Fluid dynamics between injections in incomplete anti-VEGF responders within neovascular age-related macular degeneration: a prospective observational study

BACKGROUND: The purpose of the study was to investigate the short-term response profile after an intravitreal injection (IVI) of anti-vascular endothelial growth factor (VEGF) in patients with neovascular age-related macular degeneration (nAMD) and incomplete response to anti-VEGF. METHODS: In this monocentric prospective observational study, we recruited patients with incomplete response to anti-VEGF, defined as presence of subretinal fluid (SRF) and/or intraretinal fluid (IRF) on optical coherence tomography (OCT) for at least 6 months despite monthly anti-VEGF treatment. Each patient underwent complete ophthalmic exam and imaging study (including OCT, fluorescein angiography, indocyanine green angiography, OCT-angiography) the day of their scheduled monthly IVI. Intermediate visits were performed weekly thereafter (comprising ophthalmic exam and OCT), until week 4. Fluid metrics were quantified using an artificial intelligence-based algorithm at baseline and at each subsequent weekly visit. Main outcomes were residual fluid volumes of SRF and IRF for each time point, and its relative change after treatment. Particular interest was given to each patients’ nadir point, which was used for association analysis with imaging parameters. RESULTS: A total of 28 eyes of 26 patients were included into the study. The maximal response was reached at 1.93 weeks on average. The relative fluid resolution at nadir point was 66 ± 36.7%, with quartile limits at 49.1%, 83%, and 96.1%, respectively. Mean residual fluid volume was 64.9 ± 128.8 µl at nadir point. Residual fluid was positively correlated with baseline SRF (r = 0.76, p < 0.0001) and larger pigment epithelium detachment (r = 0.65, p = 0.0001). Polypoidal choroidal vasculopathy was associated with larger residual fluid (p = 0.0013). CONCLUSIONS: Incomplete anti-VEGF responders in nAMD showed significant mean fluid resolution between injections, typically after 2 weeks. However, complete resolution was the exception, and the amount of residual fluid varied greatly. To understand the role of the unresponsive fluid, further studies are needed.