Author’s Name(s): Bernard Hurley, Srinivas Sadda, Jennifer Lim, Yiyi Wang, Derrek Hibar, Andreas Maunz, Huanxiang Lu, Thomas Albrecht, Kara Gibson, Jeffrey Willis, Dolly Chang

Author’s Disclosure Block: Bernard Hurley: Allergan, Employment/honoraria/consulting fees, Novartis, Employment/honoraria/consulting fees, Alcon Canada, Employment/honoraria/consulting fees, Bayer, Employment/honoraria/consulting fees, Roche, Employment/honoraria/consulting fees, Biogen, Employment/honoraria/consulting fees, Apellis, Employment/honoraria/consulting fees, Teva, Employment/honoraria/consulting fees; Srinivas Sadda: none; Jennifer Lim: none; Yiyi Wang: none; Derrek Hibar: none; Andreas Maunz: none; Huanxiang Lu: none; Thomas Albrecht: none; Kara Gibson: none; Jeffrey Willis: none; Dolly Chang: none

Abstract Body
Purpose:To assess the relationship between early treatment response using IRF volume reduction at 1 month and one-year anatomical and visual outcomes in patients with DME. Study Design: Data extracted from two identically designed, global, double-masked, randomized, controlled phase 3 trials (YOSEMITE and RHINE). Methods: Study eyes (n=887) from Phase 3 YOSEMITE/RHINE (NCT03622580/NCT03622593) treated with faricimab or aflibercept were included in this exploratory analysis based on availability of quantitative metrics. Measurements included IRF and SRF volume, total, outer nuclear layer and inner retinal thickness averaged over the entire 3-mm diameter ETDRS subfield. These were assessed at baseline, weeks 4 and 52 by spectral domain optical coherence tomography, analyzed via a deep learning-based segmentation model. Patients were separated into groups based on IRF volume reduction (<20%, 20-50%, >50%) at week 4 from baseline. Results: At week 4, IRF volume was reduced across the three groups: <20% n=242; 20-50% n=248; and >50% n=397 patients. At year 1, IRF volume decreased by 297, 383, and 390 nL for the respective groups adjusted for baseline IRF; total RT decreased by 93, 112, and 117 μm. There was no difference in SRF volume reduction from baseline between groups at 1 year. Patients with >50% IRF volume reduction at week 4 showed nominally greater letter gains at 1 year vs. those with less reduction (>50% 12.1 vs 20-50% 10.6 letters p=0.0502; >50% 12.1 vs. <20% 8.3 letters p<0.0001; adjusted for baseline IRF). Conclusions: Greater IRF volume reduction within 1 month correlates with improved one-year anatomical and visual outcomes in DME patients. These findings suggest the importance of rapid fluid reduction for better long-term results.