Differential Visual Outcomes in Neovascular AMD Based on Ellipsoid Zone Integrity and Fluid Presence: Insights from a Phase III Trial

Background/Objectives: To investigate the effect of ellipsoid zone (EZ) integrity and retinal fluid on best-corrected visual acuity (BCVA) in neovascular, age-related macular degeneration. Methods: This was a post hoc treatment-agnostic analysis of the phase 3 HAWK trial. Intraretinal fluid (IRF), subretinal fluid (SRF), and ellipsoid zone (EZ) integrity were quantified over 48 weeks. EZ integrity maintenance was defined as EZ-RPE central subfield thickness (CST) >20 µm; partial EZ attenuation was EZ-RPE CST >0 and ≤20 µm; total EZ attenuation was EZ-RPE CST = 0 µm. Results: During treatment, BCVA in eyes with no fluid (66.5 to 70.2 letters) was greater than in eyes with IRF (59.5 to 62.4 letters) but comparable to BCVA in eyes with SRF (64.9 to 68.8 letters). In eyes with no fluid, BCVA was consistently greater in eyes with EZ integrity maintained (73.4 to 78.4 letters) than in eyes with EZ partial attenuation (65.3 to 66.5 letters) or with EZ total attenuation (55.8 to 59.8 letters). Conclusions: Eyes without fluid with EZ preservation achieved the highest overall BCVA, especially when compared to eyes without fluid and a lack of EZ preservation and to eyes with SRF. Achieving a “dry” status with preservation of EZ integrity is important in optimizing visual outcomes.