Patient-reported outcomes (PRO's) in glaucoma: a systematic review

The aim of this review was to summarize literature in view of patient-reported outcome (PRO) instruments for glaucoma and provide guidance on how outcomes are best assessed based on evidence about their content and validity. A systematic literature review was performed on papers describing the developmental process and/or psychometric properties of glaucoma or vision-specific PRO-instruments. Each of them was assessed on their adherence to a framework of quality criteria. Fifty-three articles were identified addressing 27 PRO-instruments. In all, 18 PRO's were developed for glaucoma and 9 for diverse ophthalmologic conditions. Seven instruments addressed functional status, 11 instruments quality of life and 9 instruments disease and treatment-related factors. Most of the instruments demonstrated only partially adherence to predefined quality standards. The tools for assessing functional status were of poor quality, while the Glaucoma Quality of Life Questionnaire and the Vision Quality of Life Index were well-developed QoL measures, yet only validated using classical techniques. The Rasch-scaled QoL-tools, IVI and VCM1 need to improve their item-content for glaucoma patients. The questionnaires to measure adherence should improve their validity and the Treatment Satisfaction Survey for Intra Ocular Pressure pops out as the highest quality tool for measuring topical treatment side effects. This review revealed that most PRO-instruments demonstrated poor developmental quality, more specifically a lack of conceptual framework and item generation strategies not involving the patients' perspective. Psychometric characteristics were mostly tested using classical validation techniques

Autistic-like behaviours and hyperactivity in mice lacking ProSAP1/Shank2.

International audienceAutism spectrum disorders comprise a range of neurodevelopmental disorders characterized by deficits in social interaction and communication, and by repetitive behaviour. Mutations in synaptic proteins such as neuroligins, neurexins, GKAPs/SAPAPs and ProSAPs/Shanks were identified in patients with autism spectrum disorder, but the causative mechanisms remain largely unknown. ProSAPs/Shanks build large homo- and heteromeric protein complexes at excitatory synapses and organize the complex protein machinery of the postsynaptic density in a laminar fashion. Here we demonstrate that genetic deletion of ProSAP1/Shank2 results in an early, brain-region-specific upregulation of ionotropic glutamate receptors at the synapse and increased levels of ProSAP2/Shank3. Moreover, ProSAP1/Shank2(-/-) mutants exhibit fewer dendritic spines and show reduced basal synaptic transmission, a reduced frequency of miniature excitatory postsynaptic currents and enhanced N-methyl-d-aspartate receptor-mediated excitatory currents at the physiological level. Mutants are extremely hyperactive and display profound autistic-like behavioural alterations including repetitive grooming as well as abnormalities in vocal and social behaviours. By comparing the data on ProSAP1/Shank2(-/-) mutants with ProSAP2/Shank3αβ(-/-) mice, we show that different abnormalities in synaptic glutamate receptor expression can cause alterations in social interactions and communication. Accordingly, we propose that appropriate therapies for autism spectrum disorders are to be carefully matched to the underlying synaptopathic phenotype