Fig. 5: Theoretical framework for how vision is impaired: Ageing to early and intermediate age-related macular degeneration (AMD).

Our theoretical framework for vision loss progression is illustrated in terms of how structural changes could be associated with functional changes. At the bottom on the structural side in normal ageing, there are changes in the choriocapillaris, Bruch’s membrane and retinal pigment epithelium, and the emergence of extracellular deposits. This corresponds on the functional side to compromises in retinoid re-supply from the choroid to outer retinal cells, which leads to delayed rod-mediated dark adaptation. When there is progression to early AMD, rod photoreceptor degeneration occurs, with changes to rod outer segments and eventually cell death. Functionally, this results in loss of scotopic sensitivity deficits under steady state conditions (after the eye adapts to darkness). Finally, as intermediate AMD emerges, particularly in the later stages of intermediate AMD (at the top of Figure), neural circuitry is corrupted, leading to deficits in pattern (spatial) vision, including impaired visual acuity and contrast sensitivity. Used with permission of Springer Nature under Creative Commons license; article published here [27]. BrM Bruch’s Membrane, CFH complement factor H, RPE retinal pigment epithelium.