Deep Learning-assisted AMD Staging based on OCT and OCT Angiography
Authors: Yukun Guo, Tristan T. Hormel, An-Lun Wu, Liqin Gao, Min Gao, Steven T. Bailey, Yali Jia
Organizations: Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA · Department of Biomedical Engineering, Oregon Health & Science University, Portland, OR 97239, USA · Department of Ophthalmology, Mackay Memorial Hospital, Hsinchu 300044, Taiwan
To develop and evaluate deep learning models for automated grading of age-related macular degeneration (AMD) severity using optical coherence tomography (OCT) and OCT angiography (OCTA) data. Two hundred seventy-one participants aged >= 50 years with varying AMD severities. Central macular 6 x 6 mm OCT/OCTA volumes were acquired using a swept-source OCTA system (SOLIX; Visionix/Optovue Inc., CA). AMD severity was graded into four stages (No AMD, Early AMD, Intermediate AMD, and Advanced AMD) according to the AREDS simplified severity scale. Three deep learning models were developed using different input modalities: (1) biomarker maps derived from segmented pathological features, including retinal fluid, drusen, geographic atrophy (GA), and macular neovascularization (MNV); (2) two-dimensional (2D) en face OCT and OCTA projections; and (3) three-dimensional (3D) OCT/OCTA volumes. EfficientNet-based architectures were trained using normalized inputs, data augmentation, and five-fold cross-validation. A total of 2,030 OCT/OCTA volumes from 351 eyes of 271 participants were analyzed. All models demonstrated strong AMD staging performance with substantial agreement with the reference standard (QWK >= 0.83). The biomarker-based model achieved the highest overall performance (QWK = 0.85 +/- 0.03, mean +/- standard deviation) and the best detection of early AMD (F1-score = 0.59 +/- 0.14). The 3D model achieved performance comparable to the 2D OCT/OCTA model (QWK = 0.83 +/- 0.04 vs. 0.83 +/- 0.09), while the 2D OCT/OCTA model showed the highest precision (0.79 +/- 0.06) and most accurately identified eyes without AMD. Deep learning models using OCT/OCTA data can accurately and automatically grade AMD severity. Among the evaluated approaches, the biomarker-based model provided the most balanced performance and showed particular value for early AMD detection.
Geographic atrophy (GA) secondary to age-related macular degeneration (AMD) requires precise monitoring of relevant structural biomarkers to assess disease stage, progression, and treatment response. This paper presents a fully automated, deep learning-based framework for the high-precision, pixel-wise segmentation of key biomarkers in optical coherence tomography (OCT) imaging: retinal pigment epithelium (RPE) loss, ellipsoid zone (EZ) loss, and EZ thinning. The proposed pipeline uses three specialized semantic segmentation models to delineate RPE loss, EZ boundaries (including interruptions), and Bruch's membrane. To ensure robustness and generalizability, the models were developed on a diverse dataset of 298 SD-OCT volumes representing the full phenotypic spectrum of AMD (GA:222, intermediate AMD: 40, neovascular AMD: 17, healthy: 19) and validated on an independent external dataset (n=43). The comprehensive evaluation was further strengthened using additional datasets to assess repeatability, inter-reader reliability, the impact of B-scan density on measurement accuracy, and subgroup performance stratified by lesion size. Results demonstrated high segmentation accuracy (Dice RPE loss: 0.88, Dice EZ loss: 0.87, Pearson's r > 0.99). Total EZ thickness measurements exhibited a sub-pixel average deviation of 2.15 μm, and segmentation reliability was confirmed by a strong reproducibility score (ICC > 0.98). By accurately and consistently quantifying outer photoreceptor degeneration and RPE loss, this fully automated framework provides a highly reliable tool for GA assessment in both clinical trials and routine real-world ophthalmic care.
Wolf-Dieter Vogl, Hlynur Skulason, Oliver Leingang +3
The advent of foundation models has heralded a new era in medical artificial intelligence (AI), enabling the extraction of generalizable representations from large-scale unlabeled datasets. However, current ophthalmic AI paradigms are predominantly constrained to single-modality inference, thereby creating a dissonance with clinical practice where diagnosis relies on the synthesis of complementary imaging modalities. Furthermore, the deployment of high-performance AI in resource-limited settings is frequently impeded by the unavailability of advanced three-dimensional imaging hardware. Here, we present the Ophthalmic multimodal Masked Autoencoder (OphMAE), a multi-imaging foundation model engineered to synergize the volumetric depth of 3D Optical Coherence Tomography (OCT) with the planar context of 2D en face OCT. By implementing a novel cross-modal fusion architecture and a unique adaptive inference mechanism, OphMAE was pre-trained on a massive dataset with of 183,875 paired OCT images derived from 32,765 patients. In a rigorous benchmark encompassing 17 diverse diagnostic tasks with 48,340 paired OCT images from 8,191 patients, the model demonstrated state-of-the-art performance, achieving an Area Under the Curve (AUC) of 96.9% for Age-related Macular Degeneration (AMD) and 97.2% for Diabetic Macular Edema (DME), consistently surpassing existing single-modal and multimodal foundation models. Crucially, OphMAE exhibits robust engineering adaptability: it maintains high diagnostic accuracy, such as 93.7% AUC for AMD, even when restricted to single-modality 2D inputs, and demonstrates exceptional data efficiency by retaining 95.7% AUC with as few as 500 labeled samples. This work establishes a scalable and adaptable framework for ophthalmic AI, ensuring robust performance across different tasks.
Despite strong performance of deep learning models in retinal disease detection, most systems produce static predictions without clinical reasoning or interactive explanation. Recent advances in multimodal large language models (MLLMs) integrate diagnostic predictions with clinically meaningful dialogue to support clinical decision-making and patient counseling. In this study, OcularChat, an MLLM, was fine-tuned from Qwen2.5-VL using simulated patient-physician dialogues to diagnose age-related macular degeneration (AMD) through visual question answering on color fundus photographs (CFPs). A total of 705,850 simulated dialogues paired with 46,167 CFPs were generated to train OcularChat to identify key AMD features and produce reasoned predictions. OcularChat demonstrated strong classification performance in AREDS, achieving accuracies of 0.954, 0.849, and 0.678 for the three diagnostic tasks: advanced AMD, pigmentary abnormalities, and drusen size, significantly outperforming existing MLLMs. On AREDS2, OcularChat remained the top-performing method on all tasks. Across three independent ophthalmologist graders, OcularChat achieved higher mean scores than a strong baseline model for advanced AMD (3.503 vs. 2.833), pigmentary abnormalities (3.272 vs. 2.828), drusen size (3.064 vs. 2.433), and overall impression (2.978 vs. 2.464) on a 5-point clinical grading rubric. Beyond strong objective performance in AMD severity classification, OcularChat demonstrated the ability to provide diagnostic reasoning, clinically relevant explanations, and interactive dialogue, with high performance in subjective ophthalmologist evaluation. These findings suggest that MLLMs may enable accurate, interpretable, and clinically useful image-based diagnosis and classification of AMD.