Comparison of Multiple Reduced-dose and Standard Light Application in Photodynamic Therapy in an Animal Model of Choroidal Neovascularization

Abstract

Current photodynamic therapy (PDT) for choroidal neovascularization (CNV) uses a standard radiant exposure of 50 J/cm2 at an irradiance of 600 mW/cm2. However, low-intensity PDT with verteporfin for neovascular tissue has been shown to be more effective than regular high-intensity PDT in an animal model of healthy choroids and corneal neovascularization. Low-intensity PDT also supposedly induces less retinal damage. In this study, we compared the effect of reduced-dose and standard light application PDT in an animal model of CNV. A laser injury model was used to induce CNV 3 weeks prior to PDT in brown Norway rats. The CNV lesions were then treated with verteporfin PDT with a dose of verteporfin 6.0 mg/m2 and 5 activating doses of light energy (43, 53, 63, 73 and 83 seconds). Closure of CNV was assessed by fundus fluorescein angiography (FAG). Histopathologic study was done after the last FAG. PDT with verteporfin significantly reduced the CNV area compared with control non-treated groups 1 week after PDT (p < 0.05). Only those lesions treated for 63 seconds or longer retained their significantly attenuating effect on CNV up to 3 weeks after PDT. There was no significant difference between the inhibition effects induced by reduced-intensity light application for 63 or 73 seconds compared to the standard radiant exposure (83 seconds). Histopathologic study showed that eyes treated with PDT showed significantly less extent and vascularity of CNV lesion than control lesions. Reduced-intensity PDT with 63-second duration seemed to be as effective as standard dose for CNV suppression. Considering the possible retinal damage following standard PDT, the PDT dose might be adjusted to reduce side effects. Further preclinical study will provide more data on what constitutes appropriate dosimetry for effective and safe PDT in CNV.