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