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Faster Sensitivity Loss around Dense Scotomas than for Overall Macular Sensitivity in Stargardt Disease: ProgStar Report No. 14

2020; Elsevier BV; Volume: 216; Linguagem: Inglês

10.1016/j.ajo.2020.03.020

1879-1891

Etienne M. Schönbach, Rupert W. Strauß, Mohamed Ibrahim, Jessica L. Janes, David G. Birch, Artur V. Cideciyan, Janet S. Sunness, Beatriz Muñoz, Michael S. Ip, Srinivas R. Sadda, Hendrik P. N. Scholl, Hendrik P. N. Scholl, Rupert W. Strauß, Yulia Wolfson, Millena Bittencourt, Syed Mahmood Shah, Mohamed Ahmed, Etienne M. Schönbach, Kaoru Fujinami, Elias I. Traboulsi, Justis P. Ehlers, Meghan J. Marino, Susan Crowe, Rachael Briggs, Angela Borer, Anne Pinter, Tami Fecko, Nikki Burgnoni, Janet S. Sunness, Carol A. Applegate, Leslie Russell, Michel Michaelides, Simona Degli Esposti, Anthony T. Moore, Andrew R. Webster, Sophie Connor, Jade Barnfield, Zaid Salchi, Clara Alfageme, Victoria McCudden, Maria Pefkianaki, Jonathan Aboshiha, Gerald Liew, Graham E. Holder, Anthony G. 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, Mohamed Nafaz Illiyas, Hamida Begum, Andrew Carter, Anne Georgiou, Selma Lewism, Saddaf Shaheen, Harpreet Shinmar, Linda M. Burton, Paul S. Bernstein, Kimberley Wegner, Briana Lauren Sawyer, Bonnie Carlstrom, Kellian Farnsworth, Cyrie Fry, Melissa Chandler, Glen Jenkins, Donnel Creel, David G. Birch, Yi‐Zhong Wang, Luis Rodriguez, Kirsten Locke, Martin Klein, Paulina Mejia, Artur V. Cideciyan, Samuel G. Jacobson, Sharon Schwartz, Rodrigo Matsui, Michaela Gruzensky, Jason Charng, Alejandro J. Román, Eberhart Zrenner, Fadi Nasser, Gesa Astrid Hahn, Barbara Wilhelm, Tobias Peters, Benjamin Beier, Tilman Koenig, Susanne Krämer, José‐Alain Sahel, Saddek Mohand‐Saïd, Isabelle Audo, Caroline Laurent‐Coriat, Ieva Sliesoraitytė, Christina Zeitz, Fiona Boyard, Minh Ha Tran, Mathias Chapon, Céline Chaumette, Juliette Amaudruz, Victoria J. Ganem, Serge Sancho, Aurore Girmens, Hendrik P. N. Scholl, Rupert W. Strauß, Yulia Wolfson, Syed Mahmood Shah, Mohamed Ahmed, Etienne M. Schönbach, Robert Wojciechowski, Shazia Khan, David Emmert, Dennis Cain, Mark Herring, Jennifer Bassinger, Lisa Liberto, Sheila K. West, Ann‐Margret Ervin, Beatriz Muñoz, Xiangrong Kong, Kurt Dreger, Jennifer M. Jones, Srinivas R. Sadda, Michael S. Ip, Anamika Jha, Alexander 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 Akıl, Jhanisus Melendez, Jianqin Lei, Jianyan Huang, Jonathan Chau, Khalil Ghasemi Falavarjani, Kristina Espino, Manfred Li, Maria A. Mendoza, Muneeswar Gupta Nittala, Netali Roded, Nizar Saleh, Ping Huang, Sean Pitetta, Siva Balasubramanian, Sophie Leahy, Sowmya J. Srinivas, Swetha Bindu Velaga, Teresa Margaryan, Tudor Tepelus, Tyler Brown, Wenying Fan, Yamileth Murillo, Yue Shi, Katherine Elizabeth Gonzaga Aguilar, Cynthia Chan, Lisa Santos, Brian Seo, Christopher Sison, Silvia Pérez, 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 K. Oberoi, Mark Romero, Vivian Chiguil, Grantley Bynum-Bain, Monica Kim, Carolina Mendiguren, Xiwen Huang, Monika Smith, Teresa Margaryan, Natalie Sarreal,

Ophthalmology and Visual Impairment Studies

•This study reports a novel automated approach to quantify progression of visual dysfunction.•This automated approach was validated relative to a manual grading.•The progression rate at the disease front in Stargardt disease is reported.•The new method may allow shorter clinical trials or smaller cohorts or both. PurposeMean sensitivity (MS) derived from a standard test grid using microperimetry is a sensitive outcome measure in clinical trials investigating new treatments for degenerative retinal diseases. This study hypothesizes that the functional decline is faster at the edge of the dense scotoma (eMS) than by using the overall MS.DesignMulticenter, international, prospective cohort study: ProgStar Study.MethodsStargardt disease type 1 patients (carrying at least 1 mutation in the ABCA4 gene) were followed over 12 months using microperimetry with a Humphrey 10-2 test grid. Customized software was developed to automatically define and selectively follow the test points directly adjacent to the dense scotoma points and to calculate their mean sensitivity (eMS).ResultsAmong 361 eyes (185 patients), the mean age was 32.9 ± 15.1 years old. At baseline, MS was 10.4 ± 5.2 dB (n = 361), and the eMS was 9.3 ± 3.3 dB (n = 335). The yearly progression rate of MS (1.5 ± 2.1 dB/year) was significantly lower (β = −1.33; P < .001) than that for eMS (2.9 ± 2.9 dB/year). There were no differences between progression rates using automated grading and those using manual grading (β = .09; P = .461).ConclusionsIn Stargardt disease type 1, macular sensitivity declines significantly faster at the edge of the dense scotoma than in the overall test grid. An automated, time-efficient approach for extracting and grading eMS is possible and appears valid. Thus, eMS offers a valuable tool and sensitive outcome parameter with which to follow Stargardt patients in clinical trials, allowing clinical trial designs with shorter duration and/or smaller cohorts. Mean sensitivity (MS) derived from a standard test grid using microperimetry is a sensitive outcome measure in clinical trials investigating new treatments for degenerative retinal diseases. This study hypothesizes that the functional decline is faster at the edge of the dense scotoma (eMS) than by using the overall MS. Multicenter, international, prospective cohort study: ProgStar Study. Stargardt disease type 1 patients (carrying at least 1 mutation in the ABCA4 gene) were followed over 12 months using microperimetry with a Humphrey 10-2 test grid. Customized software was developed to automatically define and selectively follow the test points directly adjacent to the dense scotoma points and to calculate their mean sensitivity (eMS). Among 361 eyes (185 patients), the mean age was 32.9 ± 15.1 years old. At baseline, MS was 10.4 ± 5.2 dB (n = 361), and the eMS was 9.3 ± 3.3 dB (n = 335). The yearly progression rate of MS (1.5 ± 2.1 dB/year) was significantly lower (β = −1.33; P < .001) than that for eMS (2.9 ± 2.9 dB/year). There were no differences between progression rates using automated grading and those using manual grading (β = .09; P = .461). In Stargardt disease type 1, macular sensitivity declines significantly faster at the edge of the dense scotoma than in the overall test grid. An automated, time-efficient approach for extracting and grading eMS is possible and appears valid. Thus, eMS offers a valuable tool and sensitive outcome parameter with which to follow Stargardt patients in clinical trials, allowing clinical trial designs with shorter duration and/or smaller cohorts.