TY - JOUR
T1 - Incidence of atrophic lesions in Stargardt disease in the progression of atrophy secondary to Stargardt disease (ProgStar) study report No. 5
AU - for the ProgStar Study Group
AU - Strauss, Rupert W.
AU - Munoz, Beatriz
AU - Ho, Alex
AU - Jha, Anamika
AU - Michaelides, Michel
AU - Mohand-Said, Saddek
AU - Cideciyan, Artur V.
AU - Birch, David
AU - Hariri, Amir H.
AU - Nittala, Muneeswar G.
AU - Sadda, Srini Vas
AU - Scholl, Hendrik P.N.
AU - Wolfson, Yulia
AU - Bittencourt, Millena
AU - Shah, Syed Mahmood
AU - Ahmed, Mohamed
AU - Schonbach, Etienne
AU - Fujinami, Kaoru
AU - Traboulsi, Elias
AU - Ehlers, Justis
AU - Marino, Meghan
AU - Crowe, Susan
AU - Briggs, Rachael
AU - Borer, Angela
AU - Pinter, Anne
AU - Fecko, Tami
AU - Burgnoni, Nikki
AU - Sunness, Janet S.
AU - Applegate, Carol
AU - Russell, Leslie
AU - Esposti, Simona Degli
AU - Moore, Anthony
AU - Webster, Andrew
AU - Connor, Sophie
AU - Barnfield, Jade
AU - Salchi, Zaid
AU - Alfageme, Clara
AU - McCudden, Victoria
AU - Pefkianaki, Maria
AU - Aboshiha, Jonathan
AU - Liew, Gerald
AU - Holder, Graham
AU - Robson, Anthony
AU - King, Alexa
AU - Ivanova, Daniela
AU - Narvaez, Cajas
AU - Wojciechowski, Robert
AU - West, Sheila
AU - Ervin, Ann Margret
AU - Kong, Xiangrong
N1 - Funding Information:
The ProgStar studies are 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, Fort Meade, Maryland. Dr Scholl is supported by the Shulsky Foundation, New York, NY; 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). Dr Strauss is supported by grant J 3383-B23 from the Austrian Science Fund. Dr Scholl is the Dr Frieda Derdeyn Bambas Professor of Ophthalmology.
PY - 2017/7
Y1 - 2017/7
N2 - IMPORTANCE: Outcome measures that are sensitive to disease progression are needed as clinical end points for future treatment trials in Stargardt disease. OBJECTIVE: To examine the incidence of atrophic lesions of the retinal pigment epithelium in patients with Stargardt disease as determined by fundus autofluorescence imaging. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective multicenter cohort study, 217 patients 6 years and older at baseline at tertiary referral centers in Europe, the United States, and the United Kingdom who were harboring disease-causing variants in the adenosine triphosphate (ATP)-binding cassette subfamily A member 4 (ABCA4) gene and who met the following criteria were enrolled: (1) at least 1 well-demarcated area of atrophy with a minimum diameter of 300 μm, with the total area of all atrophic lesions being less than or equal to 12 mm2 in at least 1 eye at the most recent visit, and (2) fundus autofluorescence images for at least 2 visits with a minimum of 6 months between at least 2 visits. Data were collected between August 22, 2013, and December 12, 2014. Data analysis was performed from March 15, 2015, through January 31, 2017. EXPOSURES: Images were evaluated by staff at a central reading center. Areas of definitely decreased autofluorescence (DDAF) and questionably decreased autofluorescence (QDAF) were outlined and quantified. Lesion-free survival rates were estimated using Kaplan-Meier survival curves. MAIN OUTCOMES AND MEASURES: Incidence of atrophic lesions as determined by fundus autofluorescence. RESULTS: The 217 patients (mean [SD] age, 21.8 [13.3] years; 127 female [57.5%]; 148 white [68.2%]) contributed 390 eyes for which the mean (SD) follow-up time was 3.9 (1.6) years (range, 0.7-12.1 years). Among eyes without DDAF at first visit, the median time to develop a DDAF lesion was 4.9 years (95%CI, 4.3-5.6 years). Among eyes without QDAF, the median time to develop a QDAF lesion was 6.3 years (95%CI, 5.6-9.7 years). Eyes with a lesion of DDAF at the first visit were less likely to develop a QDAF lesion compared with eyes without a lesion of DDAF (hazard ratio, 0.19; 95%CI, 0.05-0.70; P = .01). CONCLUSIONS AND RELEVANCE: An estimated 50% of the eyes without DDAF at first visit will develop the lesion in less than 5 years, suggesting that incidence of DDAF could serve as an outcome measure for treatment trials.
AB - IMPORTANCE: Outcome measures that are sensitive to disease progression are needed as clinical end points for future treatment trials in Stargardt disease. OBJECTIVE: To examine the incidence of atrophic lesions of the retinal pigment epithelium in patients with Stargardt disease as determined by fundus autofluorescence imaging. DESIGN, SETTING, AND PARTICIPANTS: In this retrospective multicenter cohort study, 217 patients 6 years and older at baseline at tertiary referral centers in Europe, the United States, and the United Kingdom who were harboring disease-causing variants in the adenosine triphosphate (ATP)-binding cassette subfamily A member 4 (ABCA4) gene and who met the following criteria were enrolled: (1) at least 1 well-demarcated area of atrophy with a minimum diameter of 300 μm, with the total area of all atrophic lesions being less than or equal to 12 mm2 in at least 1 eye at the most recent visit, and (2) fundus autofluorescence images for at least 2 visits with a minimum of 6 months between at least 2 visits. Data were collected between August 22, 2013, and December 12, 2014. Data analysis was performed from March 15, 2015, through January 31, 2017. EXPOSURES: Images were evaluated by staff at a central reading center. Areas of definitely decreased autofluorescence (DDAF) and questionably decreased autofluorescence (QDAF) were outlined and quantified. Lesion-free survival rates were estimated using Kaplan-Meier survival curves. MAIN OUTCOMES AND MEASURES: Incidence of atrophic lesions as determined by fundus autofluorescence. RESULTS: The 217 patients (mean [SD] age, 21.8 [13.3] years; 127 female [57.5%]; 148 white [68.2%]) contributed 390 eyes for which the mean (SD) follow-up time was 3.9 (1.6) years (range, 0.7-12.1 years). Among eyes without DDAF at first visit, the median time to develop a DDAF lesion was 4.9 years (95%CI, 4.3-5.6 years). Among eyes without QDAF, the median time to develop a QDAF lesion was 6.3 years (95%CI, 5.6-9.7 years). Eyes with a lesion of DDAF at the first visit were less likely to develop a QDAF lesion compared with eyes without a lesion of DDAF (hazard ratio, 0.19; 95%CI, 0.05-0.70; P = .01). CONCLUSIONS AND RELEVANCE: An estimated 50% of the eyes without DDAF at first visit will develop the lesion in less than 5 years, suggesting that incidence of DDAF could serve as an outcome measure for treatment trials.
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U2 - 10.1001/jamaophthalmol.2017.1121
DO - 10.1001/jamaophthalmol.2017.1121
M3 - Article
C2 - 28542697
AN - SCOPUS:85024366951
VL - 135
SP - 687
EP - 695
JO - JAMA Ophthalmology
JF - JAMA Ophthalmology
SN - 2168-6165
IS - 7
ER -