Chronological Contrastive Learning: Few-Shot Progression Assessment in Irreversible Diseases

In this paper, we propose a novel selection strategy for contrastive learning for medical images. On natural images, contrastive learning uses augmentations to select positive and negative pairs for the contrastive loss. However, in the medical domain, arbitrary augmentations have the potential to distort small localized regions that contain the biomarkers we are interested in detecting. A more intuitive approach is to select samples with similar disease severity characteristics, since these samples are more likely to have similar structures related to the progression of a disease. To enable this, we introduce a method that generates disease severity labels for unlabeled OCT scans on the basis of gradient responses from an anomaly detection algorithm. These labels are used to train a supervised contrastive learning setup to improve biomarker classification accuracy by as much as 6% above self-supervised baselines for key indicators of Diabetic Retinopathy.

Recent advances in vision--language pretraining have enabled strong medical foundation models, yet most analyze radiographs in isolation, overlooking the key clinical task of comparing prior and current images to assess interval change. For chest radiographs (CXRs), capturing interval change is essential, as radiologists must evaluate not only the static appearance of findings but also how they evolve over time. We introduce TILA (Temporal Inversion-aware Learning and Alignment), a simple yet effective framework that uses temporal inversion, reversing image pairs, as a supervisory signal to enhance the sensitivity of existing temporal vision-language models to directional change. TILA integrates inversion-aware objectives across pretraining, fine-tuning, and inference, complementing conventional appearance modeling with explicit learning of temporal order. We also propose a unified evaluation protocol to assess order sensitivity and consistency under temporal inversion, and introduce MS-CXR-Tretrieval, a retrieval evaluation set constructed through a general protocol that can be applied to any temporal CXR dataset. Experiments on public datasets and real-world hospital cohorts demonstrate that TILA consistently improves progression classification and temporal embedding alignment when applied to multiple existing architectures.

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.