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Blue cone monochromacy (BCM) is an X-linked retinal disorder characterized by low vision, photoaversion, and poor color discrimination. BCM is due to the lack of long-wavelength-sensitive and middle-wavelength-sensitive cone photoreceptor function and caused by mutations in the OPN1LW/OPN1MW gene cluster on Xq28. Here, we investigated the prevalence and the landscape of submicroscopic structural variants (SVs) at single-base resolution in BCM patients. We found that about one-third (n = 73) of the 213 molecularly confirmed BCM families carry an SV, most commonly deletions restricted to the OPN1LW/OPN1MW gene cluster. The structure and precise breakpoints of the SVs were resolved in all but one of the 73 families. Twenty-two families-all from the United States-showed the same SV, and we confirmed a common ancestry of this mutation. In total, 42 distinct SVs were identified, including 40 previously unreported SVs, thereby quadrupling the number of precisely mapped SVs underlying BCM. Notably, there was no "region of overlap" among these SVs. However, 90% of SVs encompass the upstream locus control region, an essential enhancer element. Its minimal functional extent based on deletion mapping in patients was refined to 358 bp. Breakpoint analyses suggest diverse mechanisms underlying SV formation as well as in one case the gene conversion-based exchange of a 142-bp deletion between opsin genes. Using parsimonious assumptions, we reconstructed the composition and copy number of the OPN1LW/OPN1MW gene cluster prior to the mutation event and found evidence that large gene arrays may be predisposed to the occurrence of SVs at this locus.

Background Rare Eye Diseases (RED) are the leading cause of visual impairment and blindness for children and young adults in Europe. This heterogeneous group of conditions includes over 900 disorders ranging from relatively prevalent disorders such as retinitis pigmentosa to very rare entities such as developmental eye anomalies. A significant number of patients with RED have an underlying genetic etiology. One of the aims of the European Reference Network for Rare Eye Diseases (ERN–EYE) is to facilitate improvement in diagnosis of RED in European member states. Main body Technological advances have allowed genetic and genomic testing for RED. The outcome of genetic testing allows better understanding of the condition and allows reproductive and therapeutic options. The increase of the number of clinical trials for RED has provided urgency for genetic testing in RED. A survey of countries participating in ERN-EYE demonstrated that the majority are able to access some forms of genomic testing. However, there is significant variability, particularly regarding testing as part of clinical service. Some countries have a well-delineated rare disease pathway and have a national plan for rare diseases combined or not with a national plan for genomics in medicine. In other countries, there is a well-established organization of genetic centres that offer reimbursed genomic testing of RED and other rare diseases. Clinicians often rely upon research-funded laboratories or private companies. Notably, some member states rely on cross-border testing by way of an academic research project. Consequently, many clinicians are either unable to access testing or are confronted with long turnaround times. Overall, while the cost of sequencing has dropped, the cumulative cost of a genomic testing service for populations remains considerable. Importantly, the majority of countries reported healthcare budgets that limit testing. Short conclusion Despite technological advances, critical gaps in genomic testing remain in Europe, especially in smaller countries where no formal genomic testing pathways exist. Even within larger countries, the existing arrangements are insufficient to meet the demand and to ensure access. ERN-EYE promotes access to genetic testing in RED and emphasizes the clinical need and relevance of genetic testing in RED.

Our comprehensive cohort of 1100 unrelated achromatopsia (ACHM) patients comprises a considerable number of cases (~5%) harboring only a single pathogenic variant in the major ACHM gene CNGB3. We sequenced the entire CNGB3 locus in 33 of these patients to find a second variant which eventually explained the patients’ phenotype. Forty-seven intronic CNGB3 variants were identified in 28 subjects after a filtering step based on frequency and the exclusion of variants found in cis with pathogenic alleles. In a second step, in silico prediction tools were used to filter out those variants with little odds of being deleterious. This left three variants that were analyzed using heterologous splicing assays. Variant c.1663–1205G>A, found in 14 subjects, and variant c.1663-2137C>T, found in two subjects, were indeed shown to exert a splicing defect by causing pseudoexon insertion into the transcript. Subsequent screening of further unsolved CNGB3 subjects identified four additional cases harboring the c.1663–1205G>A variant which makes it the eighth most frequent CNGB3 variant in our cohort. Compound heterozygosity could be validated in ten cases. Our study demonstrates that whole gene sequencing can be a powerful approach to identify the second pathogenic allele in patients apparently harboring only one disease-causing variant. © 2019 Wiley Periodicals, Inc.

Objective: The purpose of this project was to evaluate the potential of electrically-induced pupil responses as an objective parameter for the function of retinal neurons. In particular, the pupillary reactions to diverse stimulation frequencies were analyzed to investigate the possibility of cell-specific[for full text, please go to the a.m. URL], Artificial Vision 2019

Background The optical accessibility of the eye and technological advances in ophthalmic diagnostics have put ophthalmology at the forefront of data-driven medicine. The focus of this study is rare eye disorders, a group of conditions whose clinical heterogeneity and geographic dispersion make data-driven, evidence-based practice particularly challenging. Inter-institutional collaboration and information sharing is crucial but the lack of standardised terminology poses an important barrier. Ontologies are computational tools that include sets of vocabulary terms arranged in hierarchical structures. They can be used to provide robust terminology standards and to enhance data interoperability. Here, we discuss the development of the ophthalmology-related component of two well-established biomedical ontologies, the Human Phenotype Ontology (HPO; includes signs, symptoms and investigation findings) and the Orphanet Rare Disease Ontology (ORDO; includes rare disease nomenclature/nosology). Methods A variety of approaches were used including automated matching to existing resources and extensive manual curation. To achieve the latter, a study group including clinicians, patient representatives and ontology developers from 17 countries was formed. A broad range of terms was discussed and validated during a dedicated workshop attended by 60 members of the group. Results A comprehensive, structured and well-defined set of terms has been agreed on including 1106 terms relating to ocular phenotypes (HPO) and 1202 terms relating to rare eye disease nomenclature (ORDO). These terms and their relevant annotations can be accessed in http://www.human-phenotype-ontology.org/ and http://www.orpha.net/; comments, corrections, suggestions and requests for new terms can be made through these websites. This is an ongoing, community-driven endeavour and both HPO and ORDO are regularly updated. Conclusions To our knowledge, this is the first effort of such scale to provide terminology standards for the rare eye disease community. We hope that this work will not only improve coding and standardise information exchange in clinical care and research, but also it will catalyse the transition to an evidence-based precision ophthalmology paradigm. Electronic supplementary material The online version of this article (10.1186/s13023-018-0980-6) contains supplementary material, which is available to authorized users.

Objective: A general assumption in the field is that a sufficiently strong stimulus will recruit most retinal neurons. However, recent evidence has shown that the responses of some retinal neurons decrease with excessively strong stimuli creating a non-monotonic response function. While the field is[for full text, please go to the a.m. URL], Artificial Vision 2017

Objective: Explantations and re-implantations of retinal implants can become indicated for many reasons, among them device failures and the patient’s wish for newer, improved implants. We have performed explantations and re-implantations in patients with retinitis pigmentosa who had received [for full text, please go to the a.m. URL], Artificial Vision 2017

Objective: Efficacy of the subretinal electronic implant RETINA IMPLANT Alpha AMS in patients with end stage hereditary retinal degeneration was assessed in two clinical trials ([link:https://www.clinicaltrials.gov/*https://www.clinicaltrials.gov/] NCT01024803[for full text, please go to the a.m. URL], Artificial Vision 2017

Hintergrund und Methoden: Retinale Implantate haben in den letzten 25 Jahren eine erstaunliche Entwicklung erlebt und können heute durch Ersatz der Photorezeptoren durch elektrische Impulse bei Blinden mit Retinitis pigmentosa wieder ein gewisses Sehvermögen wiederherstellen. Der subretinale[zum vollständigen Text gelangen Sie über die oben angegebene URL], 30. Jahrestagung der Retinologischen Gesellschaft

Das neue Retina Implantat Alpha AMS wurde bei 15 blinden RP Patienten implantiert und die Patienten ein Jahr nachverfolgt. 14/15 Patientenhatten hatten durch das Implantat assoziierte Licht Wahrnehmung und besser. Der beste Visus betrug mit Landolt Ringen bei zwei Patienten 20/546 und 20/1111.[zum vollständigen Text gelangen Sie über die oben angegebene URL], 67. Tagung der Vereinigung Norddeutscher Augenärzte (VNDA)

Objective: To restore visual functions by a photosensitive microchip with 1500 pixels (Alpha IMS from Retina Implant AG, Reutlingen, Germany, having received recently CE mark for commercial use in Europe). Material and Methods: Alpha IMS implants with wireless power and signal transmission were[for full text, please go to the a.m. URL], Artificial Vision 2013