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
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 Doroth?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:
© 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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U2 - 10.1167/tvst.5.5.10
DO - 10.1167/tvst.5.5.10
M3 - Article
AN - SCOPUS:85014612205
VL - 5
JO - Translational Vision Science and Technology
JF - Translational Vision Science and Technology
SN - 2164-2591
IS - 5
M1 - 10
ER -