Responsiveness of NEI VFQ-25 to changes in visual acuity in neovascular AMD: Validation studies from two phase 3 clinical trials

PURPOSE. To examine the responsiveness of the National Eye Institute Visual Function Questionnaire-25 (NEI VFQ-25) by using data from the MARINA and ANCHOR trials in neovascular age-related macular degeneration (AMD) and to establish the change in the NEI VFQ-25 associated with a 15-letter change in best corrected visual acuity (BCVA). METHODS. In MARINA, 716 patients were randomized to monthly intravitreal ranibizumab (0.3 or 0.5 mg) or sham injections. In ANCHOR, 423 patients were randomized to monthly ranibizumab (0.3 or 0.5 mg) with sham photodynamic therapy (PDT) or sham ocular injections with verteporfin PDT. Patients had follow-up interviews and BCVA measurements over 24 months. Data were analyzed separately for MARINA and ANCHOR, and treatment groups were pooled within each trial. The clinically relevant difference in NEI VFQ-25 was estimated based on regression models of change from baseline to month 12 in BCVA. RESULTS. Subgroups categorized by BCVA change (≥15 letters gained, >= 15 letters lost or gained, or ≥15 letters lost) differed substantially in mean change in NEI VFQ-25 composite scores and three pre-specified subscale scores (near activities, distance activities, and vision-specific dependency) over 12 months. According to the regression models, the difference associated with a 15-letter change was 4 to 6 points for the composite score and the three pre-specified subscales. CONCLUSIONS. These data support the use of the NEI VFQ-25 as a responsive and sensitive measure of vision-related function in neovascular AMD populations. Based on MARINA and ANCHOR data, a 4-to 6-point change in NEI VFQ-25 scores represents a clinically meaningful change corresponding to a 15-letter change in BCVA.