TY - JOUR
T1 - Progression of stargardt disease as determined by fundus autofluorescence in the retrospective progression of stargardt disease study (ProgStar report no. 9)
AU - ProgStar Study Group
AU - Strauss, Rupert W.
AU - Muñoz, Beatriz
AU - Ho, Alexander
AU - Jha, Anamika
AU - Michaelides, Michel
AU - Cideciyan, Artur V.
AU - Audo, Isabelle
AU - Birch, David G.
AU - Hariri, Amir H.
AU - Nittala, Muneeswar G.
AU - Sadda, Srini Vas
AU - West, Sheila
AU - Scholl, Hendrik P.N.
N1 - 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.
Funding Information:
completed and submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Strauss reported receiving support from project number: J 3383-B23 from the Austrian Science Fund and Foundation Fighting Blindness Clinical Research Institute. Dr Birch reported serving as a consultant for AGTC, Acucela Inc, Shire Pharmaceuticals, Ionis/GSK, QLT, and Thrombogenics. Dr Sadda reported receiving financial support from Optos, Carl Zeiss Meditec, Nidek, and Topcon Medical Systems. Dr West reported serving on the Scientific Technical Advisory Committee for Alcon Research Institute and Research to Prevent Blindness Inc. Dr. Scholl reported serving as a paid consultant for Astellas Institute for Regenerative Medicine, Boehringer Ingelheim Pharma GmbH & Co KG, Daiichi Sankyo Inc, Gerson Lehrman Group, Guidepoint, and Shire; serving as a member of the Scientific Advisory Board of Gensight Biologics, Vision Medicines Inc, and Intellia Therapeutics Inc; serving as a member of the Data Monitoring and Safety Board/ Committee of Genentech Inc/F. Hoffmann-La Roche Ltd, Genzyme Corp./Sanofi, and ReNeuron Group Plc/Ora Inc; and serving as a past member of the Ophthalmic Devices Panel of the Medical Devices Advisory Committee, US Food and Drug Administration. These arrangements have been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. Johns Hopkins University and Bayer Pharma AG have an active research collaboration and option agreement. These arrangements have also been reviewed and approved by the University of Basel (Universitätsspital Basel [USB]) in accordance with its conflict of interest policies. Dr Scholl reported serving as the principal investigator of grants at the USB sponsored by Acucela Inc, NightstaRx Ltd, and QLT Inc. Grants at USB are negotiated and administered by the institution (USB) that receives them on its proper accounts. Individual investigators who participate in the sponsored project(s) are not directly compensated by the sponsor but may receive salary or other support from the institution to support their effort on the project(s). No other disclosures were reported.
Funding Information:
supported by the Foundation Fighting Blindness Clinical Research Institute and grants W81-XWH-07 -1-0720 and W81XWH-09-2-0189 to the Foundation Fighting Blindness Clinical Research Institute by the US Department of Defense US Army Medical Research and Materiel Command Telemedicine and Advanced Technology Research Center (Dr Scholl). Dr Strauss is supported by project number J 3383-B23 from the Austrian Science Fund and Foundation Fighting Blindness Clinical Research Institute. Dr Michaelides received financial support from the National Institute for Health Research Biomedical Research Centre at Moorfields Eye Hospital National Health Service Foundation Trust and University College London Institute of Ophthalmology, Retinitis Pigmentosa Fighting Blindness, the Macular Society, and a Foundation Fighting Blindess Career Development Award. Dr Cideciyan is supported in part by grant no EY013203 from the National Institutes of Health. Dr Scholl is supported by the Shulsky Foundation, Ocular Albinism Research Fund (Clark Enterprises Inc), an unrestricted grant to the Wilmer Eye Institute from Research to Prevent Blindness, and grant 1U54HG006542-01 from the Baylor–Johns Hopkins Center for Mendelian Genetics (National Human Genome Research Institute, National Institutes of Health).
Publisher Copyright:
© 2017 American Medical Association. All rights reserved.
PY - 2017/11
Y1 - 2017/11
N2 - IMPORTANCE: Sensitive outcome measures for disease progression are needed for treatment trials of Stargardt disease. OBJECTIVE: To describe the yearly progression rate of atrophic lesions in the retrospective Progression of Stargardt Disease study. DESIGN, SETTING, AND PARTICIPANTS: A multicenter retrospective cohort study was conducted at tertiary referral centers in the United States and Europe. A total of 251 patients aged 6 years or older at baseline, harboring disease-causing variants in ABCA4 (OMIM 601691), enrolled in the study from 9 centers between August 2, 2013, and December 12, 2014; of these patients, 215 had at least 2 gradable fundus autofluorescence images with atrophic lesion(s) present in at least 1 eye. EXPOSURES Areas of definitely decreased autofluorescence (DDAF) and questionably decreased autofluorescence were quantified by a reading center. 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 fundus autofluorescence. RESULTS: A total of 251 participants (458 study eyes) were enrolled. Images from 386 eyes of 215 participants (126 females and 89 males; mean [SD] age, 29.9 [14.7] years; mean [SD] age of onset of symptoms, 21.9 [13.3] years) showed atrophic lesions present on at least 2 visits and were graded for 2 (156 eyes), 3 (174 eyes), or 4 (57 eyes) visits. A subset of 224 eyes (123 female participants and 101 male participants; mean [SD] age, 33.0 [15.1] years) had areas of DDAF present on at least 2 visits; these eyes were included in the estimation of the progression of the area of DDAF. At the first visit, DDAF was present in 224 eyes (58.0%), with a mean (SD) lesion size of 2.2 (2.7) mm2. The total mean (SD) area of decreased autofluorescence (DDAF and questionably decreased autofluorescence) at first visit was 2.6 (2.8) mm2. Mean progression of DDAF was 0.51 mm2/y (95% CI, 0.42-0.61 mm2/y), and of total decreased fundus autofluorescence was 0.35 mm2/y (95% CI, 0.28-0.43 mm2/y). Rates of progression depended on the initial size of the lesion. CONCLUSIONS AND RELEVANCE: In Stargardt disease with DDAF lesions, fundus autofluorescence may serve as a monitoring tool 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 describe the yearly progression rate of atrophic lesions in the retrospective Progression of Stargardt Disease study. DESIGN, SETTING, AND PARTICIPANTS: A multicenter retrospective cohort study was conducted at tertiary referral centers in the United States and Europe. A total of 251 patients aged 6 years or older at baseline, harboring disease-causing variants in ABCA4 (OMIM 601691), enrolled in the study from 9 centers between August 2, 2013, and December 12, 2014; of these patients, 215 had at least 2 gradable fundus autofluorescence images with atrophic lesion(s) present in at least 1 eye. EXPOSURES Areas of definitely decreased autofluorescence (DDAF) and questionably decreased autofluorescence were quantified by a reading center. 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 fundus autofluorescence. RESULTS: A total of 251 participants (458 study eyes) were enrolled. Images from 386 eyes of 215 participants (126 females and 89 males; mean [SD] age, 29.9 [14.7] years; mean [SD] age of onset of symptoms, 21.9 [13.3] years) showed atrophic lesions present on at least 2 visits and were graded for 2 (156 eyes), 3 (174 eyes), or 4 (57 eyes) visits. A subset of 224 eyes (123 female participants and 101 male participants; mean [SD] age, 33.0 [15.1] years) had areas of DDAF present on at least 2 visits; these eyes were included in the estimation of the progression of the area of DDAF. At the first visit, DDAF was present in 224 eyes (58.0%), with a mean (SD) lesion size of 2.2 (2.7) mm2. The total mean (SD) area of decreased autofluorescence (DDAF and questionably decreased autofluorescence) at first visit was 2.6 (2.8) mm2. Mean progression of DDAF was 0.51 mm2/y (95% CI, 0.42-0.61 mm2/y), and of total decreased fundus autofluorescence was 0.35 mm2/y (95% CI, 0.28-0.43 mm2/y). Rates of progression depended on the initial size of the lesion. CONCLUSIONS AND RELEVANCE: In Stargardt disease with DDAF lesions, fundus autofluorescence may serve as a monitoring tool 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.2017.4152
DO - 10.1001/jamaophthalmol.2017.4152
M3 - Article
C2 - 29049437
AN - SCOPUS:85034644071
SN - 2168-6165
VL - 135
SP - 1232
EP - 1241
JO - JAMA ophthalmology
JF - JAMA ophthalmology
IS - 11
ER -