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Bilateral functional worsening following voretigene neparvovec therapy

Eye volume 37, pages 2828–2829 (2023)Cite this article

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Subretinal administration of voretigene neparvovec-rzyl (VN) was shown to improve light sensitivity, visual fields, and navigational ability under dim lighting conditions in patients with RPE65-associated retinal degeneration. Real-world evidence is mostly consistent with clinical trial results [1]. Nevertheless, some cases of considerable loss of best-corrected visual acuity (BCVA) [1], intraocular inflammation [2] and development of new or increased areas of chorioretinal atrophy [3] have been reported.

We present the case of a 45-year-old male with parental consanguinity and clinical diagnoses of early-onset rod-cone degeneration and end-stage renal disease. Whole exome sequencing (including copy number variation analysis) revealed probable homozygosity for the c.560G>A p.(Gly187Glu) likely pathogenic variant in RPE65 (NM_000329.2) and homozygosity for a pathogenic deletion of NPHP1 and partial loss of MALL: seq[GRCh37] del(2)(q13) chr2:g.110855123_110962791del. After multidisciplinary discussion, the patient was proposed for VN treatment. Bilateral, sequential (i.e., one week apart) 25G pars plana vitrectomy followed by subretinal injection of 0.3 mL of VN were performed by two senior vitreoretinal surgeons.

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Fig. 1: Multimodal retinal imaging at baseline and six months after Voretigene Neparvovec-rzyl treatment.

Data availability

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

References

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Authors and Affiliations

  1. Ophthalmology Unit, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal

    Emmanuel Rebelo Neves, Teresa Mesquita, Catarina Paiva, Mário Alfaiate, João Figueira, Joaquim Murta & João Pedro Marques

  2. Clinical Academic Center of Coimbra (CACC), Coimbra, Portugal

    Ana Luísa Carvalho, João Figueira, Joaquim Murta & João Pedro Marques

  3. Medical Genetics Unit, Centro Hospitalar e Universitário de Coimbra (CHUC), Coimbra, Portugal

    Ana Luísa Carvalho

  4. University Clinic of Medical Genetics, Faculty of Medicine, University of Coimbra (FMUC), Coimbra, Portugal

    Ana Luísa Carvalho

  5. University Clinic of Ophthalmology, Faculty of Medicine, University of Coimbra (FMUC), Coimbra, Portugal

    João Figueira, Joaquim Murta & João Pedro Marques

Authors
  1. Emmanuel Rebelo Neves
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  2. Ana Luísa Carvalho
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  3. Teresa Mesquita
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  4. Catarina Paiva
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  5. Mário Alfaiate
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  6. João Figueira
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  7. Joaquim Murta
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  8. João Pedro Marques
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Contributions

ERN was responsible for the study design, data collection, and drafting of the manuscript. JPM was responsible for study design, data collection, revision, and final approval of the manuscript. ALC was responsible for genetic testing, drafting of the manuscript, revision, and final approval of the manuscript. JF, JM, MA, CP, and TM were responsible for revision of the paper and its final approval. All authors are accountable for all aspects of this work and ensure the integrity of what it contains.

Corresponding author

Correspondence to João Pedro Marques.

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Competing interests

ERN, ALC: No relevant conflicts of interest. JPM: Consultancy fees (Novartis); PERCEIVE study Principal Investigator in CHUC. JF: Consultancy fees (Novartis); PERCEIVE study Subinvestigator in CHUC. JM: Consultancy fees (Novartis). MA, CP, TM: PERCEIVE study Subinvestigators in CHUC.

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Rebelo Neves, E., Carvalho, A.L., Mesquita, T. et al. Bilateral functional worsening following voretigene neparvovec therapy. Eye 37, 2828–2829 (2023). https://doi.org/10.1038/s41433-023-02411-4

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  • DOI: https://doi.org/10.1038/s41433-023-02411-4

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