Indocyanine green angiography and machine learning analysis determine topographic distribution of peripheral hard drusen in a Chinese cohort

Hard drusen appear as hyperfluorescent dots on indocyanine green angiography (ICGA) due to their high phospholipid content. This study aims to explore the distribution of peripheral hard drusen across age groups and retinal regions, and their correlation with macular pathology including hard drusen, soft drusen, and progression to neovascular age-related macular degeneration (nAMD). A hospital-based retrospective study was conducted at Zhongshan Ophthalmic Center. Patients who underwent ICGA over a five-year period were included and categorised into seven age groups. Hard drusen were quantified across nine retinal quadrants using the Trainable Weka Segmentation machine learning plugin. A subgroup of patients underwent imaging follow-up to assess progression to nAMD. Here we show, across 1562 normal eyes (14,058 ICGA images) quantified using a validated machine learning model (Dice coefficient: 0.697; sensitivity: 82.93%; ICC: 0.944), that age 50 represents a critical threshold for drusen accumulation, with significant increases observed across all nine quadrants. The nasal quadrants demonstrate earlier and more prominent drusen accumulation compared to the temporal quadrants (P < 0.001 across ages 20–69 years). Notably, the central superior quadrant shows consistent associations with macular hard drusen counts (Stdβ = 0.104, P = 0.010), soft drusen volume (ρ = 0.657, P = 0.020), and progression to nAMD (OR = 1.324, P = 0.040). Peripheral hard drusen accumulate preferentially in the nasal quadrants and increase markedly after age 50. Comprehensive peripheral retinal evaluation during ICGA examination may hold potential clinical value for AMD monitoring, pending further prospective validation. Age-related macular degeneration (AMD) is a leading cause of vision loss in older adults. Small deposits called drusen may be an early sign that AMD might develop later in life. Understanding where these deposits appear and how they relate to progression of AMD could help doctors identify at-risk patients earlier. We analysed 14,058 images of the retina from 1562 eyes and used a computer-assisted tool to map hard drusen across different regions of the retina. We found that drusen accumulate faster in the nasal region of the retina and that deposits in the upper-central region are linked to more advanced degeneration of the macula, which is the central part of the eye. These findings suggest that carefully examining particular regions of the peripheral retina may help identify people at higher risk of developing serious AMD. Pu et al. use machine learning to quantify peripheral hard drusen across nine retinal quadrants in 1,562 normal eyes using indocyanine green angiography. Nasal quadrants show earlier and greater drusen accumulation, and central superior drusen count independently predicts progression to neovascular age-related macular degeneration.