TY - JOUR
T1 - Faster Sensitivity Loss around Dense Scotomas than for Overall Macular Sensitivity in Stargardt Disease
T2 - ProgStar Report No. 14
AU - ProgStar Study Group
AU - Schönbach, Etienne M.
AU - Strauss, Rupert W.
AU - Ibrahim, Mohamed A.
AU - Janes, Jessica L.
AU - Birch, David G.
AU - Cideciyan, Artur V.
AU - Sunness, Janet S.
AU - Muñoz, Beatriz
AU - Ip, Michael S.
AU - Sadda, Srini Vas R.
AU - Scholl, Hendrik P.N.
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 - Applegate, Carol
AU - Russell, Leslie
AU - Michaelides, Michel
AU - Degli Esposti, Simona
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 - Cajas Narvaez, Daniela Ivanova
AU - Barnard, Katy
AU - Wojciechowski, Robert
AU - West, Sheila
AU - Ervin, Ann Margret
AU - Munoz, Beatriz
AU - Kong, Xiangrong
N1 - Funding Information:
All authors have completed and submitted the ICMJE form for Disclosure of Potential Conflicts of Interest and none were reported. Funding/Support: ProgStar was supported by Foundation Fighting Blindness (FFB), Clinical Research Institute (Columbia, Maryland), and US Army Medical Research and Materiel Command Telemedicine and Advanced Technology Research Center to FFB (Fort Meade, Maryland) grants W81-XWH-07-1-0720 and W81-XWH-09-2-0189. Financial Disclosures: R.W.S. is supported by the Austrian Science Fund (Vienna, Austria; FWF; project J 3383-B23) and FFB Clinical Research Institute (Columbia, Maryland). E.M.S. is supported by German National Academy of Sciences Leopoldina grant LPDS 2015-14. R.W.S. is supported by the Austrian Science Fund (Vienna, Austria; FWF; Project J 3383-B23) and FFB Clinical Research Institute (Columbia, Maryland). D.G.B. is a consultant for AGTC (Alachua, Florida), Genentech (South San Francisco, California), Nightstar (London, England), and Nacuity (Ft. Worth, Texas); and by FFB Clinical Research Institute (Columbia, Maryland). J.S.S. is a consultant for Genentech (San Francisco, CA); and is a member of the the scientific advisory boards of Acucela (Tokyo, Japan) and Apellis (Crestwood, Kentucky); and is a member of the data safety and monitoring committee for Cell Cure's OpRegen study (Jerusalem, Israel). M.S.I. is a consultant for Omeros, Thrombogenics and Boehringer Ingelheim. S.V.R.S. is supported by Allergan (Dublin, Republic of Ireland), Carl Zeiss Meditec (Jena, Germany), Genentech (San Francisco, CA), and Optos (Dunfermline, UK); and is a consultant for Allergan, CenterVue (Padova, Italy), Genentech, Heidelberg Engineering (Heidelberg, Germany), Iconic Therapeutics, Inc. (San Francisco, CA), NightstarX (London, UK), Novartis (Basel, Switzerland), Optos, Thrombogenics, and Topcon (Tokyo, Japan). H.P.S. is a member of the data monitoring committees for Genentech, Hoffmann-La Roche (Basel, Switzerland), Genzyme (Newark, CA)/Sanofi (Paris, France), and ReNeuron Group Plc (Guildford, UK,)/Ora Inc. (Andover, MA); and is a member of the steering committee of Novo Nordisk; and is on the scientific advisory boards of Astellas Institute for Regenerative Medicine (Chūō, Tokyo), Gensight Biologics (Paris, France), Ionis Pharmaceuticals, (Carlsbad, CA), Pharma Research and Early Development, and Hoffmann-La Roche; and is a consultant for Boehringer Ingelheim, Daiichi Sankyo, Gerson Lehrman Group (New York, NY), Guidepoint (New York, NY); and has received research support from Acucela, Kinarus AG, NightstaRx, Ophthotech, and Spark Therapeutics England. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The authors thank Dr. Marco Cattaneo, University of Basel, Switzerland, for additional statistical advice.
Funding Information:
Financial Disclosures: R.W.S. is supported by the Austrian Science Fund (Vienna, Austria; FWF; project J 3383-B23) and FFB Clinical Research Institute (Columbia, Maryland). E.M.S. is supported by German National Academy of Sciences Leopoldina grant LPDS 2015-14.
Funding Information:
Funding/Support: ProgStar was supported by Foundation Fighting Blindness (FFB) , Clinical Research Institute (Columbia, Maryland), and US Army Medical Research and Materiel Command Telemedicine and Advanced Technology Research Center to FFB (Fort Meade, Maryland) grants W81-XWH-07-1-0720 and W81-XWH-09-2-0189 .
Funding Information:
R.W.S. is supported by the Austrian Science Fund (Vienna, Austria; FWF; Project J 3383-B23) and FFB Clinical Research Institute (Columbia, Maryland). D.G.B. is a consultant for AGTC (Alachua, Florida), Genentech (South San Francisco, California), Nightstar (London, England), and Nacuity (Ft. Worth, Texas); and by FFB Clinical Research Institute (Columbia, Maryland). J.S.S. is a consultant for Genentech (San Francisco, CA); and is a member of the the scientific advisory boards of Acucela (Tokyo, Japan) and Apellis (Crestwood, Kentucky); and is a member of the data safety and monitoring committee for Cell Cure's OpRegen study (Jerusalem, Israel). M.S.I. is a consultant for Omeros, Thrombogenics and Boehringer Ingelheim. S.V.R.S. is supported by Allergan (Dublin, Republic of Ireland), Carl Zeiss Meditec (Jena, Germany), Genentech (San Francisco, CA), and Optos (Dunfermline, UK); and is a consultant for Allergan, CenterVue (Padova, Italy), Genentech, Heidelberg Engineering (Heidelberg, Germany), Iconic Therapeutics, Inc. (San Francisco, CA), NightstarX (London, UK), Novartis (Basel, Switzerland), Optos, Thrombogenics, and Topcon (Tokyo, Japan). H.P.S. is a member of the data monitoring committees for Genentech, Hoffmann-La Roche (Basel, Switzerland), Genzyme (Newark, CA)/Sanofi (Paris, France), and ReNeuron Group Plc (Guildford, UK,)/Ora Inc. (Andover, MA); and is a member of the steering committee of Novo Nordisk; and is on the scientific advisory boards of Astellas Institute for Regenerative Medicine (Chūō, Tokyo), Gensight Biologics (Paris, France), Ionis Pharmaceuticals, (Carlsbad, CA), Pharma Research and Early Development, and Hoffmann-La Roche; and is a consultant for Boehringer Ingelheim, Daiichi Sankyo, Gerson Lehrman Group (New York, NY), Guidepoint (New York, NY); and has received research support from Acucela, Kinarus AG, NightstaRx, Ophthotech, and Spark Therapeutics England. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.
Publisher Copyright:
© 2020 The Author(s)
PY - 2020/8
Y1 - 2020/8
N2 - Purpose: 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. Design: Multicenter, international, prospective cohort study: ProgStar Study. Methods: 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). Results: 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). Conclusions: 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.
AB - Purpose: 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. Design: Multicenter, international, prospective cohort study: ProgStar Study. Methods: 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). Results: 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). Conclusions: 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.
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U2 - 10.1016/j.ajo.2020.03.020
DO - 10.1016/j.ajo.2020.03.020
M3 - Article
C2 - 32222369
AN - SCOPUS:85085899720
SN - 0002-9394
VL - 216
SP - 219
EP - 225
JO - American journal of ophthalmology
JF - American journal of ophthalmology
ER -