Neovascular Age-Related Macular Degeneration: Therapeutic Management and New-Upcoming Approaches

Abstract

Age-related macular degeneration (AMD) constitutes a prevalent, chronic, and progressive retinal degenerative disease of the macula that affects elderly people and cause central vision impairment. Despite therapeutic advances in the management of neovascular AMD, none of the currently used treatments cures the disease or reverses its course. Medical treatment of neovascular AMD experienced a significant advance due to the introduction of vascular endothelial growth factor inhibitors (anti-VEGF), which dramatically changed the prognosis of the disease. However, although anti-VEGF therapy has become the standard treatment for neovascular AMD, many patients do not respond adequately to this therapy or experience a slow loss of efficacy of anti-VEGF agents after repeated administration. Additionally, current treatment with intravitreal anti-VEGF agents is associated with a significant treatment burden for patients, caregivers, and physicians. New approaches have been proposed for treating neovascular AMD. Among them, designed ankyrin repeat proteins (DARPins) seem to be as effective as monthly ranibizumab, but with greater durability, which may enhance patient compliance with needed injections.

Keywords: Ang-2; DARPins; age-related macular degeneration; anti-VEGF; neovascular AMD; neovascularization; vascular endothelial growth factor.

Figure 1

Overview of the pathophysiological leading to choroidal neovascularization. Adapted from Campochiaro [34] and Anderson et al. [41].

Figure 2

Mean change in the visual-acuity score during the first year of follow-up observed in the CATT study. Adapted from CATT Research Group et al. [100]. Rani: Ranibizumab; Beva: Bevacizumab.

Figure 3

Mean (±SE) changes in the visual acuity from baseline through 12 months observed in the ANCHOR study. As compared to the verteporfin group, the mean visual acuity was significantly greater in each of the ranibizumab groups at each month during the first year (p < 0.001). Adapted from Brown et al. [90] and Brown et al. [93]. W: Week; M: Month. Rani: Ranibizumab; Beva: Bevacizumab.

Figure 4

Mean (±SE) changes in the visual acuity from baseline through 24 months observed in the MARINA study. As compared to the sham injection group, the mean visual acuity was significantly greater in each of the ranibizumab groups at each month during the study follow-up (p < 0.001). At week 1, On day, p = 0.006 for patients receiving ranibizumab 0.3 mg and p = 0.003 for those receiving ranibizumab 0.5 mg. Adapted from Rosenfeld et al. [89]. W: Week; M. Month; Rani: Ranibizumab.

Figure 5

Mean change from baseline in visual acuity (VA) and number of intravitreal injections (IVI) in real-world studies and randomized controlled trials after 12 months of ranibizumab treatment in patients with neovascular age related macular degeneration. Real world studies results have been adapted from Chong [27] and Kim et al. [153]. RLS: Real-life studies; gm: grand means (mean of the means of the several studies); wm: weighted means (mean weighted against number of eyes per study).

Figure 6

An overview of the different causes of resistance to anti-VEGF therapy and their possible therapeutic approaches. Adapted from Broadhead et al. [154] and Yang et al. [155]. Anti-VEGF: Vascular endothelial growth factor inhibitors; AMD: Age related macular degeneration.

Figure 7

Mean changes in best corrected visual acuity (BCVA) (A) and central macular thickness (CMT) (B) from baseline in the modified intent-to-treat population of the REACH study. Adapted from Callanan et al. [193].