Several clinical trials have evaluated as-needed approaches to anti-VEGF therapy: PrONTO (Prospective Optical Coherence Tomography Imaging of Patients With Neovascular AMD Treated With Intraocular Ranibizumab), SAILOR (Study to Evaluate Ranibizumab in Subjects With Choroidal Neovascularization Secondary to AMD), SUSTAIN (Study of Ranibizumab in Patients with Subfoveal Choroidal Neovascularization Secondary to AMD), and HORIZON (Open-Label Extension Trial of Ranibizumab for Choroidal Neovascularization Secondary to AMD). In each of these studies, participants were administered 3 monthly injections, followed by various as-needed treatment regimens based on clinical and OCT-guided criteria. All of the studies had vision and OCT outcomes comparable to or reduced from those obtained with MARINA and ANCHOR. The HORIZON study was a continuation trial of patients enrolled in prior ranibizumab AMD trials. Eyes that had gained 10.2 letters on the ETDRS (Early Treatment Diabetic Retinopathy Study) eye chart during ANCHOR or MARINA after 2 years of monthly injections declined in visual acuity, ending with only a mean 2.0-letter gain compared with baseline (ie, they lost nearly 8 letters once the regimen was switched from monthly injections to an as-needed protocol). Experts believed the reason participants in the HORIZON study experienced a decline in visual acuity was because the study did not offer any re-treatment guidelines for investigators, resulting in a mean of 3.6 ranibizumab injections in the 12 months of the extension trial. HARBOR (A Study of Ranibizumab Administered Monthly or on an As-Needed Basis in Patients With Subfoveal Neovascular AMD) compared higher-dose (2.0 mg) with standard-dose (0.5 mg) ranibizumab therapy and failed to find any difference in visual acuity or anatomical outcomes between the 2 dosages.