Loss of function of RIMS2 causes a syndromic congenital cone-rod synaptic disease with neurodevelopmental and pancreatic involvement

Congenital cone-rod synaptic disorder (CRSD), also known as incomplete congenital stationary night blindness (iCSNB), is a non-progressive inherited retinal disease (IRD) characterized by night blindness, photophobia, and nystagmus, and distinctive electroretinographic features. Here, we report bi-allelic RIMS2 variants in seven CRSD-affected individuals from four unrelated families. Apart from CRSD, neurodevelopmental disease was observed in all affected individuals, and abnormal glucose homeostasis was observed in the eldest affected individual. RIMS2 regulates synaptic membrane exocytosis. Data mining of human adult bulk and single-cell retinal transcriptional datasets revealed predominant expression in rod photoreceptors, and immunostaining demonstrated RIMS2 localization in the human retinal outer plexiform layer, Purkinje cells, and pancreatic islets. Additionally, nonsense variants were shown to result in truncated RIMS2 and decreased insulin secretion in mammalian cells. The identification of a syndromic stationary congenital IRD has a major impact on the differential diagnosis of syndromic congenital IRD, which has previously been exclusively linked with degenerative IRD

De l'idée à la réalisation d'un projet de recherche clinique (la réalité pour le porteur de projet)

TOURS-BU Médecine (372612103) / SudocSudocFranceF

Deep Learning to Distinguish ABCA4-Related Stargardt Disease from PRPH2-Related Pseudo-Stargardt Pattern Dystrophy

(1) Background: Recessive Stargardt disease (STGD1) and multifocal pattern dystrophy simulating Stargardt disease (“pseudo-Stargardt pattern dystrophy”, PSPD) share phenotypic similitudes, leading to a difficult clinical diagnosis. Our aim was to assess whether a deep learning classifier pretrained on fundus autofluorescence (FAF) images can assist in distinguishing ABCA4-related STGD1 from the PRPH2/RDS-related PSPD and to compare the performance with that of retinal specialists. (2) Methods: We trained a convolutional neural network (CNN) using 729 FAF images from normal patients or patients with inherited retinal diseases (IRDs). Transfer learning was then used to update the weights of a ResNet50V2 used to classify the 370 FAF images into STGD1 and PSPD. Retina specialists evaluated the same dataset. The performance of the CNN and that of retina specialists were compared in terms of accuracy, sensitivity, and precision. (3) Results: The CNN accuracy on the test dataset of 111 images was 0.882. The AUROC was 0.890, the precision was 0.883 and the sensitivity was 0.883. The accuracy for retina experts averaged 0.816, whereas for retina fellows it averaged 0.724. (4) Conclusions: This proof-of-concept study demonstrates that, even with small databases, a pretrained CNN is able to distinguish between STGD1 and PSPD with good accuracy

Sleep and mood changes in advanced age after blue-blocking (yellow) intra ocular lens (IOLs) implantation during cataract surgical treatment: a randomized controlled trial

article en open accessInternational audienceOBJECTIVES: Both advanced age and depression are characterized by changes in sleep patterns. Light exposure is one of the main synchronizers of circadian cycles and influences sleep by inhibiting melatonin secretion, which is mostly sensitive to light of low wavelengths (blue). Blue-blocking (yellow) intraocular lenses (IOLs) have supplanted the usual UV-blocking (clear) IOLs during cataract surgery to prevent age-related macular degeneration, however, the impact of yellow IOLs on sleep and mood is unclear. The purpose of this study was to compare the effects of yellow and clear IOLs on sleep and mood in aged patients undergoing bilateral cataract surgery. METHODS: A randomized controlled superiority study was conducted within three ophthalmic surgical wards in France. A total of 204 subjects (mean age 76.2 +/- 7.5 years) were randomized into yellow or clear IOLs groups. Patients completed a sleep diary, the pictorial sleepiness scale and the Beck Depression Inventory (BDI) one week before and eight weeks after the last surgical procedure. RESULTS: According to an Intent To Treat (ITT) analysis, no significant difference was found between yellow and clear IOLs groups regarding sleep time, sleep latency, total sleep duration, quality of sleep and BDI scores. The rate of patients whose BDI score increased at the cutoff score of >/=5 after surgery was significantly higher in the yellow IOL group (n = 11, 13.1%) compared with the clear IOL group (n = 4; 4.7%); p = 0.02. CONCLUSIONS: Using yellow IOLs for cataract surgery doesn't significantly impact sleep but may induce mood changes in aging