# Diagnostic-Guided Longitudinal Modeling for Forecasting Retinal Atrophy Progression

arXiv: https://arxiv.org/abs/2604.16955 · HTML: https://mlsanity.com/paper/2604.16955/

## Key facts

- No citing papers in the map yet (data through 14 Oct 2026).
- Builds on 11 of its 20 references that are in the map.
- First posted on arXiv 18 Apr 2026.

## Builds on (most cited first, 11 of 11)

- [Deep Residual Learning for Image Recognition](https://mlsanity.com/paper/1512.03385/) (2015)
- [Denoising Diffusion Probabilistic Models](https://mlsanity.com/paper/2006.11239/) (2020)
- [Sigmoid-Weighted Linear Units for Neural Network Function Approximation in Reinforcement Learning](https://mlsanity.com/paper/1702.03118/) (2017)
- [SADM: Sequence-Aware Diffusion Model for Longitudinal Medical Image Generation](https://mlsanity.com/paper/2212.08228/) (2022)
- [Learning Spatio-Temporal Model of Disease Progression with NeuralODEs from Longitudinal Volumetric Data](https://mlsanity.com/paper/2211.04234/) (2022)
- [ImageFlowNet: Forecasting Multiscale Image-Level Trajectories of Disease Progression with Irregularly-Sampled Longitudinal Medical Images](https://mlsanity.com/paper/2406.14794/) (2024)
- [TADM: Temporally-Aware Diffusion Model for Neurodegenerative Progression on Brain MRI](https://mlsanity.com/paper/2406.12411/) (2024)
- [Brain Latent Progression: Individual-based Spatiotemporal Disease Progression on 3D Brain MRIs via Latent Diffusion](https://mlsanity.com/paper/2502.08560/) (2025)
- [Learning Patient-Specific Disease Dynamics with Latent Flow Matching for Longitudinal Imaging Generation](https://mlsanity.com/paper/2512.09185/) (2025)
- [Temporal Flow Matching for Learning Spatio-Temporal Trajectories in 4D Longitudinal Medical Imaging](https://mlsanity.com/paper/2508.21580/) (2025)
- [Choroidalyzer: An open-source, end-to-end pipeline for choroidal analysis in optical coherence tomography](https://mlsanity.com/paper/2312.02956/) (2023)

## Abstract (arXiv)

Stochastic generative models are increasingly used for longitudinal imaging, but their added complexity may provide limited benefit when predictable disease-related change is small relative to technical variability. We treat model-class selection (stochastic vs deterministic) as an empirical step determined by a task-adaptive diagnostic. For a longitudinal image prediction task complicated by irregular follow-up, acquisition variability, and device heterogeneity, the diagnostic asks whether inter-visit image change is driven by time-dependent disease progression signals or time-independent acquisition variability. If a stochastic approach fails to yield useful predictive diversity, a more parsimonious, deterministic model class is selected. We applied this strategy to fundus autofluorescence (FAF) future image prediction. Applied to a heterogeneous Optos FAF archive (24,335 images from 9,708 eyes), the diagnostic indicated that global inter-visit FAF change was weakly associated with elapsed time, and source-anchored stochastic configurations produced little endpoint-resolvable sample variation. Guided by the diagnostic, we developed Temporal Retinal U-Net (TRU), a deterministic single-pass predictor conditioned on irregular imaging history and prediction horizon. Evaluated on a held-out cohort and two independent zero-shot transfer cohorts spanning rare-disease and cross-vendor shift, TRU achieved the strongest overall performance among the evaluated classical and deep-learning comparators on image-level and eye-specific progression measures, with lower precision in the smaller cross-vendor cohort. These findings support a diagnostic-guided strategy for longitudinal image prediction and demonstrate an example where deterministic predictions outperform stochastic models.