Rabbit model of ocular indirect photodynamic therapy using a retinoblastoma xenograft.

Abstract

The goal of this project was to demonstrate the feasibility of coupling the indirect ophthalmoscope laser delivery system with the 690nm wavelength diode laser used to perform photodynamic therapy (PDT) in the treatment of retinoblastoma. 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 690nm laser unit, delivered through a 810nm Indirect ophthalmoscope headpiece and a hand-held 28-diopter indirect lens (1.0mm spot size). Four rabbits received intravenous verteporfin at doses of 0.43 or 0.86mg/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. 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 150mW/cm2 and treatment duration ranged between 1 and 3min. In the four rabbits that received verteporfin, focal retinal scars were noted at 40mW/cm2 and higher power levels. In the two control rabbits that did not receive verteporfin, thermal burns were confirmed at 75mW/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. The results of this pre-clinical study suggest verteporfin may be activated in the rabbit retina with the indirect delivery system and the 690nm laser unit (i.e., Indirect PDT). Using verteporfin, treatment effects were observed at 40-50mW/cm2 in the rabbit retina, while photocoagulation was achieved at 75mW/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.