Michelle Hendriks1, Virginie J M Verhoeven2, Gabriëlle H S Buitendijk3, Jan Roelof Polling4, Magda A Meester-Smoor3, Albert Hofman5, Maarten Kamermans6, L Ingeborgh van den Born1, Caroline C W Klaver7. 1. The Rotterdam Eye Hospital, Rotterdam, Netherlands. 2. Department of Ophthalmology, Erasmus Medical Center, Rotterdam, Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands; Department of Clinical Genetics, Erasmus Medical Center, Rotterdam, Netherlands. 3. Department of Ophthalmology, Erasmus Medical Center, Rotterdam, Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands. 4. Department of Ophthalmology, Erasmus Medical Center, Rotterdam, Netherlands. 5. Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands; Netherlands Consortium for Healthy Ageing, Netherlands Genomics Initiative, The Hague, Netherlands; Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts. 6. Netherlands Institute for Neuroscience, Amsterdam, Netherlands; Department of Neurogenetics, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. 7. Department of Ophthalmology, Erasmus Medical Center, Rotterdam, Netherlands; Department of Epidemiology, Erasmus Medical Center, Rotterdam, Netherlands; Department of Ophthalmology, Radboud University Medical Center, Nijmegen, Netherlands. Electronic address: c.c.w.klaver@erasmusmc.nl.
Abstract
PURPOSE: It is unknown which retinal cells are involved in the retina-to-sclera signaling cascade causing myopia. As inherited retinal dystrophies (IRD) are characterized by dysfunction of a single retinal cell type and have a high risk of refractive errors, a study investigating the affected cell type, causal gene, and refractive error in IRDs may provide insight herein. DESIGN: Case-control study. METHODS: Study Population: Total of 302 patients with IRD from 2 ophthalmogenetic centers in the Netherlands. Reference Population: Population-based Rotterdam Study-III and Erasmus Rucphen Family Study (N = 5550). Distributions and mean spherical equivalent (SE) were calculated for main affected cell type and causal gene; and risks of myopia and hyperopia were evaluated using logistic regression. RESULTS: Bipolar cell-related dystrophies were associated with the highest risk of SE high myopia 239.7; odds ratio (OR) mild hyperopia 263.2, both P < .0001; SE -6.86 diopters (D) (standard deviation [SD] 6.38), followed by cone-dominated dystrophies (OR high myopia 19.5, P < .0001; OR high hyperopia 10.7, P = .033; SE -3.10 D [SD 4.49]); rod dominated dystrophies (OR high myopia 10.1, P < .0001; OR high hyperopia 9.7, P = .001; SE -2.27 D [SD 4.65]), and retinal pigment epithelium (RPE)-related dystrophies (OR low myopia 2.7; P = .001; OR high hyperopia 5.8; P = .025; SE -0.10 D [SD 3.09]). Mutations in RPGR (SE -7.63 D [SD 3.31]) and CACNA1F (SE -5.33 D [SD 3.10]) coincided with the highest degree of myopia and in CABP4 (SE 4.81 D [SD 0.35]) with the highest degree of hyperopia. CONCLUSIONS: Refractive errors, in particular myopia, are common in IRD. The bipolar synapse and the inner and outer segments of the photoreceptor may serve as critical sites for myopia development.
PURPOSE: It is unknown which retinal cells are involved in the retina-to-sclera signaling cascade causing myopia. As inherited retinal dystrophies (IRD) are characterized by dysfunction of a single retinal cell type and have a high risk of refractive errors, a study investigating the affected cell type, causal gene, and refractive error in IRDs may provide insight herein. DESIGN: Case-control study. METHODS: Study Population: Total of 302 patients with IRD from 2 ophthalmogenetic centers in the Netherlands. Reference Population: Population-based Rotterdam Study-III and Erasmus Rucphen Family Study (N = 5550). Distributions and mean spherical equivalent (SE) were calculated for main affected cell type and causal gene; and risks of myopia and hyperopia were evaluated using logistic regression. RESULTS: Bipolar cell-related dystrophies were associated with the highest risk of SE high myopia 239.7; odds ratio (OR) mild hyperopia 263.2, both P < .0001; SE -6.86 diopters (D) (standard deviation [SD] 6.38), followed by cone-dominated dystrophies (OR high myopia 19.5, P < .0001; OR high hyperopia 10.7, P = .033; SE -3.10 D [SD 4.49]); rod dominated dystrophies (OR high myopia 10.1, P < .0001; OR high hyperopia 9.7, P = .001; SE -2.27 D [SD 4.65]), and retinal pigment epithelium (RPE)-related dystrophies (OR low myopia 2.7; P = .001; OR high hyperopia 5.8; P = .025; SE -0.10 D [SD 3.09]). Mutations in RPGR (SE -7.63 D [SD 3.31]) and CACNA1F (SE -5.33 D [SD 3.10]) coincided with the highest degree of myopia and in CABP4 (SE 4.81 D [SD 0.35]) with the highest degree of hyperopia. CONCLUSIONS: Refractive errors, in particular myopia, are common in IRD. The bipolar synapse and the inner and outer segments of the photoreceptor may serve as critical sites for myopia development.
Authors: Robert D Burgoyne; Nordine Helassa; Hannah V McCue; Lee P Haynes Journal: Cold Spring Harb Perspect Biol Date: 2019-05-01 Impact factor: 10.005
Authors: Virginia Miraldi Utz; Wanda Pfeifer; Susannah Q Longmuir; Richard John Olson; Kai Wang; Arlene V Drack Journal: JAMA Ophthalmol Date: 2018-04-01 Impact factor: 7.389
Authors: Milly S Tedja; Annechien E G Haarman; Magda A Meester-Smoor; Jaakko Kaprio; David A Mackey; Jeremy A Guggenheim; Christopher J Hammond; Virginie J M Verhoeven; Caroline C W Klaver Journal: Invest Ophthalmol Vis Sci Date: 2019-02-28 Impact factor: 4.799
Authors: Sanne K Verbakel; Zeinab Fadaie; B Jeroen Klevering; Maria M van Genderen; Ilse Feenstra; Frans P M Cremers; Carel B Hoyng; Susanne Roosing Journal: Mol Genet Genomic Med Date: 2019-04-04 Impact factor: 2.183
Authors: Sarah J Garnai; Michelle L Brinkmeier; Ben Emery; Tomas S Aleman; Louise C Pyle; Biliana Veleva-Rotse; Robert A Sisk; Frank W Rozsa; Ayse Bilge Ozel; Jun Z Li; Sayoko E Moroi; Steven M Archer; Cheng-Mao Lin; Sarah Sheskey; Laurel Wiinikka-Buesser; James Eadie; Jill E Urquhart; Graeme C M Black; Mohammad I Othman; Michael Boehnke; Scot A Sullivan; Gregory L Skuta; Hemant S Pawar; Alexander E Katz; Laryssa A Huryn; Robert B Hufnagel; Sally A Camper; Julia E Richards; Lev Prasov Journal: PLoS Genet Date: 2019-05-02 Impact factor: 5.917
Authors: Richard A Stone; Alice M McGlinn; Ranjay Chakraborty; Duk Cheon Lee; Victoria Yang; Ayman Elmasri; Erica Landis; James Shaffer; P Michael Iuvone; Xiangzhong Zheng; Amita Sehgal; Machelle T Pardue Journal: PLoS One Date: 2019-06-18 Impact factor: 3.240