Therapies targeting Frizzled-7/ß-catenin pathway prevent the development of pathological angiogenesis in an ischemic retinopathy model.

Retinopathies remain major causes of visual impairment in diabetic patients and premature infants. Introduction of anti-angiogenic drugs targeting vascular endothelial growth factor (VEGF) has transformed therapy for these proliferative retinopathies. However, limitations associated with anti-VEGF medications require to unravel new pathways of vessel growth to identify potential drug targets. Here, we investigated the role of Wnt/Frizzled-7 (Fzd7) pathway in a mouse model of oxygen-induced retinopathy (OIR). Using transgenic mice, which enabled endothelium-specific and time-specific Fzd7 deletion, we demonstrated that Fzd7 controls both vaso-obliteration and neovascular phases (NV). Deletion of Fzd7 at P12, after the ischemic phase of OIR, prevented formation of aberrant neovessels into the vitreous by suppressing proliferation of endothelial cells (EC) in tufts. Next we validated in vitro two Frd7 blocking strategies: a monoclonal antibody (mAbFzd7) against Fzd7 and a soluble Fzd7 receptor (CRD). In vivo a single intravitreal microinjection of mAbFzd7 or CRD significantly attenuated retinal neovascularization (NV) in mice with OIR. Molecular analysis revealed that Fzd7 may act through the activation of Wnt/ß-catenin and Jagged1 expression to control EC proliferation in extra-retinal neovessels. We identified Fzd7/ß-catenin signaling as new regulator of pathological retinal NV. Fzd7 appears to be a potent pharmacological target to prevent or treat aberrant angiogenesis of ischemic retinopathies.

Spontaneous rupture of chorioretinal coloboma in an 8-year-old child is treated by temporal fascia graft.

We report the rare case of an 8-year-old boy with spontaneous scleral perforation secondary to an isolated congenital chorioretinal coloboma. Visual acuity was 20/200 and examination revealed severe hypotony with subcapsular cataract, complete exudative retinal detachment, hypotonous optic nerve swelling, and hypotony retinal fold. In the temporal periphery, there was a chorioretinal coloboma with a central full-thickness defect. The scleral defect was successfully treated with an autologous temporalis fascia graft. One year later, and after cataract surgery, visual acuity had improved to 20/20, with normal intraocular pressure.

Multimodal Imaging of Reticular Pseudodrusen in a Population-Based Setting: The Alienor Study.

PURPOSE: To document reticular pseudodrusen (RPD) using multimodal imaging in French elderly subjects. METHODS: A total of 494 subjects (970 eyes) aged 77 years or more, from the Alienor study, were examined in 2011 and 2012. Reticular pseudodrusen were defined as definite if they were present with at least two imaging methods among color retinal photographs, macular cube (20° × 15°) of spectral-domain optical coherence tomography (SD-OCT), fundus autofluorescence (FAF), and infrared reflectance (IR). The Youden index was calculated as specificity + sensitivity - 1. RESULTS: The prevalence of definite RPD was 13.4% and was higher among women (15.6%) than men (10.2%). It increased with age and reached almost 50% in subjects over 85 years. Infrared reflectance was the most sensitive technique (100%) and color fundus photography the least sensitive (34.5% at left eyes and 48.1% at right eyes). The best Youden index was obtained with IR (0.96 at both eyes) followed by SD-OCT (0.87 at right eye and 0.78 at left eye). Reticular pseudodrusen were present in 4.6% of eyes without AMD, 13.0% with early AMD1, 62.6% with early AMD2, 34.6% with atrophic AMD, and 8.1% with neovascular AMD. Reticular pseudodrusen were significantly associated with central and pericentral intermediate soft drusen (odds ratio [OR]: 2.14; 95% confidence interval [CI] = 1.11-4.14 and OR: 1.49; 95% CI = 1.16-1.90, respectively) and central large soft drusen (OR: 1.67; 95% CI = 1.16-2.42). CONCLUSIONS: Using multimodal imaging, the prevalence of RPD appears higher than previously reported in studies based on retinal photography only. Reticular pseudodrusen frequently accompany other signs of AMD. Infrared reflectance and SD-OCT appear to be particularly relevant methods to diagnose RPD.