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Multimodal Fusion of Circular Functional Data on High-resolution Neuroretinal Phenotypes

Pyne, S.; Wainwright, B.; Ali, M. H.; Lee, H.; Ray, M. S.; Senthil, S.; Jammalamadaka, S. R.

2026-04-06 bioinformatics
10.64898/2026.04.02.716157 bioRxiv
Show abstract

Progressive optic neuropathies, particularly glaucoma, represent a significant global health challenge, and the need for precise understanding of the heterogeneous neurodegenerative phenotypes cannot be overstated. Here, we brought together two complementary sources of unstructured yet clinically-relevant information about neurotinal rim (NRR) thinning, a common clinical marker of such decay. These are based on a new dataset of Fundus digital images and a corresponding one of optical coherence tomography, both collected from a large clinical cohort of healthy eyes. First, we represented them using a common data structure that imposed a high-resolution scale of 180 equally-spaced and registered measurements on a 360{degrees} circular axis. We modeled such NRR data-points of each eye as circular curves, and aligned these multimodal curves to obtain a fused NRR curve for each eye. Unsupervised clustering of these fused curves identified 4 clusters of eyes with structural heterogeneity, which were also found to have distinctive clinical covariates. The computation of functional derivatives revealed the troughs in the curves of each cluster. Using circular statistics, we estimated the directional distributions of such troughs as potentially clinically-relevant regions of NRR decay. We also demonstrated that multimodal fusion leads to improvement in the robustness of baseline NRR data obtained from fundus imaging.

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