Journal Article

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

Memon, Muhammad A, Haller, Julia A, Vignal-Clermont, Catherine, Leruez, Stéphanie, DuBois, Lindreth, Sun, Chuanbin, Hubbard, George Baker, Moster, Mark L, Sahel, José A, Ruark, Scott, Anand, Shweta, Neuenhahn, Michael, Pina, Adelaide, Amore, Giulia, Aung, Andre, O'Keefe, Ghazala, Thurau, Stephan, Rudolph, Günther, Girmens, Jean François, Romagnoli, Martina, Gibbs, Deborah, DeBusk, Adam A, Carelli, Valerio, Esposti, Simona, Tsui, Irena, Peragallo, Jason H, Hussain, Rima, Leroy, Bart P, Al-Tamami, Jasmina, Livonius, Bettina von, Hwang, Jeong-Min, Zaeytijd, Julie De, Banik, Rudrani, Jorany, Rasha, Patel, Shriji, Verhauwen, Hilde, Urquijo, Laia Jaumendreu, Castillo, Lorena, Tollis, Heather, Dobbs, Jannah, Muñoz Negrete, Francisco J, Fortin, Elizabeth, Morgia, Chiara La, Tai, Katy, Catarino, Claudia B, Chen, Celia, Jurkute, Neringa, Gemenetzi, Maria, Barrett, Megan, Acheson, James, Sheel, Priyansha, Cho, Steve, Wang, An-Guor, Heilweil, Gad, Klopstock, Thomas, Chen, Benson S, Khemliche, Wahiba, SantaMaria, Melissa, Muth, Daniel, Taiel, Magali, Chwalisz, Bart K, D'Agati, Pietro, Contin, Manuela, Eleftheriadou, Maria

2025

Overview

ObjectivesThis 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.MethodsVRQoL 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.ResultsThe 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).ConclusionsThe 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.

• Publisher: BMJ Publishing Group Ltd,BMJ Publishing Group LTD,BMJ Publishing Group
• Subject: Adolescent / Adult / cis-trans-Isomerases - genetics / Clinical outcomes / Clinical Trial / Clinical trials / Female / Gene therapy / Genetic Therapy - methods / Genetics / Humans / Likert scale / Male / Middle Aged / National Eye Institute (U.S.) / Neuro-Ophthalmology / Optic Atrophy, Hereditary, Leber - genetics / Optic Atrophy, Hereditary, Leber - physiopathology / Optic Atrophy, Hereditary, Leber - psychology / Optic Atrophy, Hereditary, Leber - therapy / Optic Nerve / Patients / Psychometrics / Quality of life / Quality of Life - psychology / Quantitative psychology / Questionnaires / Rasch model / Sickness Impact Profile / Surveys and Questionnaires / Treatment Medical / Validity / Visual acuity / Visual Acuity - physiology / Young Adult