Geographic Atrophy: Confocal Scanning Laser Ophthalmoscopy, Histology, and Inflammation in the Region of Expanding Lesions.

PurposeTo describe the pathology of AMD in eyes with geographic atrophy (GA) using confocal scanning laser ophthalmoscopy (SLO) blue light autofluorescence (BAF), and near-infrared (IR) AF and to correlate it with the histology and immunohistochemistry analysis at the margins of the GA lesion.MethodsEnucleated, fixed eyes from seventeen donors with GA were imaged and analyzed by BAF-SLO, IRAF-SLO, and by fundus macroscopy (FM). Tissue from the margins of the GA lesions was cut and processed for resin embedding and histology or cryosectioning and fluorescence in the green and far-red channels, and immunohistochemistry to assess markers of inflammation. Isolated DNA from donors was genotyped for single nucleotide polymorphisms (SNPs) previously shown to be risk factors for the development and progression of AMD.ResultsAround the leading edge of the GA lesions we observed hypertrophic RPE cells with cytoplasm filled with granules fluorescent both in the far-red and green-red channels; abundant microglia and macrophage; deposition of complement factor H (CFH) in Bruch's membrane (BM) and increased membrane attack complex (MAC) on RPE cells.ConclusionsFluorescence imaging of cryosections of RPE cells around the leading edge of the GA lesions suggest that IRAF-SLO visualizes mostly melanin-related compounds. In addition, medium-size GA atrophy displayed the most significant changes in inflammation markers

Augmenting one-session treatment of children's specific phobias with attention training to positive stimuli

This study examined the efficacy of combining two promising approaches to treating children's specific phobias, namely attention training and one 3-h session of exposure therapy (‘one-session treatment’, OST). Attention training towards positive stimuli (ATP) and OST (ATP+OST) was expected to have more positive effects on implicit and explicit cognitive mechanisms and clinical outcome measures than an attention training control (ATC) condition plus OST (ATC+OST). Thirty-seven children (6–17 years) with a specific phobia were randomly assigned to ATP+OST or ATC+OST. In ATP+OST, children completed 160 trials of attention training responding to a probe that always followed the happy face in happy-angry face pairs. In ATC+OST, the probe appeared equally often after angry and happy faces. In the same session, children completed OST targeting their phobic situation/object. Clinical outcomes included clinician, parent and child report measures. Cognitive outcomes were assessed in terms of change in attention bias to happy and angry faces and in danger and coping expectancies. Assessments were completed before and after treatment and three-months later. Compared to ATC+OST, the ATP+OST condition produced (a) significantly greater reductions in children's danger expectancies about their feared situations/object during the OST and at three-month follow-up, and (b) significantly improved attention bias towards positive stimuli at post-treatment, which in turn, predicted a lower level of clinician-rated phobia diagnostic severity three-months after treatment. There were no significant differences between ATP+OST and ATC+OST conditions in clinician, parent, or child-rated clinical outcomes. Training children with phobias to focus on positive stimuli is effective in increasing attention towards positive stimuli and reducing danger expectancy biases. Studies with larger sample sizes and a stronger ‘dose’ of ATP prior to the OST may reveal promising outcomes on clinical measures for training attention towards positive stimuli.13 page(s

Head-to-head comparison of the diagnostic performances of Rubidium-PET and SPECT with CZT camera for the detection of myocardial ischemia in a population of women and overweight individuals

International audienceBackground: The aim of this study was to compare the diagnostic performances for the detection of myocardial ischemia of 82-Rb-PET-MPS and 99m-Tc-SPECT-MPS in overweight individuals and women.Methods and results: Men with BMI ≥ 25 and women referred for MPS were considered for inclusion. All individuals underwent 99m-Tc-SPECT-MPS with CZT cameras and 82-Rb-PET-MPS in 3D-mode. Individuals with at least one positive MPS were referred for coronary angiography (CA) with FFR measurements. A criterion for positivity was a composite endpoint including significant stenosis on CA or, in the absence of CA, the occurrence of acute coronary event during the following year. 313 patients (46% women) with mean BMI of 31.8 ± 6.5 were included. Sensitivity for the detection of myocardial ischemia was higher with 82-Rb-PET-MPS compared with 99m-Tc-SPECT-MPS (85% vs. 57%, P .05). 82-Rb-PET allowed for a more accurate detection of patients with a high-risk coronary artery disease (HR-CAD) than 99m-Tc-SPECT-MPS (AUC = 0.86 vs. 0.75, respectively; P = .04).Conclusions: In women and overweight individuals, 82-Rb-PET-MPS provides higher sensitivity for the detection of myocardial ischemia than 99m-Tc-SPECT-MPS thanks to a better image quality and an improved detection of HR-CAD

A human model of Batten disease shows role of CLN3 in phagocytosis at the photoreceptor–RPE interface

CLN3 disease is characterised by childhood-onset vision loss and premature death. Using patient-derived retinal cells, the authors show that CLN3 is required for retinal pigment epithelium (RPE) cell structure, microvilli and phagocytosis of photoreceptor outer segments that are essential for vision. They further suggest that gene-therapy targeting RPE cells can be effective for CLN3 disease