June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Partial full-field electroretinogram rescue in patients with RPE65-related retinal dystrophy following gene replacement therapy
Author Affiliations & Notes
  • Alessia Amato
    Oregon Health & Science University Casey Eye Institute, Portland, Oregon, United States
  • Wayne Tschetter
    Oregon Health & Science University Casey Eye Institute, Portland, Oregon, United States
  • Samuel J Huang
    Oregon Health & Science University Casey Eye Institute, Portland, Oregon, United States
  • Lesley Everett
    Oregon Health & Science University Casey Eye Institute, Portland, Oregon, United States
  • Steve Bailey
    Oregon Health & Science University Casey Eye Institute, Portland, Oregon, United States
  • Paul Yang
    Oregon Health & Science University Casey Eye Institute, Portland, Oregon, United States
  • Andreas K Lauer
    Oregon Health & Science University Casey Eye Institute, Portland, Oregon, United States
  • Mark E Pennesi
    Oregon Health & Science University Casey Eye Institute, Portland, Oregon, United States
  • Footnotes
    Commercial Relationships   Alessia Amato None; Wayne Tschetter None; Samuel Huang None; Lesley Everett None; Steve Bailey None; Paul Yang None; Andreas Lauer None; Mark Pennesi None
  • Footnotes
    Support  Foundation Fighting Blindness TRAP1 Award TA-NMT-0521-0803-OHSU-TRAP (Columbia, MD) (PY) Supported by grant P30 EY010572 from the National Institutes of Health (Bethesda, MD), and by unrestricted departmental funding from Research to Prevent Blindness (New York, NY)
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 5207. doi:
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    • Get Citation

      Alessia Amato, Wayne Tschetter, Samuel J Huang, Lesley Everett, Steve Bailey, Paul Yang, Andreas K Lauer, Mark E Pennesi; Partial full-field electroretinogram rescue in patients with RPE65-related retinal dystrophy following gene replacement therapy. Invest. Ophthalmol. Vis. Sci. 2023;64(8):5207.

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      © ARVO (1962-2015); The Authors (2016-present)

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Abstract

Purpose : Early studies of the RPE65 null mutation canine model demonstrated marked improvement in full-field electroretinograms (ffERG) after subretinal delivery of the defective gene, but this finding has never been reported in patients treated with voretigene neparovec-rzyl (Luxturna). We present a series of patients with RPE65-related retinal dystrophy showing a partial ffERG rescue following gene replacement therapy.

Methods : This retrospective chart review examined 17 patients treated with Luxturna at the Casey Eye Institute (2018-2022). Dark-adapted (DA) ERGs in response to a flash strength of 0.01 cd.s.m-2 and light-adapted (LA) ERGs in response to a flash strength of 3.0 cd.s.m-2 were analyzed and b-wave amplitude as a percentage of lower normal limit was measured to quantify improvement. Factors that could influence outcomes, such as age and pre-treatment ERGs, were also reviewed.

Results : Three bilaterally treated patients (5 eyes) showed a partial ERG rescue following injection. Patient 1 showed a dramatic ERG improvement 4 months post-treatment. DA b-wave amplitude increased from 8% to 52% of lower normal limit OD and from 4% to 96% OS, while LA b-wave amplitude increased from 30% to 63% OD and from 22% to 60% OS. Improvements were retained over a 50-month follow-up. In patient 2, at 14 months post-treatment, DA response increased from 29% to 54% OD and from 24% to 40% OS, while LA response increased from 21% to 32% OD and from 19% to 25% OS. One year later, DA response slightly decreased in both eyes to 41% OD and 32% OS. LA responses also decreased to 7% OD and 11% OS. In patient 3, only one eye showed a transient improvement measured 52 months after treatment. DA b-wave amplitude increased from 5% to 17% and LA b-wave amplitude from 6% to 17%. However, 2 years later responses in both eyes were unrecordable. Interestingly, in all eyes, DA and LA b-wave implicit times showed only a minor improvement or prolongation, even when the corresponding b-wave amplitude markedly increased. We found no association between ERG improvement and age at time of treatment or pre-operative ERG amplitudes.

Conclusions : This is the first series of patients treated with Luxturna showing a partial ERG rescue. Full-field ERG could be used in combination with other psychophysical tests and imaging modalities to detect response to this therapy.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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