Purpose: The vision gains reported with monthly intravitreal ranibizumab in the MARINA and ANCHOR trials led to an immediate paradigm shift in the treatment of neovascular AMD with retina physicians universally switching to the pan-VEGF blocking agents ranibizumab and bevacizumab, and patients expecting visual improvement. As these agents are primarily used on a pro re nata (PRN) dosing schedule (because neither patients nor physicians want monthly injections), the factors involved in making the treatment and retreatment decisions are very important in any attempt to maximize vision gain. Design: Analysis of literature, ongoing clinical trials, and the clinical assessments that can aid clinicians in treatment and retreatment decisions. Methods: Literature review and perspective. Results: If a monthly injection protocol is not used, clinicians should use both functional and anatomic criteria to attempt to guide treatment and retreatment decisions. Qualitative optical coherence tomography (OCT) appears to be the most sensitive and practical assessment tool to determine anatomic response to treatment but should be used in conjunction with clinical examination. Conclusions: If monthly intravitreal injections are not performed, a combination of clinical examination (looking for new hemorrhage) and qualitative OCT (to assess response to treatment and early signs of recurrent leakage) can be used to guide anti-vascular endothelial growth factor (anti-VEGF), treatments with the goal of maintaining a "normal" retinal anatomy in an attempt to maximize the benefit (visual acuity gains) to risk (number of injections required) ratio.
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