Combined Treatment Modalities for Age Related Macular Degeneration

R.      A. Das; A.      Romano; F.      Chiosi; M.      Menzione; M.      Rinaldi

Abstract

Background: Age-related macular degeneration (AMD) is a condition that accounts for 75% of cases of legal blindness in individuals over the age of 50. Objectives: The objective of this review has been to evaluate the clinical effectiveness of available combined treatments modalities in the treatment of neovascular AMD. Data Sources: Central and Medline were searched for original research studies (Phase I, II, III), abstracts, and review articles concerning combination therapies for the control of neovascular AMD. We included randomized controlled trials (RCTs). Results: The results of therapeutic trials focused on the actual options in the management of neovascular AMD are discussed. Intravitreal treatment with substances targeting all isotypes of vascular endothelial growth factor (VEGF) results in a significant increase in visual acuity in patients with neovascular AMD. The combination with occlusive therapies like verteporfin photodynamic therapy (V-PDT) potentially offers a reduction of re-treatment frequency rate and long-term maintenance of the benefit reached. Despite the promise from combining anti-VEGF therapies with V-PDT, other combinations to improve outcomes with V-PDT deserve attention. Corticosteroids demonstrated an antiangiogenic effect and targeted the extravascular components of CNV, such as inflammatory cells and fibrocytes. Nevertheless, the study on the clinical application of corticosteroids will require a better understanding of the potential complications. Further developments interacting with various steps in the angiogenic cascade are under clinical or preclinical evaluation and may soon become available. In AMD the goal of a combination regimen is to address the therapy toward neovascular, inflammatory, and proliferative components of the disease. Conclusions: Combined treatments strategies are an obvious step providing disease control when it is not achieved with a single therapeutic approach. One risk of using a single therapy to control AMD is a rebound induced by compensatory stimulation of other pathogenetic pathways. Combination therapy is a logical approach to address mechanisms of disease progression that appear to be self-sustaining once initiated.

Keywords: Choroidal neovascularisation (CNV), age related macular degeneration (AMD), retinal degeneration, vascular endothelial growth factor (VEGF), verteporfin photodynamic therapy (V-PDT), anti-angiogenic therapies, combined therapies, isotypes, visual acuity, occlusive therapies, Corticosteroids, inflammatory cells, fibrocytes, Ranibizumab, bevacizumab, pegaptanib, stroke, myocardial infarction, MARINA, ANCHOR, immunosuppressants, rapamycin, hypoxia, steroids, attenuation