We propose a novel hybrid framework for registering retinal images in the presence of extreme geometric distortions that are commonly encountered in ultra-widefield (UWF) fluorescein angiography. Our approach consists of two stages: a feature-based global registration and a vessel-based local refinement. For the global registration, we introduce a modified RANSAC algorithm that jointly identifies robust matches between feature keypoints in reference and target images and estimates a polynomial geometric transformation consistent with the identified correspondences. Our RANSAC modification particularly improves feature point matching and the registration in peripheral regions that are most severely impacted by the geometric distortions. The second local refinement stage is formulated in our framework as a parametric chamfer alignment for vessel maps obtained using a deep neural network. Because the complete vessel maps contribute to the chamfer alignment, this approach not only improves registration accuracy but also aligns with clinical practice, where vessels are typically a key focus of examinations. We validate the effectiveness of the proposed framework on a new UWF fluorescein angiography (FA) dataset and on the existing narrow-field FIRE (fundus image registration) dataset and demonstrate that it significantly outperforms prior retinal image registration methods. The proposed approach enhances the utility of large sets of longitudinal UWF images by enabling: (a) automatic computation of vessel change metrics and (b) standardized and co-registered examination that can better highlight changes of clinical interest to physicians.

We propose a deep-learning based annotation efficient framework for vessel detection in ultra-widefield (UWF) fundus photography (FP) that does not require de novo labeled UWF FP vessel maps. Our approach utilizes concurrently captured UWF fluorescein angiography (FA) images, for which effective deep learning approaches have recently become available, and iterates between a multi-modal registration step and a weakly-supervised learning step. In the registration step, the UWF FA vessel maps detected with a pre-trained deep neural network (DNN) are registered with the UWF FP via parametric chamfer alignment. The warped vessel maps can be used as the tentative training data but inevitably contain incorrect (noisy) labels due to the differences between FA and FP modalities and the errors in the registration. In the learning step, a robust learning method is proposed to train DNNs with noisy labels. The detected FP vessel maps are used for the registration in the following iteration. The registration and the vessel detection benefit from each other and are progressively improved. Once trained, the UWF FP vessel detection DNN from the proposed approach allows FP vessel detection without requiring concurrently captured UWF FA images. We validate the proposed framework on a new UWF FP dataset, PRIMEFP20, and on existing narrow field FP datasets. Experimental evaluation, using both pixel wise metrics and the CAL metrics designed to provide better agreement with human assessment, shows that the proposed approach provides accurate vessel detection, without requiring manually labeled UWF FP training data.