Spatial Distribution of Cuticular Drusen and its Association with Category-Specific Progression Risk in Intermediate AMD.

Objectives: To investigate the spatial distribution pattern of cuticular drusen using en face OCT and determine its relationship with 2-year progression of age-related macular degeneration (AMD). Methods: This study included 87 eyes from 57 participants with intermediate AMD and cuticular drusen enrolled in the Amish Eye Study who completed two years of follow-up. Multimodal imaging, including volume spectral-domain OCT, was performed. Density of cuticular drusen was quantified on en face OCT across three Early Treatment Diabetic Retinopathy Study (ETDRS) grid zones using ImageJ. K-means clustering analysis was used to categorize distribution patterns. Firth's penalized logistic regression evaluated association between cuticular drusen distribution categories and progression to late AMD at 2 years. Results: Cuticular drusen exhibited a concentric pattern within 6x6mm macular area. Mean (SD) density was highest in central zone (6.14 (3.89) count/mm2). Cluster analysis classified eyes into predominantly central (57.5%), predominantly peripheral (32.2%), and diffuse (10.3%) categories. Over 2 years, 5 eyes progressed to late AMD, 4 of which belonged to predominantly peripheral group. Firth logistic regression demonstrated that predominantly peripheral category had significantly increased risk of AMD progression compared to low-risk groups (predominantly central and diffuse), with an odds ratio of 7.2 (95% CI: 1.2-74.2, p=0.027). Conclusions: The spatial distribution of cuticular drusen exhibits a concentric, centrally-weighted pattern. A predominantly peripheral distribution of cuticular drusen is significantly associated with progression to late AMD over two years. This quantifiable distribution pattern may serve as a novel high-risk biomarker for advanced AMD.