A. H. Welsh

Chong Zhong, Yang Li, Danjuan Yang et al.

The ultra-widefield (UWF) fundus image is an attractive 3D biomarker in AI-aided myopia screening because it provides much richer myopia-related information. Though axial length (AL) has been acknowledged to be highly related to the two key targets of myopia screening, Spherical Equivalence (SE) measurement and high myopia diagnosis, its prediction based on the UWF fundus image is rarely considered. To save the high expense and time costs of measuring SE and AL, we propose the Copula-enhanced Convolutional Neural Network (CeCNN), a one-stop UWF-based ophthalmic AI framework to jointly predict SE, AL, and myopia status. The CeCNN formulates a multiresponse regression that relates multiple dependent discrete-continuous responses and the image covariate, where the nonlinearity of the association is modeled by a backbone CNN. To thoroughly describe the dependence structure among the responses, we model and incorporate the conditional dependence among responses in a CNN through a new copula-likelihood loss. We provide statistical interpretations of the conditional dependence among responses, and reveal that such dependence is beyond the dependence explained by the image covariate. We heuristically justify that the proposed loss can enhance the estimation efficiency of the CNN weights. We apply the CeCNN to the UWF dataset collected by us and demonstrate that the CeCNN sharply enhances the predictive capability of various backbone CNNs. Our study evidences the ophthalmology view that besides SE, AL is also an important measure to myopia.

Yang Li, Jianing Deng, Chong Zhong et al.

Myopia screening using cutting-edge ultra-widefield (UWF) fundus imaging and joint modeling of multiple discrete and continuous clinical scores presents a promising new paradigm for multi-task problems in Ophthalmology. The bi-channel framework that arises from the Ophthalmic phenomenon of ``interocular asymmetries'' of both eyes (OU) calls for new employment on the SOTA transformer-based models. However, the application of copula models for multiple mixed discrete-continuous labels on deep learning (DL) is challenging. Moreover, the application of advanced large transformer-based models to small medical datasets is challenging due to overfitting and computational resource constraints. To resolve these challenges, we propose OU-CoViT: a novel Copula-Enhanced Bi-Channel Multi-Task Vision Transformers with Dual Adaptation for OU-UWF images, which can i) incorporate conditional correlation information across multiple discrete and continuous labels within a deep learning framework (by deriving the closed form of a novel Copula Loss); ii) take OU inputs subject to both high correlation and interocular asymmetries using a bi-channel model with dual adaptation; and iii) enable the adaptation of large vision transformer (ViT) models to small medical datasets. Solid experiments demonstrate that OU-CoViT significantly improves prediction performance compared to single-channel baseline models with empirical loss. Furthermore, the novel architecture of OU-CoViT allows generalizability and extensions of our dual adaptation and Copula Loss to various ViT variants and large DL models on small medical datasets. Our approach opens up new possibilities for joint modeling of heterogeneous multi-channel input and mixed discrete-continuous clinical scores in medical practices and has the potential to advance AI-assisted clinical decision-making in various medical domains beyond Ophthalmology.

Mitchell L. Prevett, Francis K. C. Hui, Zhi Yang Tho et al.

Linear mixed models are widely used for clustered data, but their reliance on parametric forms limits flexibility in complex and high-dimensional settings. In contrast, gradient boosting methods achieve high predictive accuracy through nonparametric estimation, but do not accommodate clustered data structures or provide uncertainty quantification. We introduce Gradient Boosted Mixed Models (GBMixed), a framework and algorithm that extends boosting to jointly estimate mean and variance components via likelihood-based gradients. In addition to nonparametric mean estimation, the method models both random effects and residual variances as potentially covariate-dependent functions using flexible base learners such as regression trees or splines, enabling nonparametric estimation while maintaining interpretability. Simulations and real-world applications demonstrate accurate recovery of variance components, calibrated prediction intervals, and improved predictive accuracy relative to standard linear mixed models and nonparametric methods. GBMixed provides heteroscedastic uncertainty quantification and introduces boosting for heterogeneous random effects. This enables covariate-dependent shrinkage for cluster-specific predictions to adapt between population and cluster-level data. Under standard causal assumptions, the framework enables estimation of heterogeneous treatment effects with reliable uncertainty quantification.

Yang Li, Qiuyi Huang, Chong Zhong et al.

Myopia screening using cutting-edge ultra-widefield (UWF) fundus imaging is potentially significant for ophthalmic outcomes. Current multidisciplinary research between ophthalmology and deep learning (DL) concentrates primarily on disease classification and diagnosis using single-eye images, largely ignoring joint modeling and prediction for Oculus Uterque (OU, both eyes). Inspired by the complex relationships between OU and the high correlation between the (continuous) outcome labels (Spherical Equivalent and Axial Length), we propose a framework of copula-enhanced adapter convolutional neural network (CNN) learning with OU UWF fundus images (OUCopula) for joint prediction of multiple clinical scores. We design a novel bi-channel multi-label CNN that can (1) take bi-channel image inputs subject to both high correlation and heterogeneity (by sharing the same backbone network and employing adapters to parameterize the channel-wise discrepancy), and (2) incorporate correlation information between continuous output labels (using a copula). Solid experiments show that OUCopula achieves satisfactory performance in myopia score prediction compared to backbone models. Moreover, OUCopula can far exceed the performance of models constructed for single-eye inputs. Importantly, our study also hints at the potential extension of the bi-channel model to a multi-channel paradigm and the generalizability of OUCopula across various backbone CNNs.