Test-retest variability of functional and structural parameters in patients with stargardt disease participating in the SAR422459 gene therapy trial

Maria A. Parker; Dongseok Choi; Laura R. Erker; Mark E. Pennesi; Paul Yang; Elvira N. Chegarnov; Peter N. Steinkamp; Catherine L. Schlechter; Claire Marie Dhaenens; Saddek Mohand-Said; Isabelle Audo; Jose Sahel; Richard G. Weleber; David J. Wilson

doi:10.1167/tvst.5.5.10

Test-retest variability of functional and structural parameters in patients with stargardt disease participating in the SAR422459 gene therapy trial

Maria A. Parker, Dongseok Choi, Laura R. Erker, Mark E. Pennesi, Paul Yang, Elvira N. Chegarnov, Peter N. Steinkamp, Catherine L. Schlechter, Claire Marie Dhaenens, Saddek Mohand-Said, Isabelle Audo, Jose Sahel, Richard G. Weleber, David J. Wilson

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

36 Scopus citations

Abstract

Purpose: The goal of this analysis was to determine the test-retest variability of functional and structural measures from a cohort of patients with advanced forms of Stargardt Disease (STGD) participating in the SAR422459 (NCT01367444) gene therapy clinical trial. Methods: Twenty-two participants, aged 24 to 66, diagnosed with advanced forms of STGD, with at least one pathogenic ABCA4 mutation on each chromosome participating in the SAR422459 (NCT01367444) gene therapy clinical trial, were screened over three visits within 3 weeks or less. Functional visual evaluations included: best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score, semiautomated kinetic perimetry (SKP) using isopters I4e, III4e, and V4e, hill of vision (HOV) calculated from static visual fields (SVF) by using a 184n point centrally condensed grid with the stimulus size V test target. Retinal structural changes such as central macular thickness and macular volume were assessed by spectral-domain optical coherence tomography (SD-OCT). Repeatability coefficients (RC) and 95% confidential intervals (CI) were calculated for each parameter using a hierarchical mixed-effects model and bootstrapping. Results: Criteria for statistically significant changes for various parameters were found to be the following: BCVA letter score (8 letters), SKP isopters I4e, III4e, and V4e (3478.85; 2488.02 and 2622.46 deg², respectively), SVF full volume HOV (V_TOT, 14.62 dB-sr), central macular thickness, and macular volume (4.27 lm and 0.15 mm³, respectively). Conclusions: This analysis provides important information necessary to determine if significant changes are occurring in structural and functional assessments commonly used to measure disease progression in this cohort of patients with STGD. Moreover, this information is useful for future trials assessing safety and efficacy of treatments in STGD. Translational Relevance: Determination of variability of functional and structural measures in participants with advanced stages of the STGD is necessary to assess efficacy and safety in treatment trials involving STGD patients.

Original language	English (US)
Article number	10
Journal	Translational Vision Science and Technology
Volume	5
Issue number	5
DOIs	https://doi.org/10.1167/tvst.5.5.10
State	Published - Sep 2016

Keywords

Kinetic perimetry
OCT
Stargardt disease
Static perimetry
Test variability
Visual acuity

ASJC Scopus subject areas

Biomedical Engineering
Ophthalmology

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10.1167/tvst.5.5.10

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Parker, M. A., Choi, D., Erker, L. R., Pennesi, M. E., Yang, P., Chegarnov, E. N., Steinkamp, P. N., Schlechter, C. L., Dhaenens, C. M., Mohand-Said, S., Audo, I., Sahel, J., Weleber, R. G., & Wilson, D. J. (2016). Test-retest variability of functional and structural parameters in patients with stargardt disease participating in the SAR422459 gene therapy trial. Translational Vision Science and Technology, 5(5), [10]. https://doi.org/10.1167/tvst.5.5.10

Parker, MA , Choi, D, Erker, LR, Pennesi, ME , Yang, P, Chegarnov, EN, Steinkamp, PN, Schlechter, CL, Dhaenens, CM, Mohand-Said, S, Audo, I, Sahel, J, Weleber, RG & Wilson, DJ 2016, 'Test-retest variability of functional and structural parameters in patients with stargardt disease participating in the SAR422459 gene therapy trial', Translational Vision Science and Technology, vol. 5, no. 5, 10. https://doi.org/10.1167/tvst.5.5.10

@article{f3b316036d3245869626d8e7568ec896,

title = "Test-retest variability of functional and structural parameters in patients with stargardt disease participating in the SAR422459 gene therapy trial",

abstract = "Purpose: The goal of this analysis was to determine the test-retest variability of functional and structural measures from a cohort of patients with advanced forms of Stargardt Disease (STGD) participating in the SAR422459 (NCT01367444) gene therapy clinical trial. Methods: Twenty-two participants, aged 24 to 66, diagnosed with advanced forms of STGD, with at least one pathogenic ABCA4 mutation on each chromosome participating in the SAR422459 (NCT01367444) gene therapy clinical trial, were screened over three visits within 3 weeks or less. Functional visual evaluations included: best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score, semiautomated kinetic perimetry (SKP) using isopters I4e, III4e, and V4e, hill of vision (HOV) calculated from static visual fields (SVF) by using a 184n point centrally condensed grid with the stimulus size V test target. Retinal structural changes such as central macular thickness and macular volume were assessed by spectral-domain optical coherence tomography (SD-OCT). Repeatability coefficients (RC) and 95% confidential intervals (CI) were calculated for each parameter using a hierarchical mixed-effects model and bootstrapping. Results: Criteria for statistically significant changes for various parameters were found to be the following: BCVA letter score (8 letters), SKP isopters I4e, III4e, and V4e (3478.85; 2488.02 and 2622.46 deg2, respectively), SVF full volume HOV (VTOT, 14.62 dB-sr), central macular thickness, and macular volume (4.27 lm and 0.15 mm3, respectively). Conclusions: This analysis provides important information necessary to determine if significant changes are occurring in structural and functional assessments commonly used to measure disease progression in this cohort of patients with STGD. Moreover, this information is useful for future trials assessing safety and efficacy of treatments in STGD. Translational Relevance: Determination of variability of functional and structural measures in participants with advanced stages of the STGD is necessary to assess efficacy and safety in treatment trials involving STGD patients.",

keywords = "Kinetic perimetry, OCT, Stargardt disease, Static perimetry, Test variability, Visual acuity",

author = "Parker, {Maria A.} and Dongseok Choi and Erker, {Laura R.} and Pennesi, {Mark E.} and Paul Yang and Chegarnov, {Elvira N.} and Steinkamp, {Peter N.} and Schlechter, {Catherine L.} and Dhaenens, {Claire Marie} and Saddek Mohand-Said and Isabelle Audo and Jose Sahel and Weleber, {Richard G.} and Wilson, {David J.}",

note = "Funding Information: The authors thank Doroth{\'e}e Dagostinoz, Alexandre Leseigneur, Serge Sancho, and Mathias Chapon for their help in patient testing and coordination as well as Fiona Boyard for assistance in genotyping in the Parisian site. DNA samples for genetic testing in Paris originate from NeuroSensCol DNA bank, part of the Bio Collections network for research in neuroscience. At the OHSU CEI site, the authors thank Maureen McBride, Mihir Wanchoo, Chris Whitebirch, and Rachael Putnam for their help in patient testing and coordination as well as John Chiang and Catherine Schlechter for assistance in genotyping. At the OHSU CEI Reading Center, the authors thank Melissa Krahmer and Ambar Faridi for quality control and reading and Edye Parker for technical support. Publisher Copyright: {\textcopyright} 2016, Association for Research in Vision and Ophthalmology Inc. All rights reserved.",

year = "2016",

month = sep,

doi = "10.1167/tvst.5.5.10",

language = "English (US)",

volume = "5",

journal = "Translational Vision Science and Technology",

issn = "2164-2591",

publisher = "Association for Research in Vision and Ophthalmology Inc.",

number = "5",

}

TY - JOUR

T1 - Test-retest variability of functional and structural parameters in patients with stargardt disease participating in the SAR422459 gene therapy trial

AU - Parker, Maria A.

AU - Choi, Dongseok

AU - Erker, Laura R.

AU - Pennesi, Mark E.

AU - Yang, Paul

AU - Chegarnov, Elvira N.

AU - Steinkamp, Peter N.

AU - Schlechter, Catherine L.

AU - Dhaenens, Claire Marie

AU - Mohand-Said, Saddek

AU - Audo, Isabelle

AU - Sahel, Jose

AU - Weleber, Richard G.

AU - Wilson, David J.

N1 - Funding Information: The authors thank Dorothée Dagostinoz, Alexandre Leseigneur, Serge Sancho, and Mathias Chapon for their help in patient testing and coordination as well as Fiona Boyard for assistance in genotyping in the Parisian site. DNA samples for genetic testing in Paris originate from NeuroSensCol DNA bank, part of the Bio Collections network for research in neuroscience. At the OHSU CEI site, the authors thank Maureen McBride, Mihir Wanchoo, Chris Whitebirch, and Rachael Putnam for their help in patient testing and coordination as well as John Chiang and Catherine Schlechter for assistance in genotyping. At the OHSU CEI Reading Center, the authors thank Melissa Krahmer and Ambar Faridi for quality control and reading and Edye Parker for technical support. Publisher Copyright: © 2016, Association for Research in Vision and Ophthalmology Inc. All rights reserved.

PY - 2016/9

Y1 - 2016/9

N2 - Purpose: The goal of this analysis was to determine the test-retest variability of functional and structural measures from a cohort of patients with advanced forms of Stargardt Disease (STGD) participating in the SAR422459 (NCT01367444) gene therapy clinical trial. Methods: Twenty-two participants, aged 24 to 66, diagnosed with advanced forms of STGD, with at least one pathogenic ABCA4 mutation on each chromosome participating in the SAR422459 (NCT01367444) gene therapy clinical trial, were screened over three visits within 3 weeks or less. Functional visual evaluations included: best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score, semiautomated kinetic perimetry (SKP) using isopters I4e, III4e, and V4e, hill of vision (HOV) calculated from static visual fields (SVF) by using a 184n point centrally condensed grid with the stimulus size V test target. Retinal structural changes such as central macular thickness and macular volume were assessed by spectral-domain optical coherence tomography (SD-OCT). Repeatability coefficients (RC) and 95% confidential intervals (CI) were calculated for each parameter using a hierarchical mixed-effects model and bootstrapping. Results: Criteria for statistically significant changes for various parameters were found to be the following: BCVA letter score (8 letters), SKP isopters I4e, III4e, and V4e (3478.85; 2488.02 and 2622.46 deg2, respectively), SVF full volume HOV (VTOT, 14.62 dB-sr), central macular thickness, and macular volume (4.27 lm and 0.15 mm3, respectively). Conclusions: This analysis provides important information necessary to determine if significant changes are occurring in structural and functional assessments commonly used to measure disease progression in this cohort of patients with STGD. Moreover, this information is useful for future trials assessing safety and efficacy of treatments in STGD. Translational Relevance: Determination of variability of functional and structural measures in participants with advanced stages of the STGD is necessary to assess efficacy and safety in treatment trials involving STGD patients.

AB - Purpose: The goal of this analysis was to determine the test-retest variability of functional and structural measures from a cohort of patients with advanced forms of Stargardt Disease (STGD) participating in the SAR422459 (NCT01367444) gene therapy clinical trial. Methods: Twenty-two participants, aged 24 to 66, diagnosed with advanced forms of STGD, with at least one pathogenic ABCA4 mutation on each chromosome participating in the SAR422459 (NCT01367444) gene therapy clinical trial, were screened over three visits within 3 weeks or less. Functional visual evaluations included: best-corrected visual acuity (BCVA) Early Treatment Diabetic Retinopathy Study (ETDRS) letter score, semiautomated kinetic perimetry (SKP) using isopters I4e, III4e, and V4e, hill of vision (HOV) calculated from static visual fields (SVF) by using a 184n point centrally condensed grid with the stimulus size V test target. Retinal structural changes such as central macular thickness and macular volume were assessed by spectral-domain optical coherence tomography (SD-OCT). Repeatability coefficients (RC) and 95% confidential intervals (CI) were calculated for each parameter using a hierarchical mixed-effects model and bootstrapping. Results: Criteria for statistically significant changes for various parameters were found to be the following: BCVA letter score (8 letters), SKP isopters I4e, III4e, and V4e (3478.85; 2488.02 and 2622.46 deg2, respectively), SVF full volume HOV (VTOT, 14.62 dB-sr), central macular thickness, and macular volume (4.27 lm and 0.15 mm3, respectively). Conclusions: This analysis provides important information necessary to determine if significant changes are occurring in structural and functional assessments commonly used to measure disease progression in this cohort of patients with STGD. Moreover, this information is useful for future trials assessing safety and efficacy of treatments in STGD. Translational Relevance: Determination of variability of functional and structural measures in participants with advanced stages of the STGD is necessary to assess efficacy and safety in treatment trials involving STGD patients.

KW - Kinetic perimetry

KW - OCT

KW - Stargardt disease

KW - Static perimetry

KW - Test variability

KW - Visual acuity

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Test-retest variability of functional and structural parameters in patients with stargardt disease participating in the SAR422459 gene therapy trial

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