No abstract

Mutations in the EYS gene are one of the major causes of autosomal recessive retinitis pigmentosa. EYS-retinopathy presents a severe clinical phenotype, and patients currently have no therapeutic options. The progress in personalised medicine and gene and cell therapies hold promise for treating this degenerative disease. However, lack of understanding and incomplete comprehension of disease's mechanism and the role of EYS in the healthy retina are critical limitations for the translation of current technical advances into real therapeutic possibilities. This review recapitulates the present knowledge about EYS-retinopathies, their clinical presentations and proposed genotype–phenotype correlations. Molecular details of the gene and the protein, mainly based on animal model data, are analysed. The proposed cellular localisation and roles of this large multi-domain protein are detailed. Future therapeutic approaches for EYS-retinopathies are discussed.

Purpose: The aim of this study was to investigate the repercussions of peripapillary detachment on retinal nerve fiber layer (RNFL) measurements in patients with highly myopic eyes. Methods: A total of 244 highly myopic eyes underwent a complete ophthalmologic examination that included optical coherence tomography (OCT) to analyze the peripapillary retina and RNFL thickness. Based on the OCT findings, patients were grouped as follows: group A: eyes with a peripapillary intrachoroidal cavitation (PIC); group B: eyes with a peripapillary neurosensory retinal detachment (PNRD), and group C: eyes without a peripapillary detachment. Results: The OCT scans identified a peripapillary detachment in 42 eyes (17.21%). Out of these 42 eyes, 22 showed PIC (52.38%; group A) and 20 had a PNRD (47.62%; group B). The average overall RNFL thickness in groups A, B and C was 74.11 ± 10.88, 88.26 ± 25.72 and 72.75 ± 16.24 μm, respectively (ANOVA test, p = 0.00). Conclusion: Eyes with a PNRD had a significantly greater average RFNL thickness than those without peripapillary detachment in pathologic myopia due to a misidentification of the outer profile of the RFNL. This fact makes the interpretation of RNFL thickness in highly myopic eyes more challenging.

To enhance the use of Whole Genome Sequencing (WGS) in clinical practice, it is still necessary to standardize data analysis pipelines. Herein, we aimed to define a WGS-based algorithm for the accurate interpretation of variants in inherited retinal dystrophies (IRD). This study comprised 429 phenotyped individuals divided into three cohorts. A comparison of 14 pathogenicity predictors, and the re-definition of its cutoffs, were performed using panel-sequencing curated data from 209 genetically diagnosed individuals with IRD (training cohort). The optimal tool combinations, previously validated in 50 additional IRD individuals, were also tested in patients with hereditary cancer (n = 109), and with neurological diseases (n = 47) to evaluate the translational value of this approach (validation cohort). Then, our workflow was applied for the WGS-data analysis of 14 individuals from genetically undiagnosed IRD families (discovery cohort). The statistical analysis showed that the optimal filtering combination included CADDv1.6, MAPP, Grantham, and SIFT tools. Our pipeline allowed the identification of one homozygous variant in the candidate gene CFAP20 (c.337 C > T; p.Arg113Trp), a conserved ciliary gene, which was abundantly expressed in human retina and was located in the photoreceptors layer. Although further studies are needed, we propose CFAP20 as a candidate gene for autosomal recessive retinitis pigmentosa. Moreover, we offer a translational strategy for accurate WGS-data prioritization, which is essential for the advancement of personalized medicine.

Serous retinal detachment is a complication associated with vertical oval-shaped domes that seems to remain stable in terms of visual function over time without treatment.