Ranibizumab therapy is the first treatment for neovascular AMD to improve vision for most patients. The benefits apply to all angiographic subtypes of neovascular AMD and across all lesion sizes. Although the pivotal phase III trials (MARINA and ANCHOR) used monthly injections of ranibizumab for 2 years, the ongoing PIER, PrONTO, and SAILOR trials are investigating less frequent dosing regimens, and preliminary results from the PrONTO study suggest that fewer injections will most likely result in visual acuity improvements similar to the results from the phase III trials. When comparing the ANCHOR results with the FOCUS results, it also becomes apparent that the combination of ranibizumab with PDT does not necessarily result in better visual acuity outcomes, and the use of PDT may even reduce the visual acuity benefits achieved with ranibizumab alone (see Figs. 1-3). It seems unlikely that combination therapy provides any significant advantage over ranibizumab alone unless the combination of PDT and ranibizumab can decrease the need for frequent retreatment. The results from the PrONTO Study already suggest that less frequent treatment with ranibizumab is possible by using a variable dosing regimen with OCT. Ranibizumab also seems to be safe, with the 2-year MARINA data showing no increase in the incidence of systemic adverse events that could be associated with anti-VEGF therapy, such as myocardial infarction and stroke. There was a hint of a safety concern, however, in the pooled 1-year safety results from the MARINA and ANCHOR trials. Although the combined rate of myocardial infarction and stroke during the first year of the ANCHOR and MARINA trials was similar in the control and the 0.3-mg ranibizumab arms (1.3% and 1.6% respectively), these adverse events were slightly higher in the 0.5-mg ranibizumab arm (2.9%). These differences are not statistically significant, however, and probably do not represent a dose-dependent increase in risk because the 2-year results from the MARINA trial with the same monthly injection regimen showed no increased risk of thromboembolic events. In December 2005, Genentech submitted a Biologics License Application to the FDA for the use of ranibizumab in the treatment of neovascular wet AMD based on 1-year clinical efficacy and safety data from the two pivotal phase III trials, ANCHOR and MARINA, and the phase I-II FOCUS trial. Genentech has been granted a 6-month Priority Review from the FDA with a decision anticipated 6 months from the December submission date or by the end of June 2006 . By the summer of 2006, this revolutionary therapy should be available for the treatment of neovascular AMD. At that time, the major dilemma facing most retina specialists will be whether to use intravitreal ranibizumab or intravitreal bevacizumab, the low cost alternative, for the treatment of neovascular AMD.