bluuebunny/crossref_metadata_2025 huggingface dataset:
Predicting the conservation status of data‐deficient species
Authors: Bland Lucie M. , Collen Ben , Orme C. David L. , Bielby Jon
Published: August 2014

There is little appreciation of the level of extinction risk faced by one‐sixth of the over 65,000 species assessed by the International Union for Conservation of Nature. Determining the status of these data‐deficient (DD) species is essential to developing an accurate picture of global biodiversity and identifying potentially threatened DD species. To address this knowledge gap, we used predictive models incorporating species’ life history, geography, and threat information to predict the conservation status of DD terrestrial mammals. We constructed the models with 7 machine learning (ML) tools trained on species of known status. The resultant models showed very high species classification accuracy (up to 92%) and ability to correctly identify centers of threatened species richness. Applying the best model to DD species, we predicted 313 of 493 DD species (64%) to be at risk of extinction, which increases the estimated proportion of threatened terrestrial mammals from 22% to 27%. Regions predicted to contain large numbers of threatened DD species are already conservation priorities, but species in these areas show considerably higher levels of risk than previously recognized. We conclude that unless directly targeted for monitoring, species classified as DD are likely to go extinct without notice. Taking into account information on DD species may therefore help alleviate data gaps in biodiversity indicators and conserve poorly known biodiversity.

Predección del Estado de Conservación de Especies con Deficiencia de Datos
SED CONTRA
Authors: Wellbery David E. , Dutt Carsten
Published: August 2014

Sollte ein Etikett erwünscht sein, dann darf nachfolgender Beitrag als neo‐idea‐listische Positionsbestimmung verstanden werden. Er knüpft an die internationale Diskussion zum deutschen Idealismus an, die seit ungefähr fünfundzwanzig Jahren aktuelle Fragestellungen der analytischen Philosophie mit Begriffskonstruktionen zumal der Philosophie Hegels produktiv zusammen denkt.1 Eine Chance sowie eine Herausforderung stellt die erneute Aktualität der idealistischen Philosophie für die Literaturwissenschaft insofern dar, als sich deren Begriff ursprünglich im Umfeld idealistischen Denkens herauskristallisierte. Auf diese intellektuelle Situation ant‐worten die hier zur Diskussion gestellten Überlegungen. Sie setzen sich zum Ziel, die Idee der Literaturwissenschaft zu bestimmen. Mehr kann man innerhalb des engen Rahmens eines Diskussionsbeitrags nicht in Angriff nehmen.

Mit dem Begriff “Idee” ist eine konstitutive Norm gemeint, an der sich die Praxis des Literaturwissenschaftlers orientiert. Um plausibel zu machen, dass eine Idee geleitete Literaturwissenschaft überhaupt vorstellbar ist, muss zunächst die Konstitution des Gegenstandes dieser Wissenschaft, das heißt: der Literatur, erörtert werden. Man kann einen wissenschaftlichen Gegenstand durch Definitionen oder durch Beispiele einführen. Aus Gründen, die später klar werden sollen, schlage ich den zweiten Weg ein und verlasse mich auf die Evidenz des Exemplarischen. Es werden also zunächst drei Sätze zitiert, an denen sich die hier vertretene Ansicht von Literatur aufzeigen lässt. Im zweiten Abschnitt wird dann die besondere Form von Intentionalität, welche die Sätze aufweisen, unterschieden. Schließlich wird im dritten Abschnitt eine Formulierung der Idee von Literaturwissenschaft vorgeschlagen, die an Begriffsvorgaben der idealistischen Ästhetik anschließt.
Unwissen und Unfälle: Friedrich Dürrenmatts dramaturgisches Denken und das Gesetz der großen Zahl
Authors: Adams Dale
Published: August 2014

In einem Aufsatz zum “Gesetz der großen Zahl” bedient sich der Schweizer Schriftsteller und Dramatiker Friedrich Dürrenmatt der kinetischen Gastheorie (bei der einheitliche makroskopische Größen durch die zufälligen Bewegungen einer Vielzahl einzelner Teilchen erklärt werden) als Analogie für die globale Massengesellschaft. Das Gesetz, dessen Auswirkungen gerade in der Katastrophenanfälligkeit der Gegenwart zu erkennen seien, wird dabei in Anspruch genommen, um die maßgebliche Rolle zu begründen, die dem Zufall in seinem dramaturgischen Denken zukommt. In diesem Beitrag gehe ich von der These aus, dass Dürrenmatt bestimmte erkenntnistheoretische Konsequenzen, die er aus dem Gesetz der großen Zahl zieht, auch dramaturgisch verwertet, um der Komplexität der modernen Welt mit den Mitteln der Bühne beizukommen, ohne eine menschliche Perspektive aufzugeben. Der Zufall—als eine spezifische Form des Unwissens, das dazu führen kann, dass rationale Prognosen und Strategien in ihr Gegenteil umschlagen—erweist sich dabei als Bindeglied zwischen Dürrenmatts Dramaturgie und seinen erkenntnistheoretischen Reflexionen
“Es ist eben schon zuviel Gutes gemacht worden”: Zum Problem der Einflussangst in Doktor Faustus
Authors: Reidy Julian
Published: August 2014

In der vorliegenden Arbeit wird Thomas Manns Roman Doktor Faustus durch die Linse von Harold Blooms Konzept der ‘anxiety of influence’ oder ‘Einflussangst’ gelesen. Es wird zu zeigen sein, dass Mann Blooms ‘Theory of Poetry’ nicht nur in überraschender Klarheit antizipierte: Verschiedene im Bloom'schen Sinne ‘perverse’ Fehllektüren von Goethes Faust in Manns Faustus können als performative Präfiguration von Blooms These gedeutet werden, dass “wilful revisionism” die Triebfeder literarischer Originalität bildet.
Synthesis, Characterization, and Bioactivity Evaluation of Amorphous and Crystallized 58S Bioglass Nanopowders
Authors: Taghian Dehaghani Majid , Ahmadian Mehdi , Fathi Mohammadhossein
Published: August 2014

The aim of this work was synthesis and characterization of amorphous and crystallized 58S nanopowders produced via sol‐gel method. According to the thermal analysis, the nanopowders were heat‐treated at 600°C and 1100°C. X‐ray diffraction results revealed that the phases of Wollastonite and tricalcium phosphate were formed at 1100°C. The in vitro tests showed that hydroxyl carbonate apatite was precipitated on both crystallized and amorphous nanopowders, while amorphous nanopowder showed a higher bioactivity than that of crystallized nanopowder. In contrast, mechanical properties of crystallized specimen were higher than those of amorphous specimen.
Advantages and disadvantages of PTK
Authors: DOBROWOLSKI D
Published: August 2014

Phototherapeutic keratectomy (PTK) became more popular laser assisted procedure in cornel surgery in recent years. Superficial degenerations, corneal dystrofies, stromal opacities can be easily removed increasing visual comfort for the patients. Procedure however, should be carefully planed considering not only depth of stromal involvement as well as the condition of the ocular surface. Presentation includes actual guidelines for PTK and overview of potential complications of the surgery.
Laboratory work‐up and specialized investigations
Authors: PLEYER U
Published: August 2014

Based on the anatomical involvement of the eye intraocular inflammation is classified into anterior, intermediate, posterior and panuveitis. All subtypes of uveitis are potentially related to infectious and noninfectious etiologies. This presentation will assist the participants in accurately diagnosing uveitis in a step latter approach including physical and laboratory investigations. In addition, a tailored approach based on confounding clinical observations with specialized investigations will help to further differentiate clinical entities. In cases of suspected intraocular infections the option of intraocular fluid evaluation for antibody testing and polymerase chain testing against the causative agent will be presented. Taken together, this part of the course will provide a rational decision‐making strategy for diagnosis of patients with uveitis.
Therapeutic management of uveitis
Authors: DICK A
Published: August 2014

This talk will overview the contemporary therapeutic approaches to treatment of non‐infectious non‐infective ocular inflammatory disease. Treatment of non‐infectious uveitis has over past 15 years expanded from the use of traditional therapies including corticosteroids and immunosuppressants to the deployment of targetting the immune response with biologic therapies with monoclonal antibodies and immunoadhesins. Such use will be exemplified with case reports during the talk. Evidence of efficacy of immunosuppressants in the treatment of uveitis, the role of predicting steroid responsiveness, the use of monotherapy with immunosuppression and finally the pathways and evidence of success of biologic therapy will be provided.
The effect of a rock inhibitor ama0428 in a model of wet age‐related macular degeneration
Authors: HOLLANDERS K , VAN BERGEN T , VANDEWALLE E , STALMANS I
Published: August 2014

Purpose Rho kinase (ROCK) is associated with VEGF‐driven angiogenesis and is involved in inflammation and fibrosis. Therefore, the effect of a locally acting ROCK inhibitor, AMA0428, was studied in wet age‐related macular degeneration (AMD).

Methods The effect of AMA0428 on human brain microvascular endothelial cells (HBMEC), human brain vascular pericytes (HBVP) and human tenon fibroblasts (HTF) was determined by measuring cell viability (WST‐1), apoptosis (caspase 3/7) and 2 migration assays (scratch and under‐agarose) The in vivo response was investigated using a laser‐induced choroidal neovascularization (CNV) mouse model. Intravitreal injections were given on day 0, 4, 10 and 20 with AMA0428, murine anti‐VEGFR Ab (DC101) or placebo. Outcome was assessed by analysis of inflammation (CD45), angiogenesis (FITC‐dextran), vessel leakage (Texas Red‐conjugated Dextran and FITC‐labeled lectin) and fibrosis (Collagen I).

Results AMA0428 dose‐dependently reduced proliferation and VEGF‐induced migration of HBMEC and HTF. No significant effect was seen on HBVP proliferation; however, migration and pericyte recruitment were increased. There was no apoptosis induction. AMA0428 significantly reduced CNV and vessel leakage 2 weeks after lasering, comparable to DC101. In addition, AMA0428 inhibited inflammation on day 5 by 20% and collagen deposition on day 30 by 39% while DC101 had no effect on inflammation nor fibrosis.

Conclusion Our data suggest that targeting ROCK with AMA0428 not only reduces neoangiogenesis, but also blocks inflammation and fibrosis (contrary to anti‐VEGF). These results point to a potential therapeutic benefit of ROCK inhibition in wet AMD.
Microglia in mice retina contralateral to experimental glaucoma exhibit qualitative signs of activation in all retinal layers
Authors: GALLEGO B , SALAZAR JJ , DE HOZ R , ROJAS B , RAMIREZ AI , VALIENTE‐SORIANO FJ , AVILÉS‐TRIGUEROS M , VILLEGAS PEREZ MP , VIDAL‐SANZ M , TRIVINO A , RAMIREZ JM
Published: August 2014

Purpose To analyse qualitative effects of two weeks of laser‐induced ocular hypertension (OHT) in the retinal microglial of OHT‐eyes and their contralateral eyes

Methods Adult albino Swiss mice were divided into two groups: naive (n=6) and lasered (n=9). Retinal whole‐mounts immunolabelled with anti‐Iba1 were used to analyse the distribution and the morphology of Iba 1+ microglial cells

Results In naïve, contralateral and OHT‐eyes, Iba 1+ microglia was evenly distributed throughout the retina in the photoreceptor layer (PRL), outer plexiform layer (OPL), inner plexiform layer (IPL), nerve‐fibre layer (NFL) and ganglion‐cell layer (GCL). In comparison with naïve, the main differences in the microglia of contralateral eyes and OHT‐eyes were: i) the presence of ameboid microglia; ii) the retraction of cell processes; iii) a higher level of branching; iv) soma displacement; v) reorientation of processes; vi) MHC‐II up‐regulation; vii) increased CD68 immunostaining and; viii) CD86 immunolabelling in ameboid cells. In addition, rounded Iba‐1+ CD86+ cells in the NFL‐RGC layer and PRL and Ym1+ cells and rod‐like microglia in the NFL‐RGC were restricted to OHT‐eyes

Conclusion Two weeks of laser induced‐OHT triggered several signs of microglial activation that extended beyond GCL. The same features were also observed in contralateral normotensive untreated eyes. Contralateral eyes appear to be a potential of discovering points of intervention to which future therapeutics can be directed. (Support: OFTARED (Grant RD12/0034/0002 and RD12/0034/0014, ISCIII, Spanish Ministry of Science and Innovation)
Damaged photoreceptor cells initiate microglial activation in a mouse model of retinal degeneration
Authors: MAEDA A
Published: August 2014

Many degenerative retinal diseases, including AMD, illustrate retinal inflammatory changes that include infiltration of microglia/macrophages into the subretinal space. We reported microglial/macrophage activation in a Stargardt disease and AMD (SGD/AMD) mouse model. Notably, when microglia/macrophages and RPE cells phagocytosed isolated photoreceptor outer segments, these cells produced cytokines and chemokines via TLR4. Inactivation of these cells by pharmacological approaches attenuated mouse retinal degeneration. PCR array analysis of 84 chemokines and related molecules revealed 84.6‐fold elevated expression of Ccl3/MIP‐1a after light injury in SGD/AMD mice. MIP‐1 chemokines displayed a differential temporal profile compared to the other chemokines, and deficiency of Ccl3 uniquely modulated severity of diseases. Our study demonstrates an important contribution of TLR4‐mediated monocyte activation by endogenous photoreceptor proteins in retinal inflammation that aggravates retinal cell death, and that CCL3 has an essential role in regulating the severity of retinal inflammation and degeneration in these mouse models.
Ocular biometry and its relationship to incident myopia and hyperopia in children
Authors: ROSE K
Published: August 2014

Purpose Establish relationship of changes in ocular biometry in children with the development of refraction

Methods Sydney Myopia Study participants aged 6 and 12 years were re‐examined 5‐6 years later. Axial length (AL), anterior chamber depth (ACD) and corneal radius (CR) were measured using the IOLMaster (Carl Zeiss, Germany). Spherical equivalent refraction (SER) in dioptres (D) was calculated from cycloplegic autorefraction (cyclopentolate 1%; Canon RK‐F1) and myopia was defined SER ≤‐0.50D. All measures were made at baseline and follow‐up using the same methodology.

Results Longitudinal data was available 860 children at follow‐up, mean age 12.8 years and 1150 aged 17.2 years. There was significant change (p<0.0001) in SER from baseline to follow‐up for both cohorts and for all biometric measures, other than ACD in the older cohort (p=0.854). Marginal flattening of CR (0.05, 0.02mm, in younger and older cohorts respectively) was not clinically significant. Change in SER was significantly correlated in both the younger and older cohorts with AL and AL/CR (p <0.0001) with AL/CR the biometric parameter most strongly correlated with SER at both baseline and follow‐up in both cohorts (younger r = ‐0.63, 0.77, older r= ‐0.81, ‐0.86 respectively). In the younger cohort an AL/CR ratio ≤2.75 was associated with a baseline refraction of ≥+2D in all cases and 87.5% of these remained significantly hyperopic at age 12.

Conclusion Baseline AL/CR was the best biometric measure for predicting 5 year incidence myopia in both cohorts. In principle AL/CR also has the potential to resolve the ambiguity of visual acuity measures for the detection of hyperopia in younger children using a non‐invasive technique.
BAX and BCL‐2 genes in patients with Retinal Detachment with and without Proliferative Vitreoretinopathy. The Retina 4 project
Authors: GONZALEZ‐BUENDIA L , PASTOR‐IDOATE S , RODRIGUEZ‐HERNANDEZ I , ROJAS J , GONZALEZ‐SARMIENTO R , PASTOR JC
Published: August 2014

Purpose To compare the distribution of BAX G(‐248)A and BCL‐2 C(‐938)A genotypes among European subjects undergoing rhegmatogenous retinal detachment surgery in relation to further development of proliferative vitreoretinopathy (PVR).

Methods A case‐control gene association study as part of the Retina 4 Project was designed. Two promoter single nucleotide polymorphisms (rs2279115 and rs4645878) were analysed by TaqMan 5'exonuclease allelic discrimination assay, using a StepOne® system in 134 samples from patients with PVR and 421 without PVR. Proportions of genotypes and AA homozygote groups of these polymorphisms were analysed. Genotypic and allelic frequencies were compared in global sample and in sub‐samples.

Results BAX gene: In the comparison of proportions of genotypes in Spain, Spain+Portugal and in the global sample, significant differences were found. The odds ratio (OR) for A carriers in Spain and Spain+Portugal was 1.8, and 1.7 in the global sample. BCL‐2 gene: Significant differences were observed regarding proportions of genotypes in Spain+Portugal. Furthermore, a protective effect was found in the analysis of A carriers from Spain+Portugal with an OR of 0.6.

Conclusion The A allele of BAX is associated with a higher risk of developing PVR, suggesting that a down‐regulation in the apoptosis pathway could be an important key in PVR pathogenesis. Additionally, the role of BCL‐2 gene (inhibitor of necroptosis pathway) is proposed as a possible new target in PVR prophylaxis.
Comparison of optical and psychophysical methods to measure intraocular straylight
Authors: PENNOS A , GINIS HS , ARTAL P
Published: August 2014

Purpose To quantify intraocular forward scattering (straylight) by using three different methods in a group of normal subjects.

Methods Intraocular straylight was measured in the dominant eye of 10 emmetropic subjects without any known ocular pathology (30±5 years).Two different, commercially available, scatter filters (Black Pro‐Mist ¼ and Black Pro‐Mist ½ from Tiffen)where used in order to recreate the effects of higher scattering. Three measurement techniques were used:a commercially available straylight meter (C‐quant, Oculus),a prototype of an optical double‐pass based method (Sigma) and a psychophysical method that we developed.We used a Bayesian method (quick‐CSF) in a range of spatial frequencies (2 to 20 cycles/degree) with 50 2‐alternative forced choice trials.Each set of trials was repeated 2 times for each condition (with and without glare).As a glare source, a fluorescent lamp was positioned concentrically to the test area where the sinusoidal gratings were projected.All tests were presented on a screen placed at 1 meter distance from the subject and the test area was covering a total of 6.4 degrees of visual field.For Sigma and C‐Quant tests,the logarithm of Scatter coefficient was determined, whereas for the q‐CSF measurements the difference between the areas below the log contrast sensitivity curves was used as scatter metrics.

Results In the three methods, the effects of straylight were accordingly increasing with the addition of the scatter filters. A correlation between all three methods was verified.

Conclusion These results suggest the potential use of an even simplified method based on the q‐CSF to evaluate straylight complementing other existing methods.
Contribution of "en face" SD‐OCT in retinal surgical diseases
Authors: CHIQUET C , GALLICE M
Published: August 2014

En face OCT is complementary Imaging procedure useful for the analysis of vitreoretinal disorders, including macular hole, epiretinal membrane, or retinal detachment. This procedure is informative before and after vitreoretinal surgery. Before surgery, characteristics of the retinal surface may be defined. After vitrectomy, en face OCT reveals changes in the retinal nerve fibers layer (dimples), residual epiretinal tissue, cystic changes, disruption of external limiting membrane and/or outer segment layer, or persistent subretinal fluid. This procedure helps us to refine high resolution imaging of each layer of the retina during the healing process of macular hole or retinal detachment.
The state of the art of diagnostic vitrectomy
Authors: DICK A
Published: August 2014

The emergence of increasingly sensitive molecular and biological assays has facilitated our diagnostic ability in uveitis. Together with the advances in surgical vitrectomy procedures, the risk to biopsy is much reduced. Combined therefore we are currently at an unprecedented state of ability to rapidly intervene and increase our diagnostic yield. The talk will highlight indications, simple techniques and evidence of how improved diagnostics have altered outcomes and discuss how diagnostic sampling should be employed in management of uveitis.
Therapeutic approaches 2: Ranibizumab
Authors: SEMOUN O , ZERBIB J , LALLOUM F , SIKORAV A , COSCAS F , COSCAS G , SOUIED E
Published: August 2014

Polypoidal choroidal vasculopathy (PCV) is an exudative maculopathy, with clinical features distinct from neovascular age‐related macular degeneration. The EVEREST trial is the only published randomized controlled clinical trial in PCV. Ranibizumab has been proposed for the treatment of PCV and has become one of the standard of care in this particular pathology. To date, a lot of studies have been published, trying to analyze the early and late morphological and functional response to intravitreal ranibizumab, in different ethnic populations, as well as predictive factors of outcome. Imaging characteristics and their changing after treatment, including choroidal modifications have been also investigated. These literature data may help to answer the controversy whether PCV is a subtype of AMD or a specific entity.
Reactive gliosis along the visual system in rodent models of ocular hypertension
Authors: VIDAL‐SANZ M , GALINDO‐ROMERO C , SALINAS‐NAVARRO M , VALIENTE‐SORIANO FJ , GALLEGO B , ROJAS B , DE HOZ R , RAMIREZ AI , SALAZAR JJ , AVILES M , TRIVINO A , RAMIREZ JM , AGUDO M , VILLEGAS PEREZ MP
Published: August 2014

Glaucoma is a complex disease that causes the loss of retinal ganglion cells (RGCs) and eventually blindness. The mechanisms leading to the progressive RGC death in glaucoma are still a matter of debate. It is known that the main risk factor is an elevated intraocular pressure (IOP) that triggers the initial insult: presumably a crush‐like injury to the RGC axons at the level of the optic nerve head. Current research indicates that neuroinflammation, mediated by the activation of glial cells and the release of cytokines, pro‐inflammatory and neurotoxic molecules, plays an important role in the pathogenesis of glaucoma, aggravating and spreading the initial insult. Ocular hypertension in rats and mice causes permanent damage to the outer and inner retinal layers that cannot be the result of RGC axonal damage and may thus be secondary to an ischemic or neurotoxic insult. Ocular hypertension also induces a glial response that may affect the whole visual system. Activated microglial and macroglial cells are found not only in the ocular hypertensive but also in the contralateral retina and these cells may be the mediators of neuroprotective or neurotoxic reactions to injury.
Assessing stereopsis in preverbal children
Authors: HOUTMAN AC
Published: August 2014

Stereovision became a hype when Wheatley presented his theory in 1838. Stereoscopes became popular. Stereoperception was recognized as the ultimate stage of binocular vision in strabismus theories of the 19th century.Stereopsis is assessed as part of the normal strabismologic examination. Most tests depend on the subject’s active response. In babies the assessment of stereopsis is more cumbersome and rarely done outside a research setting.Stereopsis can be demonstrated from the age of around 3 months by FCPL techniques. Interestingly, this can also be demonstrated to a similar degree in babies with infantile esotropia but the number in which this can be done declines rapidly over months. In the age‐old controversy regarding the timing of surgery for this condition the potential for stereovision is rarely taken into account. Yet this may be an important prognostic factor; it would seem that in the presence of demonstrable stereopsis offering very early surgery makes sense. However, a quick and reliable test for stereopsis in babies is hard to find.This part of the work‐shop will look into the history and background of stereotesting, available tests, recent advances and our own research into developing such a test.
Scleral lenses as a high tech, versatile and cost efficient tool for the treatment of ocular surface disease in less developed countries
Authors: MEKKI MB , YAHIAOUI S , BELAOUDMOU R , MOKHTARI MA
Published: August 2014

Scleral lens has a double interest: Thanks to its anterior optically perfect surface without any contact with the cornea nor the limbus, it erases the irregularities of cornea whatever the degree of ectasia. On the other hand, it provides a favorable microenvironment for regeneration of diseased corneal epithelium. We present our short Algerian experience in cases of challenging cornea, typically requiring keratoplasty (expensive, often unavailable and with unpredictable results), fitted with scleral lens: Primary corneal ectasia (stage IV keratoconus, pellucid marginal degeneration, globus), secondary post Lasik ectasia, failure of corneal reshaping surgery (Lasik, PKR, radial keratotomy and intracorneal ring segment implantation), irregular corneal graft and traumatic or post infectious corneal scar. We present the functional outcome and the quality of life of these patients. Therapeutic scleral lenses have a magical result, we illustrate it with trophic ulcer cases of various etiologies, resistant to conventional treatment and who healed very quickly under scleral lens wear alone. Finally, we present our pilot study on total UV filter scleral lens to protect ocular surface of children with Xeroderma Pigmentosum.

Commercial interest
Effect of resveratrol on RPE cells and its potential role in AMD prevention
Authors: KAARNIRANTA K
Published: August 2014

Abstract not provided
A new and standardized method to sample and analyse vitreous biopsies in unsolved uveitis by the Cellient® automated cell block system
Authors: VAN CALSTER J , VAN GINDERDEUREN R
Published: August 2014

Purpose In this prospective study a universal protocol for sampling and analyzing vitreous material was investigated. Vitreous biopsies are difficult to handle because of the paucity of cells and the gelatinous structure of the vitreous. Histopathological analysis of the vitreous is useful in difficult uveitis cases to differentiate uveitis from lymphoma or infection and to define the type of cellular reaction.

Methods After isolation of vitreous content by a single port biopsy or by a standardized 23G vitrectomy, 170 consecutive vitreous samples were analyzed with the Cellient® tissue processor (Hologic). This machine is a fully automated processor starting from a specified container with PreservCyt® (fixative fluid) with cells to paraffin. Cytology was compared with fixatives Cytolyt® (contains a mucolytic agent) and Preservcyt®. Routine histochemical and immunostainings were evaluated.

Results In 79 cases (46%) a single port biopsy and in 91 cases (54%) a tree port pars plana vitrectomy was performed. In 94% of the cases, sufficient material was found for establishing the diagnosis. In 18%, a Cytolyt® wash was necessary to prevent clotting of the tubes in the Cellient® due to the viscosity of the sample. In 21% the diagnosis was an acute inflammation (presence of granulocytes), in 32% chronic active inflammation (presence of T‐lymphocytes), in 35% low‐grade inflammation (presence of CD68 cells, without T‐lymphocytes); and in 5% a malignant process. In 9% a granulomatous inflammation was detected, in 5% glial tissue (floaters). In 6% no diagnosis was found.

Conclusion A standardized protocol for sampling and handling vitreous biopsies, fixing in PreservCyt® and processing by the Cellient® system gives a superior result in morphology, number of cells, and possibility of immuno‐histochemical stainings. The diagnosis can be established or confirmed in more than 90% of cases.
Study of TOXO KO vaccine efficiency on the ophtalmological damage bound to Toxoplasmaa gondii, on a mouse model of ocular toxoplasmosis
Authors: LEMEE G , MORISSE S , TARFAOUI N , DIMIER‐POISSON I , SECHE E , PISELLA P
Published: August 2014

Purpose The toxoplasmosis is one of the most wild‐spread parasitoses, affecting almost a third of the world population, and as the main symptomatic demonstration : eye infringement.The aim of this study is to test, on a murin model, the efficiency of a vaccine candidate named Toxo KO, developped by genetic engineering against this pathology.

Methods Ninety Swiss Webster mice (OF1), were filled up with fifty cysts of the 76K strain of Toxoplasmaa gondii (type II). A part of these mice received the TOXO KO vaccine intraperitoneally before. Ophtalmological examination and immunological investigation were performed on aqueous humor samples. The intra retinal cysts were also counted after dissection of the entire retinal tissue.

Results After vaccination, we observed a decrease of 69% of ophtalmological damage and 90% of intra‐retinal cysts. Besides, this group presented no secretion of IFN‐γ in aqueous humor, testifying of an absence of deleterious inflammation in these eyes unlike those of the control group.

Conclusion Our results are highly significant. This proof of concept lets think that the forward use of such a tool of prevention is possible, to fight more effectively and prematurely against ocular toxoplasmosis.
Infectious keratitis: 4 years in a tertiary hospital
Authors: ANJOS R , VICENTE A , BORGES B , VIEIRA L , PINTO M , MADURO V , ALVES N , CANDELARIA P
Published: August 2014

Purpose To evaluate the clinical presentation, microbiological results and treatment used in cases of infectious keratitis diagnosed in Centro Hospitalar Lisboa Central (CHLC) between July 2009 and July 2013

Methods Retrospective analysis of data from patients who underwent microbiological examination for suspected infectious keratitis between July 2009 and July 2013 in the CHLC (n=86 patients)

Results The most prevalent risk factor was the use of contact lenses. Of the 93 samples taken, 59 (63.4%) were positive for at least one pathogen. A total of 64 microorganisms were isolated with 35 (54.8%) being Gram‐negative, 25 (41.9%) Gram‐positive and 2 (3.2%) fungi. The most prevalent pathogen was Pseudomonas aeruginosa. In two patients, Acanthamoeba cysts were isolated by confocal microscopy. Hospitalization was needed in 64.0% of cases. The treatment of choice was the use of fortified eyedrops of vancomycin and ceftazidime. In seven patients surgical therapy was needed for infection control.

Conclusion Our work draws attention to the morbidity associated with this disease and reinforces the importance of conducting microbiological studies in these patients. The main predisposing factor in our population was the use of contact lens, with Gram‐negative microorganisms being isolated in the majority of cases.
3D shape perception in strabismus subjects
Authors: SAWAMURA H , GILLEBERT C , TODD JT , VANDENBERGHE R , ORBAN GA
Published: August 2014

Purpose To evaluate 3D shape perception in strabismus subjects, psychophysical experiment was performed using 3D shapes extracted from four different visual cues (shading, texture, motion and disparity), comparing normal and strabismus subjects.

Methods The 11 randomly generated complex 3D shape visual stimuli were created and rendered in 4 modalities (3D shape from shading, texture, motion and disparity) and displayed on a PC monitor. The subjects were required to indicate the global maximum of the 3D shape as accurately as possible by displacing a red cross using the computer mouse. The distance in depth (cm) between the global maximum indicated by the subject and the true global maximum was calculated. Strabismus subjects (n=43; 6‐65 years of age) and normal subjects (n=18: 6‐57 years of age) participated in the task. All the subjects have normal or corrected normal visual acuity. Stereo acuity was also evaluated by titmus stereo test.

Results 3D shapes extracted from disparity were more difficult to perceive than those extracted from texture (ANOVA, p<0.03), motion (p<0.01) and shading (p<0.01) in both normal and strabismus subjects. The 3D shape perception in normal and strabismus subjects differed only for the binocular stereopsis cue, not the other visual cues of motion, shading and texture. In addition, 3D shape perception of motion, shading and texture was not affected by the stereo acuity in either normal or strabismus subjects.

Conclusion Even the strabismus patients with weak or no stereopsis can use other visual cues, such as motion, texture and shading to perceive 3D shape to the same degree as normal subjects.
Clinical experience with Raxone® (Idebenone) in the treatment of patients with Leber’s hereditary optic neuropathy (LHON)
Authors: METZ G , GALLENMÜLLER C , VON LIVONIUS B , LOB F , COPPARD N , MEIER T , KLOPSTOCK T
Published: August 2014

Purpose LHON is an orphan mitochondrial disorder affecting the retinal ganglion cells leading to permanent blindness from which recovery is rare. Here we report visual acuity outcomes for patients with recent onset who received Raxone® (idebenone) under an ongoing global Expanded Access Program (EAP).

Methods Visual acuity was measured in 3‐monthly intervals. Clinically relevant recovery was defined as (i) improvement from nadir by at least 10 letters on the ETDRS chart or (ii) improvement from “off‐chart” at nadir to being able to read at least 5 letters on‐chart.

Results Currently there are 61 LHON patients enrolled, of which 48 patients have been treated for an average of 11 months. So far, 24 of 48 patients (50%) have experienced a clinically relevant and stable recovery in VA (89% for T14484C, 70% for G3460A and 31% for G11778A). The average treatment effect size in patients with recovery was 29 letters and 84 % recovered within 12 months of the initiation of the EAP.

Conclusion A high proportion of LHON patients treated with idebenone under a global EAP experienced a clinically meaningful recovery of vision, further demonstrating the therapeutic potential of idebenone in the treatment of LHON.

Commercial interest
Electrophysiology in the diagnosis of albinism
Authors: HOLDER GE , NEVEU MM
Published: August 2014

Albinism is a genetically determined disorder of melanin synthesis associated with intracranial visual pathway misrouting, with the majority of fibres from each eye usually decussating to the contralateral cerebral hemisphere. The presentation will detail the use of flash and pattern appearance VEPs in the demonstration of this albino misrouting. It will be demonstrated that the misrouting has a highly variable expression, including uni‐ocular misrouting, and is a spectrum of disease rather than an all‐or‐none phenomenon.
Azithromycin and MGD: Is it possible to turn an off‐label treatment into an on‐label therapy?
Authors: SULLIVAN DA , KAM WR , DING J , LIU Y
Published: August 2014

Meibomian gland dysfunction (MGD) is the primary cause of dry eye disease (DED), which afflicts hundreds of millions of people, predominantly women, and is a leading cause of patient visits to eye care practitioners. The impact of moderate to severe DED is comparable to conditions such as dialysis and severe angina, and is associated with significant pain, role limitations, low vitality and poor general health. There is no cure for MGD. The most frequent pharmaceutical treatment in the United States for the management of MGD is the off‐label use of topical azithromycin. This antibiotic is presumed to be effective because of its anti‐inflammatory and anti‐bacterial actions, which may suppress the MGD‐associated posterior blepharitis and growth of lid bacteria. We hypothesize that azithromycin can act directly on human meibomian gland epithelial cells to stimulate their differentiation, enhance the quality and quantity of their lipid production, promote their holocrine secretion and ameliorate MGD pathophysiology. Our results support our hypotheses and may help lead to the approval of topical azithromycin as a safe and effective therapy for human MGD and thereby improve the quality of life of countless people throughout the world.

Commercial interest
Biological mechanism of myopia development
Authors: SCHAEFFEL F
Published: August 2014

Purpose. Describing biological mechanisms of visual control of eye growth, based on experiments in animal models. Methods. To induce refractive errors, emmetropic eyes are treated with positive lenses (causing development of hyperopia), negative lenses or diffusers (causing myopia). Ocular biometry by ultrasonography or low coherence interferometry, refractions measured by infrared photoretinoscopy, transcription of candidate genes in fundus by realtime PCR, dopamine and metabolites by HPLC, proteins by immunohistochemistry. Receptor agonists or antagonists are intravitreally injected. Results. Eye growth is locally controlled by the retina which detects the sign of defocus to accelerate or reduce axial eye growth but underlying image processing is not understood. Major retinal signals are dopamine, glucagon (in chick), acetylcholine, NO and retinoic acid. Signals can be divided in image blur, light and diurnally controlled (dopamine) or sign of defocus controlled (glucagon, ZENK/Egr1, retinoic acid). Conclusions. The amount of knowledge accumulated on visual control of eye growth over the past 25 years is abundant but cannot yet prevent myopia that is induced by changes in visual experience in our industrialized world.
Virtual glaucoma clinic in Wales
Authors: MORGAN JE
Published: August 2014

The effective clinical review of increasing numbers of glaucoma patients remains a major challenge. To meet this, we have developed a virtual clinic review module using the OpenEyes electronic medical record for Ophthalmology. OpenEyes is Open Source and browser‐based, allowing considerable flexibility in where patients are seen. The virtual clinic module allows the review of condensed data for any given patient and acts as a link to a summary containing patient visual fields, clinical diagnosis and IOP data. Data are collected by technicians appointed at a level appropriate to the task. Patient data are then reviewed by the supervising clinician. To date the system has been used to managed over 100,000 visual field examinations and 11,000 patient events on over 3,500 patients. The data handling requirements for modern browser based applications (LINUX, Apache, MySQL, PHP) are low, ensuring a rapid data refresh and robust data curation. OpenEyes is highly scaleable and can be run over fixed or wireless networks to provide clinical data provision at the point of care regardless of geographic location. It is available royalty free and provides a firm foundation for collaborative software development.
Cytoskeletal regulators are implicated in fibrosis in mechanical injury and infection in the mouse cornea
Authors: BEUERMAN R
Published: August 2014

Purpose: Mechanical injury as well as infection can result in corneal fibrosis and loss of transparency. We have used a mouse model of cornea insult using sterile mechanical injury and infection. Methods: Corneas of 8 week old C57BL6 mice underwent either an anterior keratectomy (AK) wound or infection with Pseudomonas aeruginosa (PA), and animals were sacrificed at 2 and 7 days, as well as 2 and 4 weeks after the procedures. The isolated stroma was used to monitor the expression and location of moesin, phospho‐moesin, TGF‐β1 and α‐SMA. Results: TGF‐β1 and phospho‐moesin were not detected in normal corneal stromas. However, after either treatment, TGF‐β1 expression increased, along with phospho‐moesin and moesin in the wounded corneal stroma from day 2 to 7, and decreased after 2 weeks. No expression of TGF‐β1 and phospho‐moesin was found at PO week 4. Myofibroblasts positive for α‐SMA associated with either treatment were detected from day 2 to week 4 and peaked at week 2. Conclusion: The results suggest a role for moesin signaling in corneal fibrosis. Interfering with the action of moesin is a potential target for interventive strategies to avert corneal fibrosis.
TGF‐beta in ocular angiogenesis
Authors: WANG X , ABRAHAM S , JEFFS N , SWIRE M , LUHMANN U , LANGE C , BAINBRIDGE J , MOSS S , GREENWOOD J
Published: August 2014

Abnormal angiogenesis is associated with many blinding eye diseases. Targeting VEGF, a master regulator of blood vessel formation, has shown improved outcomes in ocular vascular disorders. However, many patients do not respond or respond poorly to anti‐VEGF therapy, which is not surprising as angiogenesis is regulated by a delicate balance of diverse molecular signals. Combination therapeutics targeting alternative or complementary pathways may circumvent resistance and enhance efficacy of anti‐VEGF treatment. TGFβ1, a multifunctional cytokine, plays an important but contradictory role during angiogenesis. We recently identified a novel regulator of TGFβ signaling pathway, namely leucine rich α‐2‐glycoprotein‐1 (LRG1). LRG1 defines the context‐dependent effect of TGFβ1 and promotes blood vessel formation by driving the pro‐angiogenic TGFβ1/Smad1/5/8 pathway. Unlike VEGF, LRG1 is specifically required for abnormal blood vessel formation in the eye. LRG1 antibody blockade attenuates the ocular angiogenesis either on its own or in combination with an anti‐VEGF neutralizing antibody. Together, our study provided compelling evidence that LRG1 is an attractive target for therapeutic intervention in ocular vascular complications.
Functional and molecular characterization of ex vivo cultured neuronal‐ and glial‐ like cells from idiopathic epiretinal membranes
Authors: PETROVSKI G , LUMI X , YAN X , GRAW J , FACSKO A , HAWLINA M , ANDJELIC S
Published: August 2014

Purpose To test the proliferating potential and characterize the functional and molecular profile of cells growing out of human idopathic epiretinal membranes (iERMs) ex vivo.

Methods iERMs were obtained from uneventful vitrectomies from cases with iERM. Preoperative and postoperative BCVA, CFT and TMV were compared. Ex vivo cultivation under adherent conditions was carried out and followed up to 6 days. Morphological and immunocytochemical characterization of the cells was carried out. The dynamics of the intracellular calcium was measured using fluorescent dye Fura‐2 and imaged in response to pharmacological stimulation by acetylcholine (ACh) or mechanostimulation.

Results Visual acuity improved in 9/10 patients. CFT and TMV dereased significantly 3 months after surgery. The cells from the iERMs formed sphere‐like structures when cultured ex vivo. The diameter of the spheres increased by 5% at day 6 and kept an increasing tendency over a month. The cells growing out of the iERM spheres had mainly a glial‐ and some neuronal‐ like morphology. Stimulation of these cells with ACh or mechanostimulation induced intracellular calcium propagation in both cell phenotypes – in the neuronal‐like cells resembling action potential from the soma to the dendrites. Immunocytochemistry confirmed presence of glial‐ and neuronal cell phenotype in the iERMs, as well as presence of pluripotency marker.

Conclusion iERMs contain cells of neuronal‐ and glial‐ like origin which have proliferative and pluripotent potential, show functionality reflected through calcium dynamics upon ACh and mechano‐ stimulation, and a corresponding molecular phenotype.
Crystalline retinopathy
Authors: NADIM N
Published: August 2014

Refractile crystalline deposits in the retina may be a manifestation of drug toxicity.The five drugs known to produce this side effect are: (1)Tamoxifen‐non steroidal estrogen antagonist used in the treatment of breast cancer. (2)Canthaxanthine‐tanning agent for skin pigmentation in vitiligo and for the treatment of photosensitivity in psoriasis and erythrotic porphyrias. (3)Crashed tablets of Methadone, Mepiridine hydrochloride and Methylphenylate that are injected intravenously in drug abusers‐Talc Retinopathy. (4)Methoxyflurane‐an inhalational anesthetic agent . (5)Nitrofurantoin‐an antibiotic used in the treatment of urinary tract infections. Daily doses and cumulative doses that give rise to these deposits will be presented and the fundus/clinical features of each drug as well. Since primary ocular disorders (Bietti's crystalline retinopathy, idiopathic parafoveal telengiectasis, calcified macular drusen) and systemic disorders (oxalosis, cystinosis,Sjogren Larsson syndrome) are known to be associated with crystals in the retina,the differential diagnosis of this clinical entity will be discussed.
Eviscerated eyes unexpectedly containing uveal melanoma
Authors: VAN GINDERDEUREN R , MOMBAERTS I
Published: August 2014

Purpose To present two cases with eviscerated eyes containing uveal melanoma and review the literature

Methods All the evisceration specimens from a 15 year period were analyzed for malignancies. A literature search on the accidental finding of intraocular malignancy after evisceration was performed

Results We found an incidence of intraocular malignant melanoma of 0.7% (2/315). In these 2 cases, a standard evisceration procedure with implantation of an acrylic ball had been performed for pain in a longstanding blind eye with opaque media. Both patients had a history of glaucoma and massive intraocular hemorrhage, confirmed by repetitive ocular ultrasound (US) and orbital CT. Histopathology showed a large intraocular uveal melanoma with substantial necrosis and haemorrhage After negative screening for metastases, one week following the evisceration an enucleation of the scleral shell and implant was performed, with implantation of a new acrylic ball with donor sclera. External beam radiation of 5,000 cGy was given to the orbital socket. The first patient died from liver metastases 3 years after the diagnosis, without evidence of local recurrence. The second patient has a too short follow‐up The literature is scarce on this subject, with only 9 published cases. US is the mainstay in the screening for intraocular tumors in opaque eyes. There are no guidelines on the management after accidental evisceration of uveal melanoma

Conclusion Ultrasound can not always distinguish primary choroidal hemorrhage from secondary hemorrhage due to uveal melanoma with necrosis. An atypical clinical history of a blind painful opaque eye with prolonged massive intraocular hemorrhage and ocular hypertension may be suspect for malignant melanoma, in which case evisceration should be avoided
Update on adenoid cystic carcinomas
Authors: VON HOLSTEIN S
Published: August 2014

Adenoid Cystic Carcinoma of the Lacrimal Gland: MYB Gene Activation, Genomic Imbalances, and Clinical Characteristics Purpose: To investigate genetic alterations in lacrimal gland adenoid cystic carcinomas (ACC) in relation to clinical data and survival. Methods: The expression and identity of MYB‐NFIB fusion transcripts were studied using RT‐PCR and nucleotide sequence analyses. Q‐PCR and immunohistochemistry were used to evaluate the expression of MYB and MYB‐NFIB target genes. High‐resolution array‐based comparative genomic hybridization (arrayCGH) and FISH were used to study copy number alterations and MYB rearrangements. Results: The median age of the patients were 43 years and the median time of survival was 8.6 years. The MYB‐NFIB fusion was expressed in 7/14 ACCs. All non‐ACC tumors were fusion‐negative. All 13 ACCs tested stained positive for the MYB protein and for the MYB targets KIT and BCL2, 12 were positive for MYC and CCNE1, and nine for CCNB1. Rearrangements of MYB were detected in 8/13 cases. ArrayCGH analysis revealed recurrent copy number alterations with losses involving 6q23‐q27, 12q12‐q14.1, 17p13.3‐p12 and gains involving 19q12, 19q13.31‐qter, 8q24.13‐q24.21, 11q12.3‐q14.1, and 6q23.3. Neither MYB‐NFIB fusion nor any copy number alteration correlated with survival. Conclusions: Lacrimal gland ACCs are genetically and clinically similar to their salivary gland counterparts and MYB‐NFIB is a useful biomarker for ACC. Our data also suggests that MYB and its downstream targets are potential therapeutic targets for these tumors.