Rasch analysis of the NEI-VFQ-25: vision-related quality of life in Leber hereditary optic neuropathy after lenadogene nolparvovec gene therapy

Abstract

Objectives: This study aimed to evaluate the suitability of the National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) for measuring vision-related quality of life (VRQoL) in patients with Leber hereditary optic neuropathy receiving lenadogene nolparvovec gene therapy in three Phase III randomised controlled clinical trials.

Methods: VRQoL was assessed using the NEI-VFQ-25 at baseline (n=174) and 2 years after treatment (n=152). All participants received lenadogene nolparvovec in at least one eye. The scoring structure of the original NEI-VFQ-25 was evaluated for fit to the Rasch model, and a post hoc revision was created and psychometrically reevaluated. Stacked analysis was conducted to compare Rasch-revised scores at baseline and 2 years after treatment.

Results: The original NEI-VFQ-25 exhibited multiple issues including limitations in response functioning and scale dimensionality. These issues were rectified by revising the NEI-VFQ25 into two separate unidimensional scales measuring 'Vision-related Activity Limitation' (VAL) and 'Socioemotional Functioning' (SEF). Participants' mean VAL score at baseline on a Rasch-transformed 0-100 scale was 46.1 (11.7), improving to 48.4 (13.7) after treatment (F(1, 324) = 2.67, p=0.103). On the SEF scale, there was a significant difference 2 years after treatment, with participants improving from a mean score of 40.1 (14.1) at baseline to 49.6 (17.6) (F(1, 324) = 29.1, p<0.001).

Conclusions: The scoring structure of the original NEI-VFQ-25 has limitations that undermine its psychometric validity as a measure of VRQoL. Using the Rasch-revised NEI-VFQ-25, we determined that improvement in VRQoL after treatment with lenadogene nolparvovec was driven predominantly by an improvement in socioemotional functioning.

Keywords: Clinical Trial; Genetics; Optic Nerve; Treatment Medical.

Figure 1. Person-item threshold distribution map for the Rasch-revised Vision-Related Activity Limitation (VAL) scale. The blocks in the upper part of the chart (above the x-axis) represent groups of study participants across a continuum of vision-related activity limitation, represented by the x-axis (‘Location’ in logits), at baseline (in blue) and at 2 years post-treatment (in red). The underlying scale represents higher levels of vision-related activity limitation (or lower levels of visual functioning) toward the left of the plot, and lower levels of vision-related activity limitation (or higher levels of visual functioning) toward the right of the plot. The blocks in the lower part of the chart (below the x-axis) represent the location of item thresholds and their distribution.

Figure 2. Person-item threshold distribution map for the Rasch-revised Socioemotional Functioning (SEF) scale. The blocks in the upper part of the chart (above the x-axis) represent groups of study participants across a continuum of socioemotional functioning, represented by the x-axis (‘Location’ in logits), at baseline (in blue) and at 2 years post-treatment (in red). The underlying scale represents lower levels of socioemotional functioning toward the left of the plot, and higher levels of socioemotional functioning toward the right of the plot. The blocks in the lower part of the chart (below the x-axis) represent the location of item thresholds and their distribution.