Fluid fluctuations assessed with artificial intelligence during the maintenance phase impact anti-vascular endothelial growth factor visual outcomes in a multicentre, routine clinical care national age-related macular degeneration database.

Aim: To evaluate the impact of fluid volume fluctuations quantified with artificial intelligence in optical coherence tomography scans during the maintenance phase and visual outcomes at 12 and 24 months in a real-world, multicentre, national cohort of treatment-naïve neovascular age-related macular degeneration (nAMD) eyes.

Methods: Demographics, visual acuity (VA) and number of injections were collected using the Fight Retinal Blindness tool. Intraretinal fluid (IRF), subretinal fluid (SRF), pigment epithelial detachment (PED), total fluid (TF) and central subfield thickness (CST) were quantified using the RetinAI Discovery tool. Fluctuations were defined as the SD of within-eye quantified values, and eyes were distributed according to SD quartiles for each biomarker.

Results: A total of 452 naïve nAMD eyes were included. Eyes with highest (Q4) versus lowest (Q1) fluid fluctuations showed significantly worse VA change (months 3-12) in IRF -3.91 versus 3.50 letters, PED -4.66 versus 3.29, TF -2.07 versus 2.97 and CST -1.85 versus 2.96 (all p<0.05), but not for SRF 0.66 versus 0.93 (p=0.91). Similar VA outcomes were observed at month 24 for PED -8.41 versus 4.98 (p<0.05), TF -7.38 versus 1.89 (p=0.07) and CST -10.58 versus 3.60 (p<0.05). The median number of injections (months 3-24) was significantly higher in Q4 versus Q1 eyes in IRF 9 versus 8, SRF 10 versus 8 and TF 10 versus 8 (all p<0.05).

Conclusion: This multicentre study reports a negative effect in VA outcomes of fluid volume fluctuations during the maintenance phase in specific fluid compartments, suggesting that anatomical and functional treatment response patterns may be fluid-specific.