Daniel C Chung1, Mette Bertelsen2, Birgit Lorenz3, Mark E Pennesi4, Bart P Leroy5, Christian P Hamel6, Eric Pierce7, Juliana Sallum8, Michael Larsen2, Knut Stieger3, Markus Preising3, Richard Weleber4, Paul Yang4, Emily Place7, Emily Liu9, Grace Schaefer9, Julie DiStefano-Pappas8, Okan U Elci8, Sarah McCague10, Jennifer A Wellman9, Katherine A High9, Kathleen Z Reape9. 1. Research and Development, Spark Therapeutics, Inc, Philadelphia, Pennsylvania, USA. Electronic address: daniel.chung@sparktx.com. 2. Department of Ophthalmology, Rigshospitalet, Glostrup, Denmark. 3. Department of Ophthalmology, Justus-Liebig-University Giessen, Giessen, Germany. 4. Ophthalmic Genetics Division, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, USA. 5. Department of Ophthalmology, Ghent University Hospital and Ghent University, Ghent, Belgium; Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA; Division of Ophthalmology, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA. 6. Maladies Sensorielles Génétiques, Montpellier, France; Équipe Génétique et Thérapie des Cécités Rétiniennes et du Nerf Optique, INSERM U1051, Institute for Neurosciences of Montpellier, Montpellier, France. 7. Department of Ophthalmology, Massachusetts Eye and Ear Infirmary, Boston, Massachusetts, USA. 8. Department of Ophthalmology, Escola Paulista de Medicina (EPM), Universidade Federal de São Paulo (UNIFESP), São Paulo, Brazil; Biostatistics and Data Management Core, Westat, Philadelphia, Pennsylvania, USA. 9. Research and Development, Spark Therapeutics, Inc, Philadelphia, Pennsylvania, USA. 10. Center for Cellular and Molecular Therapeutics, Children's Hospital of Philadelphia, Philadelphia, Pennsylvania, USA.
Abstract
PURPOSE: To delineate the natural history of visual parameters over time in individuals with biallelic RPE65 mutation-associated inherited retinal dystrophy (IRD); describe the range of causative mutations; determine potential genotype/phenotype relationships; and describe the variety of clinical diagnoses. DESIGN: Global, multicenter, retrospective chart review. METHODS: Study Population: Seventy individuals with biallelic RPE65 mutation-associated IRD. PROCEDURES: Data were extracted from patient charts. MEASUREMENTS: Visual acuity (VA), Goldmann visual field (GVF), optical coherence tomography, color vision testing, light sensitivity testing, and electroretinograms (retinal imaging and fundus photography were collected and analyzed when available). RESULTS: VA decreased with age in a nonlinear, positive-acceleration relationship (P < .001). GVF decreased with age (P < .0001 for both V4e and III4e), with faster GVF decrease for III4e stimulus vs V4e (P = .0114, left eye; P = .0076, right eye). On average, a 1-year increase in age decreased III4e GVF by ∼25 sum total degrees in each eye while V4e GVF decreased by ∼37 sum total degrees in each eye, although individual variability was observed. A total of 78 clinical diagnoses and 56 unique RPE65 mutations were recorded, without discernible RPE65 mutation genotype/phenotype relationships. CONCLUSIONS: The number of clinical diagnoses and lack of a consistent RPE65 mutation-to-phenotype correlation underscore the need for genetic testing. Significant relationships between age and worsening VA and GVF highlight the progressive loss of functional retina over time. These data may have implications for optimal timing of treatment for IRD attributable to biallelic RPE65 mutations.
PURPOSE: To delineate the natural history of visual parameters over time in individuals with biallelic RPE65 mutation-associated inherited retinal dystrophy (IRD); describe the range of causative mutations; determine potential genotype/phenotype relationships; and describe the variety of clinical diagnoses. DESIGN: Global, multicenter, retrospective chart review. METHODS: Study Population: Seventy individuals with biallelic RPE65 mutation-associated IRD. PROCEDURES: Data were extracted from patient charts. MEASUREMENTS: Visual acuity (VA), Goldmann visual field (GVF), optical coherence tomography, color vision testing, light sensitivity testing, and electroretinograms (retinal imaging and fundus photography were collected and analyzed when available). RESULTS: VA decreased with age in a nonlinear, positive-acceleration relationship (P < .001). GVF decreased with age (P < .0001 for both V4e and III4e), with faster GVF decrease for III4e stimulus vs V4e (P = .0114, left eye; P = .0076, right eye). On average, a 1-year increase in age decreased III4e GVF by ∼25 sum total degrees in each eye while V4e GVF decreased by ∼37 sum total degrees in each eye, although individual variability was observed. A total of 78 clinical diagnoses and 56 unique RPE65 mutations were recorded, without discernible RPE65 mutation genotype/phenotype relationships. CONCLUSIONS: The number of clinical diagnoses and lack of a consistent RPE65 mutation-to-phenotype correlation underscore the need for genetic testing. Significant relationships between age and worsening VA and GVF highlight the progressive loss of functional retina over time. These data may have implications for optimal timing of treatment for IRD attributable to biallelic RPE65 mutations.
Authors: Callie Deng; Peter Y Zhao; Kari Branham; Dana Schlegel; Abigail T Fahim; Thiran K Jayasundera; Naheed Khan; Cagri G Besirli Journal: Graefes Arch Clin Exp Ophthalmol Date: 2022-01-10 Impact factor: 3.535
Authors: Daniel Viriato; Natalie Bennett; Raisa Sidhu; Elizabeth Hancock; Hannah Lomax; David Trueman; Robert E MacLaren Journal: Adv Ther Date: 2020-02-07 Impact factor: 3.845
Authors: Heather G Mack; Fred K Chen; John Grigg; Robyn Jamieson; John De Roach; Fleur O'Hare; Alexis Ceecee Britten-Jones; Myra McGuinness; Nicole Tindill; Lauren Ayton Journal: BMJ Open Date: 2021-06-22 Impact factor: 2.692