Objectives: Conventional two-dimensional (2D) cephalometric radiography is an integral part of orthodontic patient diagnosis and treatment planning. One must be mindful of its limitations as it indeed is a 2D representation of a vaster three-dimensional (3D) object. Issues with projection errors, landmark identification, and measurement inaccuracies impose significant limitations, which may now be overcome with the advent of cone-beam computed tomography (CBCT). A systematic review of the reliability of different 3D cephalometric landmarks in CBCT imaging was conducted. Materials and Methods: Electronic database searches were administered until October 2017 using PubMed, MEDLINE via OvidSP, EBMR and EMBASE via OvidSP, Scopus, and Web of Science. Google Scholar was used as an adjunctive search tool. Results: Thirteen articles considering CBCT scans of human subjects from preexisting data sets were selected and reviewed. Most of the studies had methodological limitations and were of moderate quality. Because of their heterogeneity, key data from each could not be combined and were reported qualitatively. Overall, in 3D, midsagittal plane landmarks demonstrated greater reliability compared with bilateral landmarks. A minimum number of dental landmarks were reported, although most were recommended for use. Conclusions: Further research is required to evaluate the reliability of 3D cephalometric landmarks when evaluating 3D craniofacial complexes.

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