Treatment of age-related macular degeneration: focus on ranibizumab

Abstract

Ranibizumab, a humanized antigen-binding fragment (Fab) that binds all isoforms of VEGF-A, significantly slows down loss of vision and causes significant visual improvement in many patients with choroidal neovascularization (CNV) due to exudative age-related macular degeneration (AMD). These benefits of intravitreal ranibizumab apply to all angiographic subtypes of neovascular AMD and across all lesion sizes when the drug is injected at monthly intervals as shown in two pivotal phase III trials (ANCHOR and MARINA). The results from the PrONTO study suggest that less frequent treatment with ranibizumab through a variable dosing regimen dependent on optical coherence tomography (OCT) findings is a treatment option that results in comparably favorable visual outcomes. Currently, it is unclear whether combination therapy of ranibizumab with photodynamic therapy (PDT) provides any significant advantage over ranibizumab monotherapy (FOCUS trial); however, the combination of PDT and ranibizumab may decrease the need for frequent retreatment. This question will be addressed in the SUMMIT trial. Therapy with ranibizumab is generally very well tolerated with a low rate of seriously adverse ocular events or systemic side-effects. The advent of vascular endothelial growth factor (VEGF) inhibitors has revolutionized the therapy of neovascular AMD. Ranibizumab at the moment appears to be the most effective approved treatment for neovascular AMD.

Keywords: Lucentis; age-related macular degeneration (AMD); exudative AMD; neovascular; ranibizumab; treatment; vascular endothelial growth factor (VEGF).

Figure 1

MARINA trial design.

Figure 2

MARINA trial: after 2 years mean visual acuity had increased by 6.6 lines in the ranibizumab 0.5 mg group versus a decrease of 14.9 lines in the sham group. This favorable outcome was independent of membrane type (minimally classic or purely occult CNV), the initial visual acuity, or the lesion size. Adapted with permission from Rosenfeld PJ, Brown DM, Heier JS, et al. 2006a. Ranibizumab for neovascular age-related macular degeneration. N Eng J Med, 355:1419–31. Copyright © 2006. Massachusetts Medical Society. All rights reserved.

Figure 3

ANCHOR trial design.

Figure 4

In patients with classic subfoveal CNV due to AMD, ranibizumab prevented visual loss in a significantly higher number of patients than PDT (12-month results modified according to Brown et al 2006; 24-month results according to Schmidt-Erfurth et al 2007).

Figure 5

In patients with classic subfoveal CNV due to AMD, ranibizumab improved vision significantly in up to 41% of patients (12-month results modified according to Brown et al 2006; 24-month results according to Schmidt-Erfurth et al 2007).