Population Structure Analysis of an Inbred Population using Quantitative Shape Phenotyping from Stereo Retinal Photographs

There has been a tremendous amount of image processing and machine learning research to measure and classify disease progression from live optical coherence tomography (OCT) imaging of the retina. The images considered here are large, complex, three-dimensional (3-D) and difficult to visualize effectively. Many current supervised machine learning approaches, e.g. neural networks, are non-metric meaning that any features or measurements generated can introduce systematic distortion that may be correlated with underlying non-meaningful physiological differences. Here we present a metric learning approach using the normalized compression distance (NCD) combined with anisotropic structure-enhancing filters to quantify and visualize the principal differences among a collection of 3-D retinal images. We validate the NCD-measured structural differences between pairs of images against the physician-measured change in visual field function, achieving a prediction error of $\sim$ 0.5 dB, more accurate than non-metric deep learning approaches. The normalized compression vectors (NCV) are proposed as a feature set measuring visual differences among a collection of 3-D microscopy images. The utility of the NCV for visualizing and measuring patterns of change is demonstrated for a human with moderate non-progressing glaucoma and for a non-human primate model using intraocular pressure setting manipulation. We conclude with a brief simulation of non-metric embedding features, e.g. from neural networks, introducing class-correlated statistical distortion.

Valid segmentation of the optic disc (OD) and optic cup (OC) from fundus photographs is essential for glaucoma screening. Unfortunately, existing deep learning methods do not guarantee clinical validness including star-convexity and nested structure of OD and OC, resulting corruption in diagnostic metric, especially under cross-dataset domain shift. To adress this issue, this paper proposed NPS-Net (Nested Polar Shape Network), the first framework that formulates the OD/OC segmentation as nested radially monotone polar occupancy estimation.This output representation can guarantee the aforementioned clinical validness and achieve high accuracy. Evaluated across seven public datasets, NPS-Net shows strong zero-shot generalization. On RIM-ONE, it maintains 100% anatomical validity and improves Cup Dice by 12.8% absolute over the best baseline, reducing vCDR MAE by over 56%. On PAPILA, it achieves Disc Dice of 0.9438 and Disc HD95 of 2.78 px, an 83% reduction over the best competing method.

Color fundus photography (CFP) is the mainstay of large-scale retinal screening, but its diagnostic capacity is limited by the lack of depth-resolved structure, which optical coherence tomography (OCT) provides yet is less accessible at population scale. We present EyeMVP, a cross-modal retinal foundation model that uses paired CFP--OCT pretraining to learn OCT-informed CFP representations while requiring only CFP at inference. Pretrained on 674,893 same-eye same-day CFP--OCT triples from 112,642 patients across eight hospitals, EyeMVP uses cross-modal masked reconstruction to enrich CFP features with OCT-associated supervision, and combines source-constrained cross-attention with CFP-derived structural masks to accommodate the non-aligned geometry of en-face CFP and cross-sectional OCT. Across 15 dataset-level settings spanning classification and segmentation, under both full-data and few-shot regimes, EyeMVP performs on par with or better than representative retinal foundation models, with consistent gains on macular and optic-nerve tasks; it attains AUROCs of 0.923 for macular edema and 0.867 for myopic macular schisis, two conditions poorly resolved in CFP. In an exploratory reader study, EyeMVP surpasses junior and intermediate ophthalmologists but not seniors on macular edema, while exceeding all groups on myopic macular schisis. These results indicate that cross-modal reconstruction can enrich CFP representations with OCT-associated supervision, offering a practical route to stronger CFP-based screening.