Correlation of 3-Dimensionally Quantified Intraretinal and Subretinal Fluid With Visual Acuity in Neovascular Age-Related Macular Degeneration

Importance Robust and sensitive imaging biomarkers for visual function are an unmet medical need in the management of neovascular age-related macular degeneration. Objective To determine the correlation of 3-dimensionally quantified intraretinal cystoid fluid (IRC) and subretinal fluid (SRF) with best-corrected visual acuity (BCVA) in treatment-naive neovascular age-related macular degeneration and during antiangiogenic therapy. Design, Setting, and Participants Retrospective cohort study between November 2009 and November 2011 at an institutional referral center and reading center of patients with treatment-naive subfoveal choroidal neovascularization receiving intravitreal ranibizumab or aflibercept over 12 months. All individual IRC and SRF lesions were manually delineated on each of the 128 B-scan sections of spectral-domain optical coherence tomographic volume scans at baseline and months 1, 6, and 12. Correlations were computed between the IRC and SRF parameters and the baseline BCVA, final BCVA, and BCVA change. A systematic parameter search was conducted to detect annotation-derived variables with best predictive value. An exponential model for BCVA change balancing for the ceiling effect was constructed. Main Outcomes and Measures Goodness of fit of correlations between the IRC and SRF parameters and the baseline BCVA, final BCVA, and BCVA change. Results Thirty-eight patients were included (25 female, 13 male; mean [SD] age at enrollment, 78.49 [8.23] years; mean [SD] BCVA score at baseline, 54 [16] Early Treatment Diabetic Retinopathy Study letters [Snellen equivalent approximately 20/160], with a gain to 63 [19] letters [Snellen equivalent approximately 20/100] at month 12). A total of 19 456 scans underwent complete quantification of IRC and SRF. The best correlation with BCVA at baseline was achieved using a coverage-based, foveal area–weighted IRC parameter ( R 2  = 0.59; P R 2  = 0.21; P  = .003). The BCVA gain correlated with IRC decrease in the exponential model ( R 2  = 0.40; P R 2  = 0.25; P  = .002). No robust associations were found between SRF and baseline BCVA ( R 2  = 0.06; P  = .14) or BCVA change ( R 2  = 0.14; P  = .02). Conclusions and Relevance In this proof-of-principle study, IRC-derived morphometric variables correlated well with treatment-naive BCVA and BCVA outcomes in antiangiogenic therapy. While IRC reduction was associated with BCVA gains, some IRC-mediated neurosensory damage remained permanent.