Jesse D Sengillo1, Winston Lee2, Takayuki Nagasaki2, Kaspar Schuerch2, Lawrence A Yannuzzi3, K Bailey Freund3, Janet R Sparrow4, Rando Allikmets4, Stephen H Tsang5. 1. Department of Ophthalmology, Columbia University, New York, New York, USA; State University of New York at Downstate Medical Center, Brooklyn, New York, USA. 2. Department of Ophthalmology, Columbia University, New York, New York, USA. 3. Vitreous Retina Macula Consultants of New York, New York, New York, USA. 4. Department of Ophthalmology, Columbia University, New York, New York, USA; Department of Pathology & Cell Biology, Stem Cell Initiative, Columbia University, New York, New York, USA. 5. Jonas Children's Vision Care, and Bernard & Shirlee Brown Glaucoma Laboratory, New York, New York, USA; Department of Ophthalmology, Columbia University, New York, New York, USA; Department of Pathology & Cell Biology, Stem Cell Initiative, Columbia University, New York, New York, USA; Institute of Human Nutrition, Vagelos College of Physicians and Surgeons, Columbia University, New York, New York, USA. Electronic address: sht2@cumc.columbia.edu.
Abstract
PURPOSE: Mutations in the eyes shut homolog (EYS) gene are a frequent cause of autosomal recessive retinitis pigmentosa (arRP). This study used multimodal retinal imaging to elucidate genotype-phenotype correlations in EYS-related RP (EYS-RP). DESIGN: Cross-sectional study. METHODS: Multimodal retinal imaging and electrophysiologic testing were assessed for 16 patients with genetic confirmation of EYS-RP. RESULTS: A total of 27 unique EYS variants were identified in 16 patients. Seven patients presented with an unusual crescent-shaped hyperautofluorescent (hyperAF) ring on fundus autofluorescence (FAF) imaging encompassing a large nasal-superior area of the posterior pole. Three patients had a typical circular or oval perifoveal hyperAF ring and 6 patients had no hyperAF ring. Spectral-domain (SD) and en face optical coherence tomography (OCT) showed preserved ellipsoid zone and retinal thickness spatially corresponding to areas within the hyperAF rings. Eleven patients presented with a rod-cone dystrophy on full-field electroretinogram (ffERG), 1 patient presented with cone-rod dystrophy, and 4 patients did not undergo ffERG testing. A significant spatial association was found between EYS variant position and FAF phenotype, with variants occurring at a nucleotide position greater than GRCh37 6:65300137 (c.5617C) being more associated with patients exhibiting hyperAF rings at presentation. CONCLUSIONS: EYS-RP is a heterogeneous manifestation. Variants occurring in positions closer to the C-terminus of EYS are more common in patients presenting with hyperAF rings on FAF imaging.
PURPOSE: Mutations in the eyes shut homolog (EYS) gene are a frequent cause of autosomal recessive retinitis pigmentosa (arRP). This study used multimodal retinal imaging to elucidate genotype-phenotype correlations in EYS-related RP (EYS-RP). DESIGN: Cross-sectional study. METHODS: Multimodal retinal imaging and electrophysiologic testing were assessed for 16 patients with genetic confirmation of EYS-RP. RESULTS: A total of 27 unique EYS variants were identified in 16 patients. Seven patients presented with an unusual crescent-shaped hyperautofluorescent (hyperAF) ring on fundus autofluorescence (FAF) imaging encompassing a large nasal-superior area of the posterior pole. Three patients had a typical circular or oval perifoveal hyperAF ring and 6 patients had no hyperAF ring. Spectral-domain (SD) and en face optical coherence tomography (OCT) showed preserved ellipsoid zone and retinal thickness spatially corresponding to areas within the hyperAF rings. Eleven patients presented with a rod-cone dystrophy on full-field electroretinogram (ffERG), 1 patient presented with cone-rod dystrophy, and 4 patients did not undergo ffERG testing. A significant spatial association was found between EYS variant position and FAF phenotype, with variants occurring at a nucleotide position greater than GRCh37 6:65300137 (c.5617C) being more associated with patients exhibiting hyperAF rings at presentation. CONCLUSIONS:EYS-RP is a heterogeneous manifestation. Variants occurring in positions closer to the C-terminus of EYS are more common in patients presenting with hyperAF rings on FAF imaging.
Authors: Ana B Garcia-Delgado; Lourdes Valdes-Sanchez; Maria Jose Morillo-Sanchez; Beatriz Ponte-Zuñiga; Francisco J Diaz-Corrales; Berta de la Cerda Journal: Orphanet J Rare Dis Date: 2021-05-17 Impact factor: 4.123