Abstract and Introduction
Abstract
Neovascular age-related macular degeneration is responsible for the overwhelming majority of vision loss in age-related macular degeneration. Not too long ago, the disease was poorly controlled with few treatment options. Today, angiogenesis is the central focus in the pathogenesis of this disease, with VEGF identified as a major mediator of this process. These advances have opened the door for targeted anti-VEGF therapy, leading to significant improvements in visual outcomes for a majority of patients. There is, however, a portion of the population that responds poorly to initial treatment with little explanation as to why this occurs. Combination therapies are now being investigated to tackle anti-VEGF monotherapy nonresponders.
Introduction
There is no debate that age-related macular degeneration (AMD) is a serious disease with the potential for increasingly significant morbidity as our population ages. Within the scope of AMD, neovascular disease has even more devastating visual consequences. Fortunately, as our understanding of neovascular AMD improves, so do our options for treatment. VEGF has emerged as one of the primary mediators accounting for not only angiogenesis but also vascular permeability. It was not until 1997 that Kliffen and colleagues reported an increased expression of VEGF in neovascular AMD, essentially opening the door for targeted therapy. Now, with the results of prospective, randomized clinical trials, anti-VEGF therapy remains the mainstay of treatment for neovascular AMD.
The late German philosopher, Johann Wolfgang von Goethe, once said, "The solution of every problem is another problem". For almost two decades, laser photocoagulation was the only evidence-based treatment that merely limited the spread of neovascular AMD until the advent of more focal photodynamic therapy (PDT). Just a few years later, the US FDA approved the first anti-VEGF agent in ocular disease, headlining a paradigm shift in the treatment of neovascular disease of the eye. For a large percentage of patients with wet AMD, science has significantly improved their lives; however, amidst the new wave of solutions, the problem of anti-VEGF nonresponders emerges. This article aims to review anti-VEGF therapy for neovascular AMD and shed light on how we can tackle treatment failures.