bluuebunny/crossref_metadata_2025_split huggingface dataset:
Clinics, biopsy and pathology
Authors: ROBERT P 
Published: November 2013

AbstractEtiological diagnosis of orbital inflammation drives the general handling, states on specific/non specific status of inflammation, and may lead to simple survey of long‐lasting immunosuppressive treatment. Handling a orbital patient is always challenging for the clinician, but specific signs from clinical exam, imaging, biological checkup or histological samples may be critical. Clinical exam of the orbit must be directed towards ocular inflammation, sensitive and oculomotor signs, optic nerve function, and comparative orbital morphology. Imaging can disclose vascular, inflammatory, compressive, or bone‐desctructive lesions. Biological and systemic checkup must target signs of granulomatous, vasculitis, infectious, hematological and immunological diseases. Fine‐needle biopsy is still controversial since it allows a first histological exploration under local anesthesia, but may be at risk of bleeding, perforating a noble organ (globe, muscle, optic nerve, lacrimal gland) or misdiagnosing a heterogenous or small lesion, when compared to explorative biopsy under general anesthesia. Progresses on immunohistochemistry and histological markers have made the proportion of “non‐specific” orbital inflammation decrease these 10 last years We review these techniques through demonstrative clinical cases.
Inflammatory orbital lesions (IOI)
Authors: DE KEIZER RJW , BIJLSMA WR 
Published: November 2013

AbstractIdiopathic orbital inflammation is a diagnosis by exclusion and therefore a rather heterogeneous patient group. By definition the terms exclude lesions with an identifiable aetiology as bacterial, fungal and parasitic infections. Many classification schemes for IOI exists, but we didn’t know which one is best so we like to share with the audience the outcome of our quest for the best classification system for idiopathic orbital inflammation. The classification systems could be tested for the five properties of a good classification system being Reliability , Feasibility, Face validity, Content validity, Distinction. A combined histology/imaging localization classification system is best for idiopathic orbital inflammation. The presentation will be including the topics idiopathic inflammatory orbital disease, which has to differentiate from the vasculitis and isolated sclerosing pseudotumor. The new classification schedules of the international vasculitis group will be shortly outlined. Also some research findings, where several attempts were done, to find relations with
The endolysosomal system and AMD: Insights from a novel genetically engineered mouse model
Authors: SINHA D , VALAPALA M , ZIGLER JS , HOSE S 
Published: November 2013

AbstractIn phagocytic cells, the endolysosomal system is a crucial regulator of both phagocytosis and autophagy, thereby helping to maintain cellular homeostasis. Prime examples of this are retinal pigmented epithelial (RPE) cells, which are not only among the most actively phagocytic cells, continuously phagocytosing shed photoreceptor outer segments (OS), but also are post‐mitotic cells having high metabolic activity and a high rate of autophagy. For proper RPE function, and to ensure the functional integrity of the neural retina, both phagocytosis and autophagy need to be in balance. We show that in the RPE, bA3/A1‐crystallin is required for normal lysosomal‐mediated waste removal. Our studies suggest that bA3/A1‐crystallin acts via the AMPK‐mTORC1 signaling pathway. Based on our findings, we postulate that loss of bA3/A1‐crystallin inhibits these signaling pathways, leading to a defect in the V‐ATPase‐mediated acidification of the lysosomal machinery. Since bA3/A1‐crystallin has been reported to be present in human drusen and a possible role for lysosomes in age‐related macular degeneration (AMD) has been suggested, it is possible that perturbation of normal phagocytosis/autophagy in RPE could cause some manifestations of AMD.
A novel role for the immunoproteasome in retinal function
Authors: FERRINGTON D 
Published: November 2013

AbstractThe immunoproteasome (i‐proteasome) is a protease that is abundant in cells of the immune system and is known to generate peptides for MHC class I presentation. I‐proteasome is also present in tissues outside the immune system, including retina and RPE cells, suggesting alternative functions are possible. We have previously shown that i‐proteasome is upregulated in the retina of donors with AMD, in response to acute injury in the retina and brain, and chronic oxidative stress in cultured RPE. These results suggest a novel role in the cellular stress response. Our recent focus has been on defining how i‐proteasome is involved in regulating two key stress response pathways, NFkB and autophagy. To investigate i‐proteasome’s role, we used RPE cells derived from WT and KO mice lacking either one (lmp2‐/‐) or two (lmp7‐/‐/mecl‐/‐) i‐proteasome catalytic subunits. Results show that cells deficient in the LMP2 subunit demonstrate differences in the alternative pathway of NFkB signaling, as well as a diminished response to autophagic stimuli. Thus, i‐proteasome upregulation with AMD, and with chronic and acute injury, may be a compensatory response that is required to help regulate these two stress response pathways.
Baseline characteristics predictive of pharmacologic vitreomacular adhesion resolution in the ocriplasmin MIVI‐TRUST program
Authors: GANDORFER A 
Published: November 2013

AbstractPurpose The ocriplasmin MIVI‐TRUST program included two phase III, multicenter, randomized, double‐masked trials to determine the efficacy and safety of ocriplasmin for the treatment of vitreomacular traction (VMT). We sought to identify baseline characteristics that were predictive of pharmacologic vitreomacular adhesion (VMA) resolution at Day 28 after an injection of ocriplasmin or placebo.Methods Patients with OCT‐confirmed VMA were randomized to receive a single intravitreal injection of ocriplasmin 125 µg (n=464) or placebo (n=188). The primary end point was VMA resolution at 28 days post‐injection. A multivariate regression analysis was performed to determine independent baseline anatomic and non‐anatomic characteristics that were significantly associated with pharmacologic VMA at Day 28.Results Pharmacologic VMA resolution at Day 28 was observed in a significantly larger proportion of patients in the ocriplasmin group (26.5%) compared with placebo (10.1%; p<0.001). Independent baseline anatomic characteristics predictive of VMA resolution included the presence of a full‐thickness macular hole (equivalent to stage II; p=0.019), VMA diameter ≤1500 µm (p<0.001), phakic lens status (p<0.001), and the absence of an epiretinal membrane (p<0.001). Independent non‐anatomic baseline characteristics predictive of VMA resolution included treatment with ocriplasmin (p<0.001) and age <65 years (p<0.001).Conclusion The identification of specific baseline anatomic characteristics predictive of response is informative in the consideration of treatment options for patients with VMT.
Commercial interest
Myths and misconceptions about glaucoma blindness
Authors: HONDEGHEM K 
Published: November 2013

AbstractBlindness is a major global problem, with many associated socioeconomic impacts. Glaucoma is responsible for much of this worldwide blindness. Glaucoma is the leading cause of irreversible vision loss. We will take a closer look at ten common myths and misconceptions about (glaucoma) blindness. We will also briefly discuss some exciting new technologies that can be a tremendous aid to the blind.
Myths and misconceptions in treatment adherence
Authors: KOTECHA A 
Published: November 2013

AbstractOnce diagnosed, the glaucoma patient requires lifelong treatment, usually with topical IOP lowering medication. The aim of glaucoma treatment is to reduce IOP, a ‘clinician‐based’ measure, and thus treatment has no obvious effect on the patient’s vision or their ability to carry out every‐day tasks. There is evidence to suggest that medication underuse occurs in patients with glaucoma. Deliberate medication underuse occurs when the patient is concerned with aspects relating to either the treatment safety, or treatment efficacy and necessity. In glaucoma, medication misuse may lead to inappropriate conclusions regarding treatment inefficacy, resulting in unnecessary changes and additions to treatment, and, more seriously, avoidable, irreversible visual loss. Improving patient adherence to their treatment is a complex issue influenced by a number of factors. This talk will explore some of the issues regarding glaucoma medication misuse and the role of the 'doctor‐patient' relationship in promoting adherence to treatment.
Novel strategies for angioregression at the ocular surface
Authors: BOCK F , CURSIEFEN C 
Published: November 2013

AbstractThe normal human cornea is avascular. This avascularity is actively maintained by expression of antiangiogenic and antilymphangiogenic factors. Corneal neovascularization (NV) can occur after numerous corneal diseases and leads to decreased visual acuity and poor prognosis in subsequent corneal transplantation since corneal immune privilege is lost. We recently demonstrated that bevacizumab eye drops significantly inhibit progressive corneal angiogenesis. In contrast, limited treatment options exist for mature corneal vessels, which — because of their pericyte‐covered vessel wall—do not depend on VEGF anymore. Here, we report on the short‐ and long‐term visual acuity changes and changes in vascularized corneal area after e.g. feeder vessel coagulation combined with topical bevacizumab application for the treatment of mature pathological corneal NV . These angioregressive therapies may not only improve corneal transparency but also “preconditions” such a cornea for future keratoplasty.
Transcriptional profiling of human corneal epithelium using laser capture microdissection and massive parallel sequencing
Authors: BATH C , MUTTUVELU D , EMMERSEN J , VORUM H , HJORTDAL J , ZACHAR V 
Published: November 2013

AbstractThis study was conducted to perform global transcriptomic profiling and biomarker discovery on undisturbed human corneal epithelial subpopulations using a novel approach combining laser capture microdissection (LCM) and RNA sequencing. LCM facilitated the harvest of four cellular compartments along the corneal epithelial differentiation pathway: Stroma, basal limbal crypt (BLC), superficial limbal crypt (SLC), and cornea. Compartments were analyzed using massive parallel sequencing and bioinformatics. Specificity of LCM was confirmed by imaging, expression of epithelial markers, and gene ontology analysis of biological processes. Interestingly, many significant upregulated genes in SLC mapped to processes involved in regulation of vasculature like sFLT1. In contrast, BLC had many upregulated genes mapping to neurogenic and developmental processes. The primitive nature of BLC was confirmed by KEGG pathway analysis. We present full gene lists of unique expressed genes in both BLC and cornea representing candidate biomarkers. Possible novel regulators of limbal epithelial stem cells (LESCs) include Lrig1 and SOX9. The presented molecular insight in LESC biology is expected to be beneficial for both research and clinical translation.
Suitability of a fish scale‐derived collagen matrix (FSCM) as artificial cornea
Authors: VAN ESSEN TH , VAN ZIJL L , SPARKS SJ , CHEN G , LIN CC , LAI HJ , LUYTEN GPM , GHALBZOURI AEL , JAGER MJ 
Published: November 2013

AbstractPurpose: A naturally occurring, easily obtainable fish scale‐derived collagen matrix (FSCM) may be a cheap alternative to current keratoprostheses. We assessed its suitability by measuring light transmission, scattering, and immunogenicity. Methods: Light transmission and scatter characteristics of the FSCM were measured. The FSCM was implanted subconjunctivally in rats, to assess swelling and neovascularization, and subcutaneously to observe the cellular immune response. Results: The FSCM had a light scattering of log(s) =1.62 and a light transmission of 90%. Local swelling and neovascularization appeared similar to an implant already used in glaucoma surgery. Both subcutaneous implants elicited an initial and mild immune reaction with only a few lymphocytes after 2.5 months, and did not induce immune sensitization. The FSCMs were well tolerated, while a small fibrous capsule was also observed. Conclusions: We demonstrate that the first prototype of this easily obtainable, naturally occurring FSCM has proper optical clarity, and low immunogenicity. These properties demonstrate its potential as a candidate for reconstructing the avascular cornea.
Commercial interest
Small molecule induction promotes corneal epithelial cell differentiation from human pluripotent stem cells
Authors: SKOTTMAN H , MIKHAILOVA A , UUSITALO H , ILMARINEN T 
Published: November 2013

AbstractPurpose Corneal epithelium is maintained by limbal stem cells, and their transplantation has been used to treat limbal stem cell deficiency (LSCD). However, this is only possible if enough healthy limbal tissue is available. Thus, novel cell sources for treating LSCD are needed. Human induced pluripotent stem cells (hiPSCs) provide unique opportunities for differentiation of limbal and corneal epithelial cells for cell transplantations.Methods In order to improve the efficiency and reproducibility of hiPSCs differentiation towards corneal epithelial progenitor cells, signaling cues active during ocular surface ectoderm development was replicated with two small‐molecule inhibitors in combination with growth factors. The extent of differentiation was evaluated by following the expression of key markers using immunocytochemistry and qPCR at several time‐points.Results Small‐molecule induction down‐regulated the expression of pluripotency marker OCT4 while up‐regulating the eye‐field transcription factor PAX6. Protein expression of the corneal epithelial progenitor marker p63 was greatly enhanced, with up to 95% of cells being p63‐positive after five weeks of differentiation. Finally, after a total of six weeks in differentiation culture, the two markers specific to terminally differentiated corneal epithelium, cytokeratins 3 and 12, were expressed in an average of 35% and 71% of cells, respectively.Conclusion In contrast to all earlier studies, corneal epithelial cells were differentiated in serum‐free culture conditions without the use of amniotic membrane or other undefined culture substrates. This highly efficient differentiation method could potentially be used for treating LSCD in the future.
Commercial interest
Comparative gene expression analysis of corneal stroma mesenchymal stem cell‐like cells, limbal epithelial stem cells and bone marrow‐derived mesenchymal stem cells
Authors: VEREB Z , POLISKA SZ , ALBERT R , OLSTAD OK , MOE MC , FESUS L , PETROVSKI G 
Published: November 2013

AbstractPurpose Purpose Stem cells in the central part of the cornea serve an important regenerative and homeostatic function. We aimed to describe the genetic fingerprint of these cells and compare that to limbal epithelial stem cells (LESC) and bone marrow‐derived MSCs (bmMSCs).Methods Corneal tissue and bmMSCs were harvested from cadavers and healthy donors, respectively (according to the Guidelines of the Helsinki Declaration) and cultured ex vivo. MSC‐specific cell surface markers‐ and genome‐wide microarray analysis were performed using FACS and Affymetrix GeneChip Human Gene 1.0 ST Array (~23,000 gene transcripts).Results Genes related to stemness (228), differentiation and lineage (220), cell cycle (108) and HOX, SOCS, Notch signaling (218) were collected into functional groups and clustered hierarchically: 45 genes were found to be specific for corneal stroma (CS)‐MSCs, 62 for LESCs and 9 for bmMSCs. The hierarchical clustering clearly separated the CS‐MSCs from the LESCs and bmMSCs, but formed a higher cluster with the later. The top 10 genes related to the differences were VCAM1, FNDC1, MFAP5, SFRP2, IGF2, MMP, ITGA2, COLEC12, SEMA3A and MGARP. Number of molecules functioning in cellular movement (381), cellular growth and proliferation (408), development (370) and cellular development (360) were found with top biological functions in CSMSCs compared to LESCs or bmMSCs (p<0.001).Conclusion Our data show clear distinction between the studied stem cells based upon their gene expression patterns and strengthen the hypothesis that CSMSCs are derived from bmMSCs and not from LESCs.
Strabismus and diplopia revealing rhabdomyosarcoma in a 7‐year‐old girl
Authors: AZIZ A , MATONTI F , FAKHOURY O , DENIS D 
Published: November 2013

AbstractPurpose This case report presents the diagnosis and management of seven‐years‐old girl with persistant diplopia revealing orbital rhabdomyosarcoma ,a rare and malign type of tumor among children. Few cases have been reported.The clinical presentation, complementary exams, and treatment for this condition are reviewed.Methods A 7‐year‐old girl was referred to our department for persistant diplopia ,and unilateral exophtalmia on her left eye that had been lasting for 5 months.The orthoptic examination showed no visual acuity loss, vicious head tilt bent on the left side, exotropia with quick restitution, limitation of abduction and elevation on left eye. The Lancaster test confirmed the limitation.The eye fundus examination revealed signs of extrinsic compression.Results Magnetic resonance imaging, and ocular and orbital echography showed an intra conical tumor of 18x21millimeters, displacing the ocular nerve and invading the superior rectus muscle. Tumor biopsy revealed undifferenciated rhabdomyosarcoma. Metastatic work‐up was negative and included thoracic and abdominal CT, bone scintigraphy and bone marrow biopsy. The treatment consisted in chemotherapy and permitted tumor volume regression of 85%. The patient has successfully manage with muscle surgery, not on the cicatricial site but on the other eye.Conclusion Ocular rhabdomyosarcoma is a rare tumor among children, but the most frequent malign orbital tumor, with possible secondary localisation. Early diagnosis and early treatment are determinant for the prognosis and the survival rate of these patients. This case report shows all the utility of strabismological examination to detect the first signs of the condition, even without any symptoms relative to visual acuity.
Non graves orbital inflammations: Rationale for a diagnostic approach
Authors: FISCH AL , GAVARD PERRET A , LAGIER J , ROBERT PY 
Published: November 2013

AbstractPurpose To propose a diagnostic approach for clinicians who manage a patient with non Graves’ orbital inflammation.Methods A review of the diagnostic process for sixty one patients with diagnostic of orbital inflammation between january 2002 and january 2013 at Niceand Limoges Universitary Hospitals.Results Sixty one patients presenting with orbital inflammation were included. More common presentations were orbital fat inflammation (60%), myositis (26%) and lacrimal gland enlargement (18%). In few cases, optic nerve and sclera were involved (respectively 9,8 and 3,2%). The final diagnostic was idiopathic orbital inflammation (25 patients), specific orbital inflammation (17 patients) and orbital lymphoma (19 patients). Thirty six patients had biopsy first and 25 patients did not, in first, but only after failure to the initial therapy. Our results showed that doing biopsy in the initial management of orbital inflammation provides a more great number of specific diagnosis than doing treatment tests directly after blood tests or CT scans ( p>0,01).Conclusion The diagnostic process of orbital inflammation must include blood testing, imaging of the orbit and sinuses, and biopsy in first intention as far as possible.
Mitochondrial dynamics in mitochondrial optic neuropathies
Authors: POULTON J , LIAO C , ASHLEY N 
Published: November 2013

AbstractOPA1 mutations are the commonest cause of dominantly inherited optic atrophy (DOA) and so‐called DOA plus. The Opa1 protein is essential for normal mitochondrial fusion. In mouse DOA, autophagy (recycling of spent cellular components) is dysregulated in retinal ganglion cells (RGCs), and mitophagy (mitochondrial recycling) has been implicated. We validated and used novel ImageStream technology to quantitate mitophagy in primary cells. Co‐localisation of mitochondria and autophagosomes was increased in fibroblasts in five patients from four families with severe OPA1 phenotypes indicating increased mitophagy. ImageStream also showed that basal mitophagy was increased when control cultures were depleted of Opa1 by siRNA. Western blotting confirmed increased basal autophagy and autophagic flux in the presence of activators. Increased mitochondrial fragmentation, mitophagy and failure of mitochondrial transport may together cause local depletion of mitochondria in critical regions of the retinal ganglion cells, such as axons or synapses. Fragmentation may also impair stress induced mitochondrial hyperfusion. Increased mitochondrial fragmentation, mislocalisation and mitophagy thus link low OPA1 to neurodegeneration.
Consequences of storage on the donor corneal tissue
Authors: ARMITAGE J 
Published: November 2013

AbstractNo storage method for biological materials preserves the full functional integrity of all cells in a given population. The loss of cells during storage of tissues for transplantation has to be accepted and the purpose of storage is to minimize both cell loss and maintain functional integrity. This is especially important for tissues where integrated cellular function is essential for normal, overall physiological function of the tissue. This is the case for cornea intended for transplants that require an intact and functioning corneal endothelial monolayer, such as for endothelial disease. The three main approaches to corneal preservation, viz., organ culture, hypothermic storage and cryopreservation, all pose their own unique challenges to cells and present a range of differing mechanisms of damage. Hypothermia relies on the suppression of metabolism by reduced temperature. Organ culture attempts to maintain metabolism. Cryopreservation completely suppresses all biochemical reactions and offers the prospect of indefinite storage. A better understanding of these mechanisms may lead to improvements in the quality of tissue after storage.
The therapeutic impact of office‐hours diurnal pressure measurements in the management of glaucoma patients
Authors: LAMPE M , POURJAVAN S 
Published: November 2013

AbstractPurpose To assess, primarily, the impact of office‐hours diurnal IOP measurements on our clinical treatment attitude for glaucoma patients. Secondly, to determine, specific risk factors which allow us to select the group of patients where performing an IOP diurnal curve can be useful.Methods 20 patients were included in this retrospective study. We examined the files of the patient who underwent a diurnal IO pressure curve between 01/01/2012 and 01/03/2013. Age, gender, race, diagnosis, the ophthalmological surgical and medical history, number of IOP measurements and the length of the diurnal curve on the examination day, the min and max IOP, and finally the therapeutic impact of these measurements and change in the treatment of patients.Results The mean age was 58.6 ± 14.8 years. There was min 4 to max 5 IOP measurements during 8.4 ± 0.5 hours. The mean IOP of all the patients was 17.7 ± 3.2 mmHg with a variation 2.3 ± 1.4 mmHg (1 to 6 mmHg max) during the day. There were only 50% of the measurements which led to a change of the clinical treatment. In this group of patients the higher max IOP during the day and the higher IOP variation were the common feature.Conclusion In our study we found that only 50% of the office‐hours diurnal intraocular pressure curve led to a new clinical treatment. The patient selection should be stricter because of the time‐consuming examination. Patients with higher IOP should be taken into account for diurnal IOP measurements where there are signs of progression.