Dry age-related macular degeneration: A currently unmet clinical need.

Age-related macular degeneration (AMD) is a leading cause of severe visual impairment and disability in older people worldwide. Although considerable advances in the management of the neovascular form of AMD have been made in the last decade, no therapy is yet available for the advanced dry form of AMD (geographic atrophy). This review focuses on current trends in the development of new therapies targeting specific pathophysiological pathways of dry AMD.

NMNAT1 mutations cause Leber congenital amaurosis.

Leber congenital amaurosis (LCA) is an infantile-onset form of inherited retinal degeneration characterized by severe vision loss(1,2). Two-thirds of LCA cases are caused by mutations in 17 known disease-associated genes(3) (Retinal Information Network (RetNet)). Using exome sequencing we identified a homozygous missense mutation (c.

Treating retinal vein occlusions in France, Germany, and Italy: an analysis of treatment patterns, resource consumption, and costs.

Purpose: To describe treatment patterns among patients with central or branch retinal vein occlusion (CRVO or BRVO) in France, Germany, and Italy, and to estimate retinal vein occlusion (RVO)-related direct medical costs.

Methods: We used a retrospective chart review to determine 18-month RVO-related resource utilization and calculate 12-month health care costs. Country-specific unit costs (€) were assigned to each resource from the perspective of the health care payer.

Genome-wide association study of age-related macular degeneration identifies associated variants in the TNXB-FKBPL-NOTCH4 region of chromosome 6p21.3.

Age-related macular degeneration (AMD) is a leading cause of visual loss in Western populations. Susceptibility is influenced by age, environmental and genetic factors. Known genetic risk loci do not account for all the heritability.

CXCR3 antagonism of SDF-1(5-67) restores trabecular function and prevents retinal neurodegeneration in a rat model of ocular hypertension.

Glaucoma, the most common cause of irreversible blindness, is a neuropathy commonly initiated by pathological ocular hypertension due to unknown mechanisms of trabecular meshwork degeneration. Current antiglaucoma therapy does not target the causal trabecular pathology, which may explain why treatment failure is often observed. Here we show that the chemokine CXCL12, its truncated form SDF-1(5-67), and the receptors CXCR4 and CXCR3 are expressed in human glaucomatous trabecular tissue and a human trabecular cell line.

Spectral domain optical coherence tomography evolutive features in acute macular neuroretinopathy.

Purpose: To demonstrate the usefulness of spectral domain optical coherence tomography (SD-OCT) in investigating the evolution of the retinal outer lesions seen in acute macular neuroretinopathy (AMN).

Methods: A 32-year-old woman presented with a 1-day history of paracentral dark spot in the left eye, preceded by a flulike illness. A full ophthalmologic examination, color vision, visual field examination, and conventional imaging of the retina were done.

Taurine deficiency damages retinal neurones: cone photoreceptors and retinal ganglion cells.

In 1970s, taurine deficiency was reported to induce photoreceptor degeneration in cats and rats. Recently, we found that taurine deficiency contributes to the retinal toxicity of vigabatrin, an antiepileptic drug. However, in this toxicity, retinal ganglion cells were degenerating in parallel to cone photoreceptors.

Temporal properties of visual perception on electrical stimulation of the retina.

Purpose: To investigate the elementary temporal properties of electrically evoked percepts in blind patients chronically implanted with an epiretinal prosthesis.

Methods: Nine subjects were presented with isolated stimuli of variable duration and pulse rate. Stimulation amplitude was set to the upper comfortable level and a group of 2 × 2 adjacent electrodes was simultaneously activated.

Nxnl2 splicing results in dual functions in neuronal cell survival and maintenance of cell integrity.

The rod-derived cone viability factors, RdCVF and RdCVF2, have potential therapeutical interests for the treatment of inherited photoreceptor degenerations. In the mouse lacking Nxnl2, the gene encoding RdCVF2, the progressive decline of the visual performance of the cones in parallel with their degeneration, arises due to the loss of trophic support from RdCVF2. In contrary, the progressive loss of rod visual function of the Nxnl2-/- mouse results from a decrease in outer segment length, mediated by a cell autonomous mechanism involving the putative thioredoxin protein RdCVF2L, the second spliced product of the Nxnl2 gene.

Whole-exome sequencing identifies mutations in GPR179 leading to autosomal-recessive complete congenital stationary night blindness.

Congenital stationary night blindness (CSNB) is a heterogeneous retinal disorder characterized by visual impairment under low light conditions. This disorder is due to a signal transmission defect from rod photoreceptors to adjacent bipolar cells in the retina. Two forms can be distinguished clinically, complete CSNB (cCSNB) or incomplete CSNB; the two forms are distinguished on the basis of the affected signaling pathway.

Development and application of a next-generation-sequencing (NGS) approach to detect known and novel gene defects underlying retinal diseases.

Background: Inherited retinal disorders are clinically and genetically heterogeneous with more than 150 gene defects accounting for the diversity of disease phenotypes. So far, mutation detection was mainly performed by APEX technology and direct Sanger sequencing of known genes. However, these methods are time consuming, expensive and unable to provide a result if the patient carries a new gene mutation.

Interim results from the international trial of Second Sight's visual prosthesis.

Purpose: This study evaluated the Argus II Retinal Prosthesis System (Second Sight Medical Products, Inc., Sylmar, CA) in blind subjects with severe outer retinal degeneration.

Design: Single-arm, prospective, multicenter clinical trial.

℮-conome: an automated tissue counting platform of cone photoreceptors for rodent models of retinitis pigmentosa.

Background: Retinitis pigmentosa is characterized by the sequential loss of rod and cone photoreceptors. The preservation of cones would prevent blindness due to their essential role in human vision. Rod-derived Cone Viability Factor is a thioredoxin-like protein that is secreted by rods and is involved in cone survival.

Transcriptomic analysis of human retinal detachment reveals both inflammatory response and photoreceptor death.

Background: Retinal detachment often leads to a severe and permanent loss of vision and its therapeutic management remains to this day exclusively surgical. We have used surgical specimens to perform a differential analysis of the transcriptome of human retinal tissues following detachment in order to identify new potential pharmacological targets that could be used in combination with surgery to further improve final outcome.

Methodology/principal Findings: Statistical analysis reveals major involvement of the immune response in the disease.

Downregulation of apoptosis-inducing factor in Harlequin mice induces progressive and severe optic atrophy which is durably prevented by AAV2-AIF1 gene therapy.

The Harlequin mutant mouse, characterized by loss of function of apoptosis-inducing factor, represents a reliable genetic model that resembles pathologies caused by human mitochondrial complex I deficiency. Therefore, we extensively characterized the retinal morphology and function of Harlequin mice during the course of neuronal cell death leading to blindness, with the aim of preventing optic atrophy. Retinas and optic nerves from these mice showed an isolated respiratory chain complex I defect correlated with retinal ganglion cell loss, optic atrophy, glial and microglial cell activation.

CRB1 mutations in inherited retinal dystrophies.

Mutations in the CRB1 gene are associated with variable phenotypes of severe retinal dystrophies, ranging from leber congenital amaurosis (LCA) to rod-cone dystrophy, also called retinitis pigmentosa (RP). Moreover, retinal dystrophies resulting from CRB1 mutations may be accompanied by specific fundus features: preservation of the para-arteriolar retinal pigment epithelium (PPRPE) and retinal telangiectasia with exudation (also referred to as Coats-like vasculopathy). In this publication, we report seven novel mutations and classify over 150 reported CRB1 sequence variants that were found in more that 240 patients.

RP1 and autosomal dominant rod-cone dystrophy: novel mutations, a review of published variants, and genotype-phenotype correlation.

Rod-cone dystrophies (retinitis pigmentosa [RP]) are a clinically and genetically heterogeneous group of inherited retinal disorders characterized by photoreceptor degeneration. RP1 is a major gene underlying autosomal dominant (ad) RP, though prevalence figures vary depending on the origin of the cases from 0-10% of all adRP. Some mutations in RP1 also lead to autosomal recessive (ar) RP.

Optogenetic therapy for retinitis pigmentosa.

Retinitis pigmentosa (RP) refers to a diverse group of progressive, hereditary diseases of the retina that lead to incurable blindness and affect two million people worldwide. Artificial photoreceptors constructed by gene delivery of light-activated channels or pumps ('optogenetic tools') to surviving cell types in the remaining retinal circuit has been shown to restore photosensitivity in animal models of RP at the level of the retina and cortex as well as behaviorally. The translational potential of this optogenetic approach has been evaluated using in vitro studies involving post-mortem human retinas.

Reevaluation of dystrophin localization in the mouse retina.

PURPOSE. The roles of dystrophins in retinal physiology remain elusive. The lack of proper clustering of the potassium channel Kir4.

[Intraocular foreign bodies (IOFB) of the posterior segment: retrospective analysis and management of 57 cases].

Purpose: To determine the influence of prognostic factors and the type of tamponade agent in surgical management of intraocular foreign bodies (IOFBs) for better visual outcome.

Patients And Methods: Fifty-seven consecutive cases were retrospectively reviewed at the XV-XX National Hospital (Paris) between 1 January 2004 and 31 December 2007. Univariate and multivariate analyses were performed to identify prognostic variables.

CYFIP dependent actin remodeling controls specific aspects of Drosophila eye morphogenesis.

Cell rearrangements shape organs and organisms using molecular pathways and cellular processes that are still poorly understood. Here we investigate the role of the Actin cytoskeleton in the formation of the Drosophila compound eye, which requires extensive remodeling and coordination between different cell types. We show that CYFIP/Sra-1, a member of the WAVE/SCAR complex and regulator of Actin remodeling, controls specific aspects of eye architecture: rhabdomere extension, rhabdomere terminal web organization, adherens junctions, retina depth and basement membrane integrity.

Ptf1a/Rbpj complex inhibits ganglion cell fate and drives the specification of all horizontal cell subtypes in the chick retina.

During development, progenitor cells of the retina give rise to six principal classes of neurons and the Müller glial cells found within the adult retina. The pancreas transcription factor 1 subunit a (Ptf1a) encodes a basic-helix-loop-helix transcription factor necessary for the specification of horizontal cells and the majority of amacrine cell subtypes in the mouse retina. The Ptf1a-regulated genes and the regulation of Ptf1a activity by transcription cofactors during retinogenesis have been poorly investigated.

Randomized clinical trial France DMLA2: effect of trimetazidine on exudative and nonexudative age-relatedmacular degeneration.

Purpose: To evaluate the effect of trimetazidine (TMZ) in a randomized, double-blind, placebo-controlled clinical trial on the occurrence of choroidal neovascularization or geographic atrophy in age-related macular degeneration.

Methods: A total of 1,086 patients from France, Belgium, and Spain with soft drusen and/or retinal pigment epithelium abnormalities in the study eye and choroidal neovascularization in the contralateral eye were randomly assigned to receive orally placebo or TMZ 70 mg daily (35 mg × 2) and followed-up for 3 years to 5 years.

Results: Treatment duration ranged between 0.

Foveal shape and structure in a normal population.

Purpose: The shape of the human fovea presents important but still poorly characterized variations. In this study, the variability of the shape and structure of normal foveae were examined.

Methods: In a group of 110 eyes of 57 healthy adults, the shape and structure of the fovea were analyzed by automated segmentation of retinal layer on high-resolution optical coherence tomography scans.

A novel DFNB31 mutation associated with Usher type 2 syndrome showing variable degrees of auditory loss in a consanguineous Portuguese family.

Purpose: To identify the genetic defect of a consanguineous Portuguese family with rod-cone dystrophy and varying degrees of decreased audition.

Methods: A detailed ophthalmic and auditory examination was performed on a Portuguese patient with severe autosomal recessive rod-cone dystrophy. Known genetic defects were excluded by performing autosomal recessive retinitis pigmentosa (arRP) genotyping microarray analysis and by Sanger sequencing of the coding exons and flanking intronic regions of eyes shut homolog-drosophila (EYS) and chromosome 2 open reading frame 71 (C2orf71).