Investigative Ophthalmology & Visual Science Cover Image for Volume 64, Issue 8
June 2023
Volume 64, Issue 8
Open Access
ARVO Annual Meeting Abstract  |   June 2023
Longitudinal characterization of chorioretinal atrophies after subretinal gene augmentation therapy with Voretigene Neparvovec in RPE65-mediated retinal degeneration
Author Affiliations & Notes
  • Sandrine H. Künzel
    Ophthalmology, Rheinische Friedrich-Wilhelms-Universitat Bonn, Bonn, Nordrhein-Westfalen, Germany
  • Marlene Sassmannshausen
    Ophthalmology, Rheinische Friedrich-Wilhelms-Universitat Bonn, Bonn, Nordrhein-Westfalen, Germany
  • Josua Sassen
    Institute for Numerical Simulation, Rheinische Friedrich-Wilhelms-Universitat Bonn, Bonn, Nordrhein-Westfalen, Germany
  • Markus N Preising
    Ophthalmology, Justus Liebig Universitat Giessen, Giessen, Hessen, Germany
  • Frank G Holz
    Ophthalmology, Rheinische Friedrich-Wilhelms-Universitat Bonn, Bonn, Nordrhein-Westfalen, Germany
  • Birgit Lorenz
    Ophthalmology, Rheinische Friedrich-Wilhelms-Universitat Bonn, Bonn, Nordrhein-Westfalen, Germany
    Ophthalmology, Justus Liebig Universitat Giessen, Giessen, Hessen, Germany
  • Philipp Herrmann
    Ophthalmology, Rheinische Friedrich-Wilhelms-Universitat Bonn, Bonn, Nordrhein-Westfalen, Germany
  • Footnotes
    Commercial Relationships   Sandrine H. Künzel Novartis Basel, Code C (Consultant/Contractor), Carl Zeiss MediTec, Jena, Germany; CenterVue, Padua, Italy; Heidelberg Engineering, Heidelberg, Germany; Optos, Dunfermline, UK, Code F (Financial Support), Chiesi, Hamburg, Germany, Code R (Recipient); Marlene Sassmannshausen Heidelberg Engineering, Centervue, Zeiss, Code F (Financial Support); Josua Sassen None; Markus Preising Novartis Pharma Basel, Switzerland , Code F (Financial Support); Frank Holz Acucela, Alexion, Alzheon, Apellis, Astellas, Bayer, Boehringer-Ingelheim, Bioeq/Formycon, Roche/Genentech, Geuder, Graybug, Gyroscope, Heidelberg Engineering, IvericBio, Janssen, Kanghong, LinBioscience, Novartis, Oxurion, PixiumVision, Oxurion, Stealth BioTherapeutics, Zeiss, Code C (Consultant/Contractor), Acucela, Allergan, Apellis, Bayer, Formycon, CenterVue, Roche/Genentech, Geuder, Heidelberg Engineering, IvericBio, Kanghong, NightStarX, Novartis, Optos, Pixium Vision, Zeiss, Code F (Financial Support), Grade Reading Center, Code O (Owner); Birgit Lorenz Novartis Pharma Basel, Switzerland, Janssen Pharmaceutica NV, Beerse, Belgium, Code C (Consultant/Contractor), Novartis Pharma Basel, Switzerland, Heidelberg Engineering, Germany, Janssen Pharmaceutica NV, Beerse, Belgium, Code F (Financial Support); Philipp Herrmann Heidelberg Engineering, Novartis, Zeiss, Code F (Financial Support), Allergan, Bayer, Janssen, Novartis, Code R (Recipient)
  • Footnotes
    Support  None
Investigative Ophthalmology & Visual Science June 2023, Vol.64, 5006. doi:
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      Sandrine H. Künzel, Marlene Sassmannshausen, Josua Sassen, Markus N Preising, Frank G Holz, Birgit Lorenz, Philipp Herrmann; Longitudinal characterization of chorioretinal atrophies after subretinal gene augmentation therapy with Voretigene Neparvovec in RPE65-mediated retinal degeneration. Invest. Ophthalmol. Vis. Sci. 2023;64(8):5006.

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

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Abstract

Purpose : RPE65-biallelic mutation-associated inherited retinal degeneration (RPE65-IRD) is the only IRD with approved gene therapy: Voretigene Neparvovec (VN). Successful phase 1 - 3 and follow-up studies showed improved rod functionality. However, recent studies indicated that new or accentuated chorioretinal atrophies develop following treatment in some patients. This study aims to characterize the development, localization, and topography of such atrophies over time.

Methods : The data of all RPE65-IRD patients treated with VN at a single center were analyzed. All patients were assessed with multimodal imaging, including 55° fundus autofluorescence (FAF) and 55° infrared reflectance imaging (IR) at baseline and at approx. 3-, 6-, 9- and 12- months. Functional testing included best-corrected visual acuity (BCVA) and full-field stimulus threshold testing (FST). The FAF and IR images were manually segmented for the occurrence of new atrophies by two independent graders. The resulting regions were measured with pixel accuracy and converted to mm2. From these areas, average atrophy sizes and growth rates were deduced. In addition, the localization of atrophic lesions with respect to the macula and the subretinal injection site was documented.

Results : A total of 30 eyes of 19 patients with a mean age of 24.4±9.6 years at baseline were analyzed. Mean BCVA was 1.15±0.7 logMAR (n=30 eyes) before surgery and 1.1±0.8 logMAR 12 months after surgery (n=24). Of all treated eyes, after one year, 10/24 (42%) developed new chorioretinal atrophies, 10/10 eyes central atrophic areas, 8/10 eyes at the injection site, and 9/10 eyes peripheral areas. At 12M, the median atrophy area visible in the IR images was 14.2 mm2 (n=10). For the eyes where IR and FAF were available, the median atrophy area was 14.5mm2 in the IR and 15.9 mm2 in the FAF images, respectively (n=7). However, FST results improved in 8/10 eyes with new atrophic lesions after surgery.

Conclusions : Treatment with VN led to sustained improvements in overall rod functionality and no significant changes in visual acuity in the first year following treatment. In some patients progressing atrophic lesions developed. Whenever FAF is impossible, IR imaging is a suitable alternative to detect and quantify these changes. Here we show that the atrophic lesions appear larger in FAF than in IR imaging.

This abstract was presented at the 2023 ARVO Annual Meeting, held in New Orleans, LA, April 23-27, 2023.

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