Strain-relief by single dislocation loops in calcite crystals grown on self-assembled monolayers

Most of our knowledge of dislocation-mediated stress relaxation during epitaxial crystal growth comes from the study of inorganic heterostructures. Here we use Bragg coherent diffraction imaging to investigate a contrasting system, the epitaxial growth of calcite (CaCO3) crystals on organic self-assembled monolayers, where these are widely used as a model for biomineralization processes. The calcite crystals are imaged to simultaneously visualize the crystal morphology and internal strain fields. Our data reveal that each crystal possesses a single dislocation loop that occupies a common position in every crystal. The loops exhibit entirely different geometries to misfit dislocations generated in conventional epitaxial thin films and are suggested to form in response to the stress field, arising from interfacial defects and the nanoscale roughness of the substrate. This work provides unique insight into how self-assembled monolayers control the growth of inorganic crystals and demonstrates important differences as compared with inorganic substrates

Repeatability of Foveal Measurements Using Spectralis Optical Coherence Tomography Segmentation Software

PURPOSE: To investigate repeatability and reproducibility of thickness of eight individual retinal layers at axial and lateral foveal locations, as well as foveal width, measured from Spectralis spectral domain optical coherence tomography (SD-OCT) scans using newly available retinal layer segmentation software. METHODS: High-resolution SD-OCT scans were acquired for 40 eyes of 40 young healthy volunteers. Two scans were obtained in a single visit for each participant. Using new Spectralis segmentation software, two investigators independently obtained thickness of each of eight individual retinal layers at 0°, 2° and 5° eccentricities nasal and temporal to foveal centre, as well as foveal width measurements. Bland-Altman Coefficient of Repeatability (CoR) was calculated for inter-investigator and inter-scan agreement of all retinal measurements. Spearman's ρ indicated correlation of manually located central retinal thickness (RT0) with automated minimum foveal thickness (MFT) measurements. In addition, we investigated nasal-temporal symmetry of individual retinal layer thickness within the foveal pit. RESULTS: Inter-scan CoR values ranged from 3.1μm for axial retinal nerve fibre layer thickness to 15.0μm for the ganglion cell layer at 5° eccentricity. Mean foveal width was 2550μm ± 322μm with a CoR of 13μm for inter-investigator and 40μm for inter-scan agreement. Correlation of RT0 and MFT was very good (ρ = 0.97, P 0.05); however this symmetry could not be found at 5° eccentricity. CONCLUSIONS: We demonstrate excellent repeatability and reproducibility of each of eight individual retinal layer thickness measurements within the fovea as well as foveal width using Spectralis SD-OCT segmentation software in a young, healthy cohort. Thickness of all individual retinal layers were symmetrical at 2°, but not at 5° eccentricity away from the fovea

BMC Ophthalmol

BACKGROUND: This was an updated network meta-analysis (NMA) of anti-vascular endothelial growth factor (VEGF) agents and laser photocoagulation in patients with diabetic macular edema (DME). Unlike previous NMA that used meta-regression to account for potential confounding by systematic variation in treatment effect modifiers across studies, this update incorporated individual patient-level data (IPD) regression to provide more robust adjustment. METHODS: An updated review was conducted to identify randomised controlled trials for inclusion in a Bayesian NMA. The network included intravitreal aflibercept (IVT-AFL) 2 mg bimonthly (2q8) after 5 initial doses, ranibizumab 0.5 mg as-needed (PRN), ranibizumab 0.5 mg treat-and-extend (T&E), and laser photocoagulation. Outcomes included in the analysis were change in best-corrected visual acuity (BCVA), measured using an Early Treatment Diabetic Retinopathy Study (ETDRS) chart, and patients with >/=10 and >/= 15 ETDRS letter gains/losses at 12 months. Analyses were performed using networks restricted to IPD-only and IPD and aggregate data with (i) no covariable adjustment, (ii) covariable adjustment for baseline BVCA assuming common interaction effects (against reference treatment), and (iii) covariable adjustments specific to each treatment comparison (restricted to IPD-only network). RESULTS: Thirteen trials were included in the analysis. IVT-AFL 2q8 was superior to laser in all analyses. IVT-AFL 2q8 showed strong evidence of superiority (95% credible interval [CrI] did not cross null) versus ranibizumab 0.5 mg PRN for mean change in BCVA (mean difference 5.20, 95% CrI 1.90-8.52 ETDRS letters), >/=15 ETDRS letter gain (odds ratio [OR] 2.30, 95% CrI 1.12-4.20), and >/=10 ETDRS letter loss (OR 0.25, 95% CrI 0.05-0.74) (IPD and aggregate random-effects model with baseline BCVA adjustment). IVT-AFL 2q8 was not superior to ranibizumab 0.5 mg T&E for mean change in BCVA (mean difference 5.15, 95% CrI -0.26-10.61 ETDRS letters) (IPD and aggregate random-effects model). CONCLUSIONS: This NMA, which incorporated IPD to improve analytic robustness, showed evidence of superiority of IVT-AFL 2q8 to laser and ranibizumab 0.5 mg PRN. These results were irrespective of adjustment for baseline BCVA

Functional expression of Rab escort protein 1 following AAV2-mediated gene delivery in the retina of choroideremia mice and human cells ex vivo

Choroideremia (CHM) is an X-linked retinal degeneration of photoreceptors, the retinal pigment epithelium (RPE) and choroid caused by loss of function mutations in the CHM/REP1 gene that encodes Rab escort protein 1. As a slowly progressing monogenic retinal degeneration with a clearly identifiable phenotype and a reliable diagnosis, CHM is an ideal candidate for gene therapy. We developed a serotype 2 adeno-associated viral vector AAV2/2-CBA-REP1, which expresses REP1 under control of CMV-enhanced chicken β-actin promoter (CBA) augmented by a Woodchuck hepatitis virus post-transcriptional regulatory element. We show that the AAV2/2-CBA-REP1 vector provides strong and functional transgene expression in the D17 dog osteosarcoma cell line, CHM patient fibroblasts and CHM mouse RPE cells in vitro and in vivo. The ability to transduce human photoreceptors highly effectively with this expression cassette was confirmed in AAV2/2-CBA-GFP transduced human retinal explants ex vivo. Electroretinogram (ERG) analysis of AAV2/2-CBA-REP1 and AAV2/2-CBA-GFP-injected wild-type mouse eyes did not show toxic effects resulting from REP1 overexpression. Subretinal injections of AAV2/2-CBA-REP1 into CHM mouse retinas led to a significant increase in a- and b-wave of ERG responses in comparison to sham-injected eyes confirming that AAV2/2-CBA-REP1 is a promising vector suitable for choroideremia gene therapy in human clinical trials. © 2013 The Author(s)

Induced pluripotent stem cell therapies for retinal disease.

PURPOSE OF REVIEW: This review will discuss how recent advances with induced pluripotent stem (iPS) cells have brought the science of stem cell biology much closer to clinical application for patients with retinal degeneration. RECENT FINDINGS: The ability to generate embryonic stem cells by reprogramming DNA taken from adult cells was demonstrated by the cloning of Dolly, the sheep, by somatic cell nuclear transfer, over 10 years ago. Recently, it has been shown that adult cells can be reprogrammed directly, without the need for a surrogate oocyte, through the generation of iPS cells. The method of reprogramming has since been optimized to avoid the use of retroviruses, making the process considerably safer. Last year, human iPS cells were isolated from an 80-year-old patient with neurodegenerative disease and differentiated into neurons in vitro. SUMMARY: For stem cell therapies, the retina has the optimal combination of ease of surgical access, combined with an ability to observe transplanted cells directly through the clear ocular media. The question now is which retinal diseases are most appropriate targets for clinical trials using iPS cell approaches

The visual field in toxoplasmic retinochoroiditis

Aims: To document loss of central field in patients with scars from toxoplasmic retinochoroiditis close to the disc after resolution of disease. Methods: Patients with a clinical diagnosis of toxoplasmic retinochoroiditis were enrolled from four centres. Automated central visual field testing was performed when their disease had settled and retinal photographs of the lesions were taken. The type of central field defect (whether absolute or relative) and whether it broke out to the periphery were correlated with the size of the retinochoroidal scar and its proximity to the optic nerve head. Results: 69 eyes were enrolled; 16 (26%) were discarded because of poor field performance. Of the 53 remaining eyes, 31 showed absolute defects and 20 relative defects. Scars within one disc diameter of the disc were more likely to be associated with absolute defects breaking out to the periphery. Conclusion: The scarring induced by toxoplasmic retinochoroiditis is associated with considerable field loss when it occurs close to the optic nerve head. Current treatment is unlikely to ameliorate this situation. The degree of visual field loss should be an outcome measure for future trials of the efficacy of treatment trials for the disease

Diabetic retinopathy:pathogenesis, clinical grading, management and future developments

Decades of research into the pathophysiology and management of diabetic retinopathy have revolutionized our understanding of the disease process. Diabetic retinopathy is now more accurately defined as a neurovascular rather than a microvascular disease as neurodegenerative disease precedes and coexists with microvascular changes. However, the complexities of the pathways involved in different stages of disease severity continue to remain a challenging issue for drug discovery. Currently, laser photocoagulation is the mainstay of treatment for proliferative diabetic retinopathy, but is gradually being superseded for diabetic macular oedema. However, it is destructive and at best results in a gradual but modest improvement in vision in the long term. So, diabetic retinopathy remains the most prevalent cause of visual impairment in the working-age population despite established screening programmes, early diagnosis and treatment of the condition. The recent discovery of inhibitors of vascular endothelial growth factor is revolutionizing the management of diabetic retinopathy, particularly diabetic macular oedema. However, not all patients respond to anti-vascular endothelial growth factor agents, reinforcing the fact that diabetic retinopathy is a multifactorial disease. Studies are still required to improve our understanding of how retinal structure correlates with visual function. It is hoped that these will lead to better characterization of the disease phenotype based on treatment responses to different agents and allow an algorithm to be developed that will guide the management of diabetic retinopathy and diabetic macular oedema at different stages of severity

QUADRIS : Qualité des données dans les systèmes d'informations multi-sources

Journées Panorama des Recherches incitatives en STIC (PaRiSTIC'07), Cité des Sciences de la Villette, Paris, 5 - 6 - 7 novembr

QUADRIS : Qualité des données dans les systèmes d'informations multi-sources

Journées Panorama des Recherches incitatives en STIC (PaRiSTIC'07), Cité des Sciences de la Villette, Paris, 5 - 6 - 7 novembr