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Injection pressure levels for creating blebs during subretinal gene therapy

Abstract

Retinal damage has been associated with increased injection pressure during subretinal gene therapy delivery in various animal models, yet there are no human clinical data regarding the pressures required to initiate and propagate subretinal blebs. This study characterized the intraoperative pressure levels for subretinal gene therapy delivery across eight retinal conditions. A total of 116 patients with retinal degenerative diseases have been treated with subretinal gene therapy at OHSU-Casey Eye Institute as of June 2020; seventy patients (60.3%) were treated using a pneumatic-assisted subretinal delivery system. All retinal blebs were performed using a 41-gauge injection cannula, and use of a balanced salt solution (BSS) “pre-bleb” prior to gene therapy delivery was performed at the discretion of the surgeon. Patient age and intraoperative data for BSS and vector injections were analyzed in a masked fashion for all patients who received pneumatic-assisted subretinal gene therapy. The median age of the patients was 35 years (range 4–70). No significant differences in injection pressures were found across the eight retinal conditions. In this study, patient age was shown to affect maximum injection pressures required for bleb propagation, and the relationship between age and pressure varied based on retinal condition. These data have important implications in optimizing surgical protocols for subretinal injections.

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Fig. 1: Subretinal bleb formation using intraoperative optical coherence tomography (OCT) and foot-pedal controlled delivery.
Fig. 2: Subretinal bleb propagation duration and rate.
Fig. 3: Intraoperative pressure levels for bleb propagation.
Fig. 4: Patient age and retinal condition affect intraoperative pressure levels required for bleb propagation.

Data availability

The data generated or analysed during this study can be found within the published article and its supplementary files.

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Acknowledgements

We acknowledge the support of NIH P30EY010572, The Heed Foundation, and an unrestricted grant to the Casey Eye Institute Department of Ophthalmology from Research to Prevent Blindness, Inc. New York, NY. We would like to thank Sheila Markwardt, MPH for her expertise and assistance in statistical analysis.

Funding

We acknowledge the support of NIH P30EY010572, NIH K08EY026650 (PY), Foundation Fighting Blindness Career Development Award CD-NMT-0714-0648 (PY), The Heed Foundation (BAS), and an unrestricted grant to the Casey Eye Institute Department of Ophthalmology from Research to Prevent Blindness, Inc. New York, NY.

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BAS was responsible for the conception and design, collection and/or assembly of data, data analysis and interpretation, and manuscript writing. HMV was responsible for the conception and design, collection and/or assembly of data, and data analysis and interpretation. MMDP was responsible for collection and/or assembly of data and data analysis and interpretation. KK was responsible for collection and/or assembly of data and data analysis and interpretation. MEP was responsible for data analysis and interpretation and manuscript writing. PY was responsible for data analysis and interpretation and manuscript writing. STB was responsible for collection and/or assembly of data, data analysis and interpretation, and manuscript writing. AKL was responsible for the conception and design, collection and/or assembly of data, financial support, administrative support, data analysis and interpretation, manuscript writing, and final approval of manuscript.

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Correspondence to Andreas K. Lauer.

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Competing interests

AKL has received consulting fees or funds in support of clinical research from AGTC, Allergan, Atsena, Biogen, Cambridge Consulting, Genentech, IvericBio, Oxford BioMedic, Regenxbio, TeamedOn. MKP has received consulting fees from Adverum, AGTC, Allergan, Astellas Pharmaceuticals, Biogen, BlueRock, Editas, Iveric Bio, Novartis, Ora, RegenexBio, Roche, Viewpoint Therapeutics. MKP serves on the scientific advisor boards for Atsena, DTx Therapeutics, Endogena, Eyevensys, Horama, Nayan, Nacuity Pharmaceuticals, Ocugen, Sparing Vision, and Vedere. PY has received consulting fees from Adverum, AGTC, Nanoscope Therapeutics. All other authors declare no potential competing interests.

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Institutional Review Board approval at OHSU was obtained for review of all operative notes of patients receiving subretinal delivery of gene therapy.

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Scruggs, B.A., Vasconcelos, H.M., Matioli da Palma, M. et al. Injection pressure levels for creating blebs during subretinal gene therapy. Gene Ther 29, 601–607 (2022). https://doi.org/10.1038/s41434-021-00294-2

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