Abstract
Abstract: :
Purpose: Current PDT–treatment for age–related macular degeneration uses a standard radiant exposure of 50J/cm2 at an irradiance of 600mW/cm2. In using higher irradiances a question has been raised as to whether the rate of photochemical production of singlet oxygen may be limited by not sufficiently oxygenized neovascular tissue. It was the aim of this study to evaluate the efficacy of Verteporfin (Visudyne®) photoactivation to induce thrombosis of intraocular capillaries and experimental induced corneal neovascularization in rabbits by varying irradiant and retinal radiant exposure. Methods: The light–dose–threshold to induce micro–thrombosis in the normal choriocapillaries (7 eyes) and in pathologic corneal neovascularizations (8eyes) of Chinchilla bread rabbits using different retinal irradiances (100 and 600mW/cm2) at different radiant exposures (20, 10, 5, 2.5, 1.2, 0.62 and 0.3 J/cm2) was evaluated. Induction of neovascularizations was performed 7 days prior to PDT treatment using intracorneal silk sutures. 2mg/kg Verteporfin was intravenously infused 10 minutes before standard PDT. The criterion for vascular thrombosis was vessel closure as determined by fluorescein angiography one hour and one day post exposure. Results: Experiments on the choroid revealed vessel closure 1 hour after irradiation at ED50 = 10.8 J/cm2 (both 600 and 100mW/cm2) and after 24 hours at ED50 = 2.4 J/cm2 (600mW/cm2) versus 1.8 J/cm2 (100mW/cm2). Vessel closure was slightly enhanced at irradiation with 100mW/cm2. 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/cm2 (1 hour) and 0.41 J/cm2 (1 day) for 100mW/cm2 and 0.99 J/cm2 (1 hour) and 0.62 J/cm2 (1 day) for 600mW/cm2. Thus in both experiments threshold light dose for vessel closure were reduced by a factor of 1.5 for the lower irradiance of laser light. Histology revealed vessel occlusion with less RPE and photoreceptor changes for 100mW/cm2 rather than 600mW/cm2 irradiance at the related threshold dose. Conclusions: Lower intensity laser application with Verteporfin for neovascular tissue seems to be more effective than regular PDT of high intensity laser application. Future preclinical trials should address the issue of proper dosimetry regarding effective PDT in AMD.
Keywords: age–related macular degeneration • laser • neovascularization