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Registration of retinal images taken at different times frequently is required to measure changes caused by disease or to document retinal location of visual stimuli. Cross-correlation has been used previously for such registration, but it is computationally intensive. We have modified a faster algorithm, sequential similarity detection (SSD), to use only the portion of the template that contains retinal vessels. When compared to standard SSD and cross-correlation, this modification improves the reliability of detection for a variety of retinal imaging modalities. The improved reliability enables implementation of a two-stage registration strategy that further decreases the amount of computation and increases the speed of registration.