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

• Published in: BMJ Open Ophthalmology
• Main Authors: Jason H Peragallo, Nancy J Newman, Valérie Biousse, Jeong-Min Hwang, Francesco Bandello, Ghazala O'Keefe, Julia A Haller, Armin Wolf, Bettina von Livonius, Thomas Klopstock, Celia Chen, Marco Battista, Patrick Yu-Wai-Man, Siegfried Priglinger, Virginia García, Sean Donahue, Scott Ruark, Rima Hussain, Prem S Subramanian, Daniel Muth, Bart P Leroy, Alfredo A Sadun, JAMES ACHESON, Mike Horton, Maria Gemenetzi, Michele Carbonelli, Piero Barboni, Steve Cho, Rod Foroozan, Maria Eleftheriadou, Claudia B Catarino, William R Tucker, Manuela Contin, Robert C Sergott, Mark L Moster, Benson S Chen, Catherine Vignal-Clermont, Rabih Hage, Bart K Chwalisz, Claudia Priglinger, Susan Mohamed, Giulia Amore, Sapna Gangaputra, Sarah Thornton, Jannah Dobbs, Lindreth DuBois, Deborah Gibbs, An-Guor Wang, Valerio Carelli, Rudrani Banik, Magali Taiel, Katy Tai, Maria Lucia Cascavilla, Rustum Karanjia, Stephan Thurau, Lidia Di Vito, Marc Mathias, Hui-Chen Cheng, Shriji Patel, Angelika Pressler, Günther Rudolph, Stéphanie Perot, Chiara La Morgia, Martina Romagnoli, Sara Silvestri, Pietro D'Agati, George Baker Hubbard, Andrew M Hendrick, Michael Dattilo, Eman Hawy, Alcides Fernandes Filho, Andre Aung, Hayley Boston, Simona Esposti, Lauren Leitch-Devlin, Neringa Jurkute, Asma Burale, Shweta Anand, Muhammad A Memon, Rasha Jorany, Priyansha Sheel, Melissa SantaMaria, Heather Tollis, Adam A DeBusk, Maria Massini, Paula Pecen, Mary Preston, José A Sahel, Jean François Girmens, Lise Plaine, Wahiba Khemliche, Chuanbin Sun, Megan Barrett, Saige Wilkins, Julie De Zaeytijd, Caroline Van Cauwenbergh, Hilde Verhauwen, Jasmina Al-Tamami, Cosima Schertler, Martin Hildebrandt, Michael Neuenhahn, Gad Heilweil, Irena Tsui, Gema Rebolleda Fernández, Laia Jaumendreu Urquijo, Francisco J Muñoz Negrete, Elizabeth Fortin, Dean Cestari, Lorena Castillo, Antonio Morilla, Francesca Calcagno, Adelaide Pina, Stéphanie Leruez
• Format: Article
• Language: English
• Published: BMJ Publishing Group 2025-09-01
• Online Access: https://bmjophth.bmj.com/content/10/1/e002164.full
• ISSN: 2397-3269

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.