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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.

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

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.

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.

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.

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.