As physicians, our primary goal is to provide the best possible care for our patients. To that end, retina specialists and patients have been extremely fortunate in the past few years to benefit from anti-VEGF therapies like bevacizumab (Avastin, Genentech) and ranibizumab (Lucentis, Genentech). These agents not only retard vision loss in many of our patients with age-related macular degeneration (AMD), but can actually improve vision in significant numbers. Patients tell us they're doing better and the clinical science supports it. Forty percent of patients in the pivitol phase 3 MARINA and ANCHOR trials at 20/40 or better vision is a high efficacy standard indeed! In the American Society of Retina Specialists Preferences and Trends Survey, however, the vast majority of our retina colleagues are not giving mandatory monthly injections. There are treatment burdens and costs that reach beyond the expensive nature of the drug itself.

The quest for improvement in medical therapy never truly ends, however, and subsequent to the US Food and Drug Administration (FDA) approval of ranibizumab, efforts immediately turned to finding strategies by which the monthly dosing on the FDA label could be reduced. Can we refine injection therapies for individual patients? Should we "treat and extend" for similar efficacy and less frequent injections? Although the benchmark is high, can we improve our efficacy by raising the bar even higher among those who gain significant vision? What are our endpoints for treatment? Could combining therapies to attack other cellular components (ie, inflammatory cells, fibroblasts) of the pathobiology of choroidal neovascularization help? Is there a role for targeted radiation in a combination therapy? Retina specialists by nature push forward and ask and answer questions in the context of evidence-based data on behalf of our patients—this is no time for exception, as the stakes remain high in AMD.

In the PIER trial, investigators hoped to find that a quarterly dosing scheme would prove successful, but although patients who were treated quarterly were better off than if they had not been treated at all, the gains seen with monthly dosing were lost when the frequency was reduced in PIER. In my view, the compilation of ranibizumab monotherapy trials support frequent treatment. In practice, if I am considering a repeat ranibizumab or bevacizumab injection, then I reinject. It is unfortunate that, from the standpoint of treatment cost and burden, the evidence shows that this is the best current strategy in fighting for every letter of vision.

Combination Therapy for AMD
Combination therapy takes a different approach. In antivascular endothelial growth factor (anti-VEGF) therapy, we address only one mechanism by which choroidal neovascularization (CNV) occurs in AMD; not all of our patients respond to ranibizumab, so clearly there are other factors that must be addressed. Several studies have linked CNV not only to VEGF, but also to inflammation. Additionally, it is possible that using therapies in concert with one another to address the multiple factors in CNV will have the added benefit of mitigating the negative effects of one or more treatments. Examples of this include the boost that photodynamic therapy (PDT) provides anti-VEGF treatment in some patients who experience loss of effect, and conversely, when anti-VEGF therapy is used to address negative effects of PDT.

In this issue of Retina Today, our cover focus is on combination therapy for AMD. We have sought to include articles that represent efforts to study the efficacy and safety of various combination schemes. It is the hope of many retina specialists that we can raise the existing high standard of efficacy for our patients while reducing overall treatment costs and burden.