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Purpose To assess the safety and efficacy of E10030 (Fovista; Ophthotech, New York, NY), a platelet-derived growth factor (PDGF) antagonist, administered in combination with the anti–vascular endothelial growth factor (VEGF) agent ranibizumab (Lucentis; Roche, Basel, Switzerland) compared with ranibizumab monotherapy in patients with neovascular age-related macular degeneration (nAMD). Design Phase IIb global, multicenter, randomized, prospective, double-masked, controlled superiority trial. Participants Four hundred forty-nine patients with treatment-naive nAMD. Methods Participants were randomized in a 1:1:1 ratio to 1 of the following 3 intravitreal treatment groups: E10030 0.3 mg in combination with ranibizumab 0.5 mg, E10030 1.5 mg in combination with ranibizumab 0.5 mg, and sham in combination with ranibizumab 0.5 mg (anti-VEGF monotherapy). Drugs were administered monthly in each of the groups for a total duration of 24 weeks. Main Outcome Measures The prespecified primary end point was the mean change in visual acuity (VA; Early Treatment Diabetic Retinopathy [ETDRS] letters) from baseline to 24 weeks. Results No significant safety issues were observed in any treatment group. The E10030 (1.5 mg) combination therapy regimen met the prespecified primary end point of superiority in mean VA gain compared with anti-VEGF monotherapy (10.6 compared with 6.5 ETDRS letters at week 24; P = 0.019). A dose-response relationship was evident at each measured time point commencing at 4 weeks. Visual acuity outcomes favored the E10030 1.5 mg combination therapy group regardless of baseline VA, lesion size, or central subfield thickness on optical coherence tomography. All clinically relevant treatment end points of visual benefit (≥15 ETDRS letter gain, final VA ≥20/40 or ≥20/25) and visual loss (≥1 ETDRS line loss, ≥2 ETDRS line loss, final VA ≤20/125 or ≤20/200) favored the E10030 1.5 mg combination group. Conclusions In this phase IIb clinical trial, a 62% relative benefit from baseline was noted in the E10030 1.5 mg combination therapy group compared with the anti-VEGF monotherapy group. A favorable safety and efficacy profile of E10030 combination therapy for nAMD was evident across multiple clinically relevant end points. This highly powered study provides strong rationale for a confirmatory phase III clinical trial.

Purpose To assess the association of clinical and biological factors with extensive macular atrophy with pseudodrusen (EMAP) characterized by bilateral macular atrophy occurring in patients aged 50 to 60 years and a rapid progression to legal blindness within 5 to 10 years. Design A national matched case-control study. Participants Participants were recruited in 10 French Departments of Ophthalmology and their associated clinical investigation centers. All 115 patients with EMAP had symptoms before the age of 55 years due to bilateral extensive macular atrophy with a larger vertical axis and diffuse pseudodrusen. Three controls without age-related macular degeneration (AMD) or retinal disease at fundus examination were matched for each patient with EMAP by gender, age, and geographic area (in total 415). Methods Subjects and controls underwent an eye examination including color, red-free autofluorescent fundus photographs and spectral-domain optical coherence tomography with macular analysis. The interviews collected demographic, lifestyle, family and personal medical history, medications, and biological data. Associations of risk factors were estimated using conditional logistic regression. Main Outcome Measures Extensive macular atrophy with pseudodrusen status (cases vs. controls). Results Extensive macular atrophy with pseudodrusen most frequently affected women (70 women, 45 men). After multivariate adjustment, family history of glaucoma or AMD was strongly associated with EMAP (odds ratio [OR], 2.3, P = 0.008 and OR, 1.5, P = 0.01, respectively). No association was found with cardiac diseases or their risk factors. Mild and moderate kidney disease and higher neutrophil rate were associated with a reduced risk of EMAP (OR, 0.58, P = 0.04; OR, 0.34, P = 0.01; and OR, 0.59, P = 0.003, respectively). On the contrary, eosinophilia (OR, 1.6; P = 0.0002), lymphocytosis (OR, 1.84; P = 0.0002), increased erythrocyte sedimentation rate (OR, 6.5; P = 0.0005), decreased CH50 ( P = 0.001), and high plasma C3 level ( P = 0.023) were significantly associated with a higher risk of EMAP. Conclusions This study documents an association between EMAP and family history of AMD and glaucoma, a clear female predominance, and a systemic inflammatory profile. The reduced CH50 and increased C3 plasma values could reflect a more severe complement pathway dysfunction than in AMD, leading to early pseudodrusen and rapid development of geographic atrophy. There is no association of EMAP with AMD cardiac diseases or cardiac risks, including cigarette smoking.

Resume Contexte L’avenement de la tomographie en coherence optique (OCT) a modifie considerablement la facon d’aborder les pathologies vitreomaculaires, notamment celles des trous maculaires (TM). L’OCT apporte des precisions sur les diagnostics differentiels (trou lamellaire, pseudo-trou) et certains elements comme la taille du trou, le statut vitreen du sujet, l’etat des differentes couches de la retine. L’evolution des moyens de diagnostic mais aussi de prise en charge impose un nouveau regard sur la classification de ces pathologies vitreomaculaires. Methode Un groupe d’ophtalmologistes specialistes de la retine s’est reuni plusieurs fois pour echanger sur la classification internationale, publiee recemment par The International Vitreomacular Traction Study Group, s’interessant aux adherences vitreomaculaires (AVM) et tractions vitreomaculaires (TVM) ainsi qu’aux TM. Elle a ete comparee a la classification actuellement utilisee en France, basee sur la classification ophtalmoscopique de Gass, puis precisee par les etudes OCT de Gaudric, pour proposer une adaptation francaise de la classification internationale. Resultats Une classification adaptee a la pratique clinique francaise, en connexion avec la classification internationale, est proposee. Les AVM sont classees en « isolee » ou « associee » selon l’existence ou non d’une pathologie maculaire. Les TM se distinguent en « primaire » ou « secondaire » selon que leur origine est connue ou pas, en « petit », « moyen » et « grand » selon la taille du trou et selon la presence ou non d’une TVM. Enfin, les TVM sont decrites selon la presence concomitante ou non d’une membrane epimaculaire et selon la largeur de l’adherence.

EMAP (Extensive Macular Atrophy with Pseudodrusen) is a maculopathy we recently described that shares pseudodrusen and geographic atrophy with Age-related Macular Disease (AMD). EMAP differs from AMD by an earlier age of onset (50-55 years) and a characteristic natural history comprising a night blindness followed by a severe visual loss. In a prospective case-control study, ten referral centers included 115 EMAP (70 women, 45 men) patients and 345 matched controls to appraise dietary, environmental, and genetic risk factors. The incidence of EMAP (mean 2.95/1.106) was lower in Provence-Côte d’Azur with a Mediterranean diet (1.9/1.106), and higher in regions with intensive farming or industrialized activities (5 to 20/1.106). EMAP patients reported toxic exposure during professional activities (OR 2.29). The frequencies of common AMD complement factor risk alleles were comparable in EMAP. By contrast, only one EMAP patient had a rare AMD variant. This study suggests that EMAP could be a neurodegenerative disorder caused by lifelong toxic exposure and that it is associated with a chronic inflammation and abnormal complement pathway regulation. This leads to diffuse subretinal deposits with rod dysfunction and cone apoptosis around the age of 50 with characteristic extensive macular atrophy and paving stones in the far peripheral retina.

International audience; Wet macular degeneration remains a major cause of visual impairment in people over 55years. Through a group of experts belonging to the Federation France Macula, we review the treatment of wet AMD and provide recommendation with a 3 phases protocol called IOI

Wet macular degeneration remains a major cause of visual impairment in people over 55years. Through a group of experts belonging to the Federation France Macula, we review the treatment of wet AMD and provide recommendation with a 3 phases protocol called IOI.

Objective To establish whether the success rate of surgery for small idiopathic macular holes (diameter, ≤400 μm) is significantly reduced if facedown positioning is replaced by simply taking care to avoid the supine position. Design Randomized, controlled, parallel-assignment, open-label, interventional, multicenter clinical trial. Participants Sixty-nine patients from 6 specialized vitreoretinal units, randomized into 2 parallel groups and followed up after surgery for 3 months. Methods All patients underwent pars plana vitrectomy, peeling of any epiretinal membrane, and 17% C 2 F 6 gas filling. Patients then were advised randomly to observe either strict facedown positioning for 22 of 24 hours or simply to avoid the supine position for 10 days. Main Outcome Measures The primary outcome measure was the rate of anatomic closure 3 months after surgery. Main secondary measurements included Early Treatment Diabetic Retinopathy Study (ETDRS) visual acuity, progression of cataract, and frequency of complications. Results The mean size of macular holes was approximately 300 μm in both groups. Closure rates were more than 90% in both groups: 32 (91.4%) of 34 eyes in the alleviated positioning group versus 32 (94.1%) of 35 eyes in the facedown positioning group (lower margin of 95% confidence interval of difference, −14.88%). The ETDRS scores at 3 months increased in both groups by 10.23±14.64 and 10.52±14.54 letters, respectively. Progression of cataract and the rate of other complications were not significantly different in the 2 groups. Conclusions The success rate of surgery for idiopathic macular holes of 400 μm or smaller is not significantly reduced if facedown positioning is replaced by simply taking care to avoid the supine position. These macular holes can be treated by streamlined surgery, that is, with no internal limiting membrane peeling and no facedown positioning (only avoidance of the supine position) with a closure rate of more than 90% and a mean gain in visual acuity of more than 2 ETDRS lines at 3 months. Financial Disclosure(s) The author(s) have no proprietary or commercial interest in any materials discussed in this article.

The technique of intravitreous injections has been well documented for several years. Recently, a descriptive article on the intravitreous injections procedure was published in the Journal Francais d'Ophtalmologie, and the AFSSAPS (French agency for drug safety) released recommendations concerning this matter on the occasion of commercial launch of pegaptanib. Since that time, the number of intravitreal injections has considerably increased, because anti-VEGF drugs had been made available to ophthalmologists, and several teams have performed a large number of procedures, allowing them to better comprehend intravitreous injections. The present paper describes our current practice of intravitreous injections. Several specialists have exchanged their experiences and issued a common synthesis. Detailed modifications of the initial recommendations have been suggested, with such basic changes such as abandoning preoperative pupil dilatation and easing postsurgical monitoring. Follow-up examinations should be adapted to each patient rather than being systematic. The suggested modifications do not change the procedure of intravitreous injections substantially, but they simplify many steps and detail the various procedures when consensus is lacking.

But Les anti-VEGF constituent les traitements les plus recents de la neovascularisation choroidienne compliquant la DMLA. Leur mode d’administration est l’injection intravitreenne. Differentes etudes cliniques ont valide l’interet de ces produits. Cependant, les modalites de surveillance par examen complementaire de l’efficacite de ces traitements n’ont pas ete definies par ces memes etudes cliniques. Le but de cet article est de faire le point sur les pratiques realisees actuellement en France, par differents specialistes, et les examens complementaires necessaires au suivi therapeutique et aux decisions de retraitement. Methode Plusieurs reunions ont ete effectuees entre plusieurs specialistes exercant en milieu hospitalier et/ou en pratique liberale, pour definir leurs modalites actuelles de suivi et leur proposition pour un suivi rationnel et une harmonisation des pratiques. Resultats La tomographie a coherence optique (OCT) occupe une place croissante dans la surveillance post-injection intravitreenne d’anti-VEGF. Tous les auteurs reconnaissent la valeur de l’angiographie a la fluoresceine a l’initiation du traitement, mais aussi trois mois apres instauration du traitement, associee, pour certains d’entre nous, a la realisation d’une angiographie au vert d’indocyanine. Ils recommandent l’utilisation de l’angiographie a la fluoresceine chaque fois que les resultats fonctionnels ne sont pas a la hauteur de ce qu’en attendent le medecin ou le patient. Les auteurs proposent un organigramme decisionnel qui pourrait guider les decisions de retraitement. Conclusion Les auteurs suggerent l’utilisation d’un organigramme decisionnel visant a preciser, en fonction, essentiellement, de l’evolution de l’acuite visuelle et des resultats de l’OCT, les indications de retraitement les plus rationnelles pour eviter aux patients tout risque d’injection intra-vitreenne inutile.

Drugs to treat retinal diseases are often injected intravitreally. This procedure can cause severe complications. We present ways to minimize the risk for complications. Rigorous preoperative antisepsis with povidone iodine, a sterile environment (using gloves and a mask for the injector, a lid speculum, and a drape on the eye to be injected), and immediate follow-up after injection are key issues of the injection technique.

Optical coherence tomography has significantly changed the approach to vitreomacular diseases, including macular holes (MH). OCT provides information on differential diagnoses (lamellar hole, pseudo-hole), the MH size, the status of the vitreous, and the status of the various retinal layers. The evolution of diagnostic tools and treatment justifies the need for an update of the current classification of vitreomacular diseases.A group of retina specialists met several times to discuss the international classification, recently published by The International Vitreomacular Traction Study Group, focusing on vitreomacular adhesion (VMA), vitreomacular traction (VMT) and MH. It was compared to the classification currently used in France, based on the ophthalmoscopic system of Gass, then further delineated by Gaudric's OCT studies, in order to suggest a French adaptation to the international classification.An adapted classification for clinical use in France and in connection with the international classification is proposed. VMA are classified as an "associated" or "isolated" VMA respectively with or without macular disease. MH are distinguished as "primary" or "secondary" MH depending on whether the etiology is known or not, and classified as "small", "medium" and "large" depending on the size of the hole, and according to the presence or absence of VMT. Finally, VMT are described according to presence or absence of an epimacular membrane and according to the width of the adhesion.

The authors report the results of an experimental study of a series of 16 rabbit eyes that underwent prolonged tamponade by a liquid perfluorocarbon (LPFC). After vitreous compression by C3F8, a complete gas/LPFC exchange is performed and left in place for 48 h, 12 days and 21 days. Study of the retina by light and electron microscopy showed numerous lesions: vacuolization in the nerve fiber layer, progressive defects of the outer photoreceptor segments and presence of pseudomyelinic bodies in the inner plexiform layer. The axonal fiber loss is shown by a specific marker. The analysis of the results underlines the mechanical toxicity of LPFCs used in prolonged tamponade, which are too heavy for the neurosensory retina.

The technique of intravitreous injections has been well documented for several years. Recently, a descriptive article on the intravitreous injections procedure was published in the Journal Français d'Ophtalmologie, and the AFSSAPS (French agency for drug safety) released recommendations concerning this matter on the occasion of commercial launch of pegaptanib. Since that time, the number of intravitreal injections has considerably increased, because anti-VEGF drugs had been made available to ophthalmologists, and several teams have performed a large number of procedures, allowing them to better comprehend intravitreous injections. The present paper describes our current practice of intravitreous injections. Several specialists have exchanged their experiences and issued a common synthesis. Detailed modifications of the initial recommendations have been suggested, with such basic changes such as abandoning preoperative pupil dilatation and easing postsurgical monitoring. Follow-up examinations should be adapted to each patient rather than being systematic. The suggested modifications do not change the procedure of intravitreous injections substantially, but they simplify many steps and detail the various procedures when consensus is lacking.

In this paper, we present GASPARD (Graphical Array Specification for Parallel and Distributed computing), our visual programming environment devoted to the development of parallel applications. Task and data parallelism paradigms of parallel computing are mixed in GASPARD to achieve a simple programming interface. We use the printed circuit metaphor. The programmer specifies tasks and instantiates by plugging them into a slot (task parallelism). Data parallelism is achieved by specifying the data the task uses. By mixing textual and visual programming, we achieve a convenient interface useful for scientific programming. The interface is also well suited for meta-computing deployment. This kind of programming is very useful for numerical simulation.

Hepatitis B vaccination has been proven to be effective and well-tolerated. Certain neurological, ocular or systemic complications have, however, been reported to be induced by the vaccine. Clinicians should be aware of exceptional ocular complications.Four patients under 50 years of age developed occlusion of the central vein of the retina after vaccination with recombinant hepatitis B vaccine. None of the classical causes of occlusion of the central vein of the retina could be evidenced.Several pathophysiological hypotheses have been proposed to explain these ocular manifestations after vaccination: role of immunocomplexes, antigenic cross-reactions, role of immediate hypersensitivity, simulation of a pathogenic lymphocyte repertoire. None of these hypotheses is entirely satisfactory. It is important however to emphasize the need for a complete general evaluation, including an ophthalmological examination in the presence of unexplained ocular manifestations following hepatitis B vaccination.

Glaucoma of the aphakic patient is often difficult to treat. The authors present a new surgical technique which uses a portion of the trabeculum as a drain placed in the anterior chamber. Thirty eyes (19 aphakic and 11 pseudophakic) in 28 patients presenting refractory glaucoma were operated on by the same surgeon. Sixteen eyes had already undergone glaucoma surgery, 17 presented vitreous in the anterior chamber. The average postoperative follow-up was 18 months. Eighteen eyes (60%) needed no further treatment, 6 eyes (20%) were stabilized with a local treatment, 6 eyes (20%) remained hypertonic. This new surgical technique, which uses a portion of the trabeculum as a drain, allows for long-lasting filtration in the aphakic or pseudophakic patient with refractory glaucoma.

Glaucoma of the aphakic patient is often difficult to treat. Classical surgical management is limited by poor quality conjunctiva and by the presence of the vitreous gel opposite the fistula. We present a new surgical technique which uses a portion of the trabeculum as a drain placed in the anterior chamber.Thirty eyes (19 aphakic and 11 pseudophakic) in 28 patients presenting refractory glaucoma were operated on by the same surgeon. Sixteen eyes had already undergone glaucoma surgery, 17 presented vitreous in the anterior chamber. Average post-operative follow-up was 18 months.Eighteen eyes (60%) needed no further treatment, 6 eyes (20%) were stabilized with a local treatment, 6 eyes (20%) remained hypertonic.This new surgical technique, which uses a portion of the trabeculum as a drain, allows for long lasting filtration in the aphakic or pseudophakic patient with refractory glaucoma.

Conservative treatment of uveal melanomas by Gamma Knife Radiosurgery is based on the use of cross fire technique with 201 Cobalt60 sources. A following of 13 months is available for the first case operated by Gamma-Knife Surgery in France. Technical baselines and one year preliminary results are reported. The diagnosis of uveal melanoma T3NOMO was established by converging results of clinical examination, angiography and echography. The definition of the target was based on stereotactic MRT examination. We delivered a dose of 50 Gys to the marginal isodose (50%). Today, one year after treatment the tumor decreased, the visual function was preserved. There were no side effect or complication.

The function of RPE is well known in PVR. Pharmacological agents have been extensively studied both experimentally and clinically. Few reports have detailed the interactions of antimitotic drugs on the microtubule network. The aim of this study is to visualize by indirect immunofluorescence the effects of colchicine and paclitaxel on the microtubule network of cultured pig RPE cells in interphase.Pigs were killed at the slaughter-house, their eyes were enucleated. RPE cells were isolated and cultured. RPE cells were plated onto glass cover-slips at a density of 2,000,000 cells/ml, cultured and treated with the drugs during 4 and 24 hours at 37 degrees C at different concentrations. Immunofluorescence reaction was developped using antitubulin and fluoresceinated anti-mouse antibodies. The cytoskeletons were visualized employing a Zeiss photomicroscope equipped with epiilumination, a 63 x lens and appropriate filters for fluoresceine.The cytoplasmic microtubules of RPE cells were disrupted in a concentration and time-dependant manner by colchicine. Between 10 and 100 nm Veveral degrees of depolymarization of the microtubule network were observed. Paclitaxel between 1 micron and 10 microns was found to induce several degrees of microtubule "bundling" after 4 and 24 hours of incubation. Actin network was modified neither by colchicine and paclitaxel used in the same conditions.The results show that low doses of antimitotic drugs inhibit the microtubule network formation by depolymerization (colchicine) or stabilize it (paclitaxel). These actions inhibit cell division, which is one of the mechanisms implicated in PVR.

Perfluorocarbon liquids are used in vitreoretinal surgery due to their high specific gravity. Studies of retinal tolerance to prolonged tamponade with these liquids are discordant. Our experimental study uses a highly purified perfluorodecalin molecule (DKline) for prolonged retinal tamponade. The retinal lesions observed are described and analyzed.[corrected] Twenty pigmented rabbit eyes were studied. 1.2 to 1.5 ml of DKline were injected into the vitreous cavity after pneumatic compression. Histological and ultrastructural studies were performed after tamponade lasting 48 hours (5 eyes), 12 days (6 eyes), 21 days (5 eyes) and controls (4 eyes).After 48 hours: vacuolization of the nerve fiber layer is observed without ultrastructural changes; undulation of the photoreceptor outer segments is seen. After 12 days: vacuolization and undulation increase, with modifications in the junction between photoreceptors and the pigment epithelium. After 21 days: major vacuolization is seen, with disorganization of the photoreceptor architecture. The inner limiting membrane is respected and no surface proliferation is observed.DKline used in prolonged tamponade induces histological lesions as early as 48 hours; they increase with time. The nerve fiber and photoreceptor outer segment layers are the most severely affected. These lesions appear to be mainly of mechanical origin. Prolonged retinal tamponade with DKline would not seem possible.

Introduction L’etude Vitrilase a pour but de comparer l’efficacite de la vitrectomie, des IVT iteratives de triamcinolone et du laser dans le traitement de l’œdeme maculaire diffus chez le diabetique. Sa duree est de 2 ans. Nous rapportons les caracteristiques initiales des patients inclus dans l’etude. Objectifs et Methodes Etude multicentrique, prospective, randomisee et ouverte. Ont ete inclus des patients diabetiques de type I ou II, presentant un œdeme maculaire diffus, une acuite visuelle comprise entre 1 et 4/10. Le critere principal de l’etude est le pourcentage de patients presentant une amelioration de l’acuite visuelle de 3 lignes ETDRS ou plus apres 2 ans de suivi. Resultats 67 patients ont ete randomises dans les trois groupes de traitement : Discussion Les resultats sont attendus pour novembre 2009. Conclusion Cette etude devrait permettre d’aider a determiner quelle est la meilleure strategie therapeutique pour l’œdeme maculaire diffus diabetique.

Orbital hydatid cysts are extremely rare in France. The authors report two cases in young adults of North African origin, one being a recurrence. Echography and CT scan were the most useful paraclinical investigations. The cysts were surgically excised with difficulty via an anterior approach adapted to the localisation. After 5 years follow up, both patients survived, however, there was major visual loss (blindness, or requirement for enucleation), due to the delay in diagnosis.

A fighting mayor calls for prompt action to end state and federal usurpation of powers and duties of cities.

A 85 year old man was admitted with an acute endolphtalmitis, a high intraocular pressure (60 mm Hg) and a visual acuity with only light perception. The diagnosis was a phacolytic glaucoma by diffusion of lens proteins through the small preexisting perforation of the lens capsule. The lens was removed by an intracapsular extraction without intraocular lens. The intraocular pressure was normal on the first postoperative day and the visual acuity was improved to 6/10 P2.