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Combination therapy with verteporfin and anti-VEGF agents in neovascular age-related macular degeneration: where do we stand?
  1. Peter K Kaiser
  1. Correspondence to Dr Peter K Kaiser, Cole Eye Institute, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Desk i3, Cleveland, OH 44195, USA; pkkaiser{at}

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Choroidal neovascularisation (CNV) secondary to age-related macular degeneration (AMD) is responsible for 75% of the severe vision loss attributable to AMD.1 The pathogenesis of CNV is complex, involving angiogenic and vascular components.2 3 The current treatment modalities include antivascular endothelial growth factor (anti-VEGF) therapies such as pegaptanib (Macugen, Eyetech, New York), bevacizumab (Avastin, Genentech, South San Francisco, California), ranibizumab (Lucentis, Genentech, South San Francisco, California and Novartis Pharma AG, Basel, Switzerland) and photodynamic therapy (PDT) with verteporfin (Visudyne, Novartis Pharma AG, Basel, Switzerland and QLT Vancouver, British Columbia, Canada). The predominant effect of anti-VEGF agents in AMD appears to be a reduction in vessel permeability, in addition to targeting angiogenesis by inhibiting the development of newly formed vessels. These agents have shown promising responses in terms of visual outcome, but there are some limitations. Optimal visual outcomes require aggressive monitoring and may even require monthly treatments, posing a significant burden on both patients and physicians. In addition, evidence suggests that anti-VEGF agents become less effective as neovascularisation matures, especially as the vessels become enveloped by pericytes. These pericytes may serve to buffer the neovascularisation from the anti-VEGF agents and even secrete VEGF themselves. Thus, anti-VEGF therapy may have a limited effect on the more established vasculature observed in the later stages of exudative AMD.4–6

Verteporfin PDT has a different mechanism of action from anti-VEGF therapy that targets the vascular component of CNV by occluding the newly formed vessels within the CNV lesion. The long-term clinical efficacy and safety of verteporfin PDT has been proven in several multicentre, double-masked, randomised placebo-controlled studies.7 8 However, studies have also shown that PDT may affect the physiological choriocapillary bed surrounding the pathological …

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  • Funding The Cole Eye Institute, PKK's employer, receives research grant support on his behalf from Novartis, QLT and Genentech.

  • Competing interests PKK has received honoraria from Genentech, QLT and Novartis that have been disclosed and approved by the Cleveland Clinic Conflict of Interest Committee.

  • Ethics approval Ethics approval was provided by the sites in the SUMMIT programme.

  • Patient consent Obtained.

  • Provenance and peer review Commissioned; externally peer reviewed.

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