Longitudinal Changes of Fixation Location and Stability Within 12 Months in Stargardt Disease: ProgStar Report No. 12

ProgStar Study Group

doi:10.1016/j.ajo.2018.06.003

Longitudinal Changes of Fixation Location and Stability Within 12 Months in Stargardt Disease: ProgStar Report No. 12

ProgStar Study Group

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

Purpose: To investigate the natural history of Stargardt disease (STGD1) using fixation location and fixation stability. Design: Multicenter, international, prospective cohort study. Methods: Fixation testing was performed using the Nidek MP-1 microperimeter as part of the prospective, multicenter, natural history study on the Progression of Stargardt disease (ProgStar). A total of 238 patients with ABCA4-related STGD1 were enrolled at baseline (bilateral enrollment in 86.6%) and underwent repeat testing at months 6 and 12. Results: Outcome measures included the distance of the preferred retinal locus from the fovea (PRL) and the bivariate contour ellipse area (BCEA). After 12 months of follow-up, the change in the eccentricity of the PRL from the anatomic fovea was −0.0014 degrees (95% confidence interval [CI], −0.27 degrees, 0.27 degrees; P =.99). The deterioration in the stability of fixation as expressed by a larger BCEA encompassing 1 standard deviation of all fixation points was 1.21 degrees squared (deg ² ) (95% CI, −1.23 deg ² , 3.65 deg ² ; P =.33). Eyes with increases and decreases in PRL eccentricity and/or BCEA values were observed. Conclusions: Our observations point to the complexity of fixation parameters. The association of increasingly eccentric and unstable fixation with longer disease duration that is typically found in cross-sectional studies may be countered within individual patients by poorly understood processes like neuronal adaptation. Nevertheless, fixation parameters may serve as useful secondary outcome parameters in selected cases and for counseling patients to explain changes to their visual functionality.

Original language	English (US)
Pages (from-to)	54-61
Number of pages	8
Journal	American journal of ophthalmology
Volume	193
DOIs	https://doi.org/10.1016/j.ajo.2018.06.003
State	Published - Sep 2018

ASJC Scopus subject areas

Ophthalmology

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10.1016/j.ajo.2018.06.003

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@article{63f8c63af9da4916a30bf1209fdedeb6,

title = "Longitudinal Changes of Fixation Location and Stability Within 12 Months in Stargardt Disease: ProgStar Report No. 12",

abstract = " Purpose: To investigate the natural history of Stargardt disease (STGD1) using fixation location and fixation stability. Design: Multicenter, international, prospective cohort study. Methods: Fixation testing was performed using the Nidek MP-1 microperimeter as part of the prospective, multicenter, natural history study on the Progression of Stargardt disease (ProgStar). A total of 238 patients with ABCA4-related STGD1 were enrolled at baseline (bilateral enrollment in 86.6%) and underwent repeat testing at months 6 and 12. Results: Outcome measures included the distance of the preferred retinal locus from the fovea (PRL) and the bivariate contour ellipse area (BCEA). After 12 months of follow-up, the change in the eccentricity of the PRL from the anatomic fovea was −0.0014 degrees (95% confidence interval [CI], −0.27 degrees, 0.27 degrees; P =.99). The deterioration in the stability of fixation as expressed by a larger BCEA encompassing 1 standard deviation of all fixation points was 1.21 degrees squared (deg 2 ) (95% CI, −1.23 deg 2 , 3.65 deg 2 ; P =.33). Eyes with increases and decreases in PRL eccentricity and/or BCEA values were observed. Conclusions: Our observations point to the complexity of fixation parameters. The association of increasingly eccentric and unstable fixation with longer disease duration that is typically found in cross-sectional studies may be countered within individual patients by poorly understood processes like neuronal adaptation. Nevertheless, fixation parameters may serve as useful secondary outcome parameters in selected cases and for counseling patients to explain changes to their visual functionality.",

author = "{ProgStar Study Group} and Sch{\"o}nbach, {Etienne M.} and Strauss, {Rupert W.} and Xiangrong Kong and Beatriz Mu{\~n}oz and Ibrahim, {Mohamed A.} and Sunness, {Janet S.} and Birch, {David G.} and Hahn, {Gesa Astrid} and Fadi Nasser and Eberhart Zrenner and Sadda, {Srini Vas R.} and West, {Sheila 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 Robert Wojciechowski and Ervin, {Ann Margret}",

note = "Funding Information: Funding/Support: The ProgStar studies are supported by the Foundation Fighting Blindness (FFB) Clinical Research Institute (Columbia, Maryland, USA) and a grant by the U.S. Department of Defense USAMRMC TATRC to FFB (Fort Meade, Maryland, USA; grant numbers W81-XWH-07-1-0720 and W81-XWH-09-2-0189). Rupert W. Strauss is supported by the Austrian Science Fund (Vienna, Austria; FWF; Project number: J 3383-B23) and the Foundation Fighting Blindness Clinical Research Institute (Columbia, Maryland, USA). Etienne M. Sch{\"o}nbach is supported by the German National Academy of Sciences Leopoldina, Grant Number LPDS 2015-14 (Halle, Germany) and the Foundation Fighting Blindness Clinical Research Institute (Columbia, Maryland, USA). Financial Disclosures: Etienne M. Sch{\"o}nbach is supported by the German National Academy of Sciences Leopoldina, Grant Number LPDS 2015-14 (Halle, Germany) and the Foundation Fighting Blindness Clinical Research Institute (Columbia, Maryland, USA). Rupert W. Strauss is supported by the Austrian Science Fund (Vienna, Austria; FWF; Project number: J 3383-B23) and the Foundation Fighting Blindness Clinical Research Institute (Columbia, Maryland, USA). Janet S. Sunness is a consultant for Genentech (San Francisco, California, USA) and is on the scientific advisory board of Acucela (Tokyo, Japan) and Apellis (Crestwood, Kentucky, USA) and on the data safety and monitoring committee for Cell Cure's OpRegen study (Jerusalem, Israel). David G. Birch is a consultant for AGTC (Alachua, Florida, USA), Ionis (Carlsbad, California, USA), Genentech (South San Francisco, California, USA), Nightstar (London, England), and Nacuity (Ft. Worth, Texas, USA), and is supported by the Foundation Fighting Blindness Clinical Research Institute (FFB CRI, Columbia, Maryland). SriniVas R. Sadda is financially supported by Allergan (Dublin, Ireland), Carl Zeiss Meditec (Jena, Germany), Genentech (San Francisco, California, USA), and Optos (Dunfermline, UK), and is a consultant for Allergan (Dublin, Ireland), CenterVue (Padova, Italy), Genentech (San Francisco, California, USA), Heidelberg Engineering (Heidelberg, Germany), Iconic Therapeutics, Inc (San Francisco, California, USA), NightstarX (London, UK), Novartis (Basel, Switzerland), Optos (Dunfermline, UK), Thrombogenics (Leuven, Belgium), and Topcon (Tokyo, Japan). Sheila K. West is a scientific technical advisory committee member for the Alcon Research Institute (Fort Worth, Texas), and for Research to Prevent Blindness (New York, New York). Dr. Scholl is a paid consultant of the following entities (not including the National Institutes of Health): Fovea Pharmaceuticals/Sanofi (Paris, France); Trevena Inc. (Chesterbrook, PA); Guidepoint Global, LLC (New York, NY); Gerson Lehrman Group (New York, NY); Shire (Dublin, Republic of Ireland). Dr. Scholl is a member of the Scientific Advisory Board of Vision Medicines, Inc. Hendrik P.N. Scholl is a member of the Data Monitoring Committee of the following entities (not including the National Institutes of Health): Genentech Inc (San Francisco, California, USA)/F. Hoffmann-La Roche Ltd (Basel, Switzerland); StemCells, Inc (Newark, California, USA); Genzyme Corp (Boston, Massachusetts, USA)/Sanofi (Paris, France); he also serves as a member of the Ophthalmic Devices Panel of the Medical Devices Advisory Committee, Food and Drug Administration (FDA, Silver Spring, Maryland, USA). These arrangements have been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. Hendrik P.N. Scholl is principal investigator of grants at The Johns Hopkins University sponsored by the following entity (not including the National Institutes of Health): QLT, Inc (Vancouver, Canada). Grants to investigators at Johns Hopkins University are negotiated and administered by the institution (such as the School of Medicine) which receives the grants, typically through the Office of Research and Administration. Individual investigators who participate in the sponsored project(s) are not directly compensated by the sponsor but may receive salary or other support from the institution to support their effort on the project(s). The following authors have no financial disclosures: Xiangrong Kong, Beatriz Mu{\~n}oz, Mohamed A. Ibrahim, Gesa-Astrid Hahn, Fadi Nasser, and Eberhart Zrenner. All authors attest that they meet the current ICMJE criteria for authorship. Publisher Copyright: {\textcopyright} 2018 Elsevier Inc.",

year = "2018",

month = sep,

doi = "10.1016/j.ajo.2018.06.003",

language = "English (US)",

volume = "193",

pages = "54--61",

journal = "American journal of ophthalmology",

issn = "0002-9394",

publisher = "Elsevier USA",

}

TY - JOUR

T1 - Longitudinal Changes of Fixation Location and Stability Within 12 Months in Stargardt Disease

T2 - ProgStar Report No. 12

AU - ProgStar Study Group

AU - Schönbach, Etienne M.

AU - Strauss, Rupert W.

AU - Kong, Xiangrong

AU - Muñoz, Beatriz

AU - Ibrahim, Mohamed A.

AU - Sunness, Janet S.

AU - Birch, David G.

AU - Hahn, Gesa Astrid

AU - Nasser, Fadi

AU - Zrenner, Eberhart

AU - Sadda, Srini Vas R.

AU - West, Sheila 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 - Wojciechowski, Robert

AU - Ervin, Ann Margret

N1 - Funding Information: Funding/Support: The ProgStar studies are supported by the Foundation Fighting Blindness (FFB) Clinical Research Institute (Columbia, Maryland, USA) and a grant by the U.S. Department of Defense USAMRMC TATRC to FFB (Fort Meade, Maryland, USA; grant numbers W81-XWH-07-1-0720 and W81-XWH-09-2-0189). Rupert W. Strauss is supported by the Austrian Science Fund (Vienna, Austria; FWF; Project number: J 3383-B23) and the Foundation Fighting Blindness Clinical Research Institute (Columbia, Maryland, USA). Etienne M. Schönbach is supported by the German National Academy of Sciences Leopoldina, Grant Number LPDS 2015-14 (Halle, Germany) and the Foundation Fighting Blindness Clinical Research Institute (Columbia, Maryland, USA). Financial Disclosures: Etienne M. Schönbach is supported by the German National Academy of Sciences Leopoldina, Grant Number LPDS 2015-14 (Halle, Germany) and the Foundation Fighting Blindness Clinical Research Institute (Columbia, Maryland, USA). Rupert W. Strauss is supported by the Austrian Science Fund (Vienna, Austria; FWF; Project number: J 3383-B23) and the Foundation Fighting Blindness Clinical Research Institute (Columbia, Maryland, USA). Janet S. Sunness is a consultant for Genentech (San Francisco, California, USA) and is on the scientific advisory board of Acucela (Tokyo, Japan) and Apellis (Crestwood, Kentucky, USA) and on the data safety and monitoring committee for Cell Cure's OpRegen study (Jerusalem, Israel). David G. Birch is a consultant for AGTC (Alachua, Florida, USA), Ionis (Carlsbad, California, USA), Genentech (South San Francisco, California, USA), Nightstar (London, England), and Nacuity (Ft. Worth, Texas, USA), and is supported by the Foundation Fighting Blindness Clinical Research Institute (FFB CRI, Columbia, Maryland). SriniVas R. Sadda is financially supported by Allergan (Dublin, Ireland), Carl Zeiss Meditec (Jena, Germany), Genentech (San Francisco, California, USA), and Optos (Dunfermline, UK), and is a consultant for Allergan (Dublin, Ireland), CenterVue (Padova, Italy), Genentech (San Francisco, California, USA), Heidelberg Engineering (Heidelberg, Germany), Iconic Therapeutics, Inc (San Francisco, California, USA), NightstarX (London, UK), Novartis (Basel, Switzerland), Optos (Dunfermline, UK), Thrombogenics (Leuven, Belgium), and Topcon (Tokyo, Japan). Sheila K. West is a scientific technical advisory committee member for the Alcon Research Institute (Fort Worth, Texas), and for Research to Prevent Blindness (New York, New York). Dr. Scholl is a paid consultant of the following entities (not including the National Institutes of Health): Fovea Pharmaceuticals/Sanofi (Paris, France); Trevena Inc. (Chesterbrook, PA); Guidepoint Global, LLC (New York, NY); Gerson Lehrman Group (New York, NY); Shire (Dublin, Republic of Ireland). Dr. Scholl is a member of the Scientific Advisory Board of Vision Medicines, Inc. Hendrik P.N. Scholl is a member of the Data Monitoring Committee of the following entities (not including the National Institutes of Health): Genentech Inc (San Francisco, California, USA)/F. Hoffmann-La Roche Ltd (Basel, Switzerland); StemCells, Inc (Newark, California, USA); Genzyme Corp (Boston, Massachusetts, USA)/Sanofi (Paris, France); he also serves as a member of the Ophthalmic Devices Panel of the Medical Devices Advisory Committee, Food and Drug Administration (FDA, Silver Spring, Maryland, USA). These arrangements have been reviewed and approved by the Johns Hopkins University in accordance with its conflict of interest policies. Hendrik P.N. Scholl is principal investigator of grants at The Johns Hopkins University sponsored by the following entity (not including the National Institutes of Health): QLT, Inc (Vancouver, Canada). Grants to investigators at Johns Hopkins University are negotiated and administered by the institution (such as the School of Medicine) which receives the grants, typically through the Office of Research and Administration. Individual investigators who participate in the sponsored project(s) are not directly compensated by the sponsor but may receive salary or other support from the institution to support their effort on the project(s). The following authors have no financial disclosures: Xiangrong Kong, Beatriz Muñoz, Mohamed A. Ibrahim, Gesa-Astrid Hahn, Fadi Nasser, and Eberhart Zrenner. All authors attest that they meet the current ICMJE criteria for authorship. Publisher Copyright: © 2018 Elsevier Inc.

PY - 2018/9

Y1 - 2018/9

N2 - Purpose: To investigate the natural history of Stargardt disease (STGD1) using fixation location and fixation stability. Design: Multicenter, international, prospective cohort study. Methods: Fixation testing was performed using the Nidek MP-1 microperimeter as part of the prospective, multicenter, natural history study on the Progression of Stargardt disease (ProgStar). A total of 238 patients with ABCA4-related STGD1 were enrolled at baseline (bilateral enrollment in 86.6%) and underwent repeat testing at months 6 and 12. Results: Outcome measures included the distance of the preferred retinal locus from the fovea (PRL) and the bivariate contour ellipse area (BCEA). After 12 months of follow-up, the change in the eccentricity of the PRL from the anatomic fovea was −0.0014 degrees (95% confidence interval [CI], −0.27 degrees, 0.27 degrees; P =.99). The deterioration in the stability of fixation as expressed by a larger BCEA encompassing 1 standard deviation of all fixation points was 1.21 degrees squared (deg 2 ) (95% CI, −1.23 deg 2 , 3.65 deg 2 ; P =.33). Eyes with increases and decreases in PRL eccentricity and/or BCEA values were observed. Conclusions: Our observations point to the complexity of fixation parameters. The association of increasingly eccentric and unstable fixation with longer disease duration that is typically found in cross-sectional studies may be countered within individual patients by poorly understood processes like neuronal adaptation. Nevertheless, fixation parameters may serve as useful secondary outcome parameters in selected cases and for counseling patients to explain changes to their visual functionality.

AB - Purpose: To investigate the natural history of Stargardt disease (STGD1) using fixation location and fixation stability. Design: Multicenter, international, prospective cohort study. Methods: Fixation testing was performed using the Nidek MP-1 microperimeter as part of the prospective, multicenter, natural history study on the Progression of Stargardt disease (ProgStar). A total of 238 patients with ABCA4-related STGD1 were enrolled at baseline (bilateral enrollment in 86.6%) and underwent repeat testing at months 6 and 12. Results: Outcome measures included the distance of the preferred retinal locus from the fovea (PRL) and the bivariate contour ellipse area (BCEA). After 12 months of follow-up, the change in the eccentricity of the PRL from the anatomic fovea was −0.0014 degrees (95% confidence interval [CI], −0.27 degrees, 0.27 degrees; P =.99). The deterioration in the stability of fixation as expressed by a larger BCEA encompassing 1 standard deviation of all fixation points was 1.21 degrees squared (deg 2 ) (95% CI, −1.23 deg 2 , 3.65 deg 2 ; P =.33). Eyes with increases and decreases in PRL eccentricity and/or BCEA values were observed. Conclusions: Our observations point to the complexity of fixation parameters. The association of increasingly eccentric and unstable fixation with longer disease duration that is typically found in cross-sectional studies may be countered within individual patients by poorly understood processes like neuronal adaptation. Nevertheless, fixation parameters may serve as useful secondary outcome parameters in selected cases and for counseling patients to explain changes to their visual functionality.

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UR - http://www.scopus.com/inward/citedby.url?scp=85049539585&partnerID=8YFLogxK

U2 - 10.1016/j.ajo.2018.06.003

DO - 10.1016/j.ajo.2018.06.003

M3 - Article

C2 - 29890160

AN - SCOPUS:85049539585

SN - 0002-9394

VL - 193

SP - 54

EP - 61

JO - American journal of ophthalmology

JF - American journal of ophthalmology

ER -

Longitudinal Changes of Fixation Location and Stability Within 12 Months in Stargardt Disease: ProgStar Report No. 12

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