Photodynamic Therapy Induced Apoptosis in Choroidal Neovascularization Membranes

Abstract

Abstract: : Purpose: To evaluate the impact of verteporfin photodynamic therapy (PDT) on the induction of apoptosis in choroidal neovascular membranes (CNVM) secondary to age related macular degeneration (AMD). Methods: Retrospective review of an interventional case series 22 surgically excised CNVM secondary to AMD. Twelve of these patients were treated with PDT 3 to 146 days previously. Apoptosis was detected by staining with the TUNEL technique and compared with the expression of the panendothelial marker CD 34, CD 105, a marker for activated endothelial cells and the nuclear cell proliferation marker Ki–67. Immunohistological results were correlated with clinics and fundus fluorescein angiography (FA). Results: CNVM without pre–treatment disclosed a sporadic distribution of few apoptopic cells within the stroma and the RPE–cell layer. Three days after PDT angiography disclosed non–perfusion of the treated area. CNVM excised at this time were characterized both by collapsed and patent vessels. All endothelial cells appeared severely affected and displayed a positive TUNEL–reaction. Both RPE as well as other cells within the stroma were sporadically apoptotic, while the proliferative activity within these specimens was reduced. CNVM excised 1 – 5 months after PDT in contrast, displayed a good vascularization, high proliferative activity and only sporadic TUNEL–positive reaction within the stroma and the RPE–cell layer. Conclusions: Verteporfin PDT characteristically induces a hypoperfusion of the treated area. The effect of the treatment is based on a selective damage of endothelial cells. Both patent and occluded vessels were lined by apoptotic endothelial cells. This finding associated with an increased expression of Ki–67 and CD105 suggests that vascularization at later time points is the result of neoangiogenesis rather than recanalization.

Keywords: age-related macular degeneration • photodynamic therapy • apoptosis/cell death