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Real-world outcomes of Voretigene Neparvovec: a single-centre consecutive case series

Eye volume 39, pages 1356–1363 (2025)Cite this article

Subjects

Abstract

Purpose

To present functional and anatomical outcomes of subretinal therapy with Voretigene Neparvovec (VN) in patients treated in one of the four specialist UK gene therapy centres.

Methods

Single-centre, retrospective case series of patients affected by an inherited retinal dystrophy (IRD) caused by a pathogenic biallelic RPE65 mutation and treated with VN. Complete ophthalmic examination was planned preoperatively and 2, 4 and 8 weeks and 3, 6, 12, 18 and 24 months after surgery, and included visual acuity (VA) assessment (normal and low luminance), colour vision, contrast sensitivity, dark-adapted full-field stimulus threshold, macular optical coherence tomography (OCT) and fundus autofluorescence.

Results

Fourteen eyes of 8 patients were included with a mean follow-up of 26 months. Mean final VA improved by 2 lines, and improvements were noted in most other functional tests. Central retina thickness (CRT) remained fairly stable in the majority of patients, whereas 2 eyes experienced a reduction >30 μm. The status of ellipsoid band and external limiting membrane remained stable in all patients, except one. Peripapillary atrophy (PPA) was present in 5 eyes of 3 patients at the baseline; postoperative progression was noted in both eyes of one patient. No patient developed new PPA or chorioretinal atrophy (CRA) involving the macular area after treatment. Five eyes of 3 patients developed CRA at the retinotomy site, that progressed in 3 of them.

Conclusions

Our study confirmed the effectiveness of subretinal VN therapy in terms of improvement of visual function. CRA was confirmed as a common postoperative complication, with limited functional impact.

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Fig. 1: Pre- and post-operative linear OCT scans dissecting the fovea for the right eye of Patient 4.
Fig. 2: Photopic, low photopic, mesopic visual acuity, Pelli-Robson Contrast sensitivity and Full-field Stimulus Threshold (FST) before and after surgery.

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Data availability

Data sets generated during the current study are available from the corresponding author on reasonable request.

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Author information

Authors and Affiliations

  1. Manchester Royal Eye Hospital, Manchester University Hospitals NHS Foundation Trust, Manchester, UK

    Assad Jalil, Myrta Lippera, Neil Parry, Sandra Banderas, Jane Ashworth, Sus Biswas, Georgina Hall, Jane Gray, William Newman & Tsveta Ivanova

  2. Department of Medical and Surgical Specialties, Radiological Sciences and Public Health, University of Brescia, Brescia, Italy

    Mariantonia Ferrara

  3. Eye Unit, ASST Spedali Civili di Brescia, Piazzale Spedali Civili, Brescia, Italia

    Mariantonia Ferrara

  4. School of Health Sciences, University of Manchester, Manchester, M13 9NT, United Kingdom

    Neil Parry

  5. Division of Evolution, Infection and Genomics, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, Manchester, UK

    Graeme C. Black

  6. Manchester Centre for Genomic Medicine, Saint Mary’s Hospital, Manchester University NHS Foundation Trust, Manchester, UK

    Graeme C. Black

Authors
  1. Assad Jalil
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Contributions

AJ was responsible for conceptualization, surgical treatment, investigation, interpreting results, writing—review and editing, supervision, project administration. MF was responsible for conceptualization, interpreting results, investigation, writing—original draft preparation. ML was responsible for extracting and analysing data, investigation, interpreting results, writing—original draft preparation, updating reference lists and creating the tables. NP was responsible for extracting and analysing data, investigation, interpreting results, writing—original draft preparation, creating the figures, supervision. GB was responsible for investigation, interpreting results, writing—review and editing, supervision. SB contributed to extracting and analysing data. JA, SB, GH, JG, WN were responsible for investigation, writing—review and editing. TIV was responsible for conceptualization, surgical treatment, investigation, interpreting results, writing—review and editing, supervision, project administration.

Corresponding author

Correspondence to Assad Jalil.

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Competing interests

The authors declare no competing interests.

Ethical approval and consent to participation

This study was a retrospective anonymized data collection, and hence had ethical approval exemption.

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Jalil, A., Ferrara, M., Lippera, M. et al. Real-world outcomes of Voretigene Neparvovec: a single-centre consecutive case series. Eye 39, 1356–1363 (2025). https://doi.org/10.1038/s41433-025-03637-0

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