To Treat or Not to Treat? Resolving the Question of Subretinal and Intraretinal Fluid in Age-Related Macular Degeneration: A Narrative Review.

Neovascular age-related macular degeneration (nAMD) is associated with considerable quality of life and economic burden. nAMD is characterized by pathological neovascularization, leading to the accumulation of retinal fluid. Intraretinal fluid (IRF) is a major contributor to vision loss and may predict response to treatment. In contrast, the role of subretinal fluid (SRF) is less clear. Nevertheless, complete resolution of retinal fluid accumulation is often stated to be a key goal of therapy for nAMD, even though some eyes may never achieve a fluid-free macula despite regular anti-vascular endothelial growth factor treatment. In this article, we review the current literature regarding the role of retinal fluid in nAMD disease outcomes and assess whether and when it may be beneficial to leave retinal fluid untreated. In this context, we highlight the importance of correctly identifying retinal fluid types in nAMD and avoiding confusion with other optical coherence tomography signs that may respond differently to therapy, such as subretinal pseudocysts. Current evidence shows that IRF is associated with poor outcomes and an increased risk of developing atrophy and fibrosis; resolution of this retinal fluid type should remain a treatment target. However, the literature around SRF indicates that low levels of this fluid type, potentially up to 150-200 µm in thickness, may be tolerated with minimal impact on vision, and that SRF could be protective against the development and progression of macular atrophy and fibrosis. Although mild SRF may be protective in nAMD, cause and effect between SRF and reduced or slowed atrophy has not yet been proven and requires further research. Treatment should be given for the most aggressive component; when both IRF and SRF are present, treatment should be given for IRF.