Non-exudative fluid in age-related macular degeneration: Imaging, pathophysiology, and clinical implications

Non-exudative retinal fluid in age-related macular degeneration (AMD) challenges the long-standing paradigm that any fluid on structural optical coherence tomography necessarily reflects neovascular exudation. Advances in multimodal imaging have revealed that both intraretinal fluid and subretinal fluid (SRF) may arise from non-neovascular mechanisms across intermediate AMD and geographic atrophy (GA). Non-exudative IRF encompasses 3 distinct processes: (1) degenerative mechanisms occurring in progressive atrophy, (2) "burnt-out" contraction with cavitation overlying chronic fibrotic scars, and (3) mechanical stress induced by underlying lesions (e.g., drusenoid pigment epithelium detachment [PED]), subretinal hyperreflective material) or traction at the vitreomacular interface. Non-exudative SRF reflects retinal pigment epithelium pump failure over drusen or drusenoid PEDs, but may also result from alterations within the photoreceptor outer segments (subretinal pseudocysts). Integrating these mechanisms into clinical interpretation shifts management from a fluid-based to a pathophysiology-based approach, recognizing that non-exudative fluid does not respond to anti-vascular endothelial growth factor therapy and instead signals advanced tissue stress and increased risk of GA progression.