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Voretigene neparvovec in RPE65-related inherited retinal dystrophy: the 1-year real-world study LIGHT

Eye volume 39, pages 1758–1764 (2025) Cite this article

Subjects

Abstract

Background

This retrospective real-world study evaluated the effectiveness and safety of subretinal voretigene neparvovec (VN) in French patients (six children, six adults) with inherited retinal dystrophies.

Methods

Data were collected from medical records for the year following bilateral treatment with subretinal VN. Functional vision was assessed using the Streetlab mobility course with obstacles. The main outcome was Percentage of Preferred Walking Speed (PPWS) 1 month after treatment (the average speed to navigate the obstacle course as a percentage of the speed to walk straight for 4 m without obstacles at 500 lux).

Results

PPWS median relative improvement to month 1 was 63.9% (interquartile range 47.8%; 88.5%) at 2 lux. Gains were sustained to month 6, were comparable in children and adults, with similar patterns at 7.5 and 50 lux. Course completion time and the number of collisions improved at month 1 at 2 lux. Median full-field stimulus test (FST) improved at month 1 (−33.2 [interquartile range −33.7; −19.8] dB), with improvements sustained to month 24. Over the study, best corrected visual acuity (BCVA) appeared stable, and kinetic visual field had no discernible pattern. All patients experienced at least one ocular AE related to surgery, VN, or both. One serious AE occurred (retinal detachment in a child), and was considered related to surgery. Chorioretinal atrophies occurred in four adults and one child, with no impact on FST.

Conclusions

Functional vision, measured in the Streetlab mobility course, demonstrated rapid, sustainable improvements in lower light intensities. Safety data were in line with current knowledge for VN.

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Fig. 1: Mobility testing results, measured with the Streetlab platform at 2 lux of light intensity.
The alternative text for this image may have been generated using AI.
Fig. 2: Visual function outcomes.
The alternative text for this image may have been generated using AI.

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Data availability

All data supporting the findings of this study are available within the paper and its Supplementary Information.

References

  1. Hartong DT, Berson EL, Dryja TP. Retinitis pigmentosa. Lancet. 2006;368:1795–809.

    Article  CAS  PubMed  Google Scholar 

  2. Schatz P, Preising M, Lorenz B, Sander B, Larsen M, Rosenberg T. Fundus albipunctatus associated with compound heterozygous mutations in RPE65. Ophthalmology. 2011;118:888–94.

    Article  PubMed  Google Scholar 

  3. Chung DC, Bertelsen M, Lorenz B, Pennesi ME, Leroy BP, Hamel CP, et al. The natural history of inherited retinal dystrophy due to biallelic mutations in the RPE65 gene. Am J Ophthalmol. 2019;199:58–70.

    Article  CAS  PubMed  Google Scholar 

  4. Jacobson SG, Aleman TS, Cideciyan AV, Roman AJ, Sumaroka A, Windsor EA, et al. Defining the residual vision in leber congenital amaurosis caused by RPE65 mutations. Investig Ophthalmol Vis Sci. 2009;50:2368–75.

    Article  Google Scholar 

  5. US Food and Drug Administration (FDA). Luxturna: Prescribing Information. 2017 [Available from: https://www.fda.gov/media/109906/download.

  6. European Medicines Agency (EMA). Luxturna: EPAR—Product Information. 2019 [Available from: https://www.ema.europa.eu/en/medicines/human/EPAR/luxturna.

  7. Maguire AM, Simonelli F, Pierce EA, Pugh EN Jr, Mingozzi F, Bennicelli J, et al. Safety and efficacy of gene transfer for Leber’s congenital amaurosis. N Engl J Med. 2008;358:2240–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Bennett J, Wellman J, Marshall KA, McCague S, Ashtari M, DiStefano-Pappas J, et al. Safety and durability of effect of contralateral-eye administration of AAV2 gene therapy in patients with childhood-onset blindness caused by RPE65 mutations: a follow-on phase 1 trial. Lancet. 2016;388:661–72.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Russell S, Bennett J, Wellman JA, Chung DC, Yu ZF, Tillman A, et al. Efficacy and safety of voretigene neparvovec (AAV2-hRPE65v2) in patients with RPE65-mediated inherited retinal dystrophy: a randomised, controlled, open-label, phase 3 trial. Lancet. 2017;390:849–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  10. Maguire AM, Russell S, Chung DC, Yu ZF, Tillman A, Drack AV, et al. Durability of voretigene neparvovec for biallelic RPE65-mediated inherited retinal disease: phase 3 results at 3 and 4 years. Ophthalmology. 2021;128:1460–8.

    Article  PubMed  Google Scholar 

  11. Maguire AM, Russell S, Wellman JA, Chung DC, Yu ZF, Tillman A, et al. Efficacy, safety, and durability of voretigene neparvovec-rzyl in RPE65 mutation-associated inherited retinal dystrophy: results of phase 1 and 3 trials. Ophthalmology. 2019;126:1273–85.

    Article  PubMed  Google Scholar 

  12. Deng C, Zhao PY, Branham K, Schlegel D, Fahim AT, Jayasundera TK, et al. Real-world outcomes of voretigene neparvovec treatment in pediatric patients with RPE65-associated Leber congenital amaurosis. Graefes Arch Clin Exp Ophthalmol. 2022;260:1543–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Audo I, Bujakowska KM, Léveillard T, Mohand-Saïd S, Lancelot ME, Germain A, et al. Development and application of a next-generation-sequencing (NGS) approach to detect known and novel gene defects underlying retinal diseases. Orphanet J Rare Dis. 2012;7:8.

    Article  PubMed  PubMed Central  Google Scholar 

  14. Sahel JA, Grieve K, Pagot C, Authié C, Mohand-Said S, Paques M, et al. Assessing photoreceptor status in retinal dystrophies: from high-resolution imaging to functional vision. Am J Ophthalmol. 2021;230:12–47.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Kay C, Williamson N, Bradley H, Barclay M, Sims J, Arbuckle R, et al. Qualitative interviews with patients and caregivers regarding visual function impairments and impacts on vision-dependent activities of daily living and health-related quality of life in RPE65-related Retinitis Pigmentosa and Leber Congenital Amaurosis. Investig Ophthalmol Vis Sci. 2021;62:3589.

    Google Scholar 

  16. Gange WS, Sisk RA, Besirli CG, Lee TC, Havunjian M, Schwartz H, et al. Perifoveal chorioretinal atrophy after subretinal voretigene Neparvovec-rzyl for RPE65-mediated leber congenital amaurosis. Ophthalmol Retina. 2022;6:58–64.

    Article  PubMed  Google Scholar 

  17. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17:405–24.

    Article  PubMed  PubMed Central  Google Scholar 

  18. Thompson DA, Gyürüs P, Fleischer LL, Bingham EL, McHenry CL, Apfelstedt-Sylla E, et al. Genetics and phenotypes of RPE65 mutations in inherited retinal degeneration. Investig Ophthalmol Vis Sci. 2000;41:4293–9.

    CAS  Google Scholar 

  19. Lorenz B, Gyürüs P, Preising M, Bremser D, Gu S, Andrassi M, et al. Early-onset severe rod-cone dystrophy in young children with RPE65 mutations. Investig Ophthalmol Vis Sci. 2000;41:2735–42.

    CAS  Google Scholar 

  20. Yang U, Gentleman S, Gai X, Gorin MB, Borchert MS, Lee TC, et al. Utility of in vitro mutagenesis of RPE65 protein for verification of mutational pathogenicity before gene therapy. JAMA Ophthalmol. 2019;137:1381–8.

    Article  PubMed  PubMed Central  Google Scholar 

  21. American Academy of Ophthalmology Clinical Education/Guidelines/Clinical Statements. Recommendations on Clinical Assessment of Patients with Inherited Retinal Degenerations 2016 [Available from: https://www.aao.org/clinical-statement/recommendations-on-clinical-assessment-of-patients.

  22. Chung DC, McCague S, Yu ZF, Thill S, DiStefano-Pappas J, Bennett J, et al. Novel mobility test to assess functional vision in patients with inherited retinal dystrophies. Clin Exp Ophthalmol. 2018;46:247–59.

    Article  PubMed  Google Scholar 

  23. Sengillo JD, Gregori NZ, Sisk RA, Weng CY, Berrocal AM, Davis JL, et al. Visual acuity, retinal morphology, and patients’ perceptions after voretigene neparovec-rzyl therapy for RPE65-associated retinal disease. Ophthalmol Retina. 2022;6:273–83.

    Article  PubMed  Google Scholar 

  24. Stingl K, Kempf M, Jung R, Kortüm F, Righetti G, Reith M, et al. Therapy with voretigene neparvovec. How to measure success? Prog Retin Eye Res. 2023;92:101115.

  25. Reichel FF, Seitz I, Wozar F, Dimopoulos S, Jung R, Kempf M, et al. Development of retinal atrophy after subretinal gene therapy with voretigene neparvovec. Br J Ophthalmol. 2023;107:1331–35.

  26. Stingl K, Stingl K, Schwartz H, Reid MW, Kempf M, Dimopoulos S, et al. Full-field scotopic threshold improvement after voretigene neparvovec-rzyl treatment correlates with chorioretinal atrophy. Ophthalmology. 2023;130:764–70.

    Article  PubMed  Google Scholar 

  27. Bommakanti N, Young BK, Sisk RA, Berrocal AM, Duncan JL, Bakall B, et al. Classification and growth rate of chorioretinal atrophy after voretigene neparvovec-rzyl for rpe65-mediated retinal degeneration. Ophthalmol Retina. 2024;8:42–8.

    Article  PubMed  Google Scholar 

  28. Kessel L, Christensen UC, Klemp K. Inflammation after voretigene neparvovec administration in patients with RPE65-related retinal dystrophy. Ophthalmology. 2022;129:1287–93.

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Acknowledgements

Paid medical writing support was provided by Dr. Fiona Dunlevy and Matrix Consultants.

Funding

This is a research collaboration where the Quinze-Vingts National Ophthalmology Hospital was the sponsor and Novartis SAS France funded and participated in the design and conduct of the study.

Author information

Authors and Affiliations

  1. Centre Hospitalier National d’Ophtalmologie des Quinze-Vingts, Centre de Référence Maladies Rares REFERET and INSERM-DGOS CIC 1423, F-75012 Paris, France

    Isabelle Audo, Pierre-Olivier Barale, Céline Devisme, Saddek Mohand-Said, Camille Andrieu & Jose-Alain Sahel

  2. Sorbonne Université, INSERM, CNRS, Institut de la Vision Paris France, Paris, France

    Isabelle Audo, Vasily M. Smirnov, Christina Zeitz & Jose-Alain Sahel

  3. National centre for rare diseases, Sensory inherited diseases, University hospital of Montpellier and Institut des Neurosciences de Montpellier, INSERM, Université de Montpellier, Montpellier, France

    Isabelle Meunier

  4. Université de Lille, Faculté de Medicine, Lille, France

    Vasily M. Smirnov

  5. Exploration de la vision et Neuro-Ophtalmologie CHU de Lille, Lille, France

    Vasily M. Smirnov

  6. University of Lille, INSERM, CHU Lille, U1172-LilNCog-Lille Neuroscience & Cognition, Lille, France

    Claire-Marie Dhaenens

  7. Streetlab, Institut de la Vision, Paris, France

    Chloé Pagot

  8. Novartis Pharma SAS, Rueil-Malmaison, France

    Pascaline Barbier, Malka Tindel & Perrine Chapon

  9. Department of Ophthalmology, The University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Jose-Alain Sahel

Authors
  1. Isabelle Audo
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  2. Pierre-Olivier Barale
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  3. Céline Devisme
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  4. Saddek Mohand-Said
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  5. Isabelle Meunier
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  6. Vasily M. Smirnov
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  8. Camille Andrieu
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  9. Christina Zeitz
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  10. Chloé Pagot
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  11. Pascaline Barbier
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  12. Malka Tindel
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  13. Perrine Chapon
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  14. Jose-Alain Sahel
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Contributions

IA Conceptualization, investigation, methodology, validation, resources, and writing; P-OB Resources, investigation, critical review of the manuscript; CD Resources, investigation, SM-S Resources, investigation; IM Resources, investigation; VMS Resources, investigation, C-MD Investigation; CA Resources, investigation; CZ Resources, investigation, critical review of the manuscript; CP Resources, investigation, critical review of the manuscript, PB Resources; MT Resources; PC Conceptualization, investigation, methodology, validation, visualization, and writing; J-AS Conceptualization, investigation, methodology, validation, visualization, and writing.

Corresponding author

Correspondence to Isabelle Audo.

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Competing interests

The authors report no conflicts of interest, except for JAS who reports holding stock options in GenSight Biologics, Sparing Vision, Prophesee, Chronolife, Tilak Healthcare, VegaVect Inc., Avista, Tenpoint, SharpEye. He also reports paid or unpaid involvement in GenSight Biologics, SparingVision, Avista, Fondation Voir & Entendre, Foundation Fighting Blindness, Gilbert Foundation and Foundation Fighting Blindness.

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Audo, I., Barale, PO., Devisme, C. et al. Voretigene neparvovec in RPE65-related inherited retinal dystrophy: the 1-year real-world study LIGHT. Eye 39, 1758–1764 (2025). https://doi.org/10.1038/s41433-025-03691-8

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