Modelling Geographic Atrophy Progression using Implicit Neural Representations

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.

Modelling how a disease progresses over time requires longitudinal imaging cohorts, which are scarce and small, whereas cross-sectional data -- one image per participant -- is abundant. Self-supervised pre-training on such data offers a way to bridge this gap, but it is unclear which strategy best supports progression modelling, or how that answer depends on the amount of labelled longitudinal data. We study this for age-related macular degeneration (AMD), pre-training encoders on the large cross-sectional NAKO cohort and predicting time to late AMD on the longitudinal AREDS dataset. We compare in-house self-supervised encoders against a general-purpose (DINOv2) and a domain-specific (RETFound) foundation model, across contrastive, masked-autoencoding, and self-distillation objectives, under frozen and fine-tuned protocols, and across labelled training sets from 100 to 32,250 examples. Which model performs best depends on how the encoder is used. When the encoder is frozen and labels are few -- the regime typical of longitudinal cohorts -- pre-trained representations reach clinically reasonable discrimination from a few hundred labelled samples, while models trained from scratch do not; this advantage fades under fine-tuning. Transfer is governed by the self-supervision objective rather than corpus scale or domain match, so that an encoder pre-trained on a modest cross-sectional cohort matches or exceeds a far larger in-domain foundation model. Together, these results offer a practical recipe for building progression models where longitudinal data is scarce: a frozen self-supervised encoder with a lightweight survival head.

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.