Visual acuity change over 24 months and its association with foveal phenotype and genotype in individuals with stargardt disease progstar study report no. 10

Xiangrong Kong; Kaoru Fujinami; Rupert W. Strauss; Beatriz Munoz; Sheila K. West; Artur V. Cideciyan; Michel Michaelides; Mohamed Ahmed; Ann Margret Ervin; Etienne Schönbach; Janet K. Cheetham; Hendrik P.N. Scholl; Hendrik P.N. Scholl; Rupert W. Strauss; Yulia Wolfson; Millena Bittencourt; Syed Mahmood Shah; Mohamed Ahmed; Etienne Schönbach; Kaoru Fujinami; Elias Traboulsi; Justis Ehlers; Meghan Marino; Susan Crowe; Rachael Briggs; Angela Borer; Anne Pinter; Tami Fecko; Nikki Burgnoni; Janet S. Sunness; Carol Applegate; Leslie Russell; Michel Michaelides; 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 Lewis; 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; David Birch; Yi Zhong Wang; Luis Rodriguez; Kirsten Locke; Martin Klein; Paulina Mejia; Artur V. Cideciyan; 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; José Alain Sahel; Saddek Mohand-Said; Isabelle Audo; Caroline Laurent-Coriat; Ieva Sliesoraityte; Christina Zeitz; Fiona Boyard; Minh Ha Tran; Mathias Chapon; Céline Chaumette; Juliette Amaudruz; Victoria Ganem; Serge Sancho; Aurore Girmens; Hendrik P.N. Scholl; Rupert W. Strauss; Yulia Wolfson; Syed Mahmood Shah; Mohamed Ahmed; Etienne Schönbach; Robert Wojciechowski; Shazia Khan; David G. Emmert; Dennis Cain; Mark Herring; Jennifer Bassinger; Lisa Liberto; Sheila K. West; Beatriz Munoz; Kong Kong; Kurt Dreger; Jennifer Jones; Robert Burke; Srinivas Sadda; Michael S. Ip; Anamika Jha; Alex Ho; 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

doi:10.1001/jamaophthalmol.2018.2198

Visual acuity change over 24 months and its association with foveal phenotype and genotype in individuals with stargardt disease progstar study report no. 10

Xiangrong Kong, Kaoru Fujinami, Rupert W. Strauss, Beatriz Munoz, Sheila K. West, Artur V. Cideciyan, Michel Michaelides, Mohamed Ahmed, Ann Margret Ervin, Etienne Schönbach, Janet K. Cheetham, Hendrik P.N. Scholl, Hendrik P.N. Scholl, Rupert W. Strauss, Yulia Wolfson, Millena Bittencourt, Syed Mahmood Shah, Mohamed Ahmed, Etienne Schönbach, Kaoru FujinamiElias Traboulsi, Justis Ehlers, Meghan Marino, Susan Crowe, Rachael Briggs, Angela Borer, Anne Pinter, Tami Fecko, Nikki Burgnoni, Janet S. Sunness, Carol Applegate, Leslie Russell, Michel Michaelides, 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 Lewis, 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, David Birch, Yi Zhong Wang, Luis Rodriguez, Kirsten Locke, Martin Klein, Paulina Mejia, Artur V. Cideciyan, 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, José Alain Sahel, Saddek Mohand-Said, Isabelle Audo, Caroline Laurent-Coriat, Ieva Sliesoraityte, Christina Zeitz, Fiona Boyard, Minh Ha Tran, Mathias Chapon, Céline Chaumette, Juliette Amaudruz, Victoria Ganem, Serge Sancho, Aurore Girmens, Hendrik P.N. Scholl, Rupert W. Strauss, Yulia Wolfson, Syed Mahmood Shah, Mohamed Ahmed, Etienne Schönbach, Robert Wojciechowski, Shazia Khan, David G. Emmert, Dennis Cain, Mark Herring, Jennifer Bassinger, Lisa Liberto, Sheila K. West, Beatriz Munoz, Kong Kong, Kurt Dreger, Jennifer Jones, Robert Burke, Srinivas Sadda, Michael S. Ip, Anamika Jha, Alex Ho, 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: Contribution to journal › Article › peer-review

22 Scopus citations

Abstract

IMPORTANCE: Limited data from prospective studies are available to understand the natural history of ABCA4-related Stargardt disease (STGD1). Such data are important for determining appropriate outcome measures for future STGD1 trials. OBJECTIVE: To estimate the rate of loss of best-corrected visual acuity (BCVA) during 2 years and to estimate the associations of BCVA loss with foveal phenotype and genotype in patients with STGD1. DESIGN, SETTING, AND PARTICIPANTS This multicenter prospective cohort study included 259 participants (489 study eyes) with molecularly confirmed STGD1 who were 6 years or older. The participants were enrolled at 9 centers in the United States and Europe and were followed up every 6 months for 2 years. EXPOSURES: Baseline BCVA and presence and type of foveal lesion (determined via fundus autofluorescence images) and genotype (classified into 4 groups based on the number and pathogenicity of ABCA4 mutations). MAIN OUTCOMES AND MEASURES: Rate of BCVA change per year. RESULTS: The mean (SD) age was 33 (15) years. Of 259 the participants, 141 (54%) were female, and 222 (85%) were white. The overall rate of BCVA loss was 0.55 (95% CI, 0.20-0.90) letters per year during the 2 years. Eyes with baseline BCVA worse than 20/200 showed an improvement of 0.65 (95% CI, 0.1-1.2) letters per year. At baseline, the mean BCVA for eyes without foveal lesion was 20/32, and their BCVA change rate over time was 0.1 (95% CI, −1.2 to 1.35) letters per year (P = .89). Eyes with a foveal lesion but having BCVA of 20/70 or better at baseline lost BCVA at a rate of 3 (95% CI, 1.5-4.4) letters per year (P < .001). Genotype was neither associated with baseline BCVA nor with the rate of BCVA change during the follow-up. CONCLUSIONS AND RELEVANCE: A clinically small BCVA loss was observed during 2 years, and the change rate varied depending on baseline BCVA. Eyes without lesion in the fovea had better BCVA at baseline and showed minimal change of BCVA throughout 2 years. Eyes with no or modest acuity impairment but with a foveal lesion at baseline had the fastest loss rate. For trials of STGD1 with 2 years of duration, it may be difficult to show efficacy using BCVA as an end point owing to its slow rate of change over this time.

Original language	English (US)
Pages (from-to)	920-928
Number of pages	9
Journal	JAMA ophthalmology
Volume	136
Issue number	8
DOIs	https://doi.org/10.1001/jamaophthalmol.2018.2198
State	Published - Aug 2018

ASJC Scopus subject areas

Ophthalmology

Access to Document

10.1001/jamaophthalmol.2018.2198

Cite this

Kong, X., Fujinami, K., Strauss, R. W., Munoz, B., West, S. K., Cideciyan, A. V., Michaelides, M., Ahmed, M., Ervin, A. M., Schönbach, E., Cheetham, J. K., Scholl, H. P. N., Scholl, H. P. N., Strauss, R. W., Wolfson, Y., Bittencourt, M., Shah, S. M., Ahmed, M., Schönbach, E., ... Smith, M. (2018). Visual acuity change over 24 months and its association with foveal phenotype and genotype in individuals with stargardt disease progstar study report no. 10. JAMA ophthalmology, 136(8), 920-928. https://doi.org/10.1001/jamaophthalmol.2018.2198

Kong, X, Fujinami, K, Strauss, RW, Munoz, B, West, SK, Cideciyan, AV, Michaelides, M, Ahmed, M, Ervin, AM, Schönbach, E, Cheetham, JK, Scholl, HPN, Scholl, HPN, Strauss, RW, Wolfson, Y, Bittencourt, M, Shah, SM, Ahmed, M, Schönbach, 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, Michaelides, M, 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, Narvaez, DIC, Barnard, K, Grigg, C, Dunbar, H, Obadeyi, Y, Girard-Claudon, K, Swann, H, Rughani, A, Amoah, C, Carrington, D, Bibi, K, Ting Co, E, Illiyas, MN, Begum, H, Carter, A, Georgiou, A, Lewis, S, Shaheen, S, Shinmar, H, Burton, L, Bernstein, P, Wegner, K, Sawyer, BL, Carlstrom, B, Farnsworth, K, Fry, C, Chandler, M, Jenkins, G, Creel, D, Birch, D, Wang, YZ, Rodriguez, L, Locke, K, Klein, M, Mejia, P, Cideciyan, AV, 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, Mohand-Said, S, 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, Scholl, HPN, Strauss, RW, Wolfson, Y, Shah, SM, Ahmed, M, Schönbach, E, Wojciechowski, R, Khan, S, Emmert, DG, Cain, D, Herring, M, Bassinger, J, Liberto, L, West, SK, Munoz, B, Kong, K, Dreger, K, Jones, J, Burke, R, Sadda, S, Ip, MS, Jha, A, Ho, A, 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 2018, 'Visual acuity change over 24 months and its association with foveal phenotype and genotype in individuals with stargardt disease progstar study report no. 10', JAMA ophthalmology, vol. 136, no. 8, pp. 920-928. https://doi.org/10.1001/jamaophthalmol.2018.2198

@article{7cf8669ff4dc43358270ad6745ad6a27,

title = "Visual acuity change over 24 months and its association with foveal phenotype and genotype in individuals with stargardt disease progstar study report no. 10",

abstract = "IMPORTANCE: Limited data from prospective studies are available to understand the natural history of ABCA4-related Stargardt disease (STGD1). Such data are important for determining appropriate outcome measures for future STGD1 trials. OBJECTIVE: To estimate the rate of loss of best-corrected visual acuity (BCVA) during 2 years and to estimate the associations of BCVA loss with foveal phenotype and genotype in patients with STGD1. DESIGN, SETTING, AND PARTICIPANTS This multicenter prospective cohort study included 259 participants (489 study eyes) with molecularly confirmed STGD1 who were 6 years or older. The participants were enrolled at 9 centers in the United States and Europe and were followed up every 6 months for 2 years. EXPOSURES: Baseline BCVA and presence and type of foveal lesion (determined via fundus autofluorescence images) and genotype (classified into 4 groups based on the number and pathogenicity of ABCA4 mutations). MAIN OUTCOMES AND MEASURES: Rate of BCVA change per year. RESULTS: The mean (SD) age was 33 (15) years. Of 259 the participants, 141 (54%) were female, and 222 (85%) were white. The overall rate of BCVA loss was 0.55 (95% CI, 0.20-0.90) letters per year during the 2 years. Eyes with baseline BCVA worse than 20/200 showed an improvement of 0.65 (95% CI, 0.1-1.2) letters per year. At baseline, the mean BCVA for eyes without foveal lesion was 20/32, and their BCVA change rate over time was 0.1 (95% CI, −1.2 to 1.35) letters per year (P = .89). Eyes with a foveal lesion but having BCVA of 20/70 or better at baseline lost BCVA at a rate of 3 (95% CI, 1.5-4.4) letters per year (P < .001). Genotype was neither associated with baseline BCVA nor with the rate of BCVA change during the follow-up. CONCLUSIONS AND RELEVANCE: A clinically small BCVA loss was observed during 2 years, and the change rate varied depending on baseline BCVA. Eyes without lesion in the fovea had better BCVA at baseline and showed minimal change of BCVA throughout 2 years. Eyes with no or modest acuity impairment but with a foveal lesion at baseline had the fastest loss rate. For trials of STGD1 with 2 years of duration, it may be difficult to show efficacy using BCVA as an end point owing to its slow rate of change over this time.",

author = "Xiangrong Kong and Kaoru Fujinami and Strauss, {Rupert W.} and Beatriz Munoz and West, {Sheila K.} and Cideciyan, {Artur V.} and Michel Michaelides and Mohamed Ahmed and Ervin, {Ann Margret} and Etienne Sch{\"o}nbach and Cheetham, {Janet K.} and Scholl, {Hendrik P.N.} and Scholl, {Hendrik P.N.} and Strauss, {Rupert W.} and Yulia Wolfson and Millena Bittencourt and Shah, {Syed Mahmood} and Mohamed Ahmed and Etienne Sch{\"o}nbach 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 Michel Michaelides 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 Narvaez, {Daniela Ivanova Cajas} 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 {Ting Co}, Emerson and Illiyas, {Mohamed Nafaz} and Hamida Begum and Andrew Carter and Anne Georgiou and Selma Lewis and Saddaf Shaheen and Harpreet Shinmar and Linda Burton and Paul Bernstein and Kimberley Wegner and Sawyer, {Briana Lauren} and Bonnie Carlstrom and Kellian Farnsworth and Cyrie Fry and Melissa Chandler and Glen Jenkins and Donnel Creel and David Birch and Wang, {Yi Zhong} and Luis Rodriguez and Kirsten Locke and Martin Klein and Paulina Mejia and Cideciyan, {Artur V.} 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, {Jos{\'e} Alain} and Saddek Mohand-Said and Isabelle Audo and Caroline Laurent-Coriat and Ieva Sliesoraityte and Christina Zeitz and Fiona Boyard and Tran, {Minh Ha} and Mathias Chapon and C{\'e}line Chaumette and Juliette Amaudruz and Victoria Ganem and Serge Sancho and Aurore Girmens and Scholl, {Hendrik P.N.} and Strauss, {Rupert W.} and Yulia Wolfson and Shah, {Syed Mahmood} and Mohamed Ahmed and Etienne Sch{\"o}nbach and Robert Wojciechowski and Shazia Khan and Emmert, {David G.} and Dennis Cain and Mark Herring and Jennifer Bassinger and Lisa Liberto and West, {Sheila K.} and Beatriz Munoz and Kong Kong and Kurt Dreger and Jennifer Jones and Robert Burke and Srinivas Sadda and Ip, {Michael S.} and Anamika Jha and Alex Ho 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",

year = "2018",

month = aug,

doi = "10.1001/jamaophthalmol.2018.2198",

language = "English (US)",

volume = "136",

pages = "920--928",

journal = "JAMA ophthalmology",

issn = "2168-6165",

publisher = "American Medical Association",

number = "8",

}

TY - JOUR

T1 - Visual acuity change over 24 months and its association with foveal phenotype and genotype in individuals with stargardt disease progstar study report no. 10

AU - Kong, Xiangrong

AU - Fujinami, Kaoru

AU - Strauss, Rupert W.

AU - Munoz, Beatriz

AU - West, Sheila K.

AU - Cideciyan, Artur V.

AU - Michaelides, Michel

AU - Ahmed, Mohamed

AU - Ervin, Ann Margret

AU - Schönbach, Etienne

AU - Cheetham, Janet K.

AU - Scholl, Hendrik P.N.

AU - Strauss, Rupert W.

AU - Wolfson, Yulia

AU - Bittencourt, Millena

AU - Shah, Syed Mahmood

AU - Ahmed, Mohamed

AU - Schönbach, 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 - Michaelides, Michel

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 - Narvaez, Daniela Ivanova 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 - Ting Co, Emerson

AU - Illiyas, Mohamed Nafaz

AU - Begum, Hamida

AU - Carter, Andrew

AU - Georgiou, Anne

AU - Lewis, Selma

AU - Shaheen, Saddaf

AU - Shinmar, Harpreet

AU - Burton, Linda

AU - Bernstein, Paul

AU - Wegner, Kimberley

AU - Sawyer, Briana Lauren

AU - Carlstrom, Bonnie

AU - Farnsworth, Kellian

AU - Fry, Cyrie

AU - Chandler, Melissa

AU - Jenkins, Glen

AU - Creel, Donnel

AU - Birch, David

AU - Wang, Yi Zhong

AU - Rodriguez, Luis

AU - Locke, Kirsten

AU - Klein, Martin

AU - Mejia, Paulina

AU - Cideciyan, Artur V.

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, José Alain

AU - Mohand-Said, Saddek

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, Céline

AU - Amaudruz, Juliette

AU - Ganem, Victoria

AU - Sancho, Serge

AU - Girmens, Aurore

AU - Scholl, Hendrik P.N.

AU - Strauss, Rupert W.

AU - Wolfson, Yulia

AU - Shah, Syed Mahmood

AU - Ahmed, Mohamed

AU - Schönbach, Etienne

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 K.

AU - Munoz, Beatriz

AU - Kong, Kong

AU - Dreger, Kurt

AU - Jones, Jennifer

AU - Burke, Robert

AU - Sadda, Srinivas

AU - Ip, Michael S.

AU - Jha, Anamika

AU - Ho, Alex

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

PY - 2018/8

Y1 - 2018/8

N2 - IMPORTANCE: Limited data from prospective studies are available to understand the natural history of ABCA4-related Stargardt disease (STGD1). Such data are important for determining appropriate outcome measures for future STGD1 trials. OBJECTIVE: To estimate the rate of loss of best-corrected visual acuity (BCVA) during 2 years and to estimate the associations of BCVA loss with foveal phenotype and genotype in patients with STGD1. DESIGN, SETTING, AND PARTICIPANTS This multicenter prospective cohort study included 259 participants (489 study eyes) with molecularly confirmed STGD1 who were 6 years or older. The participants were enrolled at 9 centers in the United States and Europe and were followed up every 6 months for 2 years. EXPOSURES: Baseline BCVA and presence and type of foveal lesion (determined via fundus autofluorescence images) and genotype (classified into 4 groups based on the number and pathogenicity of ABCA4 mutations). MAIN OUTCOMES AND MEASURES: Rate of BCVA change per year. RESULTS: The mean (SD) age was 33 (15) years. Of 259 the participants, 141 (54%) were female, and 222 (85%) were white. The overall rate of BCVA loss was 0.55 (95% CI, 0.20-0.90) letters per year during the 2 years. Eyes with baseline BCVA worse than 20/200 showed an improvement of 0.65 (95% CI, 0.1-1.2) letters per year. At baseline, the mean BCVA for eyes without foveal lesion was 20/32, and their BCVA change rate over time was 0.1 (95% CI, −1.2 to 1.35) letters per year (P = .89). Eyes with a foveal lesion but having BCVA of 20/70 or better at baseline lost BCVA at a rate of 3 (95% CI, 1.5-4.4) letters per year (P < .001). Genotype was neither associated with baseline BCVA nor with the rate of BCVA change during the follow-up. CONCLUSIONS AND RELEVANCE: A clinically small BCVA loss was observed during 2 years, and the change rate varied depending on baseline BCVA. Eyes without lesion in the fovea had better BCVA at baseline and showed minimal change of BCVA throughout 2 years. Eyes with no or modest acuity impairment but with a foveal lesion at baseline had the fastest loss rate. For trials of STGD1 with 2 years of duration, it may be difficult to show efficacy using BCVA as an end point owing to its slow rate of change over this time.

AB - IMPORTANCE: Limited data from prospective studies are available to understand the natural history of ABCA4-related Stargardt disease (STGD1). Such data are important for determining appropriate outcome measures for future STGD1 trials. OBJECTIVE: To estimate the rate of loss of best-corrected visual acuity (BCVA) during 2 years and to estimate the associations of BCVA loss with foveal phenotype and genotype in patients with STGD1. DESIGN, SETTING, AND PARTICIPANTS This multicenter prospective cohort study included 259 participants (489 study eyes) with molecularly confirmed STGD1 who were 6 years or older. The participants were enrolled at 9 centers in the United States and Europe and were followed up every 6 months for 2 years. EXPOSURES: Baseline BCVA and presence and type of foveal lesion (determined via fundus autofluorescence images) and genotype (classified into 4 groups based on the number and pathogenicity of ABCA4 mutations). MAIN OUTCOMES AND MEASURES: Rate of BCVA change per year. RESULTS: The mean (SD) age was 33 (15) years. Of 259 the participants, 141 (54%) were female, and 222 (85%) were white. The overall rate of BCVA loss was 0.55 (95% CI, 0.20-0.90) letters per year during the 2 years. Eyes with baseline BCVA worse than 20/200 showed an improvement of 0.65 (95% CI, 0.1-1.2) letters per year. At baseline, the mean BCVA for eyes without foveal lesion was 20/32, and their BCVA change rate over time was 0.1 (95% CI, −1.2 to 1.35) letters per year (P = .89). Eyes with a foveal lesion but having BCVA of 20/70 or better at baseline lost BCVA at a rate of 3 (95% CI, 1.5-4.4) letters per year (P < .001). Genotype was neither associated with baseline BCVA nor with the rate of BCVA change during the follow-up. CONCLUSIONS AND RELEVANCE: A clinically small BCVA loss was observed during 2 years, and the change rate varied depending on baseline BCVA. Eyes without lesion in the fovea had better BCVA at baseline and showed minimal change of BCVA throughout 2 years. Eyes with no or modest acuity impairment but with a foveal lesion at baseline had the fastest loss rate. For trials of STGD1 with 2 years of duration, it may be difficult to show efficacy using BCVA as an end point owing to its slow rate of change over this time.

UR - http://www.scopus.com/inward/record.url?scp=85051348236&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85051348236&partnerID=8YFLogxK

U2 - 10.1001/jamaophthalmol.2018.2198

DO - 10.1001/jamaophthalmol.2018.2198

M3 - Article

C2 - 29902293

AN - SCOPUS:85051348236

SN - 2168-6165

VL - 136

SP - 920

EP - 928

JO - JAMA ophthalmology

JF - JAMA ophthalmology

IS - 8

ER -

Visual acuity change over 24 months and its association with foveal phenotype and genotype in individuals with stargardt disease progstar study report no. 10

Abstract

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this