Ultra-widefield (UWF) fundus images are replacing traditional fundus images in screening, detection, prediction, and treatment of complications related to myopia because their much broader visual range is advantageous for highly myopic eyes. Spherical equivalent (SE) is extensively used as the main myopia outcome measure, and axial length (AL) has drawn increasing interest as an important ocular component for assessing myopia. Cutting-edge studies show that SE and AL are strongly correlated. Using the joint information from SE and AL is potentially better than using either separately. In the deep learning community, though there is research on multiple-response tasks with a 3D image biomarker, dependence among responses is only sporadically taken into consideration. Inspired by the spirit that information extracted from the data by statistical methods can improve the prediction accuracy of deep learning models, we formulate a class of multivariate response regression models with a higher-order tensor biomarker, for the bivariate tasks of regression-classification and regression-regression. Specifically, we propose a copula-enhanced convolutional neural network (CeCNN) framework that incorporates the dependence between responses through a Gaussian copula (with parameters estimated from a warm-up CNN) and uses the induced copula-likelihood loss with the backbone CNNs. We establish the statistical framework and algorithms for the aforementioned two bivariate tasks. We show that the CeCNN has better prediction accuracy after adding the dependency information to the backbone models. The modeling and the proposed CeCNN algorithm are applicable beyond the UWF scenario and can be effective with other backbones beyond ResNet and LeNet.

Domain adaptation (DA) has been widely applied in the diabetic retinopathy (DR) grading of unannotated ultra-wide-field (UWF) fundus images, which can transfer annotated knowledge from labeled color fundus images. However, suffering from huge domain gaps and complex real-world scenarios, the DR grading performance of most mainstream DA is far from that of clinical diagnosis. To tackle this, we propose a novel source-free active domain adaptation (SFADA) in this paper. Specifically, we focus on DR grading problem itself and propose to generate features of color fundus images with continuously evolving relationships of DRs, actively select a few valuable UWF fundus images for labeling with local representation matching, and adapt model on UWF fundus images with DR lesion prototypes. Notably, the SFADA also takes data privacy and computational efficiency into consideration. Extensive experimental results demonstrate that our proposed SFADA achieves state-of-the-art DR grading performance, increasing accuracy by 20.9% and quadratic weighted kappa by 18.63% compared with baseline and reaching 85.36% and 92.38% respectively. These investigations show that the potential of our approach for real clinical practice is promising.