Visual acuity improvements in participants of the PIER (Phase 3b, Multicenter, Randomized, Double-Masked, Sham Injection-Controlled Study of the Efficacy and Safety of Ranibizumab in Subjects With Subfoveal Choroidal Neovascularization With or Without Classic Choroidal Neovascularization Secondary to AMD) and EXCITE (Efficacy and Safety of Ranibizumab in Patients With Subfoveal Choroidal Neovascularization Secondary to AMD) studies were similar to the improvements seen in the MARINA and ANCHOR studies over the first 3 months; however, treatment effects declined in participants undergoing quarterly (every 3 months) ranibizumab dosing as opposed to monthly dosing. These results suggest that quarterly treatment is suboptimal. However, accepted anti-VEGF treatment methods that deviate from the FDA-approved monthly injections include “as needed” and “treat and extend.” On the as-needed regimen, regular treatment is administered until the macula appears dry clinically and on OCT; after that, treatment is only resumed when signs of recurrent exudation appear. The treat-and-extend regimen also involves administration of regular monthly treatment until the macula is dry; after that, treatment continues at progressively increasing intervals. This more cautious second approach continues to treat inactive CNV (albeit at longer intervals between injections) to avoid sudden recurrence of exudation (see Fig 4-14).