Correlation of retinal fluid and photoreceptor and RPE loss in neovascular AMD by automated quantification, a real‐world FRB! analysis

Purpose To quantify ellipsoid zone (EZ) loss during anti‐VEGF therapy for neovascular age‐related macular degeneration (nAMD) and correlate these findings with nAMD disease activity using artificial intelligence‐based algorithms. Methods Spectral domain optical coherence tomography (Spectralis, Heidelberg Engineering) images from nAMD treatment‐naïve patients from the Fight Retinal Blindness! (FRB!) Registry from Zürich, Switzerland were processed at baseline and over 3 years of follow‐up. An approved deep learning algorithm (Fluid Monitor, RetInSight) was used to automatically quantify intraretinal fluid (IRF), subretinal fluid (SRF) and pigment epithelial detachment (PED). An ensemble U‐net deep learning algorithm was used to automated quantify EZ integrity based on EZ layer thickness. The impact of fluid volumes on EZ thickness and late‐stages outcomes were calculated using Wilcoxon rank‐sum tests, a linear mixed model and a longitudinal panel regression model. Results Two hundred and eleven eyes from 158 patients were included. The mean ± SD EZ loss area in the central 6 mm was 1.81 ± 2.68 mm$^{2}$ at baseline and reached 6.21 ± 6.15 mm$^{2}$ at month 36. Higher fluid volumes (top 25%) of IRF and PED in the central 1 and 6 mm of the macula were significantly associated with more advanced EZ thinning and loss compared to the low fluid volume subgroup. The high SRF subgroup in the linear regression model showed no statistically significant association with EZ integrity in the central macula; however, the longitudinal analysis revealed an increased EZ thickness with no additional loss. Conclusions Intraretinal fluid and PED volumes and their resolution pattern have an impact on alteration of the underlying EZ layer. AI‐supported quantifications are helpful in quantifying early signs of macular atrophy and providing individual risk profiles as a basis for tailored therapies for optimized visual outcomes.