Response-Aware Multimodal Learning for Post-Treatment Visual Acuity Forecasting
Authors: Phuoc-Nguyen Bui, Van-Vi Vo, Duc-Tai Le, Junghyun Bum, Van-Nguyen Pham, Ki-Young Kim, Seung-Young Yu, Hyunseung Choo
Organizations: Research Convergence Institute, Sungkyunkwan University, Korea · Dept. of AI Systems Engineering, Sungkyunkwan University, Korea · College of Computing and Informatics, Sungkyunkwan University, Korea · Dept. of Ophthalmology, Kyung Hee University Medical Center, Korea · Dept. of Electrical and Computer Engineering, Sungkyunkwan University, Korea
Abstract
Long-term visual acuity (VA) outcomes after anti-VEGF therapy are central to patient counseling, expectation setting, and follow-up planning in diabetic macular edema (DME). However, in clinical practice, physicians must often estimate long-term visual trajectories based only on early post-treatment findings, making reliable prognostication difficult. Although prior OCT-based learning approaches have largely focused on short-term response or single-endpoint prediction, modeling VA trajectories across multiple future time points from early longitudinal observations remains insufficiently explored. In this study, we assembled a real-world cohort of 188 anti-VEGF--treated DME patients with paired baseline and month-1 OCT scans, along with tabular OCT-derived biomarkers and non-imaging clinical variables. Using only these early data, we formulate a multi-horizon VA forecasting problem aimed at predicting visual outcomes at 3, 6, 12, 18, and 24 months, reflecting clinically meaningful follow-up intervals. We propose \textbf{ReVA}, a response-aware multimodal framework that integrates structural features from baseline and month-1 OCT with the tabular variables to capture baseline disease status and early treatment response. ReVA uses spatial attention to preserve localized prognostic imaging features and a dependency-aware tabular encoder to model interactions among clinical variables. These multimodal representations are fused to predict patient-specific long-term visual acuity trajectories. The proposed framework achieves MAE =0.1246, RMSE =0.1621, and R2=0.6064 for 24-month VA prediction, with consistent performance across all forecast horizons. Our findings show that incorporating early treatment-response signals enables clinically meaningful long-term visual acuity forecasting, supporting data-driven decision support for routine anti-VEGF management.
Precision medicine in ophthalmology requires accurate longitudinal predictions, but the fragmented nature of multimodal clinical data remains a barrier to forecasting. We introduce OphthaDT, an LLM-based digital twin for ophthalmology that serializes longitudinal patient histories from 3,220 patients across four Phase III clinical trials into structured narratives to forecast best corrected visual acuity (BCVA). In benchmarks spanning up to 100 weeks, OphthaDT demonstrated the lowest prediction error in neovascular age-related macular degeneration (nAMD), achieving an average mean absolute error (MAE) reduction of 6.0% compared to all baselines. In diabetic macular edema (DME), OphthaDT demonstrated competitive performance against all baselines while outperforming Random Forest and XGBoost by an average MAE reduction of 2.6% and 6.9%, respectively. Results reveal that OphthaDT's predictive advantage scales with trajectory complexity: whereas linear models remain effective for the more stable treatment responses of DME, OphthaDT's capacity is better suited for capturing the high longitudinal variability of nAMD. Finally, OphthaDT handles irregular sampling without imputation, positioning LLM-based clinical trajectory modeling as a methodology that could reduce patient burden and accelerate drug development.
Pietro Belligoli, Nikita Makarov, Sayedali Shetab Boushehri +3
Forecasting visual fields (VFs) is critical for personalized monitoring and treatment planning in glaucoma. This is inherently uncertain due to heterogeneous disease progression and measurement variability, yet most existing methods produce single deterministic predictions that fail to represent this uncertainty. We formulate VF forecasting as a probabilistic prediction problem and the use of conditioned denoising diffusion models to generate distributions of plausible future VFs from longitudinal observations with irregular follow-up intervals. Experiments on two independent VF cohorts show that diffusion-based predictions produce well-calibrated distributions for clinically relevant VF measures. When reduced to a standard point-estimate, the proposed approach achieves state-of-the-art accuracy compared to clinical baselines and prior learning-based methods. Our results highlight the advantages of distributional modeling for VF forecasting and support a shift from point-estimate prediction toward uncertainty-aware, clinically interpretable risk assessment in glaucoma.
Marta Colmenar Herrera, Pablo Márquez Neila, Şerife Seda Kucur Ergünay +2
Even balanced multimodal learning methods do not consistently translate additional modalities into better regression performance. To understand this limitation, we revisit the optimization mechanism of balanced multimodal learning, using MMPareto as a representative case. We reveal a previously overlooked issue: MMPareto uses a fixed gradient modulation strength throughout training, while different training stages favor different strengths; an inappropriate modulation strength can instead hinder subsequent optimization. To address this issue, we propose SGM, which adapts the modulation strength according to the current training behavior. We provide theoretical and empirical analyses to characterize and validate the modulation decisions made by SGM. We further build a two-stage multimodal regression framework that integrates AM for unimodal regression representation learning and SGM for adaptive multimodal optimization. Extensive experiments under the same total training budget demonstrate consistent improvements over strong unimodal and multimodal baselines. Our code is provided in the supplementary material.