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

Autor:	Fahim AT; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA ahteich@med.umich.edu., Bouzia Z; Moorfields Eye Hospital NHS Foundation Trust, London, UK.; Institute of Ophthalmology, University College London, London, UK., Branham KH; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA., Kumaran N; Moorfields Eye Hospital NHS Foundation Trust, London, UK.; Institute of Ophthalmology, University College London, London, UK., Vargas ME; Department of Ophthalmology, Oregon Health & Science University - Casey Eye Institute, Portland, Oregon, USA., Feathers KL; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA., Perera ND; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA., Young K; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA., Khan NW; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA., Heckenlively JR; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA., Webster AR; Moorfields Eye Hospital NHS Foundation Trust, London, UK.; Institute of Ophthalmology, University College London, London, UK., Pennesi ME; Department of Ophthalmology, Oregon Health & Science University - Casey Eye Institute, Portland, Oregon, USA., Ali RR; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA.; Institute of Ophthalmology, University College London, London, UK., Thompson DA; Department of Ophthalmology and Visual Sciences, University of Michigan, Ann Arbor, Michigan, USA.; Department of Biological Chemistry, University of Michigan, Ann Arbor, Michigan, USA., Michaelides M; Moorfields Eye Hospital NHS Foundation Trust, London, UK.; Institute of Ophthalmology, University College London, London, UK.
Jazyk:	angličtina
Zdroj:	The British journal of ophthalmology [Br J Ophthalmol] 2019 Dec; Vol. 103 (12), pp. 1789-1796. Date of Electronic Publication: 2019 Apr 12.
DOI:	10.1136/bjophthalmol-2018-313580
Abstrakt:	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. Competing Interests: Competing interests: ATF reports a grant from the Vitreoretinal Surgery Foundation and a K12 grant from the National Institute of Health, during the conduct of the study; other from Ionis Pharamceuticals, outside the submitted work. RRA reports a patent on RDH12 gene therapy. DAT reports a grant from the Foundation Fighting Blindness, during the conduct of the study; In addition, DAT has a patent for viral vectors comprising RDH12 coding regions and methods of treating retinal dystrophies pending. (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)
Databáze:	MEDLINE
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