Persistent subretinal fluid in neovascular AMD: clinical significance and implications for treatment

In neovascular age-related macular degeneration (AMD), complete resolution of retinal fluid has traditionally been regarded as the hallmark of successful treatment, yet accumulating evidence suggests that residual subretinal fluid (SRF) may not be uniformly harmful. In this report, the cumulative evidence supporting and qualifying an 'SRF-tolerating' treatment approach is summarized.

Relevant articles were identified through a search of the PubMed/MEDLINE database until April 2026, using terms including 'subretinal fluid,' 'intraretinal fluid,' 'neovascular AMD,' and 'anti-vascular endothelial growth factor.' The report discusses post hoc analyses of major clinical trials (CATT, VIEW, HARBOR, ARIES, and In-Eye), the randomized FLUID study, real-world cohorts, and a recent meta-analysis, covering the association of residual SRF with visual acuity and macular atrophy, contrasting evidence linking large-volume, fluctuating, or prolonged SRF with poorer outcomes, and the distinct behavior of SRF in type 3 macular neovascularization.

The impact of persistent SRF on outcomes has not yet been fully established, and its clinical significance is likely to depend on its volume, location, stability, duration, and the underlying lesion subtype. An SRF-tolerating approach may be considered in selected patients, but strict monitoring of fluid status and visual acuity are required to prevent undertreatment.