Table 2.

Overview of the results, outcomes, and conclusions of the included studies

Author, year, design	Title	Subject group	Outcome assessed	Method of outcome assessment	Results	Conclusions
Hennessy et al. [18] (2016) RCT	A randomized clinical trial comparing mandibular incisor proclination produced by fixed labial appliances and clear aligners	Invisalign vs. fixed appliances	Mandibular incisor proclination produced by fixed appliances and Invisalign® aligners when treating patients with mild mandibular crowding	Comparison of pre-treatment and near-end treatment lateral cephalograms; the main outcome was the cephalometric change in mandibular incisor inclination to the mandibular plane at the end of treatment	- Mn incisor proclination: fixed appliances, 5.3 ± 4.3°; Invisalign®: 3.4 ± 3.2° (P > 0.05)	No difference in the amount of Mn incisor proclination produced by Invisalign® and fixed labial appliances in mild crowding cases
Li et al. [19] (2015) RCT	The effectiveness of the Invisalign appliance in extraction cases using the the ABO model grading system: a multicenter randomized controlled trial	Invisalign vs. fixed appliances	Treatment outcomes of the Invisalign® system by comparing the results of Invisalign® treatment with that of fixed appliances in class I adult extraction cases	The DI was used to analyze pretreatment records (study casts and lateral cephalograms) to control for initial severity of malocclusion. The ABO-OGS was used to systematically grade both pre- and post-treatment records	- Improved total mean scores of the OGS categories after treatment for both groups in terms of alignment, marginal ridges, occlusal relations, overjet, inter-proximal contacts, and root angulation - Invisalign® scores were significantly lower than fixed appliance scores for b-l inclination and occlusal contacts - Invisalign® had longer treatment duration (31.5 months) compared to fixed appliances (22 months)	Both Invisalign® and fixed appliances were successful in treating class I adult extraction cases, though Invisalign® required more time and showed worse performance in certain fields
Bollen et al. [20] (2003) RCT	Activation time and material stiffness of sequential removable orthodontic appliances. Part 1: Ability to complete treatment	Invisalign groups	Effects of activation time and material stiffness on the ability to complete the initial series of aligners, designed to fully correct each subject’s malocclusion	Initial PAR scores calculation, clinical evaluation and orthodontic records (progress study models and photographs) every 4 months	- 15/51 completed the initial regimen of aligners - 2 weeks activation interval more likely to lead to completion than 1 week (37% vs 21%) - No substantial differences between soft- and hard appliance in completion rate (27% vs 32%) - Highest completion rate (46%) for non-extraction and initial PAR score < 15 - Lowest completion rate (0%) in patients with ≥ 2 extractions	Greater likelihood for completion of the initial set of aligners for subjects with a non-extraction, 2 weeks activation regimen and low initial PAR scores
Solano-Mendoza et al. [21] (2016) Prospect.	How effective is the Invisalign® system in expansion movement with Ex30′ aligners?	Accuracy	A new method for measuring the predictability of expansion obtained by Invisalign® treatment and differences between the predicted (ClinCheck® models) and actual expansion at the end of treatment	Initial and final ClinCheck® virtual models measured with ToothMeasure® compared to initial and final actual 3D models measured with NemoCast® for evaluation of the following variables: canine gingival width, 1st premolar gingival width, 2nd premolar gingival width, 1st molar gingival width, canine cuspid width, 1st premolar cuspid width, 2nd premolar cuspid width, 1st molar cuspid width, canine depth, arch depth, 1st molar rotation, 1st right and left molar rotation, and 1st molar inclination	- Non-significant differences between the initial 3D models and ClinCheck® for all variables except for 1st molar cuspid width and arch depth - Statistically significant differences between the final 3D and ClinCheck® models for canine gingival width, 1st premolar gingival width, 2nd premolar gingival width, 1st molar gingival width, canine cuspid width, 1st premolar cuspid width, 2nd premolar cuspid width, 1st molar cuspid width	- Differences between the final 3D and ClinCheck® models showed that planned expansion at the end of treatment is not predictable
Buschang et al. [26] (2015) Prospect.	Predicted and actual end-of-treatment occlusion produced with aligner therapy	Accuracy	Differences between final actual models from the final virtual ClinCheck® models after treatment with Invisalign	Final ClinCheck® virtual models compared to final actual 3D models measured with MeshLab V1.30 software for evaluation of the American Board of Orthodontics (ABO) Objective Grading System (OGS)	Final virtual ClinCheck models showed significantly fewer overall OGS point deductions compared to final actual models (15 vs 24). Differences were mainly observed in alignment (1 vs 4 deductions), buccolingual inclinations (3 vs 4 deductions), occlusal contacts (2 vs 3 deductions), and occlusal relations (2 vs 4 deductions)	- The final virtual ClinCheck models do not accurately reflect the patients’ final occlusion, as measured by the OGS, at the end of active treatment
Castroflorio et al. [22] (2013) Prospect.	Upper-Incisor Root Control with Invisalign® Appliances	Accuracy	Efficiency of Align Technology’s Power Ridge in controlling the b-l inclination of upper incisors	ClinCheck® initial and final virtual setups for each upper incisor from the right and left default views compared to measurements on 3D-scans of actual dental models	- Mean torque values for the 9 upper incisors at T0: 20.9° on the virtual setups and 21.1° on the scanned casts - At T1, the torque values were 10.5° and 10.5°, respectively, and represented the torque prescription (10.4°)	- Invisalign® controls well the upper-incisor root torque, when a torque correction of about 10° is required
Pavoni et al. [23] (2011) Prospect.	Self-ligating versus Invisalign: analysis of dento-alveolar effects	Invisalign vs. fixed appliances	Dentoalveolar effects of the Invisalign® system and of self-ligating brackets treatment in relation to transverse dimension, arch perimeter and arch depth on Mx jaw	Measurements on pre- and post-treatment maxillary dental casts (intercanine-, interpremolar-, and intermolar width, arch depth, and arch perimeter)	-No significant differences in treatment duration. - Significant differences between the 2 groups with self-ligating causing further increases in the following variables as compared to Invisalign: intercanine width (cusp), 2.6 mm; first premolar width (fossa), 3.3 mm; first premolar width (gingiva), 2.3 mm; second premolar width (fossa), 2.0 mm; second premolar width (gingiva), 1.8 mm; arch perimeter, 1.3 mm	- Class I mild crowding can be treated by Invisalign® and self-ligating brackets at the same treatment duration - Invisalign® can easily tip crowns but not roots
Kravitz et al. [5] (2009) Prospect.	How well does Invisalign work? A prospective clinical study evaluating the efficacy of tooth movement with Invisalign	Accuracy	Differences between actual models and virtual ClinCheck® models in the anterior teeth, after treatment with Invisalign	DI scores (overjet, overbite, anterior open bite, and crowding) using a modified ABO-OGS on pretreatment digital models. Superimposition of virtual models of the predicted tooth position over the achieved tooth position (ToothMeasure®). Comparison between the predicted and achieved amount of tooth movement (i.e., expansion, constriction, intrusion, extrusion, mesiodistal tip, labiolingual tip, and rotation). Accuracy (%) = [(|predicted-achieved|/|predicted|) 100%]	- Invisalign® mean accuracy of tooth movement, 41% - Most accurate movement: lingual constriction (47.1%), least accurate movement: extrusion (29.6%; 18.3% for Mx and 24.5% for Mn central incisors), followed by mesio-distal tipping of the Mn canines (26.9%) - Canine rotation significantly less accurate than that of all other teeth, except for that of the Mx lateral incisors, especially at rotational movements > 15°. - Lingual crown tip significantly more accurate than labial crown tip - No statistical difference in accuracy between Mx and Mn for any movement on any specific tooth	-Further research is needed to understand the efficacy and biomechanics of the Invisalign® system -Prescription by clinicians should be made based on the patient’s treatment needs, while taking into account the limitations of the appliance
Kravitz et al. [24] (2008) Prospect.	Influence of attachments and interproximal reduction on the accuracy of canine rotation with Invisalign	Accuracy	Influence of attachments and IPR on canines undergoing rotational movement with Invisalign®	Tooth Measure® to compare the amount of canine rotations predicted with the ones achieved (in degrees). Accuracy (%) = [(|predicted-achieved|/|predicted|) 100%]	- Invisalign® mean accuracy of canine rotation was 35.8 ± 26.3% - No statistically significant difference in accuracy between the 3 groups - No statistically significant difference in rotational accuracy for Mx and Mn canines for any of the 3 groups - The vertical-ellipsoid was the most commonly prescribed attachment shape (70.5%)	The effectiveness of the Invisalign® system in canine derotation is limited and not significantly improved by vertical-ellipsoid attachments and IPR
Baldwin et al. [27] (2008) Prospect.	Activation time and material stiffness of sequential removable orthodontic appliances. Part 3: Premolar extraction patients	Invisalign only	Tipping of teeth adjacent to premolar extraction spaces during space closure with aligner appliances	Dental casts and panoramic radiographs pre-treatment and at the end of Invisalign treatment (potentially continued with fixed appliances)	- During treatment, the average radiographic changes in interdental angle were 21.5° (P < 0.0001; n = 10) in the mandible and 16.3° (P < 0.0001; n = 19) in the maxilla. On the models, the average changes were 20.8° (P < 0.0001; n = 12) in the mandible and 15.9° (P < 0.0001; n = 20) in the maxilla - No subject completed the initial series of aligners and only 1 ultimately completed treatment with aligners - The average time in the initial series of aligners before failure was 7 (range, 1–17) months and the average total time in aligners 16.6 (range, 6–28) months (treatment continued with fixed appliances)	- In premolar extraction patients treated with Invisalign, significant dental tipping occurs (it can be corrected with fixed appliances) - There is a trend for greater tipping of mandibular teeth into the extraction space and around second premolar extraction sites during treatment with aligners
Vlaskalic and Boyd [25] (2002) Prospect.	Clinical evolution of the Invisalign® appliance	Invisalign groups	Clinical evaluation of the Invisalign® system based on a feasibility study conducted in the University of the Pacific in 1997	Pre-, progress-, and post-treatment records including panoramic and lateral cephalometric radiographs, dental casts, intra-, and extraoral photographs.	Group 1: aligners need to be worn for at least 10 days each, patients tolerate aligners well, posterior open bite occurs in some patients, overcorrection of tooth position is necessary in initial 3-D setup Group 2: attachments are necessary for rotations of cylindrical shaped teeth, intrusion, extrusion, bodily tooth movement, extraction of teeth is possible Group 3: long vertical attachments are necessary from the start of treatment to maintain adequate root control in extraction cases, virtual tooth pontic system is esthetically and mechanically advantageous	-The Invisalign system is a viable alternative to conventional fixed and removable appliances - Patients in the permanent dentition with mild to moderate malocclusions may be greatly benefited when treatment is planned carefully - Further investigation is needed for the ultimate clinical potential of Invisalign®
Gu et al. [28] (2017) Retrosp.	Evaluation of Invisalign treatment effectiveness and efficiency compared with conventional fixed appliances using the Peer Assessment Rating index	Invisalign vs. fixed appliances	Effectiveness and efficiency of the Invisalign system compared with conventional fixed appliances in mild to moderate malocclusions	Comparison between patients treated with Invisalign® and fixed appliances assessing post-treatment PAR scores, post-treatment reduction in PAR scores, treatment duration, and malocclusion improvement	- Average pretreatment PAR scores: 20.81 for Invisalign and 22.79 for fixed appliances (NS) - Not statistically different posttreatment PAR scores and PAR score reduction between the 2 groups. - Invisalign® patients finished 5.7 months faster than those with fixed appliances (P = 0.0040). - All patients in both groups had > 30% reduction in PAR scores. - Odds of achieving “great improvement” in the Invisalign® group were 0.33 times greater than those in the fixed appliances group after controlling for age (P = 0.015)	- Both Invisalign® and fixed appliances are able to improve mild to moderate malocclusion - Fixed appliances were more effective than Invisalign in providing greater improvements - Treatment with Invisalign was finished on average 30% (5.7 months) faster than treatment with fixed appliances.
Khosravi et al. [29] (2017) Retrosp.	Management of overbite with the Invisalign appliance	Invisalign groups	Vertical dimension changes in patients with various pre-treatment overbite relationships treated only with Invisalign and other dental and skeletal changes	Pre- and post-treatment lateral cephalometric radiographs; cephalometric analyses by Dolphin Imaging, Chatsworth, Calif	- Deep bite patients had a median overbite opening of 1.5 mm, whereas the open bite patients had a median deepening of 1.5 mm. The median change for the normal overbite patients was 0.3 mm - Changes in incisor position were responsible for most of the improvements in the deep bite and open bite groups - Minimal changes in molar vertical position and mandibular plane angle	- Invisalign is relatively successful in managing overbite - Overbite is maintained in patients with normal overbite - Deep bite improvement primarily by proclination of Mn incisors - Invisalign corrects mild to moderate anterior open bites, primarily through incisor extrusion
Houle et al. [30] (2016) Retrosp.	The predictability of transverse changes with Invisalign	Accuracy	Differences between the initial and final actual models from the initial and final virtual ClinCheck® models after treatment with Invisalign, when planning transverse changes	- Comparison between pre- and posttreatment digital models, (created from an iTero scan) and digital models from Clincheck® (Align Technology) - Digital models were measured with Geomagic Qualify	- In the Mx, when dentoalveolar expansion was planned with Invisalign®, there was a mean accuracy of 72.8%: 82.9% at the cusp tips and 62.7% at the gingival margins, with prediction worsening toward the posterior region of the arch - For the Mn arch, there was an overall accuracy of 87.7%: 98.9% for the cusp tips and 76.4% for the gingival margins -Variance ratios for upper and lower arches were significantly different (P < 0.05)	- Clincheck® prediction of expansion involves more bodily movement of the teeth than that achieved clinically. More dental tipping was observed - Careful planning with overcorrection and other auxiliary methods of expansion may help reduce the rate of midcourse corrections and refinements, especially in the posterior region of the Mx
Ravera et al. [31] (2016) Retrosp.	Maxillary molar distalization with aligners in adult patients: a multicenter retrospective study	Invisalign group	Dentoalveolar and skeletal changes following maxillary molar distalization therapy with Invisalign in adult patients	Pre- and post-treatment lateral cephalometric radiographs	- Distal movement of the 1st molar: 2.25 mm without significant tipping and vertical movements - Distal movement of the 2nd molar: 2.52 mm without significant tipping (P = 0.056) and vertical movements - No significant movements on the lower arch. - SN-GoGn and SPP-GoGn angles showed no significant differences between pre- and post-treatment cephalograms	- Invisalign aligners are effective in distalizing Mx molars in selected end-to-end class II non-growing subjects without significant vertical and mesiodistal tipping movements - No changes to the facial height
Duncan et al. [32] (2015) Retrosp.	Changes in mandibular incisor position and arch form resulting from Invisalign correction of the crowded dentition treated nonextraction	Invisalign groups	Treatment outcomes in non-extraction cases with lower anterior crowding treated with Invisalign®	-Pre- and post-treatment records (digital study models and lateral cephalometric radiographs) -Cephalometric analysis to determine lower incisor changes - IPR and changes in arch width were also measured	- In the severe crowding group, there were statistically significant changes in lower incisor position and angulation - No significant differences in lower incisor position and angulation in the the mild and moderate crowding groups - Statistically significant increase in buccal expansion in all three groups.	- No change in the lower incisor position or angulation in mild to moderate lower anterior crowding cases -In non-extraction severe crowding cases (> 6 mm), the lower incisors tend to procline and protrude -Buccal arch expansion and IPR are important factors in crowding resolution -Intercanine, interpremolar, and intermolar widths do not differ among the three groups at post-treatment
Grünheid et al. [33] (2015) Retrosp.	Effect of clear aligner therapy on the buccolingual inclination of mandibular canines and the intercanine distance	Invisalign vs. fixed appliances	Treatment changes in b-l inclination of Mn canines and intercanine distance between patients treated with Invisalign® and conventional fixed appliances	Pre- and post-treatment CBCTs	- No significant pre-treatment difference between the groups regarding the b-l inclination of Mn canines and intercanine distance - Positive pre- and post-treatment b-l inclinations of Mn canines (i.e., their crowns were positioned buccal to their roots) for both groups - Significantly greater post-treatment b-l inclination in the Invisalign group - Significantly increased intercanine distance in the aligner group at the end of treatment	Invisalign seems to increase the Mn intercanine distance with little increase in b-l inclination compared to fixed appliances
Simon et al. [34] (2014) Retrosp.	Treatment outcome and efficacy of an aligner technique – regarding incisor torque, premolar derotation and molar distalization	Accuracy	Treatment efficacy of Invisalign® aligners for the following 3 predetermined tooth movements: incisor torque > 10°, premolar derotation > 10°, and molar distalization > 1.5 mm	- Comparison between the predicted amount of tooth movement by ClinCheck® and the amount achieved after treatment - Evaluation of the influence of auxiliaries (attachments/Power Ridge), the staging (movement/aligner), and the patient’s compliance with treatment	- Overall mean efficacy: 59 ± 0.2% - Mean accuracy for upper incisor torque: 42 ± 0.2% - Premolar derotation showed the lowest accuracy of approximately 40 ± 0.3% - Distalization of an upper molar was the most effective movement, with efficacy approximately 87 ± 0.2%	- Bodily tooth movement (molar distalization) can be effectively performed using Invisalign® aligners - Premolar derotation significantly depends on velocity and total amount of planed tooth movement - For upper incisor torque and premolar derotation, overcorrections/case refinements may be needed
Krieger et al. [35] (2012) Retrosp.	Invisalign® treatment in the anterior region. Were the predicted tooth movements achieved?	Accuracy	Differences in the anterior region between the initial and final actual models from the initial and final virtual ClinCheck® models after treatment with Invisalign	- Electronic digital caliper for measurements in casts - Evaluated parameters: upper/lower anterior arch length and intercanine distance, overjet, overbite, dental midline shift, and Little’s irregularity index - ClinCheck® was measured with ToothMeasure®	- Mx anterior crowding: initial, 5.4 (range 1.5–14.5) mm; final, 1.6 (range 0.0–4.5) mm - Mn anterior crowding: initial, 6.0 (range 2.0–11.5) mm; final, 0.8 (range 0.0–2.5) mm - Slight deviations between the initial actual and virtual ClinCheck® models in overjet (− 0.1 ± 0.3 mm), upper anterior arch length (− 0.3 ± 0.5 mm), lower anterior arch length (0.0 ± 0.5 mm), and in overbite (0.7 ± 0.9 mm)	- Moderate to severe anterior crowding can be successfully corrected with Invisalign® - Well predictable resolution of lower anterior crowding is achieved by protrusion of anterior teeth (i.e., enlargement of the anterior arch length) - In general, the achieved tooth movement was in accordance with the predicted movement for all parameters, except for overbite
Krieger et al. [36] (2011) Retrosp.	Accuracy of Invisalign® treatments in the anterior tooth region. First results	Accuracy	Differences between the initial and final actual models from the initial and final virtual ClinCheck® models after treatment with Invisalign	- Electronic dental caliper to measure pre- and post-treatment models - ToothMeasure® to measure the ClinCheck® - Examined parameters: overjet, overbite, and dental midline shift	- Slight deviations in overjet (0.1 ± 0.3 mm), overbite (0.3 ± 0.4 mm), and dental midline deviation (0.1 ± 0.4 mm) between initial actual and virtual models - Larger deviations in overjet (0.4 ± 0.7 mm), overbite (0.9 ± 0.9 mm), and dental midline shift (0.4 ± 0.5 mm) between final actual and virtual models	- Acceptable accuracy of Invisalign® technology during computerized transfer of malaligned teeth into the ClinCheck® presentation. - Tooth corrections in the vertical plane were more difficult to achieve. - Overcorrection in the final ClinCheck®, case refinement at treatment end or additional measures (e.g., horizontal beveled attachments or vertical elastics) are suggested to meet individualized therapeutic goals, especially in vertical corrections
Kuncio et al. [37] (2007) Retrosp.	Invisalign and Traditional Orthodontic Treatment Postretention Outcomes compared using the American Board of Orthodontics Objective Grading System	Invisalign vs. fixed appliances (retention)	Post-retention treatment outcomes in patients treated with Invisalign and those treated with traditional fixed appliances	- ABO-OGS analysis on panoramic radiographs and dental casts - Investigated parameters: total alignment, Mx anterior and posterior alignment, Mn anterior and posterior alignment, marginal ridges, b-l inclination, occlusal contacts, occlusal relations, overjet, interproximal contacts, root angulations - Evaluation after appliance removal (T1) and at a post-retention (T2) (3 years after appliance removal). - Efficacy in retention in comparison to Essix retainer after fixed appliances	- Post-retention worsening of total alignment and Mn anterior alignment for both groups - Higher post-retention changes in total alignment (ABO-OGS score) for Invisalign patients (− 2.9 ± 1.6) than patients treated with fixed appliances (− 1.4 ± 1.2) - Post-retention worsening of Mx anterior alignment in the Invisalign group only.	Greater relapse in the Invisalign® group for this observation period (approximately 3 years) for Invisalign than for fixed appliance group
Djeu et al. [38] (2005) Retrosp.	Outcome assessment of Invisalign and traditional orthodontic treatment compared with the American Board of Orthodontics objective grading system	Invisalign vs. fixed appliances	Treatment outcome of Invisalign compared to conventional fixed appliance treatment	- Pretreatment records (dental casts and lateral cephalograms) assessed with the DI (measurements: overjet, overbite, anterior open bite, lateral open bite, crowding, occlusion, lingual posterior crossbite, buccal posterior crossbite, cephalometrics, and other) - Posttreatment records (dental casts and panoramic radiographs) scored by ABO-OGS (measurements: alignment, marginal ridges, b-l inclination, occlusal contacts, occlusal relations, overjet, interproximal contacts, root angulation)	- Lower OGS passing rate for Invisalign® (27.1%) than that for fixed appliances - Invisalign® scores were significantly lower than fixed appliance scores for b-l inclination, occlusal contacts, occlusal relationships, and overjet (P < 0.05) - Invisalign® OGS scores negatively correlated to initial overjet, occlusion, and buccal posterior crossibite - Treatment duration on average 4 months shorter with Invisalign® than with fixed appliances (P < 0.05)	- Treatment results of fixed appliances are superior to those of Invisalign® (13 OGS points on average) - Reduced ability of Invisalign to correct large A-P discrepancies and occlusal contacts

Prospect., prospective, Retrosp., retrospective, DI discrepancy index, ABO American Board of Orthodontics, OGS Objective Grading System, Mx maxilla (or maxillary), Mn mandible (or mandibular), NS not statistically significant, b-l buccolingual