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Purpose To compare the ability to delineate and detect patterns of choroidal neovascularization (CNV) activity in patients with exudative age-related macular degeneration (AMD) after ranibizumab treatment between time-domain optical coherence tomography (TD-OCT) and 4 different spectral-domain optical coherence tomography (SD-OCT) devices. Design Prospective, consecutive case series. Participants Sixty-one eyes of 58 patients with exudative AMD after ranibizumab treatment were included in this study. Methods All patients were imaged with TD-OCT and at least 1 of 4 different SD-OCT devices at the same visit after ranibizumab treatment. The OCT images were analyzed in a masked fashion by 2 independent graders (KS, TY) to delineate and detect the presence of CNV activity defined as the presence of subretinal fluid, intraretinal cysts, intraretinal fluid, sub–retinal pigment epithelium (sub-RPE) fluid, or a combination thereof. The automated evaluation of retinal thickness also was analyzed between devices. Main Outcome Measures Evidence of CNV activity on linear B-scans and 3-dimensional so-called cube scans on SD-OCT and linear B-scan on TD-OCT. Results In linear B-scan mode, all 4 SD-OCT devices were superior in their ability to delineate sub-RPE fluid compared with TD-OCT ( P <0.05). Three of 4 SD-OCT devices were superior in delineating intraretinal fluid, and 2 of 4 SD-OCT devices were superior in delineating subretinal fluid and intraretinal cysts ( P <0.05). In the 3-dimensional so-called cube mode, all 4 SD-OCT devices were superior in detecting subretinal fluid and 2 of 4 SD-OCT devices were superior in detecting sub-RPE and intraretinal fluid ( P <0.05). There were significant correlations in center point thickness between all SD-OCT devices and TD-OCT ( P <0.01), and 3 of 4 and 1 of 3 SD-OCT devices showed significant differences from TD-OCT in center point thickness ( P <0.01) and center subfield thickness ( P <0.001), respectively. Conclusions SD-OCT is superior to TD-OCT in evaluating for CNV activity in patients with wet AMD after ranibizumab injection. Retinal thickness measurements between SD-OCT and TD-OCT also were significantly different. Financial Disclosure(s) Proprietary or commercial disclosure may be found after the references.