TY - JOUR
T1 - Progression of Stargardt Disease as Determined by Fundus Autofluorescence over a 12-Month Period
T2 - ProgStar Report No. 11
AU - Strauss, Rupert W.
AU - Kong, Xiangrong
AU - Ho, Alexander
AU - Jha, Anamika
AU - West, Sheila
AU - Ip, Michael
AU - Bernstein, Paul S.
AU - Birch, David G.
AU - Cideciyan, Artur V.
AU - Michaelides, Michel
AU - Sahel, José Alain
AU - Sunness, Janet S.
AU - Traboulsi, Elias I.
AU - Zrenner, Eberhart
AU - Pitetta, Sean
AU - Jenkins, Dennis
AU - Hariri, Amir Hossein
AU - Sadda, Srini Vas
AU - Scholl, Hendrik
N1 - Funding Information:
reports grants from the Foundation Fighting Blindness during the conduct of the study and personal fees from Spark, Acucela, Makindus, and Science Based Health, outside the submitted work.
Funding Information:
Dr Birch reports serving as a consultant for and receiving grants from Applied Genetic Technologies Corporation, Ionis, Genentech, Nightstar, 4D Molecular Therapeutics, and the Foundation Fighting Blindness; receiving personal fees from Nacuity and Editas Medicine; and receiving grants from Allergan, Second Sight Medical Products, the National Institutes of Health (grant ET09076), and the Foundation Fighting Blindness. Dr Sadda reports personal fees from Heidelberg Engineering, Centervue, Novartis, Genentech/Roche, Allergan, and Amgen; grants and personal fees from Optos; grants from Carl Zeiss Meditec; and nonfinancial support from Nidek and Topcon Medical Systems during the conduct of the study. Dr West reports membership in scientific technical advisory committee for Alcon Research Institute and Research to Prevent Blindness Inc. Dr Scholl is a paid consultant of Boehringer Ingelheim Pharma GmbH & Co, Gerson Lehrman Group, and Guidepoint; a member of the scientific advisory board of the Astellas Institute for Regenerative Medicine, ReNeuron Group plc/Ora Inc, and Vision Medicines Inc; and a member of the data monitoring and safety board/committee of Genentech Inc, Hoffmann–La Roche Ltd, and ReNeuron Group plc/Ora Inc. Dr Hendrik Scholl is a principal investigator of grants at the Universitätsspital Basel, which is sponsored by Acucela Inc, NightstaRx Ltd, and Ophthotech Corporation. Dr Strauss reports receiving stipends from the Austrian Science Fund (project number J 3383-B23) and the Foundation Fighting Blindness Clinical Research Institute. Dr Cideciyan reports receiving grants from the National Institutes of Health (grant EY013203). Dr Michaelides reports receiving career development award via the Foundation Fighting Blindness Career Development Award, the Macular Society, Retinitis Pigmentosa Fighting Blindness, Fight for Sight, and the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital National Health Services Foundation Trust and UCL Institute of Ophthalmology. Michael Ip reports serving as a consultant of Allergan, Thrombogenics, Omeros, Genentech, Quark, Alimera, and Boehringer Ingelheim. Dr Sahel reports grants from LabEx Lifesenses (grant ANR-10-LABX-65) and the Foundation Fighting Blindness during the conduct of the study; grants from ERC Synergy “Helmholtz” and Banque Publique d'Investissement outside the submitted work; and fees associated with work as a consultant for Pixium Vision, GenSight Biologics, and Genesignal, outside the submitted work; with additional personal financial interests in GenSight Biologics, Chronocam, Chronolife, Pixium Vision, Tilak Healthcare, and Sparing Vision. Dr Sunness reports personal fees from Acucela and Cell Cure, outside the submitted work. Dr Traboulsi reports serving on the data and safety monitoring committee for a study on gene therapy in Stargardt disease outside the submitted work. No other disclosures were reported.
Funding Information:
supported by the Foundation Fighting Blindness Clinical Research Institute and a grant to the Foundation Fighting Blindness Clinical Research Institute by the US Department of Defense US Army Medical Research & Materiel Command Telemedicine and Advanced Technology Research Center Research (grants W81-XWH-07-1-0720 and
Funding Information:
W81XWH-09-2-0189); Dr Scholl is supported by the Foundation Fighting Blindness Clinical Research Institute. Shulsky Foundation, National Centre of Competence in Research Molecular Systems Engineering (University of Basel and Eidgenössische Technische Hochschule Zürich), and Swiss National Science Foundation. Dr Strauss is supported by the Austrian Science Fund (project number J 3383-B23) and the Foundation Fighting Blindness Clinical Research Institute.
Funding Information:
Group Information: The ProgStar study is supported by a contract from the Foundation Fighting Blindness. The ProgStar studies consist of the Chair’s Office, 9 clinics, 2 resource centers, and 2 affiliated centers with the following members: Chair’s Office: Hendrik P. N. Scholl, MD; Rupert W. Strauss, MD; Yulia Wolfson, MD; Millena Bittencourt, MD; Syed Mahmood Shah, MD; Mohamed Ahmed, MD; Etienne Schönbach, MD; Kaoru Fujinami, MD, PhD; Cole Eye Institute, Cleveland, Ohio: Elias Traboulsi, MD; Justis Ehlers, MD; Meghan Marino, MS; Susan Crowe, BS; Rachael Briggs, COA; Angela Borer, BS; Anne Pinter, CRA; Tami Fecko; Nikki Burgnoni, MS; Greater Baltimore Medical Center, Towson, Maryland: Janet S. Sunness, MD; Carol Applegate, MLA, COT; Leslie Russell, MAc; Moorfields Eye Hospital, London, United Kingdom: Michel Michaelides, MD; Simona Degli Esposti, MD; Anthony Moore; Andrew Webster, MD; Sophie Connor, BSc; Jade Barnfield, BA; Zaid Salchi, MD; Clara Alfageme, MD; Victoria McCudden; Maria Pefkianaki, MD; Jonathan Aboshiha, MA, MB; Gerald Liew; Graham Holder, PhD; Anthony Robson, PhD; Alexa King, BA; Daniela Ivanova Cajas Narvaez, MSc; Katy Barnard, BS; Catherine Grigg, BSc; Hannah Dunbar, PhD; Yetunde Obadeyi; Karine Girard-Claudon, MST; Hilary Swann, BSc; Avani Rughani, BSc; Charles Amoah, NVQ; Dominic Carrington; Kanom Bibi, BSc; Emerson Ting Co, DMD; Mohamed Nafaz Illiyas; Hamida Begum, BSc; Andrew Carter, BSc; Anne Georgiou, PhD; Selma Lewism BSc; Saddaf Shaheen, PGDip, BSc; Harpreet Shinmar, MSc; Linda Burton, BSc; Moran Eye Center, Salt Lake City, Utah: Paul Bernstein, MD, PhD; Kimberley Wegner, BS; Briana Lauren Sawyer, MS; Bonnie Carlstrom, COA; Kellian Farnsworth, COA; Cyrie Fry, AS, CRA, OCT-C; Melissa Chandler, BS, CRC, OCT-a; Glen Jenkins, BS, COA, CRC, OCT-a; Donnel Creel, PhD. Retina Foundation of the Southwest, Dallas: David Birch, PhD; Yi-Zhong Wang, PhD; Luis Rodriguez, BS; Kirsten Locke, BS; Martin Klein, MS; Paulina Mejia, BS; Scheie Eye Institute, Philadelphia, Pennsylvania: Artur V. Cideciyan, PhD; Samuel G. Jacobson, MD, PhD; Sharon B. Schwartz, MS, CGC; Rodrigo Matsui, MD; Michaela Gruzensky, MD; Jason Charng, OD, PhD; Alejandro J. Roman, MS; University of Tübingen, Tübingen, Germany: Eberhart Zrenner, PhD; Fadi Nasser, MD; Gesa Astrid Hahn, MD; Barbara Wilhelm, MD; Tobias Peters, MD; Benjamin Beier, BSc; Tilman Koenig; Susanne Kramer, DiplBiol; The Vision Institute, Paris, France: José-Alain Sahel, MD; Saddek Mohand-Said, MD, PhD; Isabelle Audo, MD, PhD; Caroline Laurent-Coriat, MD; Ieva Sliesoraityte, MD,
Funding Information:
Required language to appear in the appropriate location of all publications using ProgStar (retrospective and prospective study) resources The ProgStar study is supported by a contract from the Foundation Fighting Blindness. The ProgStar studies consist of the ChaLU¶V 2IILFH QLQH FOLQLFV WZR UHVRXUFH FHQWHUV DQG WZR DIILOLDWHG FHQWHUV ZLWK WKH IROORZLQJ PHPEHUV
Publisher Copyright:
© 2019 American Medical Association. All rights reserved.
PY - 2019/10
Y1 - 2019/10
N2 - Importance: Sensitive outcome measures for disease progression are needed for treatment trials of Stargardt disease. Objective: To estimate the progression rate of atrophic lesions in the prospective Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) study over a 12-month period. Design, Setting, and Participants: This multicenter prospective cohort study was conducted in an international selection of tertiary referral centers from October 21, 2013, to February 15, 2017. Patients who were affected by Stargardt disease, aged 6 years and older at baseline, and harboring disease-causing variants of the ABCA4 gene were enrolled at 9 centers in the United States, United Kingdom, and continental Europe. Data analysis occurred from November 2016 to January 2017. Exposures: Autofluorescence images obtained with a standard protocol were sent to a central reading center, and areas of definitely decreased autofluorescence, questionably decreased autofluorescence, and the total combined area of decreased autofluorescence were outlined and quantified. Progression rates were estimated from linear mixed models with time as the independent variable. Main Outcomes and Measures: Yearly rate of progression, using the growth of atrophic lesions measured by autofluorescence imaging. Results: A total of 259 study participants (488 eyes; 230 individuals [88.8%] were examined in both eyes) were enrolled (mean [SD] age at first visit, 33.3 [15.1] years; 118 [54.4%] female). Gradable images were available for evaluation for 480 eyes at baseline and 454 eyes after 12 months. At baseline, definitely decreased autofluorescence was present in 306 eyes, and the mean (SD) lesion size was 3.93 (4.37) mm2. The mean total area of decreased autofluorescence at baseline was 4.07 (4.04) mm2. The estimated progression of definitely decreased autofluorescence was 0.76 (95% CI, 0.54-0.97) mm2 per year (P <.001), and the total area of both questionably and definitely decreased autofluorescence was 0.64 (95% CI, 0.50-0.78) mm2per year (P <.001). Both progression rates depended on initial lesion size. Conclusions and Relevance: In Stargardt disease, autofluorescence imaging may serve as a monitoring tool and definitely decreased autofluorescence and total area as outcome measures for interventional clinical trials that aim to slow disease progression. Rates of progression depended mainly on initial lesion size.
AB - Importance: Sensitive outcome measures for disease progression are needed for treatment trials of Stargardt disease. Objective: To estimate the progression rate of atrophic lesions in the prospective Natural History of the Progression of Atrophy Secondary to Stargardt Disease (ProgStar) study over a 12-month period. Design, Setting, and Participants: This multicenter prospective cohort study was conducted in an international selection of tertiary referral centers from October 21, 2013, to February 15, 2017. Patients who were affected by Stargardt disease, aged 6 years and older at baseline, and harboring disease-causing variants of the ABCA4 gene were enrolled at 9 centers in the United States, United Kingdom, and continental Europe. Data analysis occurred from November 2016 to January 2017. Exposures: Autofluorescence images obtained with a standard protocol were sent to a central reading center, and areas of definitely decreased autofluorescence, questionably decreased autofluorescence, and the total combined area of decreased autofluorescence were outlined and quantified. Progression rates were estimated from linear mixed models with time as the independent variable. Main Outcomes and Measures: Yearly rate of progression, using the growth of atrophic lesions measured by autofluorescence imaging. Results: A total of 259 study participants (488 eyes; 230 individuals [88.8%] were examined in both eyes) were enrolled (mean [SD] age at first visit, 33.3 [15.1] years; 118 [54.4%] female). Gradable images were available for evaluation for 480 eyes at baseline and 454 eyes after 12 months. At baseline, definitely decreased autofluorescence was present in 306 eyes, and the mean (SD) lesion size was 3.93 (4.37) mm2. The mean total area of decreased autofluorescence at baseline was 4.07 (4.04) mm2. The estimated progression of definitely decreased autofluorescence was 0.76 (95% CI, 0.54-0.97) mm2 per year (P <.001), and the total area of both questionably and definitely decreased autofluorescence was 0.64 (95% CI, 0.50-0.78) mm2per year (P <.001). Both progression rates depended on initial lesion size. Conclusions and Relevance: In Stargardt disease, autofluorescence imaging may serve as a monitoring tool and definitely decreased autofluorescence and total area as outcome measures for interventional clinical trials that aim to slow disease progression. Rates of progression depended mainly on initial lesion size.
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U2 - 10.1001/jamaophthalmol.2019.2885
DO - 10.1001/jamaophthalmol.2019.2885
M3 - Article
C2 - 31369039
AN - SCOPUS:85070190368
VL - 137
SP - 1134
EP - 1145
JO - JAMA Ophthalmology
JF - JAMA Ophthalmology
SN - 2168-6165
IS - 10
ER -