## 3 Review
### Class III
#### 3.2.1 Study Design and Treatment Interventions  
Employing the same search criteria as for the Class II condition, the nine Class III studies included were retrospective cephalometric comparative studies (Table 2). Despite a wide bibliographic search, no perspective study or systematic review on this topic was found. Retrospective studies concerning treatment decisions for Class III borderline patients focused on three main aspects:  
* Prognostic cephalometric parameters and predictive formulas (skeletal, dental, soft tissue)
* The influence of different biomechanics, such as extraction versus non-extraction orthodontic treatment plan to reach an ideal post-treatment condition
* Long-term follow-up and result stability  
Prognostic Cephalometric Parameters and Predictive Formulas  
In 1992, [PERSON] et al. [25] tried to determine some cephalometric benchmarks in adult patients with mild skeletal Class III malocclusions to find objective criteria for treatment options. They compared pre-treatment lateral cephalometric radiographs by using univariate statistical methods. Significant differences were found in the ANB Angle, maxillary-mandibular ratio, mandibular incisor inclination, and Holdaway Angle. They suggest that surgery should be performed when the ANB Angle is lower than \(-4^{\circ}\) and the IMPA lower than \(83^{\circ}\). In view of the complex interaction of skeletal and dento-alveolar parameters, recent studies recommended a multivariate approach to analyzing the relationship between cranio-facial structure and Class III malocclusion [26], whereas this study does not include sagittal measurements nor individual soft-tissue variations. In 2002, [PERSON] et al. [15], developed a formula based on a Discriminant Analysis (DA), to classify borderline Class III adults into two groups: one treatable by orthodontics-only and the other requiring orthognathic surgery. A DA is a multivariate procedure specifically designed to differentiate between two groups of subjects from the same population, using prediction models and criteria. The predictive model included many variables, but the Wits Appraisal Index turned out to be the most predictive variable. However, the DA has its limitations because a large sample size is a prerequisite to establish a sufficiently predictable model, and the selection of parameters might not include all variables required to accurately differentiate the groups. The DA could correctly allocate 97.7% of Class III patients who were treated with an orthodontic-only approach; however, 13.6% of those who needed surgery were misclassified. These findings led to the hypothesis that additional factors may be determining for the necessity of surgical intervention, such as transverse variables. In 2011, [PERSON] et al. [27] introduced their upgraded model by adding a new transverse parameter: a lower midline deviation greater than 3 mm. The four variables of the new formula where the Wits Appraisal Index, Mandibular/Maxilla Ratio, Saddle Angle, and Lower Midline Deviation (LMD). Despite this, the success rate of this improved equation was only 91.2%; therefore, the authors suggest using both formulas to determine which would be the best treatment for each patient. Furthermore, they emphasize the fact that the equation is a statistical model, so it may not fit every patient nor every ethnicity. Both [PERSON]'s and [PERSON]'s equations are used to calculate a critical score: if the patient's score is higher than the critical score, they can be successfully treated with an orthodontic-only camouflage. In 2008, [PERSON] et al. [26] conducted a cephalometric retrospective study, selecting skeletal Class III with an ANB Angle greater than \(-5^{\circ}\), treated with an extractive orthodontic-only approach or the combined orthodontic-surgical approach. Authors used a stepwise DA through which the Holdaway Angle proved to be the most reliable parameter: patients with a Holdaway Angle inferior to 12\({}^{\circ}\) would require surgical treatment.