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Retinal image registration is commonly required in order to combine the complementary information in different retinal modalities. In this paper, a new automatic scheme to register retinal images is presented and is currently tested in a clinical environment. The scheme considers the suitability and efficiency of different image transformation models and function optimization techniques, following an initial preprocessing stage. Three different transformation models-affine, bilinear and projective-as well as three optimization techniques-downhill simplex method, simulated annealing and genetic algorithms-are investigated and compared in terms of accuracy and efficiency. The registration of 26 pairs of fluoroscein angiography and indocyanine green chorioangiography images with the corresponding red-free retinal images, showed the superiority of combining genetic algorithms with the affine and bilinear transformation models. A comparative study of the proposed automatic registration scheme against the manual method, commonly used in clinical practice, is finally presented showing the advantage of the proposed automatic scheme in terms of accuracy and consistency.