bluuebunny/crossref_metadata_2025_split huggingface dataset:
Is there an anti‐adenoviral drug on the horizon?
Authors: ROMANOWSKI E 
Published: August 2012

AbstractAdenovirus ocular infections (epidemic keratoconjunctivitis [EKC], follicular conjunctivitis, and pharyngeal conjunctival fever) are the most common ocular viral infections worldwide, including more than 1,000,000 cases annually in Japan. To date, there is no US FDA or European Medicines Agency approved antiviral therapy for these infections. Little progress on anti‐adenoviral development was made until our group developed the first reliable animal model for ocular anti‐adenoviral testing 20 years ago. Using that animal model, our group was instrumental in the preclinical development of the first topical antiviral drug for the treatment of adenoviral conjunctivitis tested in clinical trials, the nucleoside analog cidofovir. However, toxicity concerns, not efficacy, caused the sponsor to discontinue development. Since then, there has been considerable progress made regarding the discovery and development of antivirals by both academia and the pharmaceutical industry. Preclinical in vitro and in vivo studies have identified several new antiviral candidates such as 2,3‐dideoxycytidine (ddC), cyclopentenylcytosine (CPE‐C), intravenous immune globulin (IVIG), NVC‐422, and FST‐100. These preclinical studies have led to industry sponsored clinical trials which have been initiated with several agents NVC‐422 (NovaBay), Zirgan (0.15% Ganciclovir gel, Bausch + Lomb), and FST‐100 (0.4% povidone‐iodine/0.1% dexamethasone, Foresight Biotherapeutics). The first antiviral to treat adenovirus ocular infections will hopefully be available in the not too distant future.
Commercial interest
Management of inflammation in RVO
Authors: LOEWENSTEIN A 
Published: August 2012

AbstractMacular edema (ME) is a leading cause of vision loss in retinal disease including retinal vein occlusion. The development of macular edema is mediated by angiogenic as well as Inflammatory processes. There is increasing evidence that management of the inflammatory part is important in the treatment of the edema. Therefore, theoretically steroid therapy has a good potential in the treatment of macular edema. Regarding retinal vein occlusion specifically treatment by Ozurdex implant, containing dexamethasoe provides visual recovery with excellent safety outcomes.
Metabolism in glaucoma using retinal oximetry
Authors: STALMANS I 
Published: August 2012

AbstractCollaborative studies between the Ophthalmology departments in Leuven and Reykjavik have shown that in glaucoma patients, venous oxygen saturation increases with increasing severity of disease (i.e. with worsening visual field). Patients with considerable visual field loss show higher venous oxygen saturation than healthy individuals, while glaucoma patients with mild visual field loss have saturation similar to normal. Moreover, severe glaucomatous damage was associated with increased oxygen saturation in the retinal venules and decreased AV‐difference in retinal oxygen saturation. Finally, a positive correlation between the changes in AV difference and structural changes at the level of the optic disc and nerve fiber layer was found using HRT parameters (rim area, retinal nerve fiber layer thickness). The increase in venous saturation with increased visual field damage may be a consequence of tissue atrophy and less oxygen consumption. Longitudinal studies of glaucoma patients are needed to determine how retinal venous oxygen saturation is related to progression.
A randomized observer and subject masked trial comparing the visual outcome after treatment with ranibizumab or bevacizumab in patients with neovascular age‐related macular degeneration
Authors: TOLD R , BINDER S , KREBS I , BOLTZ A , SCHMETTERER L 
Published: August 2012

AbstractPurpose The western world health care systems are confronted with an increasing burden of patients suffering from age‐related macular degeneration (AMD). Anti‐VEGF therapy revolutionized the treatment of exudative AMD, but is associated with high costs. This study seeks to compare the treatment effects of ranibizumab and bevacizumab on best corrected distance visual acuity (BCVA) in Austrian patients with neovascular AMD.Methods This was a prospective, randomized, double blind, multicenter study. Ten clinical trial centers in Austria participated in this one year lasting study and included 321 treatment naïve patients suffering from neovascular AMD. Patients were randomized for treatment with bevacizumab or ranibizumab receiving a loading dose of three consecutive monthly intravitreal injections, followed by monthly treatment as needed.Results No significant differences were seen in BCVA between ranibizumab (n = 167) and bevacizumab (n = 154) groups. At one year bevacizumab was equivalent to ranibizumab (p=0.78 between groups). This was also not significant when adjusted for age or baseline BCVA. Also the gain and loss of 5 or 15 letters in BCVA showed no significant difference between treatment groups. Finally the analysis of serious adverse events (SAE) revealed no significant difference between the two groups, although SAEs were slightly more in the bevacizumab group.Conclusion The findings of this study showed no significant difference at one year between the two drugs used in an as needed manner, which displays todays most widely spread treatment regimen. The drugs showed similar efficacy and safety in the Austrian population.
Valproic acid (VPA), a class I and II histone deacetylase (HDAC) inhibitor and conjunctival melanoma
Authors: MADIGAN MC , MUNOZ‐ERAZO L , CONWAY RM 
Published: August 2012

AbstractPurpose To investigate the expression of histone deacetylases (HDACs) in human conjunctival melanoma (CM) cell lines and primary melanocytes, and assess the effects of VPA, a broad Class I and II HDAC inhibitor, on cell viability and growth.Methods CM cell lines (CRMM1 & 2; CM2005.1) and primary melanocytes were immunolabelled with antibodies to HDACs: Class I (HDAC1, 2 and 3), Class IIA and IIB (HDAC4 and HDAC6), and Class III (SIRT2). Antibody localisation was visualised with immunofluorescence and confocal microscopy. Dose‐response and proliferative potential following treatment with VPA was assessed for up to 72hrs using MTT and colony assays, respectively Cell cycle dynamics were also assessed.Results Differential HDAC expression was observed in CM cells and melanocytes, for both immunolocalisation (nuclear vs cytoplasmic) and cell type. CM2005.1 cells displayed lower level expression of HDACs compared to CRMM1 and 2 cells. VPA IC50 (72hrs) was 3.75mM, 5.42mM and 8.33mM for CRMM1, 2 and CM2005.1 cells, respectively. Colony assays showed similar patterns of response, with surviving fractions 0.2 and 0.5 for CRMM1 (VPA 0.3125mM) and CRMM2 (VPA 2.5mM) respectively. Cell cycle analysis showed dose‐related G1 block for CRMM1 and G2 block for CRMM2 cells at 24hrs (0mM to 1.25mM VPA).Conclusion Overall, CM2005.1 cells are more resistant to VPA compared to CRMM1 and 2 cells. VPA inhibition of CM cell growth and proliferation may be related to the observed differential expression of HDACs between cell lines. Combination therapies using VPA and other HDAC inhibitors may be potentially useful in managing the growth of primary CM. Supported by Sydney Foundation for Medical Research.
Macrophage markers and C3d in the central & peripheral choroid of young, aged and amd eyes
Authors: MADIGAN MC , VAN DEN BERG C , MORELAND A , LIANG J , LORD S , DEMIR A , JAISWAL S , JAGER MJ 
Published: August 2012

AbstractPurpose To investigate the distribution and expression of macrophage phenotypes and the complement activation protein, C3d, in human choroid/retina in young, aged and AMD eyes.Methods Paraffin sections of central and peripheral choroid/retina from young (<40 years, n=6), aged (>70 years, n=4) and AMD (>70 years, n=8) human post‐mortem eyes were co‐immunolabelled with antibodies to leukocyte and macrophage markers (CD68, CD163, Iba1 & CD45) and complement activation component, C3d. Localisation and distribution of antibodies was assessed using confocal microscopy. Counts of macrophage sub‐populations were compared in central and peripheral choroid for each group.Results Heterogeneous populations of macrophages were found in the choroid/retina of all groups. Iba1+ and CD45+ retinal microglia and macrophages, and choroidal macrophages were observed in all eyes. In AMD eyes, Iba1+ and CD45+ cells were seen in the subretinal space amongst photoreceptors, as well as in inner retina. Compared to young eyes, aged and AMD specimens showed increased numbers of CD163+ macrophages (M2, proangiogenic) in choroid, and in central vs peripheral retina. Fewer CD68+ cells were seen in all specimens, regardless of age or location. C3d was expressed in young, aged and AMD eyes, localised to Bruch’s membrane and choriocapillaris, with more extensive immunostaining in aged and AMD eyes. C3d was also seen in drusen in aged and AMD eyes, and more peripherally, compared to young eyes.Conclusion Age‐related changes in macrophage phenotypes and in complement pathway activation at the choroidal/retinal interface may play a role in development and progression of AMD. Supported by Sydney Foundation for Medical Research.
Ophthalmological manifestations of IgG4‐related disease
Authors: PHILIPPAKIS E , TOUITOU V , CHARLOTTE F , RIGOLET A , LEHOANG P , BLOCH‐QUEYRAT C , BODAGHI B 
Published: August 2012

AbstractPurpose Ig4‐related disease is a recently defined entity characterized by a mono or multi organ lymphoplasmocytic infiltrate with IgG4+staining (IgG4+/IgG+ cell ratio>40%), associated with fibrosis or sclerosis and elevated IgG4 serum rate over 135mg/dL. Purpose is to determine the ophthalmological and histological features of IgG4‐RD, and to analyse the outcome under treatment.Methods Patients with biopsy‐proven IgG4‐RD, seen between 2009 and 2011 in a single tertiary center, were retrospectively reviewed. Clinical manifestations, biological and radiological results, histological features and outcome under treatment were analyzed.Results Three caucasian women were included. Mean age was 58 years (range :50‐63). One patient presented with unilateral painful propotosis, associated with third and fifth cranial nerve palsy. One patient had recurrent anterior scleritis, and one patient presented with chronic conjonctival inflitration. None of them had extra‐ocular involvement (FDG‐PET‐scan). Other inflammatory conditions were ruled out. Histopathology demonstrated lymphoplasmocytosic proliferation with expression of IgG4+ plasma cells over 40%. IgG4 serum rate was elevated in one case. All patients primary responded to corticosteroids but 2 of them required the adjunction of an immusuppressive drug(fibrosis or relapse).third one presented with epithelial carcinoma.Conclusion IgG4‐RD is a new and rare entity, challenging to diagnose in case of isolated orbital involvement or in atypical features, such as conjonctivitis and scleritis Histopathology is the gold‐standard for diagnosis if appropriate staining is performed. Treatment is controvertial : corticosteroids are the mainstay, but many cases require associated immunosuppressors.
A patient with eyelid and anterior orbital myeloproliferative hypereosinophilic syndrome
Authors: DE KEIZER RJW , AL SABAI N , BAL TA , DE GROOT V 
Published: August 2012

AbstractPurpose the aim of the study is to evaluate the clinical‐ and histopathological discrepancy of the inflamed eyelid/anterior orbital mass featuresMethods case report and literature reviewResults the clinical picture revealed an erythemaous eyelid‐skin inflamed mass without effect on local and general antibiotic treatments . The histopathological “diagnoses was made as “chalazion material”. However the mass was superior located from the tarsus pre‐ and intraseptal with a lot of eosinophilic cell in the pathological material; where the patient already was known with a pulmonal myoblastic hypereosinophilic disease and treated with hydrea with the extra feature of a red faceConclusion knowledge of the systemic disease of a patient and the precise location of a pathologic ophthalmic process is important to made the definitive diagnosis. In difficult processes it is always necessary that pathologist and ophthalmologist consulted each other and made together the end conclusion
Role of corticosteroids
Authors: BANDELLO F 
Published: August 2012

AbstractPurpose Diabetic Macular Edema (DME) management has been revolutionized by the advent of intravitreal approach. Ain of the presentation is to describe the results of the most important studies about intravitreal corticosteroid therapy for DME.Methods Critical analysis of the most recent trials on the use of intravitreal corticosteroids for the treatment of DME.Results Most promising findings can be obtained from trials employng dexamethasone and fluocinolone acetonide. Nevertheless, complication rates, (especially bearing in mind intraocular pressure rise, and cataract) may limit the practical spread of this approach.Conclusion Long‐term trial will help define the best treatment algorithm for each form of DME.
Commercial interest
Role of anti‐VEGF
Authors: POURNARAS JA 
Published: August 2012

AbstractPurpose To assess safety and efficacy of intraocular injections of anti‐VEGF in patients with diabetic macular edema (DME)Methods The gold standard for treatment has been laser coagulation. Limitations of this therapy are refractive DME, ischemic diabetic maculopathy and complications after laser application. The need for a non‐destructive and effective strategy has led to investigations regarding VEGF inhibitors for reduction of vessel leakage and edema formation. Critical analysis of the most recent trials on the use of intravitreal anti‐VEGF will be discussed for the treatment of DME.Results For DME, intravitreal pegaptanib and bevacizumab have shown beneficial short‐term effects on both visual acuity and retinal thickness. Most recent datas concern the use of ranibizumab and will be detailled. Incidence of ocular adverse events are consistent with prior clinical trials of ranibizumab across multiple retinal diseases. VEGF‐trap study will be reported.Conclusion New therapeutic approaches based on intravitreal injections of anti‐VEGF molecules offer new hope for the management of diabetic macular edema. However, randomized studies are needed in order to attest longterm safety and efficacy profiles.
Retinal neuroprotection: the path from cell‐based high content screening, to animal models, and hopefully to the clinic
Authors: ZACK DJ 
Published: August 2012

AbstractPurpose Vision loss in glaucoma is due to the loss of retinal ganglion cells. Current therapies all act by lowering IOP. However, IOP reduction can be difficult to achieve, and even with significant lowering, RGC loss can continue. Efforts have therefore been made to develop “neuroprotective” agents that would complement IOP‐lowering by directly interfering with the RGC cell death process.Results Using a novel primary RGC‐based, high‐content phenotypic screen, in which we have tested over 10,000 compounds, we found that the FDA‐approved drug sunitinib, a broad‐spectrum receptor tyrosine kinase inhibitor, strongly promotes RGC survival. In rodent models of optic neuropathy, including a rat laser glaucoma model, an intravitreally administered slow‐release microparticle formulation of sunitinib protects RGCs from cell death. Unfortunately, at its neuroprotective concentration, sunitinib is reported to inhibit nearly 200 kinases, making it a challenge to determine the kinase(s) whose inhibition promotes survival. In order identify the biologically relevant kinase(s) whose inhibition by sunitinib promotes RGC survival, we developed a magnetic nanoparticle‐based high throughput siRNA‐based assay capable of knocking‐down individual genes in cultures of primary murine RGCs. We screened a library of 1869 siRNAs against 623 kinases for siRNAs that increased RGC survival. The top hits were dual‐leucine zipper kinase (DLK) and its substrate, mitogen activated protein kinase kinase 7 (MKK7).Conclusion Our results suggest that a major part of sunitinib’s neuroprotective activity is mediated through inhibition of DLK. As a next step, the challenges of bringing a neuroprotective molecule such as sunitinib to clinic will be discussed.
Commercial interest
Primum non nocere et non occidere
Authors: HERBORT CP 
Published: August 2012

AbstractPurpose "Primum non nocere, "first do no harm", is one of the essential princoples taught to medical students and should accompany us throughout our medical practice.Methods Case presentationsResults Illustrative example of some "killer cases induced by inappropriate therapeutic interventions will show how important it is to diagnose appropriately our uveitis cases before resorting to a treatment. In particular infectious causes should be excluded before reaching out to immunosuppressive therapies and once powerful potentially dangerous are going to be used, their side‐effects should be considered and explained to the patient.Conclusion A meticulous work‐up is necessary before potentially harmful treatments are going to be used but on the other hand exaggerated fear should not prevent us from using necessary corticosteroid and/or immunosuppressive therapeutic intervention as long as the appraisal of the patient has allowed to rule out infectious causes and as far as proper monitoring of side‐effects is taken care of.
Spectral domain OCT‐assisted “big bubble” deep anterior lamellar keratoplasty in keratoconus patients
Authors: WYLEGALA E , TARNAWSKA D , WROBLEWSKA CZAJKA E , JANISZEWSKA D , WOWRO B , DOBROWOLSKI D 
Published: August 2012

AbstractPurpose To visualize intraoperative changes of corneal thickness and bubble creation process using spectral domain OCT.Methods 15 patients underwent DALK performed using “big bubble” technique. Surgeries were assisted with intraoperative spectral domain OCT imaging (The iVue from Optovue Fremont Calfornia USA). Corneal thickness was measured preoperatively, after manual pre‐cutting and after the big‐bubble creation.Results Manual pre‐cutting of corneal stroma revealed residual bed thickness of 240‐270 µm (mean 256 µm). When residual corneal bad was thicker than 250 µm, the 27G needle was used for big‐bubble creation, when it was thinner than 250 µm, 30G needle was used. After injection of an air bubble, in 11 eyes Descemet’s membrane was completely separated from stroma, that was shown on OCT scans. In 4 eyes the separation was incomplete that was also clearly visible on OCT images. In one eye OCT imaging showed completely unseparated Descemet’s membrane and the additional injection of air bubble was necessary to effectively create the air space between the corneal layers.Conclusion Intraoperative imaging with Spectral domain OCT provides high‐resolution imaging of cornea bed thickness including visualization of the air‐bubble formation. This technique could provide enhanced information for the corneal surgeon during lamellar procedures such a DALK.
Genetic retinal diseases
Authors: LEROY BP 
Published: August 2012

AbstractPurpose To describe the current status of treatment for inherited retinal disease, and illustrate the challenges that lie ahead.Methods An overview of current treatment trials for inherited retinal disease in humans and animals will be used to illustrate where success has been achieved, but also where challenges remain. These include gene therapy trials in RPE65‐related Leber congenital amaurosis, Stargardt macular dystrophy and choroideraemia.Results Albeit that encouraging breakthroughs have been made with regard to treating inherited retinal diseases, such as in the gene therapy trials in RPE65‐related Leber congenital amaurosis, challenges lie ahead, such as gene‐specificity of gene therapy, intravitreal as opposed to subretinal injections, stem cell control, and cost.Conclusion Despite initial success of trials in inherited retinal diseases, quite a number of obstacles remain.
Circadien cycle and chronic central serous chorioretinopathy
Authors: HUBAULT B , SETROUK E , ZAMBROWSKI O , DUCASSE A , ARNDT C 
Published: August 2012

AbstractPurpose Chronic central serous chorioretinopathy (CSCR) is a multifactorial disease. The present study was designed to evaluate the prevalence of circadian disturbance and corticosteroid treatment in patients treated with chronic CSCR.Methods Patients presenting with chronic CSCR between 01/01/2009 and 30/11/2011 were prospectively enrolled. A history of corticosteroid treatment, sleep disturbances and irregular working hours was noted. Two questionnaires (PSQI and Epworth) regarding sleeping distrurbancies were applied. After a follow up of 3 months, the patients with persisting fluid and visual acuity below 20/40 were treated with photodynamic therapy (PDT).Results During the period of inclusion, among 26 included patients, 19 were treated with PDT (73%). A history of corticosteroid tretment was found in 12 patients (19%), 4 currently used psychopharmacologic drugs (15%) and 8 had irregular working hours (30%). The analysis of the Epworth questionnaire enabled to record moderate sleeping disturbances in 11 patients (42%), none of the patients were classified as having severe sleeping disturbances.Conclusion It is likely that general factors such as the existence of a corticosteroid treatment or a disruption of the circadian cycle are involved in the occurrence of patients with CSCR.
Comparative study of post‐natal retinal vascular development in mice models of iPLA2 inhibition and plasmalogen deficiency
Authors: SAAB S , BUTEAU B , LECLERE L , CREUZOT‐GARCHER C , BRON A , BRETILLON L , ACAR N 
Published: August 2012

AbstractPurpose Plasmalogens are particular phospholipids characterized by the presence of a polyunsaturated fatty acid (PUFA) at sn‐2 position of glycerol. Plasmalogen deficiency in mouse leads to developmental abnormalities in retinal vasculature. We propose that liberation of PUFA by the specific calcium‐independent phospholipase A2 (iPLA2), is involved in the mechanism by which plasmalogens control retinal vascular development. To confirm this hypothesis, we performed a comparative study of retinal vascular development in a mouse model of retinal iPLA2 inhibition and a model of plasmalogen deficiency.Methods Vessel and astrocyte networks were visualized on flat‐mounted retinas through immunostaining methods.Results Similar abnormalities were observed in retina of both mouse models. They consisted in an increased number of vessel ramifications at PN14, and in an abnormal glial cells migration from the optic nerve, at PN14 and at PN21. An activation of microglial cells was also observed at adult age.Conclusion These results confirm the implication of plasmalogen in the control of retinal vessel development through PUFA release from their sn‐2 position.