (M 68.3, SD 15.15, SE 2.062), C:D ratio (M 0.48 V 0.58 H, SD 0.19 V 0.18 H, SE 0.035 V and 0.033 H), BP (M 136/79, SD 17.71 Sys 12.04 Dia, SE 2.410 Sys, 1.639 Dia) and weight (M 75.48, SD 15.92, SE 2.486). SVPs were detected in 32 of 54 patients using direct ophthalmoscopy, and in 33 of 54 patients using a 66D lens and slit lamp. The ophthalmologists using direct ophthalmoscope and the 66D lens agreed in 49 of 54 cases, giving an inter‐rater reliability of 91%. All patients were found to have SVP on vOCT.ConclusionsOphthalmoscopically‐assessed SVP has a high inter‐observer agreement in normal subjects. However, 26% of patients with apparently normal ICP had no ophthalmoscopically detectable SVP. Conversely, SVP was detectable in all patients with apparently normal ICP by vOCT, suggesting it may be a more useful clinical assessment than ophthalmoscopically assessed SVP‐detection.
Outcomes and endpoints in glaucoma
Authors: Cordeiro M.F. 
Published: September 2017

SummaryClinical trials in glaucoma have historically relied in IOP. However, the emergence of neuroprotection in glaucoma ghas lead to a need for new measures of trial success. Several potential outcomes exist including autoimmune and genetic biomarkers, brain and retina imaging, clinical signatures of RGC disease and structural and functional endpoints. These will be covered in this talk including DARC – detection of apoptosing cells.
Misunderstanding laboratory evaluation
Authors: Neri P. , Pirani V. , Cesari C. 
Published: September 2017

SummaryIntraocular inflammations always represent a diagnostic challenge for ophthalmologists. It is often tough to make a precise etiological diagnosis in certain subsets that very often appear atypical. Recently, several advances in the investigations for uveitis have been introduced. Such scientific achievements have significantly helped uveitis specialists in the management of such clinical conditions. Although the approach to laboratory diagnosis of uveitis should be directed by the history, patient's symptoms and signs, and clinical examination, very often the ophthalmologist can be confused if such method is not rigorously followed. The matching of clinical pattern and the tests should be always considered in order to reach the goal of a correct interpretation. This review summarizes various modalities of laboratory investigations and their role in the diagnosis of uveitis, furthermore paying attention to the most common mistakes in their interpretation.
Mistaking infection for inflammation
Authors: Albini T. 
Published: September 2017

SummaryAmong the first steps in diagnosing any patient with uveitis is to identify infection. Common infections that may masquerade as autoimmune disease include herpes simplex virus, varicella zoster virus or cytomegalovirus (CMV) anterior uveitis, chronic post‐surgical endophthalmitis, endogenous endophthalmitis, acute retinal necrosis, CMV retinitis in immunocopme patients, syphilis, atypical toxoplasmosis and tuberculosis. Patient history and clinical exam can often make the diagnosis. The utility of diagnostic tests such as treponemal tests, quantiferon testing, Mantoux skin test, and toxoplasmosis serology will be covered. Case series of polymerase chain reaction (PCR) testing of anterior chamber and/or vitreous aspirate for anterior segment and posterior segment uveitis will be reviewed, with an emphasis on demonstrated clinical utility. More invasive biopsy such as vitreous biopsy via pars plana vitrectomy or chorioretinal biopsy may be necessary in some settings. Appropriate treatment and criteria for treating specific infections will be covered. Cases of polymicrobial infection will be reviewed as well. Emphasis will be placed on distinguishing infection from autoimmune disease.
Fear of the correct treatment dose
Authors: Lowder C. 
Published: September 2017

Summary• Fear of the correct treatment doseO Underdosing valacycloviro Underdosing immunosuppressive therapyUveitis can occur in all age‐groups and often has devastating effects on vision. The visual loss can have a variety of causes including cataract formation, vitritis, optic nerve damage and macular edema. In patients with active inflammatory disease resulting in reduced vision, corticosteroids are a very important part of the management, and uveitis specialists have learnt a long time ago that their use should be optimized. Even if serious side effects are associated with chronic use of systemic steroids, the correct full‐dose should be employed. The concept of optimizing the treatment by using the correct dose, then lower it to the minimum effective dose that controls inflammation, should be applied as well to the second step of uveitis treatment, immunomodulatory agent. Tailored treatments must also be extended to infectious uveitis, for which there is a low level of awareness of recommended guidelines to control the diseases. A perfect example is anti‐viral treatment in cases on herpes uveitis, which should be tailored when the causing herpes virus is identified.
Gene therapy strategies for hypoxia‐inducible angiogenesis in ocular neovascularization
Authors: ANDRE H. , Hertzman M. , Kristiansson A. , Svensson E. , Alatar S. , Ruononen J. , Lu Y. , Kvanta A. 
Published: September 2017

PurposeOur previous results have associated HIF expression in RPE cells to CNV progression, and we have shown that gene transfer of prolyl hydroxylase domain (PHD)2 in the mouse model of nAMD resulted in mitigation of HIF‐mediated angiogenesis. Here, we investigate the function of hypoxia‐regulated molecular elements in modulating the expression of transgenes in retinal pigment epithelium (RPE) cells, with putative use in gene therapy strategies for the treatment of nAMD.MethodsHypoxia‐mediated RPE‐specific expression vectors were generated using the minimum mouse Rpe65 promoter (pRpe65), while hypoxia‐mediated expression was achieved using hypoxia‐response elements (HRE) and oxygen‐dependent degradation peptides (ODP). Hypoxia‐dependent regulation of transgenes in ARPE‐19 cells was determined by green fluorescence protein (GFP) expression. Expression pattern analyses of transgenes in response to hypoxia and reoxygenation were assayed by western blot and RT‐PCR.ResultsUse of pRpe65 resulted in RPE‐specific expression of GFP. Hypoxia‐enhanced expression of GFP was achieved with HRE‐driven pRpe65, and GFP expression patterns were regulated at the transcriptional level. Fusion of ODP to GFP resulted in hypoxia‐mediated expression, under pRpe65 regulation, and GFP protein expression was subject to hypoxia‐dependent protein expression.ConclusionsOur data shows that transgenes can be expressed specifically in RPE cells and be regulated by hypoxia, both by transcriptional and post‐translational regulation, limiting the therapeutic gene expression to pathologic hypoxic RPE cells. These results may have implications for the clinical treatment of ocular vascular pathologies, such as nAMD, particularly regarding the use of gene therapy to negatively regulate neoangiogenesis.
What is the meaning of autofluorescence in retinal diseases?
Authors: Kaarniranta K. 
Published: September 2017

SummaryThe fluorophore is fluorescent chemical compound that absorbs light energy of a specific wavelength and re‐emits light at a longer wavelength. The absorbed wavelengths, energy transfer efficiency, and time before emission depend on both the fluorophore structure and its chemical environment, as the molecule in its excited state interacts with surrounding molecules. Excitation energies range from ultraviolet through the visible spectrum, and emission energies may continue from visible light into the near infrared region. Recently, fundus autofluorescence (FAF) imaging has got more role in retinal diagnosis. FAF imaging is a quick and non‐invasive method. It provides information also from inside of the cells (RPE cells). For example lysosomal lipofuscin is highly autofluorescent compound. FAF is useful for monitoring disease progression, estimate age of lesions or severity level. However, FAF imaging is unspecific and observations must be combined with other diagnostic methods. In this course we discuss benefits and limitations of FAF in retinal diseases.
Histological analysis with OCT
Authors: Paterno J. 
Published: September 2017

SummaryEach distinct retinal layer is visible on the optical coherence tomography (OCT). In clinic, the OCT has been part of diagnostics of retinal disease over 25 years, and due the technical advances, state‐of‐the‐art OCT technique provides an impressive non‐invasive tool for evaluating retinal anatomy in vivo, corresponding well to histological studies. This talk will discuss the current use and future of OCT in retinal disease research and disease models.
OCT‐A: guided treatment of diabetic retinopathy
Authors: Coscas G. , Lupidi M. , Coscas F. 
Published: September 2017

SummaryDiabetic retinopathy (DR) is the leading cause of blindness in working‐age individuals in the developed world, affecting approximately 75% of patients with diabetes mellitus after 15 years. One of the early changes in diabetic eyes is loss of pericytes and proliferation of endothelial cells leading to the development of microaneurysms. Pericyte loss impairs the blood–retinal barrier, thereby leading to venous dilation and beading. The gold standard to screen for DR is dilated biomicroscopic fundus examination, where microaneurysms in the posterior pole are typically the first sign on ophthalmoscopy. Although fluorescein angiography is more sensitive than examination to detect early DR, it is invasive, costly, and time consuming, and therefore, is not appropriate as a screening test for DR. Optical coherence tomography angiography (OCT‐A) is a fast, noninvasive imaging technique that uses motion contrast to create OCT‐angiograms by comparing the decorrelation signal among sequential OCT B‐scans. Optical coherence tomography angiography may be a valuable screening tool for DR, useful as a clinical trial endpoint, and efficient in guiding early treatment decisions in the future.
Irradiation induced retinopathy: OCT‐A in the management and treatment
Authors: Zografos L. 
Published: September 2017

SummaryIrradiation induced maculopathy is a major complication of conservative management of intraocular tumors. Risk factors include an irradiation dose of more than 20 Gy with proton beam or Gy with brachytherapy and co‐existing diabetes and high blood pressure. In irradiation induced maculopathy, we observe a disruption of the inner B/R barrier, a disruption of the outer B/R barrier and a progressive vaso‐occlusive microangiopathy. In a prospective trial, based on more than 150 cases of irradiation induced maculopathy, examined with fluoresceine angiography, OCT‐angiography, B‐mode OCT and OCT “en face”, the status of the deep capillary plexus in OCT‐A had the best correlation with the residual visual acuity. Intravitreal anti‐VEGF applied in cases with disrupted deep capillary plexus contribute to the maintain of the visual function and reduced the progressive perifoveal capillary loss.
Pars plana & ciliary sulcus drainage tubes
Authors: Bloom P. 
Published: September 2017

SummaryPrimary glaucoma surgeries, whether minimally invasive or trabeculectomy, are usually effective in lowering intra‐ocular pressure. However, in a proportion of cases the initial procedure is ineffective or the procedure fails; in this eventuality, comprehensive glaucoma specialists need to be skilled in a number or other surgical strategies.Glaucoma drainage devices (‘tubes’) have long been used in complex or advanced cases, and are increasingly being used earlier on in the glaucoma treatment paradigm. In this part of the symposium, consideration will be given to instances where drainage tubes inserted into the anterior chamber are unlikely to be effective or have a high risk of failure. In such situations, there may be advantages for the drainage tube to be implanted through the posterior limbus or the pars plana.Consideration will be given to the indications, techniques, advantages and complications of posterior tube implantation. Clinical case scenarios will be described using anterior segment photography and video presentations, so that skills and knowledge will be transferred effectively; this will allow assimilation of these techniques into the clinical practice of glaucoma specialist participants.
Ocular angiography: dual FA/ICGA scoring of posterior uveitis
Authors: Herbort C.P. 
Published: September 2017

SummaryIn the recent past uveitis has become an exact clinical science thanks, among others, to the availability of performing imaging methods. The SUN process (standardization of uveitis nomenclature) should have been the forum where these new imaging modalities should have been integrated. However SUN did just the opposite, perpetuating old and obsolete measurement methods. For the evaluation of posterior uveitis they recommended the more than 30 year old vitreous haze scoring system comparing vitreous haze to a set of 4 pictures with increasing grades of vitreous haze, recommending it as the gold standard and main outcome measure for clinical trials on new treatments in posterior uveitis. This method is subjective and has a scale of only 4 grades, improper to reach statistical significance even in cases with pronounced vitritis. Dual FA/ICGA angiography allows scoring of both retinal and choroidal inflammation with scales of respectively 40 for each. Such a numbered measurement modality is by far more adequate to measure posterior uveitis as it scores both the retinal and choroidal inflammation in entities that mostly have limited vitreitis. Several studies will illustrate the central role of FA/ICGA in monitoring posterior uveitis.