Incidence of atrophic lesions in Stargardt disease in the progression of atrophy secondary to Stargardt disease (ProgStar) study report No. 5

for the ProgStar Study Group, Rupert W. Strauss, Beatriz Munoz, Alex Ho, Anamika Jha, Michel Michaelides, Saddek Mohand-Said, Artur V. Cideciyan, David Birch, Amir H. Hariri, Muneeswar G. Nittala, Srini Vas Sadda, Hendrik P.N. Scholl, Yulia Wolfson, Syed Mahmood Shah, Syed Mahmood Shah, Mohamed Ahmed, Etienne Schonbach, Kaoru Fujinami, Elias Traboulsi & 31 others Justis Ehlers, Meghan Marino, Susan Crowe, Rachael Briggs, Angela Borer, Anne Pinter, Tami Fecko, Nikki Burgnoni, Janet S. Sunness, Carol Applegate, Leslie Russell, Simona Degli Esposti, Anthony Moore, Andrew Webster, Sophie Connor, Jade Barnfield, Zaid Salchi, Clara Alfageme, Victoria McCudden, Maria Pefkianaki, Jonathan Aboshiha, Gerald Liew, Graham Holder, Anthony Robson, Alexa King, Daniela Ivanova, Cajas Narvaez, Katy Barnard, Robert Wojciechowski, Sheila West, Ann Margret Ervin

Research output: Contribution to journalArticle

Abstract

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.

LanguageEnglish (US)
Pages687-695
Number of pages9
JournalJAMA Ophthalmology
Volume135
Issue number7
DOIs
StatePublished - Jul 1 2017
Externally publishedYes

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Atrophy
Disease Progression
Incidence
Outcome Assessment (Health Care)
Retinal Pigment Epithelium
Optical Imaging
Kaplan-Meier Estimate
Stargardt disease 1
Tertiary Care Centers
Multicenter Studies
Reading
Cohort Studies
Survival Rate
Adenosine Triphosphate
Therapeutics
Genes

ASJC Scopus subject areas

  • Ophthalmology

Cite this

Incidence of atrophic lesions in Stargardt disease in the progression of atrophy secondary to Stargardt disease (ProgStar) study report No. 5. / for the ProgStar Study Group; Shah, Syed Mahmood.

In: JAMA Ophthalmology, Vol. 135, No. 7, 01.07.2017, p. 687-695.

Research output: Contribution to journalArticle

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title = "Incidence of atrophic lesions in Stargardt disease in the progression of atrophy secondary to Stargardt disease (ProgStar) study report No. 5",
abstract = "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.",
author = "{for the ProgStar Study Group} and Strauss, {Rupert W.} and Beatriz Munoz and Alex Ho and Anamika Jha and Michel Michaelides and Saddek Mohand-Said and Cideciyan, {Artur V.} and David Birch and Hariri, {Amir H.} and Nittala, {Muneeswar G.} and Sadda, {Srini Vas} and Scholl, {Hendrik P.N.} and Yulia Wolfson and Shah, {Syed Mahmood} and Shah, {Syed Mahmood} and Mohamed Ahmed and Etienne Schonbach and Kaoru Fujinami and Elias Traboulsi and Justis Ehlers and Meghan Marino and Susan Crowe and Rachael Briggs and Angela Borer and Anne Pinter and Tami Fecko and Nikki Burgnoni and Sunness, {Janet S.} and Carol Applegate and Leslie Russell and Esposti, {Simona Degli} and Anthony Moore and Andrew Webster and Sophie Connor and Jade Barnfield and Zaid Salchi and Clara Alfageme and Victoria McCudden and Maria Pefkianaki and Jonathan Aboshiha and Gerald Liew and Graham Holder and Anthony Robson and Alexa King and Daniela Ivanova and Cajas Narvaez and Katy Barnard and Robert Wojciechowski and Sheila West and Ervin, {Ann Margret}",
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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 - Shah,Syed Mahmood

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 - Barnard,Katy

AU - Wojciechowski,Robert

AU - West,Sheila

AU - Ervin,Ann Margret

PY - 2017/7/1

Y1 - 2017/7/1

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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