P K Kaiser1. 1. Cole Eye Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA. pkkaiser@aol.com
Abstract
OBJECTIVE: To discuss the rationale for combining anti-angiogenic treatment with verteporfin (Visudyne) photodynamic therapy in the management of choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) and evaluate available evidence for the therapeutic benefits of such approaches. SCOPE: The Medline and EMBASE databases were searched in October 2006 to retrieve relevant articles. Additional articles were obtained from the reference lists of retrieved articles, as well as from recent scientific meetings and company websites. FINDINGS: Treatments for CNV due to AMD can be directed at either the vascular component of CNV (the new vessels that proliferate and leak blood and fluid) or the angiogenic component that leads to the development of the condition. Verteporfin targets the vascular component, whereas anti-angiogenic agents (such as pegaptanib and ranibizumab) target key mediators of the angiogenic cascade. The different mechanisms of action of these approaches offer the potential for additive or synergistic effects with combination therapy. In addition, anti-angiogenic agents might counteract upregulation of angiogenic factors (including VEGF) that occur after verteporfin photodynamic therapy. Results from preclinical and clinical studies of the combination of ranibizumab or pegaptanib with verteporfin warrant continued investigation. CONCLUSIONS: The use of anti-angiogenic agents in combination with verteporfin may have the potential to improve visual outcomes and reduce the number of treatments in eyes with CNV due to AMD, and requires further evaluation in randomized, controlled clinical trials.
OBJECTIVE: To discuss the rationale for combining anti-angiogenic treatment with verteporfin (Visudyne) photodynamic therapy in the management of choroidal neovascularization (CNV) due to age-related macular degeneration (AMD) and evaluate available evidence for the therapeutic benefits of such approaches. SCOPE: The Medline and EMBASE databases were searched in October 2006 to retrieve relevant articles. Additional articles were obtained from the reference lists of retrieved articles, as well as from recent scientific meetings and company websites. FINDINGS: Treatments for CNV due to AMD can be directed at either the vascular component of CNV (the new vessels that proliferate and leak blood and fluid) or the angiogenic component that leads to the development of the condition. Verteporfin targets the vascular component, whereas anti-angiogenic agents (such as pegaptanib and ranibizumab) target key mediators of the angiogenic cascade. The different mechanisms of action of these approaches offer the potential for additive or synergistic effects with combination therapy. In addition, anti-angiogenic agents might counteract upregulation of angiogenic factors (including VEGF) that occur after verteporfin photodynamic therapy. Results from preclinical and clinical studies of the combination of ranibizumab or pegaptanib with verteporfin warrant continued investigation. CONCLUSIONS: The use of anti-angiogenic agents in combination with verteporfin may have the potential to improve visual outcomes and reduce the number of treatments in eyes with CNV due to AMD, and requires further evaluation in randomized, controlled clinical trials.