Leber Congenital Amaurosis Due to <i>GUCY2D</i> Mutations: Longitudinal Analysis of Retinal Structure and Visual Function
Gene augmentation therapy is being planned for <i>GUCY2D</i>-associated Leber congenital amaurosis (LCA). To increase our understanding of the natural history of <i>GUCY2D</i>-LCA, patients were evaluated twice with an interval of 4 to 7 years between visits using safety and...
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/4/2031 |
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| author | Samuel G. Jacobson Artur V. Cideciyan Alexander Sumaroka Alejandro J. Roman Vivian Wu Malgorzata Swider Rebecca Sheplock Arun K. Krishnan Alexandra V. Garafalo |
| author_facet | Samuel G. Jacobson Artur V. Cideciyan Alexander Sumaroka Alejandro J. Roman Vivian Wu Malgorzata Swider Rebecca Sheplock Arun K. Krishnan Alexandra V. Garafalo |
| author_sort | Samuel G. Jacobson |
| collection | DOAJ |
| description | Gene augmentation therapy is being planned for <i>GUCY2D</i>-associated Leber congenital amaurosis (LCA). To increase our understanding of the natural history of <i>GUCY2D</i>-LCA, patients were evaluated twice with an interval of 4 to 7 years between visits using safety and efficacy outcome measures previously determined to be useful for monitoring this disorder. In this group of molecularly-identified LCA patients (<i>n</i> = 10; ages 7–37 years at first visit), optical coherence tomography (OCT) was used to measure foveal cone outer nuclear layer (ONL) thickness and rod ONL at a superior retinal locus. Full-field stimulus testing (FST) with chromatic stimuli in dark- and light-adapted states was used to assay rod and cone vision. Changes in OCT and FST over the interval were mostly attributable to inter-visit variability. There were no major negative changes in structure or function across the cohort and over the intervals studied. Variation in severity of disease expression between patients occurs; however, despite difficulties in quantifying structure and function in such seriously visually impaired individuals with nystagmus, the present work supports the use of OCT as a safety outcome and FST as an efficacy outcome in a clinical trial of <i>GUCY2D</i>-LCA. A wide age spectrum for therapy was confirmed, and there was relative stability of structure and function during a typical time interval for clinical trials. |
| first_indexed | 2024-03-09T00:45:36Z |
| format | Article |
| id | doaj.art-5a9ec8dc9a5c47698f92b619bedb2083 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T00:45:36Z |
| publishDate | 2021-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-5a9ec8dc9a5c47698f92b619bedb20832023-12-11T17:33:33ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224203110.3390/ijms22042031Leber Congenital Amaurosis Due to <i>GUCY2D</i> Mutations: Longitudinal Analysis of Retinal Structure and Visual FunctionSamuel G. Jacobson0Artur V. Cideciyan1Alexander Sumaroka2Alejandro J. Roman3Vivian Wu4Malgorzata Swider5Rebecca Sheplock6Arun K. Krishnan7Alexandra V. Garafalo8Department of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USADepartment of Ophthalmology, Scheie Eye Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USAGene augmentation therapy is being planned for <i>GUCY2D</i>-associated Leber congenital amaurosis (LCA). To increase our understanding of the natural history of <i>GUCY2D</i>-LCA, patients were evaluated twice with an interval of 4 to 7 years between visits using safety and efficacy outcome measures previously determined to be useful for monitoring this disorder. In this group of molecularly-identified LCA patients (<i>n</i> = 10; ages 7–37 years at first visit), optical coherence tomography (OCT) was used to measure foveal cone outer nuclear layer (ONL) thickness and rod ONL at a superior retinal locus. Full-field stimulus testing (FST) with chromatic stimuli in dark- and light-adapted states was used to assay rod and cone vision. Changes in OCT and FST over the interval were mostly attributable to inter-visit variability. There were no major negative changes in structure or function across the cohort and over the intervals studied. Variation in severity of disease expression between patients occurs; however, despite difficulties in quantifying structure and function in such seriously visually impaired individuals with nystagmus, the present work supports the use of OCT as a safety outcome and FST as an efficacy outcome in a clinical trial of <i>GUCY2D</i>-LCA. A wide age spectrum for therapy was confirmed, and there was relative stability of structure and function during a typical time interval for clinical trials.https://www.mdpi.com/1422-0067/22/4/2031coneclinical trialsrodoptical coherence tomographyoutcome measures |
| spellingShingle | Samuel G. Jacobson Artur V. Cideciyan Alexander Sumaroka Alejandro J. Roman Vivian Wu Malgorzata Swider Rebecca Sheplock Arun K. Krishnan Alexandra V. Garafalo Leber Congenital Amaurosis Due to <i>GUCY2D</i> Mutations: Longitudinal Analysis of Retinal Structure and Visual Function International Journal of Molecular Sciences cone clinical trials rod optical coherence tomography outcome measures |
| title | Leber Congenital Amaurosis Due to <i>GUCY2D</i> Mutations: Longitudinal Analysis of Retinal Structure and Visual Function |
| title_full | Leber Congenital Amaurosis Due to <i>GUCY2D</i> Mutations: Longitudinal Analysis of Retinal Structure and Visual Function |
| title_fullStr | Leber Congenital Amaurosis Due to <i>GUCY2D</i> Mutations: Longitudinal Analysis of Retinal Structure and Visual Function |
| title_full_unstemmed | Leber Congenital Amaurosis Due to <i>GUCY2D</i> Mutations: Longitudinal Analysis of Retinal Structure and Visual Function |
| title_short | Leber Congenital Amaurosis Due to <i>GUCY2D</i> Mutations: Longitudinal Analysis of Retinal Structure and Visual Function |
| title_sort | leber congenital amaurosis due to i gucy2d i mutations longitudinal analysis of retinal structure and visual function |
| topic | cone clinical trials rod optical coherence tomography outcome measures |
| url | https://www.mdpi.com/1422-0067/22/4/2031 |
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