Samuel G Jacobson1, Artur V Cideciyan2, Alexander Sumaroka2, Alejandro J Roman2, Jason Charng2, Monica Lu2, Shreyasi Choudhury3, Sharon B Schwartz2, Elise Heon4, Gerald A Fishman5, Shannon E Boye3. 1. Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. Electronic address: jacobsos@mail.med.upenn.edu. 2. Scheie Eye Institute, Department of Ophthalmology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania. 3. Department of Ophthalmology, College of Medicine, University of Florida, Gainesville, Florida. 4. Department of Ophthalmology and Vision Sciences, Program of Genetics and Genomic Biology, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada. 5. Pangere Center for Hereditary Retinal Diseases, The Chicago Lighthouse, Chicago, Illinois.
Abstract
PURPOSE: To determine outcome measures for a clinical trial of Leber congenital amaurosis (LCA) associated with mutations in the GUCY2D gene. DESIGN: Retrospective observational case series. METHODS: Twenty-eight patients with GUCY2D-LCA (aged 2-59 years) were studied clinically and with chromatic full-field sensitivity testing (FST), optical coherence tomography (OCT), pupillometry, and the NEI Visual Function Questionnaire (VFQ). RESULTS: FST permitted quantitation of cone and rod sensitivity in these patients with severe visual impairment. For most patients, the degree of rod and cone sensitivity losses showed a relationship, thereby providing an opportunity to divide patients into cohorts by severity of rod and cone dysfunction. OCT analyses indicated that retinal structure could be used not only as an objective safety measure but also as an exploratory efficacy outcome. A foveal bulge was not present in 67% of patients. The intensity of inner segment/outer segment (ellipsoid zone line) reflectivity was reduced significantly at the fovea and in the rod-dense superior retina. Based on OCT and FST parameters, most patients had dissociation of structure and function. Abnormal pupillometry sensitivity in the majority of GUCY2D-LCA patients provided another objective efficacy outcome. NEI VFQ scores showed a similar range of findings to those of other severe retinal diseases. CONCLUSION: Conventional outcome measures, such as visual acuity and the NEI VFQ, will need to be complemented by methods more specific to this GUCY2D-LCA population. Any therapeutic strategy should determine if there is an effect on rod as well as cone function and structure. FST provides a photoreceptor-based subjective outcome; and OCT in 2 retinal regions, fovea and superior retina, can assess photoreceptor structure. A change in the relationship of structure and function away from baseline becomes evidence of efficacy.
PURPOSE: To determine outcome measures for a clinical trial of Leber congenital amaurosis (LCA) associated with mutations in the GUCY2D gene. DESIGN: Retrospective observational case series. METHODS: Twenty-eight patients with GUCY2D-LCA (aged 2-59 years) were studied clinically and with chromatic full-field sensitivity testing (FST), optical coherence tomography (OCT), pupillometry, and the NEI Visual Function Questionnaire (VFQ). RESULTS: FST permitted quantitation of cone and rod sensitivity in these patients with severe visual impairment. For most patients, the degree of rod and cone sensitivity losses showed a relationship, thereby providing an opportunity to divide patients into cohorts by severity of rod and cone dysfunction. OCT analyses indicated that retinal structure could be used not only as an objective safety measure but also as an exploratory efficacy outcome. A foveal bulge was not present in 67% of patients. The intensity of inner segment/outer segment (ellipsoid zone line) reflectivity was reduced significantly at the fovea and in the rod-dense superior retina. Based on OCT and FST parameters, most patients had dissociation of structure and function. Abnormal pupillometry sensitivity in the majority of GUCY2D-LCA patients provided another objective efficacy outcome. NEI VFQ scores showed a similar range of findings to those of other severe retinal diseases. CONCLUSION: Conventional outcome measures, such as visual acuity and the NEI VFQ, will need to be complemented by methods more specific to this GUCY2D-LCA population. Any therapeutic strategy should determine if there is an effect on rod as well as cone function and structure. FST provides a photoreceptor-based subjective outcome; and OCT in 2 retinal regions, fovea and superior retina, can assess photoreceptor structure. A change in the relationship of structure and function away from baseline becomes evidence of efficacy.
Authors: Arun K Krishnan; Samuel G Jacobson; Alejandro J Roman; Bhavya S Iyer; Alexandra V Garafalo; Elise Héon; Artur V Cideciyan Journal: Vision Res Date: 2020-02-20 Impact factor: 1.886
Authors: Jason Charng; Samuel G Jacobson; Elise Heon; Alejandro J Roman; David B McGuigan; Rebecca Sheplock; Mychajlo S Kosyk; Malgorzata Swider; Artur V Cideciyan Journal: Invest Ophthalmol Vis Sci Date: 2017-06-01 Impact factor: 4.799
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Authors: Samuel G Jacobson; Artur V Cideciyan; Alexander Sumaroka; Alejandro J Roman; Vivian Wu; Malgorzata Swider; Rebecca Sheplock; Arun K Krishnan; Alexandra V Garafalo Journal: Int J Mol Sci Date: 2021-02-18 Impact factor: 5.923
Authors: Samuel G Jacobson; Artur V Cideciyan; Allen C Ho; Igor V Peshenko; Alexandra V Garafalo; Alejandro J Roman; Alexander Sumaroka; Vivian Wu; Arun K Krishnan; Rebecca Sheplock; Sanford L Boye; Alexander M Dizhoor; Shannon E Boye Journal: iScience Date: 2021-04-11