Objective Outcomes to Evaluate Voretigene Neparvovec Treatment Effects in Clinical Practice

Paolo Melillo; Francesco Testa; Valentina Di Iorio; Marianthi Karali; Amelia Citro; Michele Della Corte; Settimio Rossi; Sandro Banfi; Francesca Simonelli

doi:10.1016/j.oret.2024.01.021

Objective Outcomes to Evaluate Voretigene Neparvovec Treatment Effects in Clinical Practice

Ophthalmol Retina. 2024 Feb 1:S2468-6530(24)00047-2. doi: 10.1016/j.oret.2024.01.021. Online ahead of print.

Authors

Paolo Melillo¹, Francesco Testa¹, Valentina Di Iorio², Marianthi Karali³, Amelia Citro¹, Michele Della Corte¹, Settimio Rossi¹, Sandro Banfi⁴, Francesca Simonelli¹

Affiliations

¹ Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy.
² Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy. Electronic address: valentina.diiorio@unicampania.it.
³ Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, University of Campania "Luigi Vanvitelli", Naples, Italy; Medical Genetics, Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.
⁴ Medical Genetics, Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy; Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy.

PMID: 38295874
DOI: 10.1016/j.oret.2024.01.021

Abstract

Purpose: To assess the efficacy of voretigene neparvovec (VN) treatment by objective fixation stability and chromatic pupillometry testing in clinical practice.

Design: Retrospective cohort study with longitudinal follow-up.

Subjects: Twelve patients (aged 7-34 years) with RPE65-related inherited retinal dystrophies were treated at the same center with VN in both eyes.

Methods: Patients treated at the same center with VN were evaluated over a 12-month posttreatment follow-up by subjective and objective tests. Furthermore, patients treated with VN who developed atrophy were compared with those who did not.

Main outcome measures: Best-corrected visual acuity (BCVA), full-field stimulus threshold test (FST), semiautomated kinetic visual field (SKVF), microperimetry, and chromatic pupillometry over a 12-month follow-up.

Results: Significant improvements of BCVA (P < 0.001), SKVF (P < 0.05), and FST (P < 0.001) were already observed 45 days after treatment and were maintained at the 12-month timepoint. Fixation stability, assessed by microperimetry, improved significantly (P < 0.05) after treatment. Chromatic pupillometry showed significant improvements (P < 0.05) at the 6- and 12-month timepoints. The increase in maximum pupillary constriction significantly (P < 0.001) correlated with higher retinal sensitivity in FST. Four patients developed multifocal retinal atrophy in both eyes, detected at the 6-month timepoint, but this atrophy was not generally associated with worse visual function outcomes.

Conclusions: This study explores objective outcomes in order to demonstrate the efficacy of VN treatment in addition to the tests normally performed in clinical practice. Our findings show a significant improvement of retinal function both in subjective assessments, such as BCVA, SKVF, and FST, and in objective measurements of fixation stability and maximum pupillary constriction. Moreover, the significant correlation between maximum pupillary constriction and light sensitivity thresholds corroborates the introduction of chromatic pupillometry as an objective test to better assess treatment outcomes in patients with inherited retinal dystrophies.

Financial disclosure(s): Proprietary or commercial disclosure may be found after the references in the Footnotes and Disclosures at the end of this article.

Keywords: Chromatic pupillometry; Gene therapy; Inherited retinal dystrophy; RPE65 gene; Voretigene neparvovec.