Modified Verteporfin Photodynamic Therapy (PDT), PDT Combined With Angiostatin In Vitro and In Vivo

Abstract

Abstract: : Purpose: To investigate the selectivity and the efficacy ofPDT combined with the anti-angiogenic drug angiostatin in vitroand in vivo. Methods: (in vitro) Human retinal pigment epithelial(hRPE) and bovine retinal microvascular endothelial cells (bRME)were maintained in conditioned media. Verteporfin PDT was performedon cells with or without prior exposure to 100ng/mL of angiostatin.Cellular survival was assessed at 24 hours after PDT. (in vivo)Choroidal neovascular membranes (CNV) were induced in Brown-Norwayrats using Argon/Dye laser. Four groups were studied: 1. controlrats (placebo), 2. angiostatin alone (50mg/kg) 1 and 2 weeksafter CNV induction, 3. verteporfin PDT alone and 4. PDT plus50mg/kg of angiostatin 12 and 24 hours prior to PDT at verteporfindose of 3mg/m2 using an irradiance of 600mW/cm2 and fluenceof 10 and 25 J/cm2. Fluorescein angiography was performed at3 and 4 weeks after CNV induction and at 24 hours and 7 daysafter PDT, and graded in a masked standardized fashion. Results:In vitro results showed increased cytotoxicity for bRME butfor hRPE when angiostatin was combined with verteporfn PDT.In vivo results showed that angiostatin alone did not preventCNV (table 1), and there was no increased efficacy when angiostatinwas administered prior to verteporfin PDT (table 2) at the dosestested. Table 1 Angiographically leaking CNV after laser induction;number (%)  

Table 2 Lesions without angiographic leakage after PDT: number(%) 

Conclusion: Angiostatin potentiated the efficacyof verteporfin PDT for microvascular endothelium. However, invivo angiostatin did not appear to potentiate the effect ofverteporfin PDT on CNV at the doses tested.

Keywords: 308 age-related macular degeneration • 516 photodynamic therapy • 346 choroid: neovascularization