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

Research output: Contribution to journalArticle

3 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2363-2373
Number of pages11
JournalGraefe's Archive for Clinical and Experimental Ophthalmology
Volume255
Issue number12
DOIs
StatePublished - Dec 1 2017

Keywords

  • Indirect ophthalmoscope
  • Laser treatment
  • Photodynamic therapy
  • Retinoblastoma
  • Xenograft

ASJC Scopus subject areas

  • Ophthalmology
  • Sensory Systems
  • Cellular and Molecular Neuroscience

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