June 2022
Volume 63, Issue 7
Open Access
ARVO Annual Meeting Abstract  |   June 2022
Short-term follow up after Large-Area RPE Removal by Microsecond Laser followed by hiPS-RPE suspension transplantation in rabbits
Author Affiliations & Notes
  • Sami Al-Nawaiseh
    opthalmology, Eye clinic sulzbach, Sulzbach, Saarland, Germany
    opthalmology, University of Muenster, Münster, North Rhine-Westphalia, Germany
  • Christian Burri
    Institute for Human Centered Engineering, Berner Fachhochschule, Bern, Bern, Switzerland
    Institute of Applied Physics, Universitat Bern, Bern, Bern, Switzerland
  • André Schulz
    opthalmology, Eye clinic sulzbach, Sulzbach, Saarland, Germany
    Klaus Heimann Eye Research Institute, Sulzbach, Saarland, Germany
  • Philip Wakili
    opthalmology, Eye clinic sulzbach, Sulzbach, Saarland, Germany
  • Gerardo Farese
    opthalmology, Eye clinic sulzbach, Sulzbach, Saarland, Germany
  • Christina Kroetz
    Fraunhofer IBMT, Sulzbach, Saarland, Germany
  • Simon Salzmann
    Institute for Human Centered Engineering, Berner Fachhochschule, Bern, Bern, Switzerland
  • Brinkmann Ralf
    Medical Laser Center Lübeck, Lübeck, Germany
    Institute of Biomedical Optics, Universitat zu Lubeck Sektion Medizin, Lubeck, Schleswig-Holstein, Germany
  • Sylvia Jane Gasparini
    DFG Center for Regenerative Therapies Dresden, Technische Universitat Dresden, Dresden, Sachsen, Germany
  • Boris Povazay
    Institute for Human Centered Engineering, Berner Fachhochschule, Bern, Bern, Switzerland
  • Martin Frenz
    Institute of Applied Physics, Universitat Bern, Bern, Bern, Switzerland
  • Peter Szurman
    opthalmology, Eye clinic sulzbach, Sulzbach, Saarland, Germany
    Klaus Heimann Eye Research Institute, Sulzbach, Saarland, Germany
  • Marius Ader
    DFG Center for Regenerative Therapies Dresden, Technische Universitat Dresden, Dresden, Sachsen, Germany
  • Boris V. Stanzel
    opthalmology, Eye clinic sulzbach, Sulzbach, Saarland, Germany
    Klaus Heimann Eye Research Institute, Sulzbach, Saarland, Germany
  • Footnotes
    Commercial Relationships   Sami Al-Nawaiseh Heidelberg Engineering, Code R (Recipient); Christian Burri Heidelberg Engineering, Code R (Recipient); André Schulz None; Philip Wakili None; Gerardo Farese None; Christina Kroetz None; Simon Salzmann None; Brinkmann Ralf None; Sylvia Gasparini None; Boris Povazay None; Martin Frenz None; Peter Szurman Geuder, Novartis, Bayer, Code C (Consultant/Contractor); Marius Ader None; Boris Stanzel Geuder, Novartis, Apellis, Code C (Consultant/Contractor), Geuder, Catalent, Vitreq, Medone Surgical, Code F (Financial Support), Bayer, Iridex, Heidelberg Engineering, Geuder, Code R (Recipient)
  • Footnotes
    Support  none
Investigative Ophthalmology & Visual Science June 2022, Vol.63, 4509 – F0296. doi:
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      Sami Al-Nawaiseh, Christian Burri, André Schulz, Philip Wakili, Gerardo Farese, Christina Kroetz, Simon Salzmann, Brinkmann Ralf, Sylvia Jane Gasparini, Boris Povazay, Martin Frenz, Peter Szurman, Marius Ader, Boris V. Stanzel; Short-term follow up after Large-Area RPE Removal by Microsecond Laser followed by hiPS-RPE suspension transplantation in rabbits. Invest. Ophthalmol. Vis. Sci. 2022;63(7):4509 – F0296.

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

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Abstract

Purpose : Cell therapy is a promising treatment for retinal pigment epithelium (RPE)-associated eye diseases. Herein, microsecond laser irradiation targeting RPE cells was used for large-area RPE removal followed by subretinal injection of human induced pluripotent stem cell derived RPE (hiPS-RPE).

Methods : 19 immunosuppressed pigmented rabbits (Chinchilla bastard hybrid) underwent a large area RPE removal using an infrared reflectance (IR) confocal scanning laser ophthalmoscope (cSLO) with spectral-domain optical coherence tomography (SD-OCT) system (Heidelberg Engineering ) extended with a prototype laser (modified Merilas 532 shortpulse ophthalmic laser photocoagulator, Meridian Medical) (wavelength, 532 nm; pulse duration, 8 µs), followed by a 25G vitrectomy. Subsequently, a suspension of hiPS-RPE (1000 cells/ µl) was grafted subretinally into the RPE laser lesion under real-time intraoperative OCT imaging (RESCAN 700, Zeiss) by manual injection via a 25/38G cannula connected to a 100µl Hamilton syringe. 5 rabbits served as a control with hiPS-RPE injected subretinally over healthy RPE. The rabbits were followed with in vivo multimodal retinal imaging at baseline after laser and then for 7 days including fluorescein (FA) and indocyanine angiography (ICGA), aw well as SD-OCT (Spectralis ®, Heidelberg Engineering).

Results : Baseline imaging of RPE laser wounds showed mild late phase FA/ICGA leakage, with normal outer retinal and choroidal reflectivity on OCT, without signs of coagulation. The size of the RPE wounds was typically 10-12mm2. Real time iOCT showed a directed spread of the bleb retinal detachment (bRD) within the lasered zone, in contrast to a circular spread in controls. Subretinal injection ranged from 5-20µl, with lesser volumes/ larger bRD areas over lasered regions. At 7 days, implanted regions showed FA/ICGA leakage, blockage due to hyperpigmentation was observed mostly at the edges of the lasered zone; OCT showed hyperreflectivity of the outer retina with RPE irregularities. Control implantation sites showed hyperreflectivity in all retinal layers and a variably thickened RPE band suggesting clumping.

Conclusions : Microsecond laser irradiation to the RPE seems to accelerate the subretinal integration of hiPS-RPE, when compared to subretinal injection over intact RPE. Future work will address correlation of multimodal imaging and histology.

This abstract was presented at the 2022 ARVO Annual Meeting, held in Denver, CO, May 1-4, 2022, and virtually.

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