Background Manual annotation of landmarks is a known source of variance, which exist in all fields of medical imaging, influencing the accuracy and interpretation of the results. However, the variability of human facial landmarks is only sparsely addressed in the current literature as opposed to e.g. the research fields of orthodontics and cephalometrics. We present a full facial 3D annotation procedure and a sparse set of manually annotated landmarks, in effort to reduce operator time and minimize the variance. Method Facial scans from 36 voluntary unrelated blood donors from the Danish Blood Donor Study was randomly chosen. Six operators twice manually annotated 73 anatomical and pseudo-landmarks, using a three-step scheme producing a dense point correspondence map. We analyzed both the intra- and inter-operator variability, using mixed-model ANOVA. We then compared four sparse sets of landmarks in order to construct a dense correspondence map of the 3D scans with a minimum point variance. Results The anatomical landmarks of the eye were associated with the lowest variance, particularly the center of the pupils. Whereas points of the jaw and eyebrows have the highest variation. We see marginal variability in regards to intra-operator and portraits. Using a sparse set of landmarks (n=14), that capture the whole face, the dense point mean variance was reduced from 1.92 to 0.54 mm. Conclusion The inter-operator variability was primarily associated with particular landmarks, where more leniently landmarks had the highest variability. The variables embedded in the portray and the reliability of a trained operator did only have marginal influence on the variability. Further, using 14 of the annotated landmarks we were able to reduced the variability and create a dense correspondences mesh to capture all facial features.
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