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Abstract
Background/aims Voretigene neparvovec (VN) is the first and only subretinal gene therapy approved by the Food and Drug Administration and European Medicines Agency. Real-world application has started in 2018 in patients with vision impairment due to biallelic retinal pigment epithelium (RPE) 65 mutation-associated inherited retinal degenerations. Herein, we evaluated the development of retinal atrophy within in a single-centre patient cohort treated with VN.
Methods 13 eyes of eight patients treated with VN were retrospectively analysed for areas of retinal atrophy over a period of 6–24 months following surgery. Ultrawide field images were used to measure the area of atrophy. Fundus autofluorescence imaging is presented as an instrument for early detection of signs of retinal atrophy in these patients.
Results Atrophic changes beyond the retinotomy site were observed in all eyes. Areas of atrophy developed within the area of detachment (bleb) in all eight patients and outside the bleb in three patients. Changes in autofluorescence preceded the development of retinal atrophy and were already evident 2 weeks after surgery in the majority of patients. The areas of atrophy increase with time and progression continued over year 1. Functional outcomes remained stable (VA, FST, visual field).
Conclusion Subretinal injection of VN can lead to RPE atrophy with consequent photoreceptor loss in and outside of the bleb area. Fundus autofluorescence is an important tool to monitor atrophic changes in patients after gene therapy. Interestingly, while areas of atrophy also included central areas, the functional benefits of the treatment did not appear to be affected and remained stable.
- Drugs
- Degeneration
- Retina
- Treatment Surgery
Data availability statement
Data are available upon reasonable request. The authors confirm that the most relevant data supporting the findings of this study are available within the article and its supplementary materials. Additional data supporting the findings of this study are available from the corresponding author, [M.D. Fischer], upon reasonable request.
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Data availability statement
Data are available upon reasonable request. The authors confirm that the most relevant data supporting the findings of this study are available within the article and its supplementary materials. Additional data supporting the findings of this study are available from the corresponding author, [M.D. Fischer], upon reasonable request.
Footnotes
Contributors Concept and design: MDF, FFR, KS, KUB-S; acquisition, analysis or interpretation of data: FFR, MDF, IS, KS, KUBS, drafting of the manuscript: FFR, MDF, KS; critical revision of the manuscript for important intellectual content: FFR, MDF, KS, IS, FW, SD, RJ, MK, SK, FCK, SO, LP, KS, KUB-S; statistical analysis: FFR, MDF, IS; administrative, technical or material support: IS, FW, SD, RJ, MK, SK, FCK, SO, LP, KS, KUB-S. Overall guarantor: MDF.
Funding Felix Reichel received funding from the German Clinician Scientist program (486-0-0).
Competing interests DF is on the advisory board of and/or consulting and/or receiving honoraria/grant money/travel support from following companies: Adelphi Values, Advent France Biotechnology, Alphasights, Arctos Medical, Atheneum, Axiom Healthcare Strategies, Biogen, Cambridge Consultants, Decision Resources, Dialectica, Frontera Therapeutics, Janssen Research & Development, Navigant, Novartis, Roche, RegenxBio, Sirion, System Analytic, and STZeyetrial. He is director of Fischer Consulting Limited and holds a patent (50%) on a gene therapy product for X-linked Retinitis Pigmentosa. FW reports personal fees from Novartis, outside the submitted work. KS reports personal fees from Novartis, outside the submitted work. SK reports grants from Charlotte & Tistou Kerstan Foundation, during the conduct of the study; personal fees from Novartis, outside the submitted work. No other disclosures were reported.
Provenance and peer review Not commissioned; externally peer reviewed.
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