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Rabbit model of ocular indirect photodynamic therapy using a retinoblastoma xenograft

  • Jonathan W. Kim
  • Bradley Jacobsen
  • Emily Zolfaghari
  • Angela Ferrario
  • Patricia Chevez-Barrios
  • Jesse L. Berry
  • Diana K. Lee
  • Grecia Rico
  • Ingy Madi
  • Narsing Rao
  • Kevin Stachelek
  • Lei-chi Wang
  • Charles Gomer
Basic Science
  • 171 Downloads

Abstract

Purpose

The goal of this project was to demonstrate the feasibility of coupling the indirect ophthalmoscope laser delivery system with the 690 nm wavelength diode laser used to perform photodynamic therapy (PDT) in the treatment of retinoblastoma.

Methods

For phase 1, a total of six pigmented rabbits were treated with the indirect laser delivery system. The laser source was provided by the Lumenis Opal 690 nm laser unit, delivered through a 810 nm Indirect ophthalmoscope headpiece and a hand-held 28-diopter indirect lens (1.0 mm spot size). Four rabbits received intravenous verteporfin at doses of 0.43 or 0.86 mg/kg, and two rabbits did not receive verteporfin (controls). A second phase of the study involved eight rabbits using a retinoblastoma xenograft to determine the effect of indirect PDT on subretinal tumors.

Results

For phase 1, a total of 20 laser treatments were performed in the right eyes of six rabbits. Laser power levels ranged between 40 and 150 mW/cm2 and treatment duration ranged between 1 and 3 min. In the four rabbits that received verteporfin, focal retinal scars were noted at 40 mW/cm2 and higher power levels. In the two control rabbits that did not receive verteporfin, thermal burns were confirmed at 75 mW/cm2 and higher power levels. Histopathology showed focal retino-choroidal scars at the site of PDT treatment, without evidence of generalized ocular damage. Using the retinoblastoma xenograft, the indirect PDT system was shown to cause areas of tumor necrosis on histopathology.

Conclusions

The results of this pre-clinical study suggest verteporfin may be activated in the rabbit retina with the indirect delivery system and the 690 nm laser unit (i.e., Indirect PDT). Using verteporfin, treatment effects were observed at 40–50 mW/cm2 in the rabbit retina, while photocoagulation was achieved at 75 mW/cm2 and higher power levels. Fundoscopic and histopathologic examination of treated areas showed circumscribed areas of retinal damage and a lack of generalized ocular toxicity, suggesting that this modality may represent a safe and localized method for treating intraocular retinoblastoma.

Keywords

Photodynamic therapy Retinoblastoma Laser treatment Indirect ophthalmoscope Xenograft 

Notes

Funding

Research to Prevent Blindness and the Las Madrinas Endowment in Experimental Therapeutics.

Compliance with ethical standards

Conflict of interest

All authors certify that they have no affiliations with or involvement in any organization or entity with any financial interest (such as honoraria; educational grants; participation in speakers’ bureaus; membership, employment, consultancies, stock ownership, or other equity interest; and expert testimony or patent-licensing arrangements), or non-financial interest (such as personal or professional relationships, affiliations, knowledge, or beliefs) in the subject matter or materials discussed in this manuscript.

Animal experiments

Ethical approval: “All applicable international, national, and/or institutional guidelines for the care and use of animals were followed.”

University of California, Los Angeles: “All procedures performed in studies involving animals were in accordance with the ethical standards of the institution or practice at which the studies were conducted.”

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Copyright information

© Springer-Verlag GmbH Germany 2017

Authors and Affiliations

  • Jonathan W. Kim
    • 1
    • 2
  • Bradley Jacobsen
    • 3
  • Emily Zolfaghari
    • 1
  • Angela Ferrario
    • 4
  • Patricia Chevez-Barrios
    • 5
  • Jesse L. Berry
    • 1
    • 2
  • Diana K. Lee
    • 2
  • Grecia Rico
    • 5
  • Ingy Madi
    • 1
  • Narsing Rao
    • 2
  • Kevin Stachelek
    • 1
  • Lei-chi Wang
    • 2
  • Charles Gomer
    • 4
  1. 1.Vision Center, Children’s Hospital Los AngelesLos AngelesUSA
  2. 2.USC Eye Institute, Keck School of Medicine of USCLos AngelesUSA
  3. 3.School of Medicine, University of California, IrvineIrvineUSA
  4. 4.Department of PediatricsChildren’s Hospital Los AngelesLos AngelesUSA
  5. 5.Department of Pathology and Genomic Medicine, Houston Methodist HospitalWeil Cornell MedicineHoustonUSA

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