Visual Acuity, Full-field Stimulus Thresholds, and Electroretinography for 4 Years in The Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) Study

Purpose: To describe progression of best-corrected visual acuity (BCVA), full-field stimulus thresholds (FST), and electroretinography (ERG) over 4 years in the USH2A-related Retinal Degeneration study and to assess their suitability as clinical trial endpoints. Design: Prospective natural history s...

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Main Authors: David G. Birch, PhD, Peiyao Cheng, PhD, Maureen G. Maguire, PhD, Jacque L. Duncan, MD, Allison R. Ayala, MS, Janet K. Cheetham, PharmD, Nicole R. Doucet, MPH, Todd A. Durham, PhD, Abigail T. Fahim, MD, PhD, Frederick L. Ferris, III, MD, Rachel M. Huckfeldt, MD, PhD, Michele Melia, ScM, Michel Michaelides, MD (Res), Mark E. Pennesi, MD, PhD, José-Alain Sahel, MD, Katarina Stingl, MD, Ajoy Vincent, MBBS, MS, Christina Y. Weng, MD, MBA
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Language:English
Published: Elsevier 2025-03-01
Series:Ophthalmology Science
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Online Access:http://www.sciencedirect.com/science/article/pii/S2666914524001842
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author David G. Birch, PhD
Peiyao Cheng, PhD
Maureen G. Maguire, PhD
Jacque L. Duncan, MD
Allison R. Ayala, MS
Janet K. Cheetham, PharmD
Nicole R. Doucet, MPH
Todd A. Durham, PhD
Abigail T. Fahim, MD, PhD
Frederick L. Ferris, III, MD
Rachel M. Huckfeldt, MD, PhD
Michele Melia, ScM
Michel Michaelides, MD (Res)
Mark E. Pennesi, MD, PhD
José-Alain Sahel, MD
Katarina Stingl, MD
Ajoy Vincent, MBBS, MS
Christina Y. Weng, MD, MBA
author_facet David G. Birch, PhD
Peiyao Cheng, PhD
Maureen G. Maguire, PhD
Jacque L. Duncan, MD
Allison R. Ayala, MS
Janet K. Cheetham, PharmD
Nicole R. Doucet, MPH
Todd A. Durham, PhD
Abigail T. Fahim, MD, PhD
Frederick L. Ferris, III, MD
Rachel M. Huckfeldt, MD, PhD
Michele Melia, ScM
Michel Michaelides, MD (Res)
Mark E. Pennesi, MD, PhD
José-Alain Sahel, MD
Katarina Stingl, MD
Ajoy Vincent, MBBS, MS
Christina Y. Weng, MD, MBA
author_sort David G. Birch, PhD
collection DOAJ
description Purpose: To describe progression of best-corrected visual acuity (BCVA), full-field stimulus thresholds (FST), and electroretinography (ERG) over 4 years in the USH2A-related Retinal Degeneration study and to assess their suitability as clinical trial endpoints. Design: Prospective natural history study. Participants: Participants (n = 105) with biallelic disease-causing sequence variants in USH2A and BCVA letter scores of ≥54 were included. Methods: BCVA, FST, fundus-guided microperimetry, static perimetry, and spectral domain OCT were performed annually and ERG at baseline and 4 years only. Mixed effects models were used to estimate annual rates of change with 95% confidence intervals. Associations of change from baseline to 4 years between BCVA, FST, ERG, and other metrics were assessed with Spearman correlation coefficients (rs). Main Outcome Measures: Best-corrected visual acuity, FST, and ERG. Results: The annual rate of decline in BCVA was 0.83 (95% confidence interval: 0.65−1.02) letters/year. For FST, the change was 0.09 (0.07−0.11) log cd.s/m2/year for white threshold, 0.10 (0.08−0.12) log cd.s/m2/year for blue threshold, and 0.05 (0.04−0.06) log cd.s/m2/year for red threshold. Changes were 22.6 (17.4−28.2)%/year for white threshold, 26.0 (20.3−32.1)%/year for blue threshold, and 12.3 (8.7−16.0)%/year for red threshold. The high percentage of eyes with undetectable ERGs at baseline limited assessment of change. Conclusions: Best-corrected visual acuity was not a sensitive measure of progression over 4 years. Full-field stimulus threshold was a more sensitive measure; however, additional information on the clinical relevance of changes in FST is needed before this test can be adopted as an endpoint for clinical trials. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.
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spelling doaj-art-b8ef91ea53a546e6ad462a40a65092cd2025-08-20T01:57:11ZengElsevierOphthalmology Science2666-91452025-03-015210064810.1016/j.xops.2024.100648Visual Acuity, Full-field Stimulus Thresholds, and Electroretinography for 4 Years in The Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) StudyDavid G. Birch, PhD0Peiyao Cheng, PhD1Maureen G. Maguire, PhD2Jacque L. Duncan, MD3Allison R. Ayala, MS4Janet K. Cheetham, PharmD5Nicole R. Doucet, MPH6Todd A. Durham, PhD7Abigail T. Fahim, MD, PhD8Frederick L. Ferris, III, MD9Rachel M. Huckfeldt, MD, PhD10Michele Melia, ScM11Michel Michaelides, MD (Res)12Mark E. Pennesi, MD, PhD13José-Alain Sahel, MD14Katarina Stingl, MD15Ajoy Vincent, MBBS, MS16Christina Y. Weng, MD, MBA17Retina Foundation of the Southwest, Dallas, TexasJaeb Center for Health Research, Tampa, FloridaJaeb Center for Health Research, Tampa, FloridaUniversity of California, San Francisco, San Francisco, CaliforniaJaeb Center for Health Research, Tampa, Florida; Correspondence: Allison R. Ayala, MS, Jaeb Center for Health Research, 15310 Amberly Drive, Tampa, FL 33647.Foundation Fighting Blindness, Columbia, MarylandJaeb Center for Health Research, Tampa, FloridaFoundation Fighting Blindness, Columbia, MarylandUniversity of Michigan, Kellogg Eye Center, Ann Arbor, MichiganOphthalmic Research Consultants, Waxhaw, North CarolinaMassachusetts Eye and Ear, Boston, MassachusettsJaeb Center for Health Research, Tampa, FloridaMoorfields Eye Hospital and UCL Institute of Ophthalmology, London, United KingdomCasey Eye Institute - Oregon Health & Science University, Portland, OregonInstitut de la Vision, Sorbonne Université, INSERM, CNRS, Paris, France; Centre Hospitalier National d'Ophtalmologie des Quinze-Vingts, Centre de Référence Maladies Rares REFERET and INSERM-DGOS CIC 1423, Paris, France; Department of Ophthalmology, The University of Pittsburgh School of Medicine, Pittsburgh, PennsylvaniaUniversity Eye Hospital, Center for Ophthalmology, University of Tübingen, Tübingen, Germany; Center for Rare Eye Diseases, University of Tübingen, Tübingen, GermanyDepartments of Ophthalmology and Vision Sciences, The Hospital for Sick Children, The University of Toronto, Toronto, Ontario, CanadaBaylor College of Medicine, Houston, TexasPurpose: To describe progression of best-corrected visual acuity (BCVA), full-field stimulus thresholds (FST), and electroretinography (ERG) over 4 years in the USH2A-related Retinal Degeneration study and to assess their suitability as clinical trial endpoints. Design: Prospective natural history study. Participants: Participants (n = 105) with biallelic disease-causing sequence variants in USH2A and BCVA letter scores of ≥54 were included. Methods: BCVA, FST, fundus-guided microperimetry, static perimetry, and spectral domain OCT were performed annually and ERG at baseline and 4 years only. Mixed effects models were used to estimate annual rates of change with 95% confidence intervals. Associations of change from baseline to 4 years between BCVA, FST, ERG, and other metrics were assessed with Spearman correlation coefficients (rs). Main Outcome Measures: Best-corrected visual acuity, FST, and ERG. Results: The annual rate of decline in BCVA was 0.83 (95% confidence interval: 0.65−1.02) letters/year. For FST, the change was 0.09 (0.07−0.11) log cd.s/m2/year for white threshold, 0.10 (0.08−0.12) log cd.s/m2/year for blue threshold, and 0.05 (0.04−0.06) log cd.s/m2/year for red threshold. Changes were 22.6 (17.4−28.2)%/year for white threshold, 26.0 (20.3−32.1)%/year for blue threshold, and 12.3 (8.7−16.0)%/year for red threshold. The high percentage of eyes with undetectable ERGs at baseline limited assessment of change. Conclusions: Best-corrected visual acuity was not a sensitive measure of progression over 4 years. Full-field stimulus threshold was a more sensitive measure; however, additional information on the clinical relevance of changes in FST is needed before this test can be adopted as an endpoint for clinical trials. Financial Disclosure(s): Proprietary or commercial disclosure may be found in the Footnotes and Disclosures at the end of this article.http://www.sciencedirect.com/science/article/pii/S2666914524001842Electroretinography (ERG)Full-field stimulus thresholds (FST)Best-corrected visual acuity (BCVA)Retinal degenerationUSH2A
spellingShingle David G. Birch, PhD
Peiyao Cheng, PhD
Maureen G. Maguire, PhD
Jacque L. Duncan, MD
Allison R. Ayala, MS
Janet K. Cheetham, PharmD
Nicole R. Doucet, MPH
Todd A. Durham, PhD
Abigail T. Fahim, MD, PhD
Frederick L. Ferris, III, MD
Rachel M. Huckfeldt, MD, PhD
Michele Melia, ScM
Michel Michaelides, MD (Res)
Mark E. Pennesi, MD, PhD
José-Alain Sahel, MD
Katarina Stingl, MD
Ajoy Vincent, MBBS, MS
Christina Y. Weng, MD, MBA
Visual Acuity, Full-field Stimulus Thresholds, and Electroretinography for 4 Years in The Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) Study
Ophthalmology Science
Electroretinography (ERG)
Full-field stimulus thresholds (FST)
Best-corrected visual acuity (BCVA)
Retinal degeneration
USH2A
title Visual Acuity, Full-field Stimulus Thresholds, and Electroretinography for 4 Years in The Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) Study
title_full Visual Acuity, Full-field Stimulus Thresholds, and Electroretinography for 4 Years in The Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) Study
title_fullStr Visual Acuity, Full-field Stimulus Thresholds, and Electroretinography for 4 Years in The Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) Study
title_full_unstemmed Visual Acuity, Full-field Stimulus Thresholds, and Electroretinography for 4 Years in The Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) Study
title_short Visual Acuity, Full-field Stimulus Thresholds, and Electroretinography for 4 Years in The Rate of Progression of USH2A-related Retinal Degeneration (RUSH2A) Study
title_sort visual acuity full field stimulus thresholds and electroretinography for 4 years in the rate of progression of ush2a related retinal degeneration rush2a study
topic Electroretinography (ERG)
Full-field stimulus thresholds (FST)
Best-corrected visual acuity (BCVA)
Retinal degeneration
USH2A
url http://www.sciencedirect.com/science/article/pii/S2666914524001842
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