Artificial Intelligence-Based Analysis of Drusen Volume in a Phase 2 Clinical Trial Evaluating RQC in Age-Related Macular Degeneration

Purpose : The risk of progression in intermediate dry age‐related macular degeneration (AMD) is determined by the size of the largest drusen, i.e., drusen >125 pm and >250 pm are associated with a 25% and 50% risk of progression to advanced AMD, respectively. In this study, we evaluated the effect of curcumin or resveratrol, quercetin, and curcumin in combination (RQC) on drusen volume over two years in patients with intermediate AMD. Methods : Participants with intermediate AMD (n=20) were randomly assigned to receive oral RQC (n=13) or curcumin (n=7) and followed for 2 years (NCT05062486). Drusen volume (mm3) was measured manually using SD‐OCT images taken at baseline, 3, 6,12,18 and 24 months. An Al‐based algorithm was used to identify and measure individual drusen across multiple scans and time points. Change from baseline was compared between RQC and curcumin as well as between medium (63‐124 μm), large (125‐249 pm) and extra‐large (≥250 μm) drusen. A responder analysis was conducted with responders and nonresponders defined as eyes with a decrease or increase of >10% from baseline.Visual acuity was measured using the ETDRS chart Results : A total of 1,154 individual drusen were identified and 6,582 measurements made across the six time points. Among the drusen identified, 368 (32%) were classified as extralarge while 314 (27%) were classified as large. Mean total drusen volume decreased significantly in the RQC group (‐0.023 mm3 , ‐19.7%, p=0.02) but not the curcumin group (0.002 mm3 , +12.1%). Change from baseline was significantly greater with RQC (p=0.03). Extra‐large, large and medium drusen decreased by 38.7%, 24.8% and 3.1%, respectively. In the RQC group, 42% of eyes were classified as responder vs. 36% in the curcumin group. Inversely, 13% of RQC eyes were classified as non‐responder versus 36% of curcumin eyes. Visual acuity mildly improved in both the RQC (+1.9 letters) and curcumin (+1.3) groups. There was no incidence of advanced AMD. Conclusions : After 2 years, participants taking RQC had significantly reduced drusen volume, improved visual acuity, and no incidence of conversion to advanced AMD. These initial results from an ongoing phase 2 clinical trial for RQC are promising and indicate that RQC could be a safe and effective treatment for dry AMD.