Aganirsen Antisense Oligonucleotide Eye Drops Inhibit Keratitis-Induced Corneal Neovascularization and Reduce Need for Transplantation: The I-CAN Study.

OBJECTIVE: Eye drops of aganirsen, an antisense oligonucleotide preventing insulin receptor substrate-1 expression, inhibited corneal neovascularization in a previous dose-finding phase II study. We aimed to confirm these results in a phase III study and investigated a potential clinical benefit on visual acuity (VA), quality of life (QoL), and need for transplantation. DESIGN: Multicenter, double-masked, randomized, placebo-controlled phase III study. PARTICIPANTS: Analysis of 69 patients with keratitis-related progressive corneal neovascularization randomized to aganirsen (34 patients) or placebo (35 patients). Patients applied aganirsen eye drops (86 μg/day/eye) or placebo twice daily for 90 days and were followed up to day 180. MAIN OUTCOME MEASURES: The primary end point was VA. Secondary end points included area of pathologic corneal neovascularization, need for transplantation, risk of graft rejection, and QoL. RESULTS: Although no significant differences in VA scores between groups were observed, aganirsen significantly reduced the relative corneal neovascularization area after 90 days by 26.20% (P = 0.014). This improvement persisted after 180 days (26.67%, P = 0.012). Aganirsen tended to lower the transplantation need in the intent-to-treat (ITT) population at day 180 (P = 0.087). In patients with viral keratitis and central neovascularization, a significant reduction in transplantation need was achieved (P = 0.048). No significant differences between groups were observed in the risk of graft rejection. However, aganirsen tended to decrease this risk in patients with traumatic/viral keratitis (P = 0.162) at day 90. The QoL analyses revealed a significant improvement with aganirsen in composite and near activity subscores (P = 0.039 and 0.026, respectively) at day 90 in the per protocol population. Ocular and treatment-related treatment-emergent adverse events (TEAEs) were reported in a lower percentage with aganirsen compared with placebo. Only 3 serious TEAEs (2 with aganirsen and 1 with placebo) were considered treatment-related. CONCLUSIONS: This first phase III study on a topical inhibitor of corneal angiogenesis showed that aganirsen eye drops significantly inhibited corneal neovascularization in patients with keratitis. The need for transplantation was significantly reduced in patients with viral keratitis and central neovascularization. Topical application of aganirsen was safe and well tolerated.

From Naples 1963 to Rome 2013 - A brief review of how the International Research Group on Ostracoda (IRGO) developed as a social communication system

The 1st International Symposium on Ostracoda (ISO) was held in Naples (1963). The philosophy behind this symposium and the logical outcome of what is now known as the International Research Group on Ostracoda (IRGO) is here reviewed, namely ostracodology over the last 50 years is sociologically analysed. Three different and important historic moments for the scientific achievements of this domain are recognised. The first one, between about 1963-1983, is related to applied research for the oil industry as well as to the great interest in the better description of the marine environment by both zoologists and palaeontologists. Another important aspect during this period was the work by researchers dealing with Palaeozoic ostracods, who had their own discussion group, IRGPO. Gradually, the merger of this latter group with those dealing with post-Palaeozoic ostracods at various meetings improved communication between the two groups of specialists. A second period was approximately delineated between 1983 and 2003. During this time-slice, more emphasis was addressed to environmental research with topics such as the study of global events and long-term climate change. Ostracodologists profited also from the research "politics" within national and international programmes. Large international research teams emerged using new research methods. During the third period (2003-2013), communication and collaborative research reached a global dimension. Amongst the topics of research we cite the reconstruction of palaeoclimate using transfer functions, the building of large datasets of ostracod distributions for regional and intercontinental studies, and the implementation of actions that should lead to taxonomic harmonisation. Projects within which molecular biological techniques are routinely used, combined with sophisticated morphological information, expanded now in their importance. The documentation of the ostracod description improved through new techniques to visualise morphological details, which stimulated also communication between ostracodologists. Efforts of making available ostracod information through newsletters and electronic media are evoked.

Dessine-moi un atelier

L'atelier d'ergothérapie est un élément du cadre et de la temporalité de l'hôpital de jour qui s'inscrit dans la structure du Centre Thérapeutique de Jour pour Adolescents depuis sa création. Dégagé des exigences scolaires ou psychologiques, l'ergothérapie est un espace structuré qui offre des possibilités thérapeutiques multiples. Ce sont certainement les attentes modestes où la performance n'est pas une priorité, qui favorisent l'apprivoisement, la sécurité et l'investissement de l'atelier. Au fil des semaines et des mois, l'adolescent peut progressivement reprendre confiance en ses compétences, mieux s'organiser, voire développer une créativité inattendue. Au-delà de sa fonction stn1cturante dans un programme d'activité interne à l'hôpital de jour, l'atelier d'ergothérapie se déploie sur l'extérieur dans sa composante écologique et sociale. Adaptables au plus près des besoins de l'adolescent, les projets en ergothérapie peuvent se réaliser en individuel ou en groupe. La relation est au coeur du processus thérapeutique, elle s'appuie sur les éléments du cadre et de permanence de cet atelier qui la rendent moins menaçante. A travers des vignettes cliniques et des illustrations concrètes, nous montrerons comment l'atelier d'ergothérapie peut rejoindre de manière métaphorique certains des ingrédients indispensables au processus d'adolescence que l'espace ainsi dessiné est en mesure de soutenir voire de relancer.