June 2020
Volume 61, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2020
The age of patients with retinal degenerative diseases affects the injection pressure required for subretinal gene therapy delivery
Author Affiliations & Notes
  • Brittni A Scruggs
    Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • Huber Martins Vasconcelos Junior
    Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • Mark E Pennesi
    Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • Steven T Bailey
    Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • Andreas K Lauer
    Ophthalmology, Casey Eye Institute, Oregon Health & Science University, Portland, Oregon, United States
  • Footnotes
    Commercial Relationships   Brittni Scruggs, None; Huber Vasconcelos Junior, None; Mark Pennesi, None; Steven Bailey, None; Andreas Lauer, AGTC (R), Allergan (F), Biogen (C), Genentech (F), IvericBio (R), Oxford BioMedica (F), Regenxbio (C)
  • Footnotes
    Support  Unrestricted Grant from Research to Prevent Blindness, New York, New York; NIH P30 EY010572 Core Grant, Bethesda, Maryland; Heed Fellowship 2019-2020
Investigative Ophthalmology & Visual Science June 2020, Vol.61, 4501. doi:
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      Brittni A Scruggs, Huber Martins Vasconcelos Junior, Mark E Pennesi, Steven T Bailey, Andreas K Lauer; The age of patients with retinal degenerative diseases affects the injection pressure required for subretinal gene therapy delivery. Invest. Ophthalmol. Vis. Sci. 2020;61(7):4501.

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

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Abstract

Purpose : Pre-clinical studies demonstrate that surgical techniques influence outcomes when performing subretinal injections, and retinal damage increases depending on injection pressure. We tested the hypotheses that the injection pressure required for subretinal gene therapy delivery differs based on retinal pathology and patient demographics. This project focuses on optimizing subretinal injection techniques needed for delivering gene therapy.

Methods : A total of 108 patients with retinal degenerative diseases have been treated with subretinal gene therapy at our institution. Of these, 87 patients underwent pars plana vitrectomy with intraoperative optical coherence tomography (OCT), and retinal blebs were performed using a 41G injection cannula and foot-pedal assisted control. All cases were performed by one of two vitreoretinal surgeons. Use of a balanced salt solution (BSS) “pre-bleb” prior to gene therapy delivery was performed at the discretion of the surgeon. Patient demographics and surgical methodology data (e.g.,maximum psi used for BSS and vector injections) have been analyzed in a masked fashion to ensure no clinical trial-specific information was disclosed. The relationship between injection pressures and patient age was analyzed using linear regression. Statistical analysis of three or more groups was performed using one-way analysis of variance (ANOVA) with Tukey post-hoc testing.

Results : The median age of the patients was 36.5 yrs (range 4-86 yrs). The patients’ ages differed across the eight retinal conditions (p<0.0001). Increased patient age was inversely related to the injection pressure required for subretinal gene therapy delivery (p=0.025). Patients <21 years required an injection pressure of 10.00±1.15 psi (range 6-16 psi) to generate a bleb using viral supernatant, whereas patients >54 years required an injection pressure of 5.88±0.44 psi (range 4-8 psi) (p=0.0064). Comparisons of intraoperative and post-operative OCT videos across disease states remain ongoing as the clinical trials continue.

Conclusions : Our data demonstrate that higher injection pressures for gene therapy delivery are required for younger patients with retinal degenerative diseases. Long-term goals of this project include developing condition-specific surgical protocols for subretinal delivery of gene therapy.

This is a 2020 ARVO Annual Meeting abstract.

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