Detailed clinical characterisation, unique features and natural history of autosomal recessive RDH12-associated retinal degeneration

BACKGROUND: Defects in retinol dehydrogenase 12 (RDH12) account for 3.4%-10.5 % of Leber congenital amaurosis and early-onset severe retinal dystrophy (EOSRD) and are a potential target for gene therapy. Clinical trials in inherited retinal diseases have unique challenges, and natural history studies are critical to successful trial design. The purpose of this study was to characterise the natural history of RDH12-associated retinal degeneration. METHODS: A retrospective chart review was performed in individuals with retinal degeneration and two likely disease-causing variants in RDH12. RESULTS: 57 subjects were enrolled from nine countries. 33 subjects had clinical records available from childhood. The data revealed an EOSRD, with average age of onset of 4.1 years. Macular atrophy was a universal clinical finding in all subjects, as young as 2 years of age. Scotopic and photopic electroretinography (ERG) responses were markedly reduced in all subjects, and a non-recordable ERG was documented as young as 1 year of age. Assessment of visual acuity, visual field and optical coherence tomography revealed severe loss of function and structure in the majority of subjects after the age of 10 years. Widefield imaging in 23 subjects revealed a unique, variegated watercolour-like pattern of atrophy in 13 subjects and sparing of the peripapillary area in 18 subjects. CONCLUSIONS: This study includes the largest collection of phenotypic data from children with RDH12-associated EOSRD and provides a comprehensive description of the timeline of vision loss in this severe, early-onset condition. These findings will help identify patients with RDH12-associated retinal degeneration and will inform future design of therapeutic trials

Advancing clinical trials for inherited retinal diseases: Recommendations from the second monaciano symposium

Major advances in the study of inherited retinal diseases (IRDs) have placed efforts to develop treatments for these blinding conditions at the forefront of the emerging field of precision medicine. As a result, the growth of clinical trials for IRDs has increased rapidly over the past decade and is expected to further accelerate as more therapeutic possibilities emerge and qualified participants are identified. Although guided by established principles, these specialized trials, requiring analysis of novel outcome measures and endpoints in small patient populations, present multiple challenges relative to study design and ethical considerations. This position paper reviews recent accomplishments and existing challenges in clinical trials for IRDs and presents a set of recommendations aimed at rapidly advancing future progress. The goal is to stimulate discussions among researchers, funding agencies, industry, and policy makers that will further the design, conduct, and analysis of clinical trials needed to accelerate the approval of effective treatments for IRDs, while promoting advocacy and ensuring patient safety

ORBIT OF COMET C/1853 E1 (SECCHI)

El Cometa C/1853 E1 (Secchi) es uno dentro de un numeroso grupo de cometas conórbitas parabólicas. Puesto que hay suficientes observaciones del cometa, 91 en ascensión recta y el mismo número en declinación, se puede mejorar laórbita. Laórbita del cometa Secchi es hiperbólica, la más hiperbólica de cualquier cometa salvo C/1980 E1 (Bowell). El cometa Secchi no está asociado de ninguna manera con el Cometa C/1664 W1. ABSTRACT Comet C/1853 E1 (Secchi) is one of a large number of comets with parabolic orbits. Given that there are sufficient observations of the comet, 91 in right ascension and the same number in declination, it proves possible to calculate a better orbit. Comet Secchi's orbit is hyperbolic, the most hyperbolic of any comet except C/1980 E1 (Bowell). Comet Secchi is in no way associated with Comet C/1664 W1

Clinical and imaging findings of choroideremia in a pediatric patient due to a novel frameshift mutation

Purpose: To describe the clinical characteristics, imaging findings and genetic testing results of a young simplex male with choroideremia. Observations: A 6-year-old Hispanic-Chinese male was referred to the retina clinic for peripheral retinal pigmentary changes observed in both eyes on routine exam. The patient has an unremarkable family history and developmental history. Best corrected visual acuity was 20/25 in both eyes. Optical coherence tomography demonstrated attenuation of the ellipsoid and interdigitation zones. Widefield fundus autofluorescence demonstrated nummular hypo-autofluorescence peripherally in both eyes. Genetic testing revealed a variant originally described as a variant of uncertain significance (VUS) a c. 1775_1814del (p.Glu592Valfs*44) identified in the CHM gene, which was reclassified as pathogenic following segregation analysis. The patient was diagnosed with choroideremia due to a CHM pathogenic variant. Conclusions: The multimodal imaging findings demonstrated here illustrate important clues to the diagnosis of Choroideremia in a simplex male

Mutations in the small nuclear riboprotein 200 kDa gene (SNRNP200) cause 1.6% of autosomal dominant retinitis pigmentosa

Purpose: The purpose of this project was to determine the spectrum and frequency of mutations in the small nuclear riboprotein 200 kDa gene (SNRNP200) that cause autosomal dominant retinitis pigmentosa (adRP). Methods: A well-characterized adRP cohort of