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This work studies retinal image registration in the context of the National Institutes of Health (NIH) Early Treatment Diabetic Retinopathy Study (ETDRS) standard. The ETDRS imaging protocol specifies seven fields of each retina and presents three major challenges for the image registration task. First, small overlaps between adjacent fields lead to inadequate landmark points for feature-basedmethods. Second, the non-uniform contrast/intensity distributions due to imperfect data acquisition will deteriorate the performance of area-based techniques. Third, high-resolution images contain large homogeneous nonvascular/texureless regions that weaken the capabilities of both feature-based and area-based techniques. In this work, we propose a hybrid retinal image registration approach for ETDRS images that effectively combines both area-based and feature-based methods. Four major steps are involved. First, the vascular tree is extracted by using an efficient local entropy-based thresholding technique. Next,