Clinical Correlation of Retinal Fluid Fluctuation Represented by Fluctuation Index in Wet Age-Related Macular Degeneration: TOWER Study Report 2.

Purpose: To explore outcomes and biomarkers associated with retinal fluid instability represented by a new parameter in neovascular age-related macular degeneration (nAMD). Methods: Patients with treatment-naïve nAMD receiving anti-vascular endothelial growth factor (VEGF) injections for a duration of 1 to 3 years were consecutively reviewed. Fluctuation Index (FI) of each eye, calculated by averaging the sum of differences in 1-mm central subfield thickness between each follow-up from months 3 to 24, was arranged into ascending order from the lowest to the highest and split equally into low, moderate, and high fluctuation groups. Outcomes were analyzed at 24 months. Results: Of 558 eyes, FI values showed a negative correlation with a degree-response gradient with 24-month visual improvement. After controlling for baseline best-corrected visual acuity and potential confounders, eyes with low fluctuation gained more Early Treatment Diabetic Retinopathy Study letters than those in the moderate and high fluctuation group (Δ, 10.1 and 14.0 letters, respectively). Significant best-corrected visual acuity improvement from baseline to month 24 (11.8 letters) was observed exclusively in the low fluctuation group despite the indifference in the number of injections and types of anti-VEGF drug used among groups. Patients presenting with central subfield thickness of ≥405 µm or intraretinal fluid coinciding with subretinal fluid showed a significant association with foveal thickness instability during the maintenance phase. Conclusions: Apart from the central subfield thickness values, unstable macular thickening represented by the FI was associated with some baseline features and may contribute to substandard visual outcomes. Translational Relevance: FI may be a valuable tool for assessing therapeutic adequacy in the treatment of nAMD.