Choriocapillaris flow impairment predicts the development and enlargement of drusen

Purpose: To evaluate the choriocapillaris flow in regions of enlarged or new incident drusen in patients with early and intermediate age-related macular degeneration (AMD). Methods: We retrospectively reviewed and analyzed structural optical coherence tomography (OCT) and OCT angiography (OCTA) images of consecutive patients with early or intermediate AMD evaluated at the Doheny-UCLA Eye Centers between 2015 and 2018. All patients were imaged using a Cirrus OCT, and only one eye was included in the study. To be eligible for this analysis, patients were required to have a 3 × 3-mm OCTA scan acquired during the first visit (considered as baseline) and a fovea-centered 512 × 128 macular cube (6 × 6 mm) acquired at both the baseline visit and after a minimum of 1 year follow-up. The drusen maps generated from the macular cubes were used to generate a drusen area (DA) measurement and compute the difference between baseline and follow-up (ΔDA). After registering the structural OCTs to the baseline choriocapillaris (CC) OCTA, we analyzed and compared the baseline flow deficits (FD) within drusen-free region (FDDF), regions into which drusen enlarged or expanded at follow-up (FDEN), and regions in which new incident drusen (FDND) appeared at follow-up. Results: Forty-six patients were eligible for the analysis and had a mean follow-up of 1.47 years. Twelve eyes of 12 subjects had a ΔDA < 0.1 mm2. In these eyes, only the FDDF was calculated (40.37 ± 2.29%) and it was not significantly different from the FDDF of eyes with ΔDA ≥ 0.1 mm2 (40.25 ± 4.37%, p = 0.849). When comparing the different regions within the eyes with ΔDA ≥ 0.1 mm2, there was no significant difference between FDED and FDND (43.61 ± 4.36% and 44.16 ± 2.38%, p = 528), but both were significantly higher than FDDF (p = 0.001 and p < 0.001, respectively). Conclusions: Significant CC flow impairment is present under regions of intact retinal pigment epithelium (RPE) where existing drusen will enlarge into or new drusen will appear within 2 years. These findings suggest that location of drusen may not be stochastic but may be driven by regional deficits in the choriocapillaris.