Full-field Scotopic Threshold Improvement after Voretigene Neparvovec-rzyl Treatment Correlates with Chorioretinal Atrophy

Katarina Stingl; Krunoslav Stingl; Hillary Schwartz; Mark W Reid; Melanie Kempf; Spyridon Dimopoulos; Friederike Kortuem; Mark S Borchert; Thomas C Lee; Aaron Nagiel

doi:10.1016/j.ophtha.2023.02.015

Full-field Scotopic Threshold Improvement after Voretigene Neparvovec-rzyl Treatment Correlates with Chorioretinal Atrophy

Ophthalmology. 2023 Jul;130(7):764-770. doi: 10.1016/j.ophtha.2023.02.015. Epub 2023 Feb 21.

Authors

Affiliations

¹ University Eye Hospital, Center for Ophthalmology, University of Tübingen, Tübingen, Germany; Center for Rare Eye Diseases, University of Tübingen, Tübingen, Germany.
² The Vision Center, Department of Surgery, Children's Hospital Los Angeles, Los Angeles, California.
³ University Eye Hospital, Center for Ophthalmology, University of Tübingen, Tübingen, Germany.
⁴ The Vision Center, Department of Surgery, Children's Hospital Los Angeles, Los Angeles, California; Roski Eye Institute, Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, California.
⁵ The Vision Center, Department of Surgery, Children's Hospital Los Angeles, Los Angeles, California; Roski Eye Institute, Department of Ophthalmology, Keck School of Medicine, University of Southern California, Los Angeles, California. Electronic address: anagiel@chla.usc.edu.

PMID: 36822437
PMCID: PMC10293034 (available on 2024-07-01)
DOI: 10.1016/j.ophtha.2023.02.015

Abstract

Purpose: To analyze demographic and ophthalmic data in patients with and without chorioretinal atrophy after voretigene neparvovec-rzyl (VN) to identify possible causes for this phenomenon.

Design: Retrospective cohort study with longitudinal follow-up.

Participants: A total of 71 eyes of 38 patients aged 2 to 44 years with RPE65-mediated retinal dystrophy treated with VN across 2 large gene therapy centers in the United States and Germany.

Methods: Patients treated with VN who developed atrophy were compared with those who did not.

Main outcome measures: Gender, age, surgical center, spherical equivalent refraction, best-corrected visual acuity (BCVA), baseline full-field scotopic threshold testing (FST), and posttreatment change in FST.

Results: A total of 20 eyes of 12 patients developed atrophy after treatment with VN (28% of all eyes). There was no significant difference in gender, age, surgical center, or spherical equivalent refraction between the atrophy group and the no atrophy group. However, patients between school age and young adulthood were predominantly affected, whereas the youngest and the oldest patients did not develop atrophy. Baseline BCVA was better in patients who developed atrophy than those who did not (P = 0.006). The postoperative improvement in FST at 1 month was significantly higher in the atrophy group than in the no atrophy group (P = 0.0005), and this difference remained statistically significant at 1 year (P = 0.0001). There was no correlation to baseline FST, to inflammation, or to which eye was treated first.

Conclusions: The degree of FST improvement after VN appears to be strongly correlated with the development of VN-related chorioretinal atrophy. This finding raises the possibility that atrophy may develop as a toxic or metabolic sequela of vector-mediated RPE65 expression. In light of the expanding number of retinal gene therapy clinical trials, this complication warrants further study because it may not be limited to VN.

Financial disclosure(s): Proprietary or commercial disclosure may be found after the references.

Keywords: Chorioretinal atrophy; FST; Gene therapy; Inherited retinal dystrophy.

MeSH terms

Adult
Humans
Refraction, Ocular*
Retina
Retinal Dystrophies* / genetics
Retinal Dystrophies* / therapy
Retrospective Studies
Visual Acuity
Young Adult

Supplementary concepts

Choroidal sclerosis

Grants and funding

K08 EY030924/EY/NEI NIH HHS/United States