Combined Treatment of Photodynamic Therapy and Bevacizumab for Choroidal Neovascularization Secondary to Age-Related Macular Degeneration

Photodynamic therapy (PDT) with verteporfin (Visudyne; Novartis Pharma AG, Basel, Switzerland) has been shown to reduce the risk of moderate and severe vision loss in patients with choroidal neovascularization (CNV) secondary to age-related macular degeneration (AMD). However, PDT rarely achieved visual improvement [1-3]. Choroidal hypoperfusion has been reported as a common side-effect after PDT [4]. Choroidal ischemia and its associated inflammation induce production of vascular endothelial growth factor (VEGF), which may lead to recurrence or new incidence of CNV [5,6]. To manage recurrence, it is necessary to repeat PDT, which may result in choroid or retina atrophy and reduce visual function [7]. Bevacizumab, a recombinant full-length humanized monoclonal antibody that binds all VEGF isoforms, was originally approved for treatment of metastatic carcinoma of the colon and rectum; however, it has been used as an off-label intravitreal treatment for CNV [8,9]. Several uncontrolled studies and case series have shown anatomical improvement and moderate vision gain when bevacizumab was used as a monotherapy [8-12]. However, repeated intravitreal injections are subject to the risk of complications, discomfort for the patient, and increased health care expense [13-16]. As CNV is a multi-factorial disease process, it was hypothesized that a combination therapy of different mechanisms of action would have additive or complementary treatment effects, and possibly result in the improvement of functional outcome as well as reduce the need for frequent retreatment [17]. Combination therapy has many options regarding sequence, interval, and number of each treatment given. Based on the report that the choroidal hypofluorescence was found in indocyanine green (ICG) angiography for 3 months after PDT [4] and that the main functional improvement was achieved after 3 consecutive ranibizumab injections [14,15,18,19], we conducted combined PDT and 3 consecutive intravitreal bevacizumab injections as treatment for patients with CNV secondary to AMD. This study was conducted to determine if this combination could achieve vision improvement and reduce the number and frequency of retreatment.