Abstract
Purpose :
Voretigene neparvovec (VN) is the first ocular gene therapy approved for patients with biallelic RPE65 mutation-associated inherited retinal dystrophy (IRD). A modified version of the Visual Function Questionnaire (mVFQ-25) was developed to address the unmet need for a patient-reported outcome for this population. This retrospective analysis of Phase III clinical trial data evaluated the psychometric properties of the mVFQ-25 as an assessment of functional vision or activities of daily living (ADLs) in IRDs due to RPE65 mutations.
Methods :
Thirty-one patients and/or their caregivers completed the mVFQ-25 at baseline (BL), days 30, 90, 180 and 1-year reporting perceived difficulty of ADLs. Patients also completed the Multi-luminance Mobility Test (MLMT), a novel endpoint assessing functional vision at various light levels experienced in ADLs. Psychometric analyses assessed item (question) response distributions, question correlations, reliability (internal consistency and test-retest reliability), construct validity (convergent and discriminative validity), responsiveness and interpretation of scores.
Results :
Findings indicated sensitivity to improvements in functional vision following VN treatment, despite skewed item response distributions across timepoints. Correlations among items were weak-to-moderate (0.00–0.66) at BL and slightly stronger at 1-year (0.00–0.87). Internal consistency was excellent across timepoints (Cronbach’s alpha=0.854–0.950) and test-retest reliability was strong between days 90–180 (Intraclass Correlation Coefficient=0.912), indicating excellent reliability. Moderate correlations with similar measures post-BL (r=−0.48 to 0.76) supported convergent validity. Statistically significant differences post-BL (p<0.001) in mean mVFQ-25 scores between groups defined by MLMT scores, supported discriminative validity. Statistically significant changes in mVFQ-25 for patients who had improved MLMT scores supported responsiveness. Distribution and anchor-based analyses to define meaningful change thresholds suggested that a 1.5-point change or more can be considered meaningful.
Conclusions :
Results support the reliability, validity and responsiveness of mVFQ-25 as a measure of functional vision for use in patients with IRD due to RPE65 mutations.
This is a 2020 ARVO Annual Meeting abstract.