Objective Reticular pseudodrusen (RPD), a key feature of age-related macular degeneration (AMD), are poorly detected by human experts on standard color fundus photography (CFP) and typically require advanced imaging modalities such as fundus autofluorescence (FAF). The objective was to develop and evaluate the performance of a novel M3 deep learning framework on RPD detection. Materials and Methods A deep learning framework M3 was developed to detect RPD presence accurately using CFP alone, FAF alone, or both, employing >8000 CFP-FAF image pairs obtained prospectively (Age-Related Eye Disease Study 2). The M3 framework includes multi-modal (detection from single or multiple image modalities), multi-task (training different tasks simultaneously to improve generalizability), and multi-attention (improving ensembled feature representation) operation. Performance on RPD detection was compared with state-of-the-art deep learning models and 13 ophthalmologists; performance on detection of two other AMD features (geographic atrophy and pigmentary abnormalities) was also evaluated. Results For RPD detection, M3 achieved area under receiver operating characteristic (AUROC) 0.832, 0.931, and 0.933 for CFP alone, FAF alone, and both, respectively. M3 performance on CFP was very substantially superior to human retinal specialists (median F1-score 0.644 versus 0.350). External validation (on Rotterdam Study, Netherlands) demonstrated high accuracy on CFP alone (AUROC 0.965). The M3 framework also accurately detected geographic atrophy and pigmentary abnormalities (AUROC 0.909 and 0.912, respectively), demonstrating its generalizability. Conclusion This study demonstrates the successful development, robust evaluation, and external validation of a novel deep learning framework that enables accessible, accurate, and automated AMD diagnosis and prognosis.
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