Impairment of Neurovascular Function in Intermediate Age-Related Macular Degeneration

Purpose: To investigate neurovascular function in eyes with age-related macular degeneration (AMD). Methods: Subjects with bilateral large drusen (intermediate AMD) and healthy controls ≥50 years old were recruited. The vasculature within the central 6 × 6-mm retinal area was captured using optical coherence tomography angiography (OCTA) and segmented to return superficial plexus, deep plexus, choriocapillaris, and choroid. OCTA scans were acquired without flicker light stimulation (conventional OCTA) and during flicker light stimulation to increase retinal activity and metabolic demand (functional OCTA). Vascular area density (VAD) and the vascular reactivity index (VRI; change in VAD induced by flicker stimulation) were determined and compared between control and AMD eyes. Results: Thirty-five subjects (19 AMD cases and 16 healthy controls) participated in the study. In healthy eyes, flicker stimulation induced an increase in VAD (positive VRI, vasodilation) in the superficial plexus (P < 0.001) and deep plexus (P < 0.001). There was a trend for increased VAD in the choriocapillaris (P = 0.077), but there was no change in the choroid (P = 0.654). In AMD eyes, there was no change in VAD in response to flicker stimulation in any of the vascular layers examined (P ≥ 0.294). Linear mixed models confirmed that AMD was associated with a reduced VRI in the superficial plexus (P < 0.001) and deep plexus (P < 0.001). Conclusions: Eyes with large drusen show a reduction in retinal vascular reactivity compared to healthy eyes, which suggests that there is impairment of retinal neurovascular function in intermediate AMD. Translational Relevance: Functional OCTA could be used to study neurovascular function in retinal diseases.