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

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

Research output: Contribution to journalArticle

16 Citations (Scopus)

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.

Original languageEnglish (US)
Article number10
JournalTranslational Vision Science and Technology
Volume5
Issue number5
DOIs
StatePublished - Sep 1 2016

Fingerprint

Gene therapy
Genetic Therapy
Visual Field Tests
Visual Fields
Visual Acuity
Clinical Trials
Functional assessment
Safety
Optical Coherence Tomography
Diabetic Retinopathy
Kinetics
Optical tomography
Chromosomes
Disease Progression
Stargardt disease 1
Mutation
Therapeutics

Keywords

  • Kinetic perimetry
  • OCT
  • Stargardt disease
  • Static perimetry
  • Test variability
  • Visual acuity

ASJC Scopus subject areas

  • Biomedical Engineering
  • Ophthalmology

Cite this

Test-retest variability of functional and structural parameters in patients with stargardt disease participating in the SAR422459 gene therapy trial. / Parker, Maria; Choi, Dongseok; Erker, Laura; Pennesi, Mark; Yang, Paul; Chegarnov, Elvira N.; Steinkamp, Peter N.; Schlechter, Catherine L.; Dhaenens, Claire Marie; Mohand-Said, Saddek; Audo, Isabelle; Sahel, Jose; Weleber, Richard; Wilson, David.

In: Translational Vision Science and Technology, Vol. 5, No. 5, 10, 01.09.2016.

Research output: Contribution to journalArticle

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AU - Pennesi, Mark

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

AU - Wilson, David

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