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Page 2 of 16                                          Tanikawa Plast Aesthet Res 2020;7:48  I  http://dx.doi.org/10.20517/2347-9264.2020.136

               surgery, the protrusion of the lower lip and asymmetry remained. Nine PCs were extracted, and seven PCs were
               selected for the regression model to discriminate two subject groups, e.g., midfacial retrusion, nasal bump, and
               chin protrusion. The MANOVA also revealed significant differences between both the Cleft and Control groups
               and the sex subgroups, and the effects of cleft on the facial morphology was found to be related to sex (all, P <
               0.01).

               Conclusion: The clinical application of GMM was confirmed to be effective. GMM detected variations of the Cleft
               group and morphological characteristics. GMM is considered to be a powerful tool to quantitatively evaluate faces
               in clinics.


               Keywords: Cleft lip and palate, face, geometric morphometric analysis, three-dimensional analysis




               INTRODUCTION
               The extent of recognition of an individual’s own face by others exerts a great sociopsychological influence
               on that individual’s sense of acceptance by his or her community. It is known that there are several
               facial deformities associated with congenital cleft lip after primary lip revision surgery. It is thus crucial
               for patients with cleft lip and/or palate to normalize their facial morphology with primary repair and
               any subsequent revision surgery. The extent and type of these facial deformities varies among patients
               due to the extent of the original abnormality and any prior surgeries performed [1-3] . Several experts
               have recommended using subjective checklists to provide assessments of the extent and type of facial
                           [4,5]
               abnormalities ; however, this could result in bias. The development of a systematic method for the
               evaluation and classification of the morphological traits of the cleft facial shape could greatly facilitate
               the surgical/orthodontic diagnosis and the design of treatment plans for the optimization of treatment
               outcomes.

               The analysis of the form of the nose and lip is important for revision surgery and many attempts have been
               made to establish systematic analytical methods. Conventional photographs have been employed in some
               studies [3,6,7] . Several three-dimensional (3D) analysis techniques, including direct anthropometry of the
                                                                                                       [15]
                         [8,9]
               human face , stereophotogrammetry [10,11] , laser scanning, gypsum cast [12-14] , and computer tomography ,
               have been employed to assess the facial morphology of patients with cleft lip. Because these analyses are
               primarily conducted with the use of linear and/or angular measurements between/among landmarks,
               the detailed morphological characteristics of the entire facial surface forms are not considered. There
               have also been a few attempts to extract detailed morphological characteristics of the entire facial surface
               forms using the slice lines. In these studies, traced nasal lines in an axial view were assessed using a curve
                                                             [12]
               fitting method that provides the extent of asymmetry , and an automatically extracted nostril shape was
               assessed . These studies succeeded in describing the morphological characteristics of the nasal surface;
                      [16]
               they mainly attempted to describe the nasal forms in an axial view and the nostril shapes before and after
               surgery. A 3D quantitative analysis of the lip was also reported, in which the morphological traits of the lip
                                                                 [17]
               surfaces were measured from the frontal and lateral views . However, thus far, few studies have reported
               the 3D holistic analysis of the entire facial form from all three views (i.e., frontal, lateral, and axial views).

               With recent computation advances, landmark-based geometric morphometric methods (GMMs) have
               recently emerged that-together with conventional measurements in medicine-have revealed some statistical
               variation in the shape and size of target objects (phenotypic variation). In developmental biology, GMMs
               use homologous landmarks, which can be defined as precise locations on biological specimens that hold
               some functional, structural, developmental, or evolutionary significance, and which are directly comparable
                                [18]
               between specimens . GMMs have four types of landmarks: Type I landmarks can be clearly defined on a
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