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Real-world outcomes of voretigene neparvovec treatment in pediatric patients with RPE65-associated Leber congenital amaurosis

  • Retinal Disorders
  • Published:
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Abstract

Purpose

To investigate real-world safety and efficacy of voretigene neparvovec gene therapy administration in pediatric patients with biallelic RPE65 disease-causing variants.

Methods

A retrospective study of 27 eyes of 14 patients with RPE65-associated Leber congenital amaurosis examined postoperative complications and longitudinal changes in photoreceptor function following treatment with subretinal injection of voretigene neparvovec. Full-field stimulus threshold testing (FST), Goldmann visual fields (GVF), best-corrected visual acuity (BCVA), and central subfield thickness (CST) on optical coherence tomography (OCT) scans were collected preoperatively and up to 12 months posttreatment.

Results

Baseline through 6–12 month follow-up FST and GVF data were obtained for 13 eyes of 7 patients. FST improved for each eye after treatment with a mean improvement of 2.1 log-units (P < 0.001) and GVF improved for each eye with a mean improvement of 221 sum degrees (P < 0.001). BCVA improved from logMAR 0.98 at baseline to logMAR 0.83 at last follow-up (P < 0.001). Across 19 eyes of 10 patients included in CST analysis, there was a small but statistically significant 9-μ decrease in mean CST from baseline to last follow-up (P < 0.001). The most common postoperative issues included elevation in intraocular pressure (59%), persistent intraocular inflammation (15%), and vitreous opacities (26%) that resolved over a period of months.

Conclusions

This report provides some of the earliest longitudinal real-world evidence of the pediatric safety and efficacy of voretigene neparvovec using multiple functional and structural measures of the retina. Outcomes demonstrate significant improvements in visual function consistent with clinical trial results.

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Availability of data and material

The lead author affirms that this manuscript is an honest, accurate, and transparent account of the study being reported and that no important aspects of the study have been omitted. All data and materials comply with field standards.

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Funding

Partial financial support was received from the Foundation Fighting Blindness Clinical/Research Fellowship Award (CD-CL-0619–0758-UMICH) to Dr. Peter Y. Zhao and Heed Ophthalmic Foundation Award to Dr. Peter Y. Zhao. Dr. Cagri Besirli is supported by an RPB Unrestricted Grant from Research to Prevent Blindness. Foundation Fighting Blindness,CD-CL-0619–0758-UMICH,Peter Y. Zhao,Heed Ophthalmic Foundation,Research to Prevent Blindness

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Author notes

  1. Callie Deng and Peter Y. Zhao are Co-first authors with equal contribution

Authors and Affiliations

  1. Department of Ophthalmology and Visual Sciences, University of Michigan W.K. Kellogg Eye Center, Ann Arbor, MI, USA

    Callie Deng, Peter Y. Zhao, Kari Branham, Dana Schlegel, Abigail T. Fahim, Thiran K. Jayasundera, Naheed Khan & Cagri G. Besirli

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  1. Callie Deng
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Correspondence to Cagri G. Besirli.

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Ethics approval

This retrospective study was performed in line with the principles of the Declaration of Helsinki. Approval was granted by the University of Michigan Institutional Review Board (date 11/24/2020/ no. HUM00104061). All potentially identifying details were omitted and data anonymized in the materials for submission.

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Conflict of interest

Dr. Cagri G. Besirli has received clinical trial support from Spark Therapeutics.

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Deng, C., Zhao, P.Y., Branham, K. et al. Real-world outcomes of voretigene neparvovec treatment in pediatric patients with RPE65-associated Leber congenital amaurosis. Graefes Arch Clin Exp Ophthalmol 260, 1543–1550 (2022). https://doi.org/10.1007/s00417-021-05508-2

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