Comparison of reduced and standard light application in photodynamic therapy of the eye in two rabbit models

Framme, C. and Flucke, B. and Birngruber, R. (2006) Comparison of reduced and standard light application in photodynamic therapy of the eye in two rabbit models. GRAEFES ARCHIVE FOR CLINICAL AND EXPERIMENTAL OPHTHALMOLOGY, 244 (7). pp. 773-781. ISSN 0721-832X,

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Abstract

Current PDT treatment for age-related macular degeneration uses a standard radiant exposure of 50 J/cm(2) stop at an irradiance of 600 mW/cm(2) stop. However; there is a general problem with the unusually high irradiance; in fact, the rate of photochemical production of singlet oxygen may be limited by insufficiently oxygenized neovascular tissue. It was the aim of this study to evaluate the efficacy of verteporfin (Visudyne) photoactivation to induce thrombosis of choriocapillaries and in experimentally induced corneal neovascularizations in rabbits by varying irradiance and retinal radiant exposure. The light-dose threshold to induce micro-thrombosis in the choriocapillaries (seven eyes) and in corneal neovascularizations (eight eyes) of Chinchilla-Bastard rabbits using different retinal irradiances (100 and 600 mW/cm(2) stop) at different radiant exposures (20, 10, 5, 2.5, 1.25, 0.62, and 0.3 J/cm(2) stop) was evaluated. Induction of neovascularizations was performed 7 days prior to PDT treatment using intracorneal silk sutures. A dose of 2 mg/kg verteporfin was intravenously infused 10 min before standard PDT. The criterion for vascular thrombosis was vessel closure as determined by fluorescein angiography 1 h and 1 day post exposure. Experiments on the choroid revealed vessel closure 1 h after irradiation at ED50 = 10.8 J/cm(2) stop (both 600 and 100 mW/cm(2) stop) and after 24 h at ED50 = 2.4 J/cm(2) stop (600 mW/cm(2) stop) versus 1.8 J/cm(2) stop (100 mW/cm(2) stop). Vessel closure was enhanced at irradiation with 100 mW/cm(2) stop. Regarding corneal neovascularizations, vessel thrombosis was observable by dark appearance of irradiated clotted neovascular tissue and angiographically by a lack of leakage at ED50 thresholds of 0.62 J/cm(2) stop (1 h) and 0.41 J/cm(2) stop (1 day) for 100 mW/cm(2) stop and of 0.99 J/cm(2) stop (1 h), and 0.67 J/cm(2)supercript stop (1 day) for 600 mW/cm(2)supercript stop. Thus in both experiments thresholds for vessel closure were reduced by a factor of 1.5 for the lower intensity. Histology revealed more selective vessel occlusion without RPE and photoreceptor damage for 100 mW/cm(2) stop rather than 600 mW/cm(2) stop intensity at threshold irradiation. Low-intensity PDT with verteporfin for neovascular tissue seems to be more effective than regular high-intensity PDT. Future preclinical trials should address the issue of proper dosimetry for effective PDT in age-related macular degeneration.

Item Type: Article
Uncontrolled Keywords: MULTICELL TUMOR SPHEROIDS; FLUENCE RATE; CORNEAL NEOVASCULARIZATION; SUBRETINAL INJECTION; DIFFUSION; KINETICS; PDT; AMD; choroidal neovascularization; radiant exposure; threshold
Subjects: 600 Technology > 610 Medical sciences Medicine
Divisions: Medicine > Lehrstuhl für Augenheilkunde
Depositing User: Dr. Gernot Deinzer
Date Deposited: 11 Feb 2021 09:01
Last Modified: 11 Feb 2021 09:01
URI: https://pred.uni-regensburg.de/id/eprint/34350

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