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 - Publisher Copyright:
© 2017 American Medical Association. All rights reserved.
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
SN - 2168-6165
VL - 135
SP - 687
EP - 695
JO - JAMA ophthalmology
JF - JAMA ophthalmology
IS - 7
ER -