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

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, Millena Bittencourt, Syed Mahmood Shah, Mohamed Ahmed, Etienne Schonbach, Kaoru Fujinami, Elias Traboulsi, Justis Ehlers & 170 others 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, Catherine Grigg, Hannah Dunbar, Yetunde Obadeyi, Karine Girard-Claudon, Hilary Swann, Avani Rughani, Charles Amoah, Dominic Carrington, Kanom Bibi, Emerson Ting Co, Mohamed Nafaz Illiyas, Hamida Begum, Andrew Carter, Anne Georgiou, Selma Lewism, Saddaf Shaheen, Harpreet Shinmar, Linda Burton, Paul Bernstein, Kimberley Wegner, Briana Lauren Sawyer, Bonnie Carlstrom, Kellian Farnsworth, Cyrie Fry, Melissa Chandler, Glen Jenkins, Donnel Creel, Yi Zhong Wang, Luis Rodriguez, Kirsten Locke, Martin Klein, Paulina Mejia, Samuel G. Jacobson, Sharon B. Schwartz, Rodrigo Matsui, Michaela Gruzensky, Jason Charng, Alejandro J. Roman, Eberhart Zrenner, Fadi Nasser, Gesa Astrid Hahn, Barbara Wilhelm, Tobias Peters, Benjamin Beier, Tilman Koenig, Susanne Kramer, Jose Alain Sahel, Isabelle Audo, Caroline Laurent-Coriat, Ieva Sliesoraityte, Christina Zeitz, Fiona Boyard, Minh Ha Tran, Mathias Chapon, Celine Chaumette, Juliette Amaudruz, Victoria Ganem, Serge Sancho, Aurore Girmens, Robert Wojciechowski, Shazia Khan, David G. Emmert, Dennis Cain, Mark Herring, Jennifer Bassinger, Lisa Liberto, Sheila West, Ann Margret Ervin, Xiangrong Kong, Kurt Dreger, Jennifer Jones, Michael S. Ip, Brendan Kramer, Ngoc Lam, Rita Tawdros, Yong Dong Zhou, Johana Carmona, Akihito Uji, Amirhossein Hariri, Amy Lock, Anthony Elshafei, Anushika Ganegoda, Christine Petrossian, Dennis Jenkins, Edward Strnad, Elmira Baghdasaryan, Eric Ito, Feliz Samson, Gloria Blanquel, Handan Akil, Jhanisus Melendez, Jianqin Lei, Jianyan Huang, Jonathan Chau, Khalil G. Falavarjani, Kristina Espino, Manfred Li, Maria Mendoza, Muneeswar Gupta Nittala, Netali Roded, Nizar Saleh, Ping Huang, Sean Pitetta, Siva Balasubramanian, Sophie Leahy, Sowmya J. Srinivas, Swetha B. Velaga, Teresa Margaryan, Tudor Tepelus, Tyler Brown, Wenying Fan, Yamileth Murillo, Yue Shi, Katherine Aguilar, Cynthia Chan, Lisa Santos, Brian Seo, Christopher Sison, Silvia Perez, Stephanie Chao, Kelly Miyasato, Julia Higgins, Zoila Luna, Anita Menchaca, Norma Gonzalez, Vicky Robledo, Karen Carig, Kirstie Baker, David Ellenbogen, Daniel Bluemel, Theo Sanford, Daisy Linares, Mei Tran, Lorane Nava, Michelle Oberoi, Mark Romero, Vivian Chiguil, Grantley Bynum-Bain, Monica Kim, Carolina Mendiguren, Xiwen Huang, Monika Smith,

Research output: Research - peer-reviewArticle

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

Fingerprint

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

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. / Strauss, Rupert W.; Munoz, Beatriz; Ho, Alex; Jha, Anamika; Michaelides, Michel; Mohand-Said, Saddek; Cideciyan, Artur V.; Birch, David; Hariri, Amir H.; Nittala, Muneeswar G.; Sadda, Srini Vas; Scholl, Hendrik P.N.; Wolfson, Yulia; Bittencourt, Millena; Shah, Syed Mahmood; Ahmed, Mohamed; Schonbach, Etienne; Fujinami, Kaoru; Traboulsi, Elias; Ehlers, Justis; Marino, Meghan; Crowe, Susan; Briggs, Rachael; Borer, Angela; Pinter, Anne; Fecko, Tami; Burgnoni, Nikki; Sunness, Janet S.; Applegate, Carol; Russell, Leslie; Esposti, Simona Degli; Moore, Anthony; Webster, Andrew; Connor, Sophie; Barnfield, Jade; Salchi, Zaid; Alfageme, Clara; McCudden, Victoria; Pefkianaki, Maria; Aboshiha, Jonathan; Liew, Gerald; Holder, Graham; Robson, Anthony; King, Alexa; Ivanova, Daniela; Narvaez, Cajas; Barnard, Katy; Grigg, Catherine; Dunbar, Hannah; Obadeyi, Yetunde; Girard-Claudon, Karine; Swann, Hilary; Rughani, Avani; Amoah, Charles; Carrington, Dominic; Bibi, Kanom; Co, Emerson Ting; Illiyas, Mohamed Nafaz; Begum, Hamida; Carter, Andrew; Georgiou, Anne; Lewism, Selma; Shaheen, Saddaf; Shinmar, Harpreet; Burton, Linda; Bernstein, Paul; Wegner, Kimberley; Lauren Sawyer, Briana; Carlstrom, Bonnie; Farnsworth, Kellian; Fry, Cyrie; Chandler, Melissa; Jenkins, Glen; Creel, Donnel; Wang, Yi Zhong; Rodriguez, Luis; Locke, Kirsten; Klein, Martin; Mejia, Paulina; Jacobson, Samuel G.; Schwartz, Sharon B.; Matsui, Rodrigo; Gruzensky, Michaela; Charng, Jason; Roman, Alejandro J.; Zrenner, Eberhart; Nasser, Fadi; Hahn, Gesa Astrid; Wilhelm, Barbara; Peters, Tobias; Beier, Benjamin; Koenig, Tilman; Kramer, Susanne; Sahel, Jose Alain; Audo, Isabelle; Laurent-Coriat, Caroline; Sliesoraityte, Ieva; Zeitz, Christina; Boyard, Fiona; Tran, Minh Ha; Chapon, Mathias; Chaumette, Celine; Amaudruz, Juliette; Ganem, Victoria; Sancho, Serge; Girmens, Aurore; Wojciechowski, Robert; Khan, Shazia; Emmert, David G.; Cain, Dennis; Herring, Mark; Bassinger, Jennifer; Liberto, Lisa; West, Sheila; Ervin, Ann Margret; Kong, Xiangrong; Dreger, Kurt; Jones, Jennifer; Ip, Michael S.; Kramer, Brendan; Lam, Ngoc; Tawdros, Rita; Zhou, Yong Dong; Carmona, Johana; Uji, Akihito; Hariri, Amirhossein; Lock, Amy; Elshafei, Anthony; Ganegoda, Anushika; Petrossian, Christine; Jenkins, Dennis; Strnad, Edward; Baghdasaryan, Elmira; Ito, Eric; Samson, Feliz; Blanquel, Gloria; Akil, Handan; Melendez, Jhanisus; Lei, Jianqin; Huang, Jianyan; Chau, Jonathan; Falavarjani, Khalil G.; Espino, Kristina; Li, Manfred; Mendoza, Maria; Nittala, Muneeswar Gupta; Roded, Netali; Saleh, Nizar; Huang, Ping; Pitetta, Sean; Balasubramanian, Siva; Leahy, Sophie; Srinivas, Sowmya J.; Velaga, Swetha B.; Margaryan, Teresa; Tepelus, Tudor; Brown, Tyler; Fan, Wenying; Murillo, Yamileth; Shi, Yue; Aguilar, Katherine; Chan, Cynthia; Santos, Lisa; Seo, Brian; Sison, Christopher; Perez, Silvia; Chao, Stephanie; Miyasato, Kelly; Higgins, Julia; Luna, Zoila; Menchaca, Anita; Gonzalez, Norma; Robledo, Vicky; Carig, Karen; Baker, Kirstie; Ellenbogen, David; Bluemel, Daniel; Sanford, Theo; Linares, Daisy; Tran, Mei; Nava, Lorane; Oberoi, Michelle; Romero, Mark; Chiguil, Vivian; Bynum-Bain, Grantley; Kim, Monica; Mendiguren, Carolina; Huang, Xiwen; Smith, Monika; for the ProgStar Study Group.

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

Research output: Research - peer-reviewArticle

Strauss, RW, Munoz, B, Ho, A, Jha, A, Michaelides, M, Mohand-Said, S, Cideciyan, AV, Birch, D, Hariri, AH, Nittala, MG, Sadda, SV, Scholl, HPN, Wolfson, Y, Bittencourt, M, Shah, SM, Ahmed, M, Schonbach, E, Fujinami, K, Traboulsi, E, Ehlers, J, Marino, M, Crowe, S, Briggs, R, Borer, A, Pinter, A, Fecko, T, Burgnoni, N, Sunness, JS, Applegate, C, Russell, L, Esposti, SD, Moore, A, Webster, A, Connor, S, Barnfield, J, Salchi, Z, Alfageme, C, McCudden, V, Pefkianaki, M, Aboshiha, J, Liew, G, Holder, G, Robson, A, King, A, Ivanova, D, Narvaez, C, Barnard, K, Grigg, C, Dunbar, H, Obadeyi, Y, Girard-Claudon, K, Swann, H, Rughani, A, Amoah, C, Carrington, D, Bibi, K, Co, ET, Illiyas, MN, Begum, H, Carter, A, Georgiou, A, Lewism, S, Shaheen, S, Shinmar, H, Burton, L, Bernstein, P, Wegner, K, Lauren Sawyer, B, Carlstrom, B, Farnsworth, K, Fry, C, Chandler, M, Jenkins, G, Creel, D, Wang, YZ, Rodriguez, L, Locke, K, Klein, M, Mejia, P, Jacobson, SG, Schwartz, SB, Matsui, R, Gruzensky, M, Charng, J, Roman, AJ, Zrenner, E, Nasser, F, Hahn, GA, Wilhelm, B, Peters, T, Beier, B, Koenig, T, Kramer, S, Sahel, JA, Audo, I, Laurent-Coriat, C, Sliesoraityte, I, Zeitz, C, Boyard, F, Tran, MH, Chapon, M, Chaumette, C, Amaudruz, J, Ganem, V, Sancho, S, Girmens, A, Wojciechowski, R, Khan, S, Emmert, DG, Cain, D, Herring, M, Bassinger, J, Liberto, L, West, S, Ervin, AM, Kong, X, Dreger, K, Jones, J, Ip, MS, Kramer, B, Lam, N, Tawdros, R, Zhou, YD, Carmona, J, Uji, A, Hariri, A, Lock, A, Elshafei, A, Ganegoda, A, Petrossian, C, Jenkins, D, Strnad, E, Baghdasaryan, E, Ito, E, Samson, F, Blanquel, G, Akil, H, Melendez, J, Lei, J, Huang, J, Chau, J, Falavarjani, KG, Espino, K, Li, M, Mendoza, M, Nittala, MG, Roded, N, Saleh, N, Huang, P, Pitetta, S, Balasubramanian, S, Leahy, S, Srinivas, SJ, Velaga, SB, Margaryan, T, Tepelus, T, Brown, T, Fan, W, Murillo, Y, Shi, Y, Aguilar, K, Chan, C, Santos, L, Seo, B, Sison, C, Perez, S, Chao, S, Miyasato, K, Higgins, J, Luna, Z, Menchaca, A, Gonzalez, N, Robledo, V, Carig, K, Baker, K, Ellenbogen, D, Bluemel, D, Sanford, T, Linares, D, Tran, M, Nava, L, Oberoi, M, Romero, M, Chiguil, V, Bynum-Bain, G, Kim, M, Mendiguren, C, Huang, X, Smith, M & for the ProgStar Study Group 2017, 'Incidence of atrophic lesions in Stargardt disease in the progression of atrophy secondary to Stargardt disease (ProgStar) study report No. 5' JAMA Ophthalmology, vol 135, no. 7, pp. 687-695. DOI: 10.1001/jamaophthalmol.2017.1121
Strauss, Rupert W. ; Munoz, Beatriz ; Ho, Alex ; Jha, Anamika ; Michaelides, Michel ; Mohand-Said, Saddek ; Cideciyan, Artur V. ; Birch, David ; Hariri, Amir H. ; Nittala, Muneeswar G. ; Sadda, Srini Vas ; Scholl, Hendrik P.N. ; Wolfson, Yulia ; Bittencourt, Millena ; Shah, Syed Mahmood ; Ahmed, Mohamed ; Schonbach, Etienne ; Fujinami, Kaoru ; Traboulsi, Elias ; Ehlers, Justis ; Marino, Meghan ; Crowe, Susan ; Briggs, Rachael ; Borer, Angela ; Pinter, Anne ; Fecko, Tami ; Burgnoni, Nikki ; Sunness, Janet S. ; Applegate, Carol ; Russell, Leslie ; Esposti, Simona Degli ; Moore, Anthony ; Webster, Andrew ; Connor, Sophie ; Barnfield, Jade ; Salchi, Zaid ; Alfageme, Clara ; McCudden, Victoria ; Pefkianaki, Maria ; Aboshiha, Jonathan ; Liew, Gerald ; Holder, Graham ; Robson, Anthony ; King, Alexa ; Ivanova, Daniela ; Narvaez, Cajas ; Barnard, Katy ; Grigg, Catherine ; Dunbar, Hannah ; Obadeyi, Yetunde ; Girard-Claudon, Karine ; Swann, Hilary ; Rughani, Avani ; Amoah, Charles ; Carrington, Dominic ; Bibi, Kanom ; Co, Emerson Ting ; Illiyas, Mohamed Nafaz ; Begum, Hamida ; Carter, Andrew ; Georgiou, Anne ; Lewism, Selma ; Shaheen, Saddaf ; Shinmar, Harpreet ; Burton, Linda ; Bernstein, Paul ; Wegner, Kimberley ; Lauren Sawyer, Briana ; Carlstrom, Bonnie ; Farnsworth, Kellian ; Fry, Cyrie ; Chandler, Melissa ; Jenkins, Glen ; Creel, Donnel ; Wang, Yi Zhong ; Rodriguez, Luis ; Locke, Kirsten ; Klein, Martin ; Mejia, Paulina ; Jacobson, Samuel G. ; Schwartz, Sharon B. ; Matsui, Rodrigo ; Gruzensky, Michaela ; Charng, Jason ; Roman, Alejandro J. ; Zrenner, Eberhart ; Nasser, Fadi ; Hahn, Gesa Astrid ; Wilhelm, Barbara ; Peters, Tobias ; Beier, Benjamin ; Koenig, Tilman ; Kramer, Susanne ; Sahel, Jose Alain ; Audo, Isabelle ; Laurent-Coriat, Caroline ; Sliesoraityte, Ieva ; Zeitz, Christina ; Boyard, Fiona ; Tran, Minh Ha ; Chapon, Mathias ; Chaumette, Celine ; Amaudruz, Juliette ; Ganem, Victoria ; Sancho, Serge ; Girmens, Aurore ; Wojciechowski, Robert ; Khan, Shazia ; Emmert, David G. ; Cain, Dennis ; Herring, Mark ; Bassinger, Jennifer ; Liberto, Lisa ; West, Sheila ; Ervin, Ann Margret ; Kong, Xiangrong ; Dreger, Kurt ; Jones, Jennifer ; Ip, Michael S. ; Kramer, Brendan ; Lam, Ngoc ; Tawdros, Rita ; Zhou, Yong Dong ; Carmona, Johana ; Uji, Akihito ; Hariri, Amirhossein ; Lock, Amy ; Elshafei, Anthony ; Ganegoda, Anushika ; Petrossian, Christine ; Jenkins, Dennis ; Strnad, Edward ; Baghdasaryan, Elmira ; Ito, Eric ; Samson, Feliz ; Blanquel, Gloria ; Akil, Handan ; Melendez, Jhanisus ; Lei, Jianqin ; Huang, Jianyan ; Chau, Jonathan ; Falavarjani, Khalil G. ; Espino, Kristina ; Li, Manfred ; Mendoza, Maria ; Nittala, Muneeswar Gupta ; Roded, Netali ; Saleh, Nizar ; Huang, Ping ; Pitetta, Sean ; Balasubramanian, Siva ; Leahy, Sophie ; Srinivas, Sowmya J. ; Velaga, Swetha B. ; Margaryan, Teresa ; Tepelus, Tudor ; Brown, Tyler ; Fan, Wenying ; Murillo, Yamileth ; Shi, Yue ; Aguilar, Katherine ; Chan, Cynthia ; Santos, Lisa ; Seo, Brian ; Sison, Christopher ; Perez, Silvia ; Chao, Stephanie ; Miyasato, Kelly ; Higgins, Julia ; Luna, Zoila ; Menchaca, Anita ; Gonzalez, Norma ; Robledo, Vicky ; Carig, Karen ; Baker, Kirstie ; Ellenbogen, David ; Bluemel, Daniel ; Sanford, Theo ; Linares, Daisy ; Tran, Mei ; Nava, Lorane ; Oberoi, Michelle ; Romero, Mark ; Chiguil, Vivian ; Bynum-Bain, Grantley ; Kim, Monica ; Mendiguren, Carolina ; Huang, Xiwen ; Smith, Monika ; for the ProgStar Study Group. / Incidence of atrophic lesions in Stargardt disease in the progression of atrophy secondary to Stargardt disease (ProgStar) study report No. 5. In: JAMA Ophthalmology. 2017 ; Vol. 135, No. 7. pp. 687-695
@article{8f8b80557f7440b88792a07af6ed6bdb,
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 = "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 Millena Bittencourt 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 Catherine Grigg and Hannah Dunbar and Yetunde Obadeyi and Karine Girard-Claudon and Hilary Swann and Avani Rughani and Charles Amoah and Dominic Carrington and Kanom Bibi and Co, {Emerson Ting} and Illiyas, {Mohamed Nafaz} and Hamida Begum and Andrew Carter and Anne Georgiou and Selma Lewism and Saddaf Shaheen and Harpreet Shinmar and Linda Burton and Paul Bernstein and Kimberley Wegner and {Lauren Sawyer}, Briana and Bonnie Carlstrom and Kellian Farnsworth and Cyrie Fry and Melissa Chandler and Glen Jenkins and Donnel Creel and Wang, {Yi Zhong} and Luis Rodriguez and Kirsten Locke and Martin Klein and Paulina Mejia and Jacobson, {Samuel G.} and Schwartz, {Sharon B.} and Rodrigo Matsui and Michaela Gruzensky and Jason Charng and Roman, {Alejandro J.} and Eberhart Zrenner and Fadi Nasser and Hahn, {Gesa Astrid} and Barbara Wilhelm and Tobias Peters and Benjamin Beier and Tilman Koenig and Susanne Kramer and Sahel, {Jose Alain} and Isabelle Audo and Caroline Laurent-Coriat and Ieva Sliesoraityte and Christina Zeitz and Fiona Boyard and Tran, {Minh Ha} and Mathias Chapon and Celine Chaumette and Juliette Amaudruz and Victoria Ganem and Serge Sancho and Aurore Girmens and Robert Wojciechowski and Shazia Khan and Emmert, {David G.} and Dennis Cain and Mark Herring and Jennifer Bassinger and Lisa Liberto and Sheila West and Ervin, {Ann Margret} and Xiangrong Kong and Kurt Dreger and Jennifer Jones and Ip, {Michael S.} and Brendan Kramer and Ngoc Lam and Rita Tawdros and Zhou, {Yong Dong} and Johana Carmona and Akihito Uji and Amirhossein Hariri and Amy Lock and Anthony Elshafei and Anushika Ganegoda and Christine Petrossian and Dennis Jenkins and Edward Strnad and Elmira Baghdasaryan and Eric Ito and Feliz Samson and Gloria Blanquel and Handan Akil and Jhanisus Melendez and Jianqin Lei and Jianyan Huang and Jonathan Chau and Falavarjani, {Khalil G.} and Kristina Espino and Manfred Li and Maria Mendoza and Nittala, {Muneeswar Gupta} and Netali Roded and Nizar Saleh and Ping Huang and Sean Pitetta and Siva Balasubramanian and Sophie Leahy and Srinivas, {Sowmya J.} and Velaga, {Swetha B.} and Teresa Margaryan and Tudor Tepelus and Tyler Brown and Wenying Fan and Yamileth Murillo and Yue Shi and Katherine Aguilar and Cynthia Chan and Lisa Santos and Brian Seo and Christopher Sison and Silvia Perez and Stephanie Chao and Kelly Miyasato and Julia Higgins and Zoila Luna and Anita Menchaca and Norma Gonzalez and Vicky Robledo and Karen Carig and Kirstie Baker and David Ellenbogen and Daniel Bluemel and Theo Sanford and Daisy Linares and Mei Tran and Lorane Nava and Michelle Oberoi and Mark Romero and Vivian Chiguil and Grantley Bynum-Bain and Monica Kim and Carolina Mendiguren and Xiwen Huang and Monika Smith and {for the ProgStar Study Group}",
year = "2017",
month = "7",
doi = "10.1001/jamaophthalmol.2017.1121",
volume = "135",
pages = "687--695",
journal = "JAMA Ophthalmology",
issn = "2168-6165",
publisher = "American Medical Association",
number = "7",

}

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 - 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 - Barnard,Katy

AU - Grigg,Catherine

AU - Dunbar,Hannah

AU - Obadeyi,Yetunde

AU - Girard-Claudon,Karine

AU - Swann,Hilary

AU - Rughani,Avani

AU - Amoah,Charles

AU - Carrington,Dominic

AU - Bibi,Kanom

AU - Co,Emerson Ting

AU - Illiyas,Mohamed Nafaz

AU - Begum,Hamida

AU - Carter,Andrew

AU - Georgiou,Anne

AU - Lewism,Selma

AU - Shaheen,Saddaf

AU - Shinmar,Harpreet

AU - Burton,Linda

AU - Bernstein,Paul

AU - Wegner,Kimberley

AU - Lauren Sawyer,Briana

AU - Carlstrom,Bonnie

AU - Farnsworth,Kellian

AU - Fry,Cyrie

AU - Chandler,Melissa

AU - Jenkins,Glen

AU - Creel,Donnel

AU - Wang,Yi Zhong

AU - Rodriguez,Luis

AU - Locke,Kirsten

AU - Klein,Martin

AU - Mejia,Paulina

AU - Jacobson,Samuel G.

AU - Schwartz,Sharon B.

AU - Matsui,Rodrigo

AU - Gruzensky,Michaela

AU - Charng,Jason

AU - Roman,Alejandro J.

AU - Zrenner,Eberhart

AU - Nasser,Fadi

AU - Hahn,Gesa Astrid

AU - Wilhelm,Barbara

AU - Peters,Tobias

AU - Beier,Benjamin

AU - Koenig,Tilman

AU - Kramer,Susanne

AU - Sahel,Jose Alain

AU - Audo,Isabelle

AU - Laurent-Coriat,Caroline

AU - Sliesoraityte,Ieva

AU - Zeitz,Christina

AU - Boyard,Fiona

AU - Tran,Minh Ha

AU - Chapon,Mathias

AU - Chaumette,Celine

AU - Amaudruz,Juliette

AU - Ganem,Victoria

AU - Sancho,Serge

AU - Girmens,Aurore

AU - Wojciechowski,Robert

AU - Khan,Shazia

AU - Emmert,David G.

AU - Cain,Dennis

AU - Herring,Mark

AU - Bassinger,Jennifer

AU - Liberto,Lisa

AU - West,Sheila

AU - Ervin,Ann Margret

AU - Kong,Xiangrong

AU - Dreger,Kurt

AU - Jones,Jennifer

AU - Ip,Michael S.

AU - Kramer,Brendan

AU - Lam,Ngoc

AU - Tawdros,Rita

AU - Zhou,Yong Dong

AU - Carmona,Johana

AU - Uji,Akihito

AU - Hariri,Amirhossein

AU - Lock,Amy

AU - Elshafei,Anthony

AU - Ganegoda,Anushika

AU - Petrossian,Christine

AU - Jenkins,Dennis

AU - Strnad,Edward

AU - Baghdasaryan,Elmira

AU - Ito,Eric

AU - Samson,Feliz

AU - Blanquel,Gloria

AU - Akil,Handan

AU - Melendez,Jhanisus

AU - Lei,Jianqin

AU - Huang,Jianyan

AU - Chau,Jonathan

AU - Falavarjani,Khalil G.

AU - Espino,Kristina

AU - Li,Manfred

AU - Mendoza,Maria

AU - Nittala,Muneeswar Gupta

AU - Roded,Netali

AU - Saleh,Nizar

AU - Huang,Ping

AU - Pitetta,Sean

AU - Balasubramanian,Siva

AU - Leahy,Sophie

AU - Srinivas,Sowmya J.

AU - Velaga,Swetha B.

AU - Margaryan,Teresa

AU - Tepelus,Tudor

AU - Brown,Tyler

AU - Fan,Wenying

AU - Murillo,Yamileth

AU - Shi,Yue

AU - Aguilar,Katherine

AU - Chan,Cynthia

AU - Santos,Lisa

AU - Seo,Brian

AU - Sison,Christopher

AU - Perez,Silvia

AU - Chao,Stephanie

AU - Miyasato,Kelly

AU - Higgins,Julia

AU - Luna,Zoila

AU - Menchaca,Anita

AU - Gonzalez,Norma

AU - Robledo,Vicky

AU - Carig,Karen

AU - Baker,Kirstie

AU - Ellenbogen,David

AU - Bluemel,Daniel

AU - Sanford,Theo

AU - Linares,Daisy

AU - Tran,Mei

AU - Nava,Lorane

AU - Oberoi,Michelle

AU - Romero,Mark

AU - Chiguil,Vivian

AU - Bynum-Bain,Grantley

AU - Kim,Monica

AU - Mendiguren,Carolina

AU - Huang,Xiwen

AU - Smith,Monika

AU - for the ProgStar Study Group

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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U2 - 10.1001/jamaophthalmol.2017.1121

DO - 10.1001/jamaophthalmol.2017.1121

M3 - Article

VL - 135

SP - 687

EP - 695

JO - JAMA Ophthalmology

T2 - JAMA Ophthalmology

JF - JAMA Ophthalmology

SN - 2168-6165

IS - 7

ER -