Importance: The association between residual subretinal fluid (SRF) and intraretinal fluid (IRF) and visual acuity following anti-vascular endothelial growth factor (VEGF) treatment is not well understood.
Objective: To examine the association of residual retinal fluid, SRF, and IRF with visual acuity following anti-VEGF treatment in patients with neovascular age-related macular degeneration (nAMD).
Data sources: A systematic literature search was performed from January 2005 to August 2021 using Ovid MEDLINE, Embase, and the Cochrane Library.
Study selection: Peer-reviewed articles reporting on visual acuity stratified by the presence or absence of any residual SRF, IRF, or any retinal fluid at last study observation after intravitreal bevacizumab, ranibizumab, aflibercept, or brolucizumab in patients with nAMD were included. Studies that were noncomparative, included fewer than 10 eyes, or reported on other anti-VEGF agents were excluded.
Data extraction and synthesis: Two independent reviewers conducted data extraction and synthesis. The Cochrane risk of bias tool 2 and ROBINS-I were used to assess risk of bias and GRADE evaluation was conducted to assess certainty of evidence.
Main outcomes and measures: Primary outcomes were BCVA at last study observation, change in BCVA from baseline, and retinal thickness at last study observation.
Results: In this systematic review and meta-analysis, 11 studies (6 randomized clinical trials [RCTs]) comprising 3092 eyes were included in our analysis. Across all included studies, the BCVA of eyes with residual SRF was better than eyes without SRF (weighted mean difference [WMD], 3.1 letter score; 95% CI, 0.05 to 6.18; P = .05; GRADE, low certainty of evidence; 6 studies; 1931 eyes) but similar in RCTs (WMD, 2.7 letter score; 95% CI, -2.40 to 7.84; P = .30; GRADE, low certainty of evidence; 3 studies; 1406 eyes). The BCVA of eyes with residual IRF was worse than that of eyes without IRF (WMD, -8.2 letter score; 95% CI, -11.79 to -4.50; P < .001; GRADE, low; 7 studies; 2114 eyes).
Conclusions and relevance: The findings suggest that the presence of residual SRF was associated with slightly better BCVA at last study observation; however, baseline differences in BCVA existed and this conclusion was primarily driven by 1 study. The presence of residual IRF was associated with substantially worse BCVA at last study observation and less improvement of BCVA from baseline. The conclusions are limited by the inclusion of data from observational studies, heterogeneity, and a low certainty of evidence.