Partial rescue of the full-field electroretinogram in patients with RPE65-related retinal dystrophy following gene augmentation therapy with voretigene neparvovec-rzyl

Doc Ophthalmol. 2024 Oct;149(2):63-75. doi: 10.1007/s10633-024-09987-6. Epub 2024 Aug 14.

Abstract

Purpose: To present a series of patients with RPE65-related retinal dystrophy showing a partial rescue of the full-field electroretinogram (ERG) following gene replacement therapy with voretigene neparovec-rzyl (Luxturna®).

Methods: This retrospective chart review examined 17 patients treated with voretigene neparovec-rzyl (VN) at the Casey Eye Institute (2018-2022). The last pre-operative ERG and all available post-operative ERGs were analyzed to identify subjects with functional rescue. Measurements of amplitudes and implicit times were compared to data from age-matched controls and the attenuation relative to the lower limit of normal (LLN) was calculated. For comparison with other functional exams, the last pre-operative and all post-treatment best-corrected visual acuity (BCVA) data, visual field (VF) tests and full-field threshold stimulus tests (FST) were also described.

Results: Of patients who underwent ERGs, most had unrecordable ERGs that did not change after treatment. However, we identified three patients, treated bilaterally, who demonstrated partial rescue of the full-field ERG in both eyes which was sustained during the course of the study.

Conclusions: This is the largest series of patients treated with VN showing a partial rescue of the ERG. This is also the first report of bilateral ERG rescue, as well as the first description of ERG recovery occurring in non-pediatric subjects. Full-field ERG could be used in combination with other psychophysical tests and imaging modalities to detect and deepen our understanding of the response to this gene therapy approach.

Keywords: Electroretinogram; Luxturna; Voretigene neparvovec-rzyl.

MeSH terms

  • Adolescent
  • Adult
  • Child
  • Dependovirus / genetics
  • Electroretinography*
  • Female
  • Genetic Therapy*
  • Genetic Vectors
  • Humans
  • Male
  • Middle Aged
  • Retina / physiopathology
  • Retinal Dystrophies* / genetics
  • Retinal Dystrophies* / physiopathology
  • Retrospective Studies
  • Visual Acuity* / physiology
  • Visual Fields / physiology
  • Young Adult
  • cis-trans-Isomerases* / genetics

Substances

  • cis-trans-Isomerases
  • retinoid isomerohydrolase