Clinical effectiveness of Invisalign® orthodontic ... · Moreover, Invisalign® aligners can...
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REVIEW Open Access
Clinical effectiveness of Invisalign®orthodontic treatment: a systematic reviewAikaterini Papadimitriou1, Sophia Mousoulea2, Nikolaos Gkantidis3 and Dimitrios Kloukos1,3*
Abstract
Background: Aim was to systematically search the literature and assess the available evidence regarding theclinical effectiveness of the Invisalign® system.
Methods: Electronic database searches of published and unpublished literature were performed. The reference listsof all eligible articles were examined for additional studies. Reporting of this review was based on the PreferredReporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.
Results: Three RCTs, 8 prospective, and 11 retrospective studies were included. In general, the level of evidence wasmoderate and the risk of bias ranged from low to high, given the low risk of bias in included RCTs and the moderate(n = 13) or high (n = 6) risk of the other studies. The lack of standardized protocols and the high amount of clinical andmethodological heterogeneity across the studies precluded a valid interpretation of the actual results through pooledestimates. However, there was substantial consistency among studies that the Invisalign® system is a viable alternativeto conventional orthodontic therapy in the correction of mild to moderate malocclusions in non-growing patients thatdo not require extraction. Moreover, Invisalign® aligners can predictably level, tip, and derotate teeth (except forcuspids and premolars). On the other hand, limited efficacy was identified in arch expansion through bodily toothmovement, extraction space closure, corrections of occlusal contacts, and larger antero-posterior and vertical discrepancies.
Conclusions: Although this review included a considerable number of studies, no clear clinical recommendations can bemade, based on solid scientific evidence, apart from non-extraction treatment of mild to moderate malocclusions in non-growing patients. Results should be interpreted with caution due to the high heterogeneity.
Keywords: Orthodontics, Invisalign, Aligner, Clinical efficiency
BackgroundOrthodontic developments, especially during the lastyears, have been accompanied by a significant increasein the esthetic demands of the patients. Patients oftenexpress the need to influence, or even determine, treat-ment aspects or objectives, along with the orthodontist,driven by the effects that orthodontic appliances havein their appearance. Conventional orthodontic methodshave been associated with a general compromise in fa-cial appearance [1] raising a major concern among pa-tients seeking orthodontic treatment [2]. Thus, esthetic
materials and techniques have been introduced in clin-ical practice aiming to overcome these limitations [3].Since its development in 1997, Invisalign® technology
has been established worldwide as an esthetic alternativeto labial fixed appliances [4–7]. CAD/CAM stereolitho-graphic technology has been used to forecast treatmentoutcomes and fabricate a series of custom-made alignersusing a single silicone or digital impression [6]. After itsintroduction, the system has been drastically developedand continually improved in many aspects; different at-tachment designs, new materials, and new auxiliaries,such as “Precision Cuts” and “Power Ridges” were de-signed to enable additional treatment biomechanics.According to the manufacturer, Invisalign® can effect-ively perform major tooth movements, such as bicuspidderotation up to 50° and root movements of upper cen-tral incisors up to 4 mm [8]. Despite the advocated
* Correspondence: [email protected] of Orthodontics and Dentofacial Orthopedics, 251 Hellenic AirForce General Hospital, P. Kanellopoulou 3, 11525 Athens, Greece3Department of Orthodontics and Dentofacial Orthopedics, University ofBern, Freiburgstrasse 7, CH-3010 Bern, SwitzerlandFull list of author information is available at the end of the article
© The Author(s). 2018 Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, andreproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link tothe Creative Commons license, and indicate if changes were made.
Papadimitriou et al. Progress in Orthodontics (2018) 19:37 https://doi.org/10.1186/s40510-018-0235-z
efficiency of the treatment, its clinical potency still re-mains controversial among professionals, with advocatesbeing convinced by the successfully demonstrated treatedcases, as indicated by clinical evidence, in contrast to op-ponents who argue about significant limitations, especiallyin the treatment of complex malocclusions [5, 9–11].Despite the available body of literature pertaining to
Invisalign® technology, its clinical performance has beenanalyzed less thoroughly and a synthesis of the results stillremains vague. Four systematic reviews about clearaligners exist in the literature: the first one was publishedback in 2005 and assessed the treatment effects of Invisa-lign; it included, nevertheless, only two studies [12]. Morerecently, another three reviews have been published. Thefirst one was last updated in June 2014; it included 11studies and evaluated the control of the clear aligners onorthodontic tooth movement [13]. The second one evalu-ated the periodontal health during clear aligner therapyand was published in the same year [14], and the most re-cent one was undertaken in October 2014 and includedfour studies, since it focused on the comparison betweenclear aligners and conventional braces [15].Therefore, the purpose of the present review was to
systematically search the literature and summarize thecurrent available scientific evidence regarding the clin-ical effectiveness of the Invisalign® system as principalorthodontic therapy to orthodontic patients of any agetreated with this method comparing either among themor those with conventional braces and evaluating thelevel of efficacy in various malocclusions.
Materials and methodsTypes of studiesRandomized clinical trials (RCTs), controlled clinical tri-als (CCTs), and prospective and retrospective studieswere considered eligible for inclusion in this review.These studies concerned to the clinical part of treatmentwith Invisalign, with no restrictions in language, age, sta-tus of publication, and cases with teeth extractions.
Types of participantsOrthodontic patients of any age who were treated with Invi-salign® either as the intervention or as the control group.
Types of interventionsInvisalign® therapy. All other aligner systems have beenexcluded.
OutcomeAny effect on clinical efficiency, effectiveness, treatmentoutcomes, movement accuracy, or predicted toothmovement in ClinCheck® of Invisalign® treatment, in-cluding changes in alignment or occlusion, treatment
duration, and completion rate, as primary outcomes. Ad-verse events/unwanted effects have also been recorded.
Search methods for identification of studiesDetailed search strategies were developed and appropri-ately revised for each database, considering the differ-ences in controlled vocabulary and syntax rules. Thefollowing electronic databases were searched: MEDLINE(via Ovid and PubMed, Appendix, from 1946 to August28, 2017), Embase (via Ovid), the Cochrane Oral HealthGroup’s Trials Register, and CENTRAL.Unpublished literature was searched on ClinicalTrials.gov,
the National Research Register, and Pro-Quest DissertationAbstracts and Thesis database.The search attempted to identify all relevant studies ir-
respective of language. The reference lists of all eligiblestudies were examined for additional studies.
Selection of studiesStudy selection was performed independently and in du-plicate by the first two authors of the review, who werenot blinded to the identity of the authors of the studies,their institutions, or the results of their research. Studyselection procedure was comprised of title-reading,abstract-reading, and full-text-reading stages. After ex-clusion of not eligible studies, the full report of publica-tions considered eligible for inclusion by either authorwas obtained and assessed independently. Disagreementswere resolved by discussion and consultation with thethird and the last author. A record of all decisions onstudy identification was kept.
Data extraction and managementThe first two authors performed data extraction inde-pendently and in duplicate. Disagreements were resolvedby discussion or the involvement of two collaborators(third author and last author). Data collection forms wereused to record the desired information. The following datawere collected on a customized data collection form:
� Author/title/year of study� Design/setting of the study� Number/age/gender of participants� Intervention and comparator/treatment duration� Type of clinical outcome� Method of outcome assessment
Measures of treatment effectFor continuous outcomes, descriptive measures, such asmean differences and standard deviations, were used tosummarize the data from each study. For dichotomousdata, number of participants with events and total num-ber of participants in experimental and control groupswere analyzed.
Papadimitriou et al. Progress in Orthodontics (2018) 19:37 Page 2 of 24
Unit of analysis issuesIn all cases, the unit of analysis was the patient.
Dealing with missing dataWe contacted study authors per e-mail to request miss-ing data where necessary. In case of no response or noprovision of the missing data, only the available reporteddata were analyzed.
Data synthesisA meta-analysis was planned only if there were at leasttwo studies of low or unclear risk of bias, reporting simi-lar comparisons, and similar outcomes at similar timepoints. Otherwise, qualitative synthesis of the includedstudies would be performed.
Quality assessment of included studiesThe risk of bias for RCT studies was assessed by two re-view authors, independently and in duplicate, using theCochrane risk of bias tool [16].Risk of bias was assessed and judged for seven separ-
ate domains.
1. Sequence generation: was the allocation sequenceadequately generated?
2. Allocation concealment: was allocation adequatelyconcealed?
3. Blinding of participants and investigators: wasknowledge of the allocated intervention adequatelyprevented during the study?
4. Blinding of outcome assessors: was knowledge ofthe allocated intervention adequately preventedbefore assessing the outcome?
5. Incomplete outcome data: were incomplete outcomedata adequately addressed?
6. Selective outcome reporting: were reports of the studyfree of suggestion of selective outcome reporting?
7. Other sources of bias: was the study apparently free ofother problems that could put it at a high risk of bias?
Each study received a judgment of low risk, high risk,or unclear risk of bias (indicating either lack of sufficientinformation to make a judgment or uncertainty over therisk of bias) for each of the seven domains. Studies werefinally grouped into the following categories:
– Low risk of bias (plausible bias unlikely to seriouslyalter the results) if all key domains of the study wereat low risk of bias.
– Unclear risk of bias (plausible bias that raises somedoubt about the results) if one or more key domainsof the study were unclear.
– High risk of bias (plausible bias that seriously weakensconfidence in the results) if one or more key domainswere at high risk of bias.
Prospective and retrospective studies were graded as low,moderate, or high risk of bias according to the followingcriteria, adapted from the Bondemark scoring system [17]:
– Low risk of bias (all criteria should be met):� Randomized clinical study or a prospective study
with a well-defined control group.� Defined diagnosis and endpoints.� Diagnostic reliability tests and reproducibility
tests described.� Blinded outcome assessment.
– Moderate risk of bias (all criteria should be met):� Cohort study or retrospective cases series with
defined control or reference group.� Defined diagnosis and endpoints.� Diagnostic reliability tests and reproducibility
tests described.– High risk of bias (one or more of the following
conditions):� Large attrition.� Unclear diagnosis and endpoints.� Poorly defined patient material.
The Grading of Recommendations Assessment,Development and Evaluation (GRADE) [16] was imple-mented to assess the overall quality of evidence for thestudies included in this systematic review, according towhich the overall evidence is rated as high, moderate,low, and very low. The outcomes included in GRADEwere divided into categories regarding the different pa-rameters that had been assessed in the primary studies.
� High quality of evidence implies that the true effectlies close to that of the estimate of the effect
� Moderate quality of evidence implies that the trueeffect is likely to be close to the estimate of theeffect, but there is a possibility that it is substantiallydifferent
� Low quality of evidence implies that our confidencein the effect estimate is limited: the true effect maybe substantially different from the estimate of theeffect
� Very low quality of evidence implies that the trueeffect is likely to be substantially different from theestimate of effect.
ResultsStudy selectionThe electronic search initially identified 227 relevant ar-ticles. One hundred fifty-eight papers remained after
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exclusion on the basis of title-reading. Five articles wereadded through hand-searching. After 49 duplicates’ re-moval, 114 papers were assessed for screening, and afterabstract-reading, 85 studies were excluded leaving 29 arti-cles to be read in full-text. After the application of specificinclusion and exclusion criteria, another seven articleswere removed. In total, 22 studies were considered eligiblefor inclusion in the final analysis (Fig. 1).
Study characteristicsThe characteristics of each study are presented in detail inTable 1. Table 2 gives an overview of the results of the in-cluded studies regarding clinical parameters. Three studies[18–20] were RCTs, eight studies were of prospective [5,21–27], and 11 of retrospective design [28–38].
Quality analysisThe quality assessment of the 22 studies is shown inTables 3 and 4.
RCTsThe three RCTs [18–20] were judged to be at an overalllow risk of bias, due to the low risk of bias that appliedto each domain based on the Cochrane risk of bias tool[16] (Table 3).
Prospective studiesThree prospective studies [21, 26, 35] were graded asmoderate and five [5, 22, 24, 25, 27] as high risk of bias.Although they were all studies of prospective design, noblinding in relation to outcome assessment was reportedin all except one [27] study, which also lacked control,among other limitations (Table 4).
Retrospective studiesTen out of the 11 identified retrospective studies [28–38]were graded as moderate risk of bias, since all thepre-determined criteria were met. Only one retrospectivestudy [34] was of high risk of bias, because it did not
Fig. 1 Studies’ flow diagram
Papadimitriou et al. Progress in Orthodontics (2018) 19:37 Page 4 of 24
Table
1Anoverview
oftheinclud
edstud
iesprovidinginform
ationon
theexpe
rimen
tald
esigns
andsettings
Autho
r(year)
Title
Stud
yde
sign
Setting,
treatm
entdu
ratio
nParticipants
(num
ber,sex)
Age
ofpatients
(meanage)
Inclusioncriteria
Interven
tiongrou
pCom
parison
grou
p
Hen
nessy
etal.[18]
(2016)
Arand
omized
clinicaltrial
comparin
gmandibu
lar
incisorproclinationproduced
byfixed
labial
appliances
andclearaligne
rs.
RCT
Setting:
n/a
Treatm
entdu
ratio
n:fixed
appliancegrou
p,11.3mon
ths;
clearalignerg
roup
,10.2mon
ths
44patients
(17M
,27F)
Invisaligngrou
p:29.1±7.5years
Fixedappliance
grou
p:23.7±7.0years
-Age
≥18
years
-Nocariesor
perio
dontal
disease
-Mild
Mncrow
ding
(<4mm)
-Non
-extractionorthod
ontic
treatm
ent
-Anterop
osterio
rskeletal
patternwith
intheaverage
rang
e(ANB1–4°)
22patientstreatedwith
Invisalign
22patients
treatedwith
fixed
appliances
(self-ligating
brackets)
Liet
al.
[19]
(2015)
Theeffectiven
essof
the
Invisalignappliancein
extractio
ncasesusingthe
ABOmodelgradingsystem
:amulticenterrandomized
controlledtrial.
RCT
2orthod
ontic
clinicsat
the
Second
AffiliatedHospital,
Zhejiang
University
Invisaligntreatm
entdu
ratio
nwas
44%
long
erthan
fixed
appliancetreatm
ent
152patients
(62M
,90F)
Invisaligngrou
p:35.2±7.3years
Fixedappliance
grou
p:32.2±8.3years
-Patientsaged
≥18
years
-Extractio
ntreatm
ent
-Patientsconsen
tedto
the
research
proced
ures
and
sign
ed-Availabilityof
pre-
and
post-treatmen
tde
ntalstud
ymod
elsandpano
ramic
filmswith
good
quality
-Classified
asbe
ingsevere
incomplexity
with
ascoreof
25usingthediscrepancy
inde
x(DI)of
theABO
phase
IIIclinicalexam
ination
-Class
Iocclusion
76patientstreatedwith
Invisalign
76patients
treatedwith
fixed
appliances
Bollenet
al.[20]
(2003)
Activationtim
eandmaterial
stiffne
ssof
sequ
ential
removab
leorthod
ontic
appliances.Part
1:Ability
tocompletetreatm
ent
RCT
University
ofWashing
ton
Region
alClinicalDen
tal
Research
Cen
ter
Prim
aryen
dpoint:
completionof
initialaligne
rs’
series
51patients
(15M
,36F)
34years
(rang
e19–55)
-Age
≥18
years
-Abilityto
attend
weekly
appo
intm
entsandto
pay
forservices
-Requ
iremen
tforregu
lar
dentalandpe
riodo
ntal
mainten
ance
prog
ram
incase
ofcariesor
perio
dontaldisease
51patientsrand
omly
assign
edto
4interven
tion
grou
ps;eith
erto
hard/soft
plastic
applianceand
1week/2weeks
activation
time
The4grou
pswere
comparedto
each
othe
r
Solano
-Men
doza
etal.[21]
(2016)
How
effectiveisthe
Invisalign®
system
inexpansionmovem
ent
with
Ex30′aligne
rs?
Prospe
ctive
Privateclinicin
Stuttgart,
Germany
Meantreatm
entdu
ratio
n:657.4±341.4days
116patients
(46M
,70F)
36.57
±11.53
years
-Treatm
entwith
Ex30
aligne
rmaterial
-Expansionof
thepo
sterior
uppe
rteeth(from
canine
to1stup
permolar)
-Presen
ceof
aninitialand
finaldigitalm
odel
-Definition
ofthethird
palatalrug
a-Nopresence
ofattachments
ontheinitialor
finalmod
el-Nomorethan
twomod
els
perpatient
Expansionwith
Invisalign;
4grou
ps:
(a)G1(n=40):expansion
≤1.99
mm
ininterm
olar
cuspid
width
(b)G2(n=45):expansion
≤3.99
mm
(c)G3(n=14):patients
subjectedto
expansion
≤5.99
mm
(d)G4(n=10):expansion
≥6mm.
7patientsun
classified
dueto
curren
tabsenceof
Initialandfinal
virtual3-D
ClinChe
ck®
mod
els
Papadimitriou et al. Progress in Orthodontics (2018) 19:37 Page 5 of 24
Table
1Anoverview
oftheinclud
edstud
iesprovidinginform
ationon
theexpe
rimen
tald
esigns
andsettings
(Con
tinued)
Autho
r(year)
Title
Stud
yde
sign
Setting,
treatm
entdu
ratio
nParticipants
(num
ber,sex)
Age
ofpatients
(meanage)
Inclusioncriteria
Interven
tiongrou
pCom
parison
grou
p
oneor
both
1stmolars
Buschang
etal.[26]
(2015)
Pred
ictedandactual
end-of-treatmen
tocclusionprod
uced
with
aligne
rtherapy
Prospe
ctive
1privatepractice,Dallas,
Texas,USA
Treatm
entdu
ratio
n:n/a
27patients
(n/a)
n/a
Con
secutivepatients
27consecutivepatients
treatedwith
Invisalign
Finalvirtual
3-DClinChe
ck®
mod
els
Castroflorio
etal.[22]
(2013)
Upp
er-in
cisor
root
control
with
Invisalign
appliances
Prospe
ctive
2private
orthod
ontic
clinicsin
ametropo
litan
area
ofno
rthw
estItaly
Treatm
ent
duratio
n:no
trepo
rted
6patients
(2M,4F)
26.3±10.2years
Nopatient
hadany
record
ofanterio
rcrossbite,anterior
prosthod
ontic
work,
previous
orthod
ontic
treatm
ent,craniofacial
trauma,surgery,TM
D,or
orofacialp
ain
Invisalign
patients
(n=6;9Mx
incisors)
need
ingpalatal
root
torque
aspartof
their
treatm
ent
Initialand
finalvirtual
3-DClin-
Che
ck®
mod
elsfor
each
uppe
rincisor
Pavoni
etal.[23]
(2011)
Self-ligatingversus
Invisalign:analysisof
dento-alveolar
effects
Prospe
ctive
Dep
artm
entof
Ortho
dontics
“Tor
Vergata,”Den
talSchoo
l,University
ofRo
me
Treatm
entdu
ratio
n:Invisalign
grou
p,18
±2mon
ths;self-
ligatinggrou
p,18
±3mon
ths
40patients
(19M
,21F)
wereeq
ually
divide
dinto
2grou
ps:
Invisalign®
grou
p(8M,
12F);self-
ligatinggrou
p(11M
,9F)
Invisaligngrou
p:18.4years
Self-ligating
grou
p:15.6years
-Class
Imalocclusion
-Mild
crow
ding
inMnarch
(mean:4.4±0.8mm)
-Perm
anen
tde
ntition
-Verteb
ralm
aturationmore
advanced
than
CS4
(post-
pube
rtal)
-Noprevious
orthod
ontic
treatm
ent
Invisalign+IPR(n=20)
Fixed
appliances
(self-ligating;
n=20)
Kravitz
etal.[5]
(2009)
How
welld
oesInvisalign
work?
Aprospe
ctive
clinicalstud
yevaluatin
gtheefficacyof
tooth
movem
entwith
Invisalign
Prospe
ctive
Dep
artm
entof
Ortho
dontics
attheUniversity
ofIllinois,
Chicago
Primaryendp
oint:com
pletion
ofinitialaligners’series.The
meannu
mbero
falignersper
treatm
entwas
10Mxand12
Mnwith
each
alignerw
orn
for2
–3weeks
37patients
(14M
,23F)
31years
-Age
≥18
years
-Anteriorcrow
ding
/spacing
<5mm
andadeq
uate
buccalinterdigitatio
n-Patientswith
posterior
eden
tulous
spaces
were
includ
ediftreatm
entdid
noten
tailspaceclosure
(1participant
hadmandibu
lar
incisorextraction)
-Clinicians
wereallowed
torequ
est/refuse
IPR,
proclination,attachmen
ts,
andovercorrectio
nson
ClinChe
ck®
37patients/401anterio
rteeth(198
Mx,203Mn)
treatedwith
Anterior
Invisalign®
Finalvirtual
3-DClinChe
ck®
mod
els
Papadimitriou et al. Progress in Orthodontics (2018) 19:37 Page 6 of 24
Table
1Anoverview
oftheinclud
edstud
iesprovidinginform
ationon
theexpe
rimen
tald
esigns
andsettings
(Con
tinued)
Autho
r(year)
Title
Stud
yde
sign
Setting,
treatm
entdu
ratio
nParticipants
(num
ber,sex)
Age
ofpatients
(meanage)
Inclusioncriteria
Interven
tiongrou
pCom
parison
grou
p
-OnlyInvisalignattachmen
tscouldbe
used
andthetray
couldno
tbe
alteredwith
scissors/the
rmop
liers
Kravitz
etal.[24]
(2008)
Influen
ceof
attachmen
tsandinterproximalredu
ction
ontheaccuracy
ofcanine
rotationwith
Invisalign
Prospe
ctive
Dep
artm
entof
Ortho
dontics,
University
ofIllinois,Chicago
Meandu
ratio
n:7mon
ths.
Primaryendp
oint:com
pletion
ofinitialaligners’series
31patients
(13M
,18F)
≥18
years
Sameas
Kravitz
etal.[5]
(2009)
31patients/53
canine
s(33
Mx,20
Mn)
treatedwith
anterio
rInvisalign®
were
divide
din
3grou
ps:
(a)attachmen
tson
ly(AO)
(b)interproximal
redu
ctionon
ly(IO
)(c)ne
ither
attachmen
tsno
rinterproximal
redu
ction(N)
Finalvirtual
3-DClinChe
ck®
mod
els
Baldwin
etal.[27]
(2008)
Activationtim
eandmaterial
stiffne
ssof
sequ
ential
removab
leorthod
ontic
appliances.Part
3:Prem
olar
extractio
npa
tients
Prospe
ctive
University
ofWashing
ton
Region
alClinicalDen
tal
Research
Cen
ter
Primaryendp
oint:com
pletion
ofinitialaligners’series
24patients
(6M,18F)
32.8(range18–54)
years
Sameas
Bollenet
al.[20]
(2003)
+at
least1prem
olar
extractio
n
24patientstreatedwith
either
hard/softplastic
applianceand1week/
2weeks
activationtim
e
Nocontrol
grou
p(pretreatm
ent
cond
ition
)
Vlaskalic
andBo
yd[25]
(2002)
Clinicalevolutionof
the
Invisalignappliance
Prospe
ctive
University
ofthePacific
Meantreatm
entdu
ratio
n:grou
p1,20
mon
ths;grou
p2,
27.2mon
ths;grou
p3,
31.5mon
ths
40patients
14–52years
-Fully
erup
tedpe
rmanen
tde
ntition
(excep
tfor3rd
molars)
-Den
talh
ealth
with
noim
med
iate
need
for
restorations
-Availabilityforeven
ing
appo
intm
ents
-Desire
tocomplywith
orthod
ontic
treatm
ent
3Invisaligngrou
psbased
onseverityof
crow
ding
:group1(n=10
mild
cases);
group2(n=15
moderate
cases),andgrou
p3
(n=15
severe
cases)
The3grou
pswere
comparedto
each
othe
r
Guet
al.
[28]
(2017)
Evaluatio
nof
Invisalign
treatm
enteffectiven
ess
andefficiencycompared
with
conven
tionalfixed
appliances
usingthePeer
Assessm
entRatin
ginde
x
Retrospe
ctive
Setting:D
ivision
ofOrth
odontics
atOhioStateUniversity
College
ofDentistry
Treatm
entdu
ratio
n:Invisaligngrou
p,13.35mon
ths;fixed
appliancegrou
p:19.1mon
ths
96patients
(34M
;62F)
Invisaligngrou
p:26
±9.7years
Fixedappliances
grou
p:22.1±7.9years
-Availablepre-
and
posttreatm
ent
records—
age≥16
years
-Noauxiliary
appliances
othe
rthan
elastics
-Non
-extractionpatients
-Noorthog
nathicsurgeryor
synd
romicpatients
-Fullpe
rmanen
tde
ntition
except
third
molars
Invisalign(n=48)
Fixed
appliances
(straigh
t-wire
edge
wise
appliances;
n=48)
Khosravi
etal.[29]
(2017)
Managem
entof
overbite
with
theInvisalignappliance
Retrospe
ctive
Setting:
3privateorthod
ontic
offices;2
locatedinthegreater
Seattle
area,W
ashand1in
Vancou
ver,British
Columbia
Treatm
entdu
ratio
n:n/a
120patients
(36M
;84F)
33years
(interquartile
rang
e:17)
-Age
≥18
years
-11
to40
aligne
rsused
for
each
arch
-Amax
useof
3revision
sets
ofaligne
rs-Non
-extractiontreatm
ent
plan
Invisalign;stratifiedstud
ysampleas
follows:68
patientsintheno
rmal
overbite
grou
p,40
patients
inthedeep-b
itegrou
p,and12
patientsinthe
open-bite
grou
p
The3grou
pswerecompared
with
each
other
Papadimitriou et al. Progress in Orthodontics (2018) 19:37 Page 7 of 24
Table
1Anoverview
oftheinclud
edstud
iesprovidinginform
ationon
theexpe
rimen
tald
esigns
andsettings
(Con
tinued)
Autho
r(year)
Title
Stud
yde
sign
Setting,
treatm
entdu
ratio
nParticipants
(num
ber,sex)
Age
ofpatients
(meanage)
Inclusioncriteria
Interven
tiongrou
pCom
parison
grou
p
-NoclassIIto
classIocclusio
nchange
-Not
sign
ificantlychange
dpo
sterior-transverse
relatio
nships
-Nofixed
appliances
-Goo
d-qu
ality
pre-
andpo
st-
treatm
entceph
alom
etric
radiog
raph
s
Hou
leet
al.[30]
(2016)
Thepred
ictabilityof
transverse
change
swith
Invisalign
Retrospe
ctive
Setting:
Dep
artm
entof
Preven
tiveDen
talScien
ce,
Divisionof
Ortho
dontics,
Scho
olof
Dentistry,University
ofManito
ba-O
rtho
dontic
practiceinAdelaide,Australia
Treatm
entdu
ratio
n:56
weeks
64patients
(23M
,41F)
31.2years
(range18–61
years)
-Age
≥18
years
-Non
-extractiontreatm
ent
with
outanyauxiliariesother
than
Invisalignattachments
Invisalign(n=64)
Initialandfinal
virtual3-D
ClinChe
ck®
mod
els
Ravera
etal.[31]
(2016)
Maxillarymolardistalization
with
aligne
rsin
adult
patie
nts:amulticen
ter
retrospe
ctivestud
y.
Retrospe
ctive
Ortho
donticprivatepractices
locatedin
Torin
o(Italy)and
Vancou
ver(Canada)
Treatm
entdu
ratio
n:24.3±4.2mon
ths
20patients
(9M,11F)
29.73±6.89
years
-Age
≥18
yearsold
-SkeletalclassIo
rIIanda
bilateralend
-to-en
dmolar
relatio
nship
-Normod
iverge
nceon
the
verticalplane
(SN-GoG
nangle<37°)
-Mild
crow
ding
intheup
per
arch
(≤4mm)
-Absen
ceof
mesialrotation
oftheup
per1stmolar
-Standardized
treatm
ent
protocol,
-Goo
dcompliance
(wearin
galigne
rtim
e,≥20
hpe
rday)
-Absen
ceor
previous
extractio
nof
theup
per3rd
molars
-Goo
dqu
ality
radiog
raph
s
Invisalign(n=20)
Nocontrol
grou
p
Dun
canet
al.[32]
(2015)
Chang
esin
mandibu
lar
incisorpo
sitio
nandarch
form
resulting
from
Invisaligncorrectio
nof
thecrow
dedde
ntition
treatedno
nextraction
Retrospe
ctive
Sing
leorthod
ontic
practice
Treatm
entdu
ratio
n:1stgrou
p,53.6±21.1weeks;
2ndgrou
p,63.7±20.7weeks;
3rdgrou
p:71.7±16.3weeks
61patients
(17M
,44F)
Adu
ltpatients
(age
n/a)
-Non
extractio
ncaseswith
orwith
outIPR
3interven
tiongrou
psaccordingto
pre-
treatm
entcrow
ding
oflower
dentition
(Carey’sanalysis):(a)
20mild
(2.0–3.9mm),
(b)22
mod
erate
(4.0–5.9mm),and(c)
19severe
(>6.0mm)cases
The3grou
pswerecompared
toeach
other
Papadimitriou et al. Progress in Orthodontics (2018) 19:37 Page 8 of 24
Table
1Anoverview
oftheinclud
edstud
iesprovidinginform
ationon
theexpe
rimen
tald
esigns
andsettings
(Con
tinued)
Autho
r(year)
Title
Stud
yde
sign
Setting,
treatm
entdu
ratio
nParticipants
(num
ber,sex)
Age
ofpatients
(meanage)
Inclusioncriteria
Interven
tiongrou
pCom
parison
grou
p
Grünh
eid
etal.[33]
(2015)
Effect
ofclearaligne
rtherapyon
thebuccolingual
inclinationofmandibular
caninesandtheintercanine
distance
Retrospe
ctive
University
ofMinne
sota
Meantreatm
entdu
ratio
n:Invisaligngrou
p,13.4±6.8mon
ths;fixed
appliancegrou
p:20.2±5.3mon
ths
60patients(30
ineach
grou
p;8M
,22F)
Invisaligngrou
p:25
±11.8years;
fixed
appliance
grou
p:26.3±13.5years
-Fully
erup
tedpe
rmanen
tde
ntition
includ
ingincisors,
canine
s,prem
olars,and1st
molars
-Ang
leclassIm
alocclusion
with
norm
alinterarchmolar
relatio
n-Nope
riodo
ntalattachmen
tloss
-Non
-extractionorthod
ontic
treatm
ent
-Pre-
andpo
sttreatm
entfull-
field
ofview
CBC
Tscans
-Bo
thmandibu
larcanine
sclearly
visiblein
theCBC
Tscans
Invisalign(n=30)
Fixed
appliances
(n=30)
Simon
etal.[34]
(2014)
Treatm
entou
tcom
eand
efficacyof
analigne
rtechniqu
e–regarding
incisortorque,p
remolar
derotatio
nandmolar
distalization
Retrospe
ctive
Privateorthod
ontic
practice
inColog
ne,G
ermany
Treatm
entdu
ratio
n:n/a
30patients
(11M
,19F)
initially,b
ut4
drop
pedou
t(n=26)
32.9±16.3years
Range13–72years
-Health
ypatients
-1of
the3followingtooth
movem
entsrequ
ired:
(1)Upp
ermed
ialincisor
torque
>10°
(2)Prem
olar
derotatio
n>10°
(3)Molar
distalizationof
anup
permolar
>1.5mm
3Invisaligngrou
ps:
(a)Incisortorque
>10°
(b)Prem
olar
derotatio
n>
10°
(c)Molar
distalization>
1.5mm.
Thegrou
pswere
subd
ivided
:inthe1st
subg
roup
,movem
ents
weresupp
ortedwith
anattachmen
t,whilein
the
2ndsubg
roup
noauxiliarieswereused
(excep
tincisortorque,in
which
Power
Ridg
eswere
used
)
Initialandfinal
virtual3-D
ClinChe
ck®
mod
els
Kriege
ret
al.[35]
(2012)
Invisalign®
treatm
entin
theanterio
rregion
.Were
thepred
ictedtooth
movem
entsachieved
?
Retrospe
ctive
Settingandtreatm
ent
duratio
n:no
trepo
rted
50patients
(16M
,34F)
33±11.2years
Fron
talM
xand/or
Mn
crow
ding
accordingto
Little’sinde
xof
irreg
ularity
Invisalign(n=50)
Initialandfinal
virtual3-D
ClinChe
ck®
mod
els
Kriege
ret
al.[36]
(2011)
Accuracyof
Invisalign®
treatm
entsin
theanterio
rtoothregion
.Firstresults
Retrospe
ctive
Settingandtreatm
ent
duratio
n:n/a
35patients
(11M
,24F)
33(rang
e15–59)
years
-Ortho
dontictreatm
ent
exclusivelywith
Invisalign
-Con
secutivepo
st-treatmen
tmod
elsandpatient
documen
tatio
n-Presen
ceof
low-m
oderate
Mxand/or
Mncrow
ding
Ortho
dontictreatm
ent
exclusivelywith
Invisalign
(n=35)
Initialandfinal
virtual3-D
ClinChe
ck®
mod
els
Papadimitriou et al. Progress in Orthodontics (2018) 19:37 Page 9 of 24
Table
1Anoverview
oftheinclud
edstud
iesprovidinginform
ationon
theexpe
rimen
tald
esigns
andsettings
(Con
tinued)
Autho
r(year)
Title
Stud
yde
sign
Setting,
treatm
entdu
ratio
nParticipants
(num
ber,sex)
Age
ofpatients
(meanage)
Inclusioncriteria
Interven
tiongrou
pCom
parison
grou
p
Kuncio
etal.[37]
(2007)
Invisalignandtradition
alorthod
ontic
treatm
ent
postretentionou
tcom
escomparedusingthe
American
Boardof
Ortho
donticsObjective
Grading
System
Retrospe
ctive
Privatepracticein
New
York
City
Treatm
entdu
ratio
n:Invisaligngrou
p,1.7±0.8years;fixed
appliancegrou
p:2.3±0.8years
22patients
(11in
each
grou
p;1M
,10F)
34yearsin
the
Invisaligngrou
p26
yearsin
the
fixed
applaince
grou
p
Non
-extractioncases
Invisalign(n=11)
Fixed
appliances
(n=11)
Djeuet
al.
[38]
(2005)
Outcomeassessmen
tof
Invisalignandtradition
alorthod
ontic
treatm
ent
comparedwith
the
American
Boardof
Ortho
donticsob
jective
gradingsystem
Retrospe
ctive
Privatepracticein
New
York
City
Treatm
entdu
ratio
n:1.4years
fortheInvisalign®
grou
p;1.7yearsforthefixed
appliancegrou
p
96patients
(gen
dern/a)
Invisalign®:33.6
±11.8years
Fixedappliances:
23.7±11.0years
Non
-extractioncases
Invisalign(n=48)
Fixed
appliances
(n=48)
Mmale,
Ffemale,
m.a
meanag
e,Mxmaxillary,Mnman
dibu
lar,IPRinterproximal
redu
ction,
CBCT
cone
-beam
compu
tedtomog
raph
y,n/ano
tavailable
Papadimitriou et al. Progress in Orthodontics (2018) 19:37 Page 10 of 24
Table
2Overview
oftheresults,outcomes,and
conclusion
sof
theinclud
edstud
ies
Autho
r,year,
design
Title
Subject
grou
pOutcomeassessed
Metho
dof
outcom
eassessmen
tResults
Con
clusions
Hen
nessyet
al.
[18]
(2016)
RCT
Arand
omized
clinical
trialcomparingmandibular
incisorproclination
prod
uced
byfixed
labial
appliances
andclear
aligne
rs
Invisalign
vs.fixed
appliances
Mandibu
larincisorproclination
prod
uced
byfixed
appliances
and
Invisalign®
aligne
rswhe
ntreatin
gpatientswith
mild
mandibu
lar
crow
ding
Com
parison
ofpre-treatm
ent
andne
ar-end
treatm
entlateral
ceph
alog
rams;themainou
tcom
ewas
theceph
alom
etric
change
inmandibu
larincisorinclinationto
themandibu
larplaneat
theen
dof
treatm
ent
-Mnincisorproclination:
fixed
appliances,5.3±4.3°;
Invisalign®:3.4±3.2°
(P>0.05)
Nodifferencein
theam
ount
ofMnincisorp
roclinationprod
uced
byInvisalign®
andfixed
labial
appliances
inmild
crow
ding
cases
Liet
al.[19]
(2015)
RCT
Theeffectiven
essof
the
Invisalignappliancein
extractio
ncasesusing
thetheABO
mod
elgradingsystem
:amulticen
terrand
omized
controlledtrial
Invisalign
vs.fixed
appliances
Treatm
entou
tcom
esof
the
Invisalign®
system
bycomparin
gtheresults
ofInvisalign®
treatm
entwith
that
offixed
appliances
inclassIadu
ltextractio
ncases
TheDIw
asused
toanalyze
pretreatmen
trecords(study
casts
andlateralcep
halogram
s)to
controlfor
initialseverityof
malocclusion.TheABO
-OGSwas
used
tosystem
aticallygradebo
thpre-
andpo
st-treatmen
trecords
-Im
proved
totalm
eanscores
oftheOGScatego
riesafter
treatm
entforbo
thgrou
psin
term
sof
alignm
ent,marginal
ridge
s,occlusalrelatio
ns,overjet,
inter-proxim
alcontacts,and
root
angu
latio
n-Invisalign®
scores
weresig
nificantly
lower
than
fixed
appliance
scores
forb-linclinationand
occlusalcontacts
-Invisalign®
hadlong
ertreatm
ent
duratio
n(31.5mon
ths)
comparedto
fixed
appliances
(22mon
ths)
Both
Invisalign®
andfixed
appliances
weresuccessful
intreatin
gclassIadu
ltextractio
ncases,thou
ghInvisalign®
requ
iredmoretim
eandshow
edworse
perfo
rmance
incertain
fields
Bollenet
al.[20]
(2003)
RCT
Activationtim
eand
materialstiffnessof
sequ
entialrem
ovable
orthod
ontic
appliances.
Part1:Abilityto
completetreatm
ent
Invisalign
grou
psEffectsof
activationtim
eand
materialstiffnesson
theability
tocompletetheinitialseriesof
aligne
rs,d
esigne
dto
fully
correct
each
subject’s
malocclusion
InitialPA
Rscores
calculation,
clinicalevaluatio
nandorthod
ontic
records(progressstud
ymod
els
andph
otog
raph
s)every4mon
ths
-15/51completed
theinitial
regimen
ofaligne
rs-2weeks
activationintervalmore
likelyto
lead
tocompletionthan
1week(37%
vs21%)
-Nosubstantiald
ifferen
ces
betw
eensoft-andhard
appliancein
completionrate
(27%
vs32%)
-Highe
stcompletionrate
(46%
)forno
n-extractio
nandinitial
PARscore<15
-Lowestcompletionrate
(0%)in
patientswith
≥2extractio
ns
Greater
likelihoo
dfor
completionof
theinitialsetof
aligne
rsforsubjectswith
ano
n-extractio
n,2weeks
activation
regimen
andlow
initialPA
Rscores
Solano
-Men
doza
etal.[21](2016)
Prospe
ct.
How
effectiveisthe
Invisalign®
system
inexpansionmovem
ent
with
Ex30′aligne
rs?
Accuracy
Ane
wmetho
dformeasurin
gthe
predictabilityof
expansionob
tained
byInvisalign®
treatmentand
differences
betweenthepredicted
(ClinCh
eck®
mod
els)andactual
expansionattheendof
treatment
InitialandfinalClinChe
ck®virtual
modelsmeasuredwith
ToothM
easure®
compa
redto
initialandfin
alactual3D
mod
elsmeasuredwith
Nem
oCast®
forevaluatio
nof
the
followingvariables:canineging
ival
width,1stprem
olarging
ivalwidth,
2ndprem
olarging
ivalwidth,1st
molarging
ivalwidth,canine
cuspidwidth,1stprem
olarcuspid
width,2nd
prem
olarcuspidwidth,
1stmolarcuspidwidth,canine
-Non
-significantdifferences
be-
tweentheinitial3D
mod
elsand
ClinChe
ck®forallvariables
ex-
cept
for1stmolar
cuspid
width
andarch
depth
-Statisticallysign
ificant
differences
betw
eenthefinal3D
andClinChe
ck®mod
elsfor
canine
ging
ivalwidth,1st
prem
olar
ging
ivalwidth,2nd
prem
olar
ging
ivalwidth,1st
molar
ging
ivalwidth,canine
-Differen
cesbe
tweenthefinal
3DandClinChe
ck®mod
els
show
edthat
planne
dexpansionat
theen
dof
treatm
entisno
tpred
ictable
Papadimitriou et al. Progress in Orthodontics (2018) 19:37 Page 11 of 24
Table
2Overview
oftheresults,outcomes,and
conclusion
sof
theinclud
edstud
ies(Con
tinued)
Autho
r,year,
design
Title
Subject
grou
pOutcomeassessed
Metho
dof
outcom
eassessmen
tResults
Con
clusions
depth,arch
depth,1stmolar
rotatio
n,1strig
htandleftmolar
rotatio
n,and1stmolarinclination
cuspidwidth,1stprem
olarcuspid
width,2nd
prem
olarcuspid
width,1stmolarcuspidwidth
Buschang
etal.
[26]
(2015)
Prospe
ct.
Predictedandactualend-
of-treatm
ento
cclusio
nprod
uced
with
aligner
therapy
Accuracy
Differen
cesbe
tweenfinalactual
mod
elsfro
mthefinalvirtual
ClinChe
ck®mod
elsafter
treatm
entwith
Invisalign
FinalC
linChe
ck®virtualm
odels
comparedto
finalactual3D
mod
elsmeasuredwith
MeshLab
V1.30softwareforevaluatio
nof
theAmerican
Boardof
Ortho
dontics(ABO
)Objective
Grading
System
(OGS)
FinalvirtualC
linChe
ckmod
els
show
edsign
ificantlyfewer
overall
OGSpo
intde
ductions
compared
tofinalactualmod
els(15vs
24).
Differen
cesweremainlyob
served
inalignm
ent(1
vs4de
ductions),
buccolingu
alinclinations
(3vs
4de
ductions),occlusalcontacts
(2vs
3de
ductions),andocclusal
relatio
ns(2
vs4de
ductions)
-ThefinalvirtualC
linChe
ckmod
elsdo
notaccurately
reflect
thepatients’final
occlusion,as
measuredby
the
OGS,at
theen
dof
active
treatm
ent
Castroflorio
etal.
[22]
(2013)
Prospe
ct.
Upp
er-IncisorRootC
ontro
lwith
Invisalign®
Appliances
Accuracy
Efficiencyof
AlignTechno
logy’s
Power
Ridg
ein
controlling
theb-l
inclinationof
uppe
rincisors
ClinChe
ck®initialandfinalvirtual
setups
foreach
uppe
rincisor
from
therig
htandleftde
fault
view
scomparedto
measuremen
tson
3D-scans
ofactualde
ntalmod
els
-Meantorque
values
forthe9
uppe
rincisorsat
T0:20.9°
onthevirtualsetup
sand21.1°on
thescanne
dcasts
-AtT1,the
torque
values
were
10.5°and10.5°,respectively,and
represen
tedthetorque
prescriptio
n(10.4°)
-Invisalign®
controlswellthe
uppe
r-incisorroot
torque,
whe
natorque
correctio
nof
abou
t10°isrequ
ired
Pavoni
etal.[23]
(2011)
Prospe
ct.
Self-ligatingversus
Invisalign:analysisof
dento-alveolar
effects
Invisalign
vs.fixed
appliances
Dentoalveolar
effectsoftheInvisalign®
system
andof
self-ligating
bracketstreatm
entin
relatio
nto
transverse
dimen
sion
,arch
perim
eter
andarch
depthon
Mx
jaw
Measuremen
tson
pre-
andpo
st-
treatm
entmaxillaryde
ntalcasts
(intercanine-,interprem
olar-,and
interm
olar
width,archde
pth,and
arch
perim
eter)
-Nosign
ificant
differences
intreatm
entdu
ratio
n.-Sign
ificant
differences
betw
een
the2grou
pswith
self-ligating
causingfurthe
rincreasesin
the
followingvariables
ascompared
toInvisalign:intercaninewidth
(cusp),2.6mm;firstprem
olar
width
(fossa),3.3mm;first
prem
olar
width
(gingiva),
2.3mm;secon
dprem
olar
width
(fossa),2.0mm;secon
dprem
olar
width
(gingiva),
1.8mm;archpe
rimeter,1.3mm
-Class
Imild
crow
ding
canbe
treatedby
Invisalign®
and
self-ligatingbracketsat
the
sametreatm
entdu
ratio
n-Invisalign®
caneasilytip
crow
nsbu
tno
troots
Kravitz
etal.[5]
(2009)
Prospe
ct.
How
welld
oesInvisalign
work?Aprospective
clinical
stud
yevaluatin
gthe
efficacyof
tooth
movem
entw
ithInvisalign
Accuracy
Differen
cesbe
tweenactual
mod
elsandvirtualC
linChe
ck®
mod
elsin
theanterio
rteeth,after
treatm
entwith
Invisalign
DIscores(overjet,overbite,
anterio
rop
enbite,and
crow
ding
)usingamod
ified
ABO
-OGSon
pretreatmen
tdigitalm
odels.
Supe
rimpo
sitio
nof
virtualm
odels
ofthepred
ictedtoothpo
sitio
nover
theachieved
toothpo
sitio
n(Too
thMeasure®).C
omparison
betweenthepredictedandachieved
amou
ntof
toothmovem
ent
(i.e.,expa
nsion,
constrictio
n,intrusion,
extrusion,
mesiodistal
-Invisalign®
meanaccuracy
oftoothmovem
ent,41%
-Mostaccurate
movem
ent:
lingu
alconstrictio
n(47.1%
),least
accurate
movem
ent:extrusion
(29.6%
;18.3%
forMxand24.5%
forMncentralincisors),followed
bymesio-distaltipping
ofthe
Mncanine
s(26.9%
)-Caninerotatio
nsign
ificantlyless
accurate
than
that
ofallo
ther
teeth,except
forthat
oftheMx
-Further
research
isne
eded
toun
derstand
theefficacyand
biom
echanics
oftheInvisalign®
system
-Prescrip
tionby
clinicians
shou
ldbe
madebasedon
thepatient’s
treatm
entne
eds,whiletaking
into
accoun
tthelim
itatio
nsof
theappliance
Papadimitriou et al. Progress in Orthodontics (2018) 19:37 Page 12 of 24
Table
2Overview
oftheresults,outcomes,and
conclusion
sof
theinclud
edstud
ies(Con
tinued)
Autho
r,year,
design
Title
Subject
grou
pOutcomeassessed
Metho
dof
outcom
eassessmen
tResults
Con
clusions
tip,labiolingu
altip
,and
rotatio
n).
Accuracy(%
)=[(|pred
icted-
achieved
|/|predicted
|)100%
]
lateralincisors,espe
ciallyat
rotatio
nalm
ovem
ents>15°.
-Ling
ualcrowntip
sign
ificantly
moreaccurate
than
labialcrow
ntip
-Nostatisticaldifferencein
accuracy
betw
eenMxandMn
foranymovem
enton
any
specifictooth
Kravitz
etal.[24]
(2008)
Prospe
ct.
Influen
ceof
attachmen
tsandinterproximal
redu
ctionon
the
accuracy
ofcanine
rotatio
nwith
Invisalign
Accuracy
Influen
ceof
attachmen
tsandIPR
oncanine
sun
dergoing
rotatio
nal
movem
entwith
Invisalign®
ToothMeasure®to
compare
the
amou
ntof
canine
rotatio
nspred
ictedwith
theon
esachieved
(inde
grees).A
ccuracy(%)
=[(|pred
icted-achieved
|/|predicted
|)100%
]
-Invisalign®
meanaccuracy
ofcanine
rotatio
nwas
35.8±26.3%
-Nostatisticallysign
ificant
differencein
accuracy
betw
een
the3grou
ps-Nostatisticallysign
ificant
differencein
rotatio
nalaccuracy
forMxandMncanine
sforany
ofthe3grou
ps-Thevertical-ellipsoidwas
the
mostcommon
lyprescribed
at-
tachmen
tshape(70.5%
)
Theeffectiven
essof
the
Invisalign®
system
incanine
derotatio
nislim
itedandno
tsign
ificantlyim
proved
byvertical-ellipsoidattachmen
tsandIPR
Baldwin
etal.
[27]
(2008)
Prospe
ct.
Activationtim
eand
materialstiffnessof
sequ
entialrem
ovable
orthod
ontic
appliances.
Part3:Prem
olar
extractio
npatients
Invisalign
only
Tipp
ingof
teethadjacent
toprem
olar
extractio
nspaces
durin
gspaceclosurewith
aligne
rappliances
Den
talcastsandpano
ramic
radiog
raph
spre-treatm
entandat
theen
dof
Invisaligntreatm
ent
(poten
tially
continuedwith
fixed
appliances)
-Duringtreatm
ent,theaverage
radiog
raph
icchange
sin
interden
talang
lewere21.5°
(P<0.0001;n
=10)in
the
mandibleand16.3°(P<0.0001;
n=19)in
themaxilla.Onthe
mod
els,theaveragechange
swere20.8°(P<0.0001;n
=12)in
themandibleand15.9°(P<
0.0001;n
=20)in
themaxilla
-Nosubjectcompleted
theinitial
seriesof
aligne
rsandon
ly1
ultim
atelycompleted
treatm
ent
with
aligne
rs-Theaveragetim
ein
theinitial
seriesof
aligne
rsbe
fore
failure
was
7(rang
e,1–17)mon
thsand
theaveragetotaltim
ein
aligne
rs16.6(rang
e,6–28)
mon
ths(treatmen
tcontinued
with
fixed
appliances)
-In
prem
olar
extractio
npatients
treatedwith
Invisalign,
sign
ificant
dentaltip
ping
occurs(it
canbe
corrected
with
fixed
appliances)
-Thereisatren
dforgreater
tipping
ofmandibu
larteeth
into
theextractio
nspaceand
arou
ndsecond
prem
olar
extractio
nsitesdu
ring
treatm
entwith
aligne
rs
Vlaskalic
and
Boyd
[25]
(2002)
Prospe
ct.
Clinicalevolutionof
the
Invisalign®
appliance
Invisalign
grou
psClinicalevaluationof
theInvisalign®
system
basedon
afeasibilitystud
ycond
uctedintheUniversity
ofthe
Pacific
in1997
Pre-,p
rogress-,and
post-
treatm
entrecordsinclud
ing
pano
ramicandlateralcephalo
metric
radiog
raph
s,de
ntalcasts,intra-,
andextraoralp
hotograp
hs.
Group
1:aligne
rsne
edto
bewornforat
least10
days
each,
patientstolerate
aligne
rswell,
posteriorop
enbite
occursin
somepatients,overcorrectio
nof
toothpo
sitio
nisne
cessaryin
-The
Invisalignsystem
isaviable
alternativeto
conven
tionalfixed
andremovableappliances
-Patientsin
thepe
rmanen
tde
ntition
with
mild
tomod
eratemalocclusions
may
Papadimitriou et al. Progress in Orthodontics (2018) 19:37 Page 13 of 24
Table
2Overview
oftheresults,outcomes,and
conclusion
sof
theinclud
edstud
ies(Con
tinued)
Autho
r,year,
design
Title
Subject
grou
pOutcomeassessed
Metho
dof
outcom
eassessmen
tResults
Con
clusions
initial3-Dsetup
Group
2:attachmentsarenecessary
forrotations
ofcylindricalshaped
teeth,intru
sion,extru
sion,bo
dily
toothmovem
ent,extractionof
teethispo
ssible
Group
3:long
vertical
attachmen
tsarene
cessaryfro
mthestartof
treatm
entto
maintain
adeq
uate
root
controlin
extractio
ncases,virtualtoo
thpo
nticsystem
isestheticallyand
mechanically
advantageo
us
begreatly
bene
fited
whe
ntreatm
entisplanne
dcarefully
-Furthe
rinvestigationisne
eded
fortheultim
ateclinical
potentialo
fInvisalign®
Guet
al.[28]
(2017)
Retrosp.
Evaluatio
nof
Invisalign
treatm
enteffectiven
ess
andefficiencycompared
with
conven
tionalfixed
appliances
usingthePeer
Assessm
entRatin
gindex
Invisalign
vs.fixed
appliances
Effectiven
essandefficiencyof
the
Invisalignsystem
comparedwith
conven
tionalfixed
appliances
inmild
tomod
eratemalocclusions
Com
parison
betw
eenpatients
treatedwith
Invisalign®
andfixed
appliances
assessingpo
st-
treatm
entPA
Rscores,p
ost-
treatm
entredu
ctionin
PAR
scores,treatmen
tdu
ratio
n,and
malocclusionim
provem
ent
-Average
pretreatmen
tPA
Rscores:20.81
forInvisalignand
22.79forfixed
appliances
(NS)
-Not
statisticallydifferent
posttreatm
entPA
Rscores
and
PARscoreredu
ctionbe
tween
the2grou
ps.
-Invisalign®
patientsfinishe
d5.7mon
thsfaster
than
those
with
fixed
appliances
(P=0.0040).
-Allpatientsin
both
grou
pshad
>30%
redu
ctionin
PARscores.
-Odd
sof
achieving“great
improvem
ent”in
theInvisalign®
grou
pwere0.33
times
greater
than
thosein
thefixed
appliances
grou
pafter
controlling
forage(P=0.015)
-Bo
thInvisalign®
andfixed
appliances
areableto
improve
mild
tomod
erate
malocclusion
-Fixedappliances
weremore
effectivethan
Invisalignin
providinggreater
improvem
ents
-Treatm
entwith
Invisalignwas
finishe
don
average30%
(5.7mon
ths)faster
than
treatm
entwith
fixed
appliances.
Khosraviet
al.
[29]
(2017)
Retrosp.
Managem
entof
overbite
with
theInvisalign
applian
ceInvisalign
grou
psVerticaldimen
sion
change
sin
patientswith
various
pre-treatm
ent
overbite
relatio
nships
treatedon
lywith
Invisalignandotherd
ental
andskeletalchanges
Pre-
andpo
st-treatmen
tlateral
ceph
alom
etric
radiog
raph
s;ceph
alom
etric
analyses
byDolph
inImaging,Ch
atsw
orth,Calif
-Deepbite
patientshada
med
ianoverbite
open
ingof
1.5mm,w
hereas
theop
enbite
patientshadamed
ian
deep
eningof
1.5mm.The
med
ianchange
fortheno
rmal
overbite
patientswas
0.3mm
-Chang
esin
incisorpo
sitio
nwere
respon
sibleformostof
the
improvem
entsin
thede
epbite
andop
enbite
grou
ps-Minim
alchange
sin
molar
verticalpo
sitio
nandmandibu
lar
planeangle
-Invisalignisrelatively
successful
inmanaging
overbite
-Overbite
ismaintaine
din
patientswith
norm
aloverbite
-Deepbite
improvem
ent
prim
arily
byproclinationof
Mn
incisors
-Invisaligncorrectsmild
tomod
erateanterio
rop
enbites,
prim
arily
throug
hincisor
extrusion
Papadimitriou et al. Progress in Orthodontics (2018) 19:37 Page 14 of 24
Table
2Overview
oftheresults,outcomes,and
conclusion
sof
theinclud
edstud
ies(Con
tinued)
Autho
r,year,
design
Title
Subject
grou
pOutcomeassessed
Metho
dof
outcom
eassessmen
tResults
Con
clusions
Hou
leet
al.[30]
(2016)
Retrosp.
Thepred
ictabilityof
transverse
change
swith
Invisalign
Accuracy
Differen
cesbe
tweentheinitial
andfinalactualmod
elsfro
mthe
initialandfinalvirtualC
linChe
ck®
modelsaftertreatmentw
ithInvisalign,
whenplanning
transverse
changes
-Com
parison
betw
eenpre-
and
posttreatm
entdigitalm
odels,
(created
from
aniTeroscan)and
digitalm
odelsfro
mClincheck®
(AlignTechno
logy)
-Digitalm
odelsweremeasured
with
Geo
magicQualify
-In
theMx,whe
nde
ntoalveo
lar
expansionwas
planne
dwith
Invisalign®,the
rewas
amean
accuracy
of72.8%:82.9%
atthe
cusp
tipsand62.7%
atthe
ging
ivalmargins,w
ithpredictio
nworsening
towardthepo
sterior
region
ofthearch
-FortheMnarch,the
rewas
anoverallaccuracyof
87.7%:98.9%
forthecusp
tipsand76.4%
for
theging
ivalmargins
-Varianceratio
sforup
perand
lower
arches
weresign
ificantly
different
(P<0.05)
-Clincheck®
pred
ictio
nof
expansioninvolves
more
bodilymovem
entof
theteeth
than
that
achieved
clinically.
Morede
ntaltip
ping
was
observed
-Careful
planning
with
overcorrectio
nandothe
rauxiliary
metho
dsof
expansion
may
help
redu
cetherate
ofmidcourse
correctio
nsand
refinem
ents,especially
inthe
posteriorregion
oftheMx
Ravera
etal.[31]
(2016)
Retrosp.
Maxillarymolardistalization
with
aligne
rsin
adult
patie
nts:a
multicen
ter
retrospe
ctivestud
y
Invisalign
grou
pDentoalveolarandskeletalchanges
followingmaxillarymolardistalization
therap
ywith
Invisalignin
adult
patie
nts
Pre-
andpo
st-treatmen
tlateral
ceph
alom
etric
radiog
raph
s-Distalm
ovem
entof
the1st
molar:2.25mm
with
out
sign
ificant
tipping
andvertical
movem
ents
-Distalm
ovem
entof
the2n
dmolar:2.52mm
with
out
sign
ificant
tipping
(P=0.056)
andverticalmovem
ents
-Nosign
ificant
movem
entson
thelower
arch.
-SN
-GoG
nandSPP-GoG
nangles
show
edno
significantdifferences
betweenpre-
andpo
st-treatment
ceph
alog
rams
-Invisalignaligne
rsareeffective
indistalizingMxmolarsin
selected
end-to-end
classII
non-grow
ingsubjectswith
out
sign
ificant
verticalandmesio-
distaltip
ping
movem
ents
-Nochange
sto
thefacial
height
Dun
canet
al.
[32]
(2015)
Retrosp.
Chang
esin
mandibu
lar
incisorpo
sitio
nandarch
form
resulting
from
Invisaligncorrectio
nof
thecrow
dedde
ntition
treatedno
nextraction
Invisalign
grou
psTreatmentoutcomesinnon-extraction
caseswith
loweranteriorcrowding
treated
with
Invisalign®
-Pre-andpo
st-treatmen
trecords
(digitalstudy
mod
elsandlateral
ceph
alom
etric
radiog
raph
s)-Cep
halometric
analysisto
determ
inelower
incisorchange
s-IPRandchange
sin
arch
width
werealso
measured
-In
thesevere
crow
ding
grou
p,therewerestatistically
sign
ificant
change
sin
lower
incisorpo
sitio
nandangu
latio
n-Nosign
ificant
differences
inlower
incisorpo
sitio
nand
angu
latio
nin
thethemild
and
mod
eratecrow
ding
grou
ps-Statisticallysign
ificant
increase
inbu
ccalexpansionin
allthree
grou
ps.
-Nochange
inthelower
incisor
positio
nor
angu
latio
nin
mild
tomod
eratelower
anterio
rcrow
ding
cases
-Inno
n-extractio
nsevere
crow
d-ingcases(>
6mm),thelower
incisorstend
toproclineand
protrude
-BuccalarchexpansionandIPR
areim
portantfactorsin
crow
ding
resolutio
n-In
tercanine,interpremolar,and
interm
olar
widthsdo
notdiffer
amon
gthethreegrou
psat
post-treatmen
t
Grünh
eidet
al.
[33]
(2015)
Retrosp.
Effect
ofclearaligne
rtherapyon
the
buccolingu
alinclination
ofmandibu
larcanine
s
Invisalign
vs.fixed
appliances
Treatm
entchang
esinb-linclination
ofMncaninesandintercaninedis-
tancebetweenpatientstreated
with
Invisalign®
andconventional
Pre-
andpo
st-treatmen
tCBC
Ts-Nosign
ificant
pre-treatm
ent
differencebe
tweenthegrou
psregardingtheb-linclinationof
Mncanine
sandintercanine
Invisalignseem
sto
increase
the
Mnintercaninedistance
with
little
increase
inb-linclination
comparedto
fixed
appliances
Papadimitriou et al. Progress in Orthodontics (2018) 19:37 Page 15 of 24
Table
2Overview
oftheresults,outcomes,and
conclusion
sof
theinclud
edstud
ies(Con
tinued)
Autho
r,year,
design
Title
Subject
grou
pOutcomeassessed
Metho
dof
outcom
eassessmen
tResults
Con
clusions
andtheintercanine
distance
fixed
appliances
distance
-Po
sitivepre-
andpo
st-treatmen
tb-linclinations
ofMncanine
s(i.e.,theircrow
nswerepo
sitioned
buccalto
theirroo
ts)for
both
grou
ps-Significantlygreaterp
ost-treatment
b-linclinationintheInvisalign
group
-Sign
ificantlyincreased
intercaninedistance
inthe
aligne
rgrou
pat
theen
dof
treatm
ent
Simon
etal.[34]
(2014)
Retrosp.
Treatm
entou
tcom
eand
efficacyof
analigne
rtechniqu
e–regarding
incisortorque,p
remolar
derotatio
nandmolar
distalization
Accuracy
Treatm
entefficacyof
Invisalign®
aligne
rsforthefollowing3
pred
etermined
toothmovem
ents:
incisortorque
>10°,prem
olar
derotatio
n>10°,andmolar
distalization>1.5mm
-Com
parison
betw
eenthe
pred
ictedam
ount
oftooth
movem
entby
ClinChe
ck®and
theam
ount
achieved
after
treatm
ent
-Evaluatio
nof
theinfluen
ceof
auxiliaries(attachm
ents/Pow
erRidg
e),the
staging(m
ovem
ent/
aligne
r),andthepatient’s
compliancewith
treatm
ent
-Overallmeanefficacy:59
±0.2%
-Meanaccuracy
forup
perincisor
torque:42±0.2%
-Prem
olar
derotatio
nshow
edthe
lowestaccuracy
ofapproxim
ately40
±0.3%
-Distalizationof
anup
permolar
was
themosteffective
movem
ent,with
efficacy
approxim
ately87
±0.2%
-Bo
dilytoothmovem
ent(m
olar
distalization)
canbe
effectively
perfo
rmed
usingInvisalign®
aligne
rs-Prem
olar
derotatio
nsign
ificantlyde
pend
son
velocity
andtotalamou
ntof
planed
toothmovem
ent
-Forup
perincisortorque
and
prem
olar
derotatio
n,overcorrectio
ns/case
refinem
entsmay
bene
eded
Kriege
ret
al.[35]
(2012)
Retrosp.
Invisalign®
treatm
entin
theanterio
rregion
.Werethepred
icted
toothmovem
ents
achieved
?
Accuracy
Differen
cesin
theanterio
rregion
betw
eentheinitialandfinal
actualmod
elsfro
mtheinitialand
finalvirtualC
linChe
ck®mod
els
aftertreatm
entwith
Invisalign
-Electron
icdigitalcaliper
for
measuremen
tsin
casts
-Evaluatedparameters:up
per/
lower
anterio
rarch
leng
thand
intercaninedistance,overjet,
overbite,d
entalm
idlineshift,
andLittle’sirreg
ularity
inde
x-ClinChe
ck®was
measuredwith
ToothM
easure®
-Mxanterio
rcrow
ding
:initial,5.4
(rang
e1.5–14.5)mm;final,1.6
(rang
e0.0–4.5)
mm
-Mnanterio
rcrow
ding
:initial,6.0
(rang
e2.0–11.5)mm;final,0.8
(rang
e0.0–2.5)
mm
-Slight
deviations
betw
eenthe
initialactualandvirtual
ClinChe
ck®mod
elsin
overjet
(−0.1±0.3mm),up
peranterio
rarch
leng
th(−
0.3±0.5mm),
lower
anterio
rarch
leng
th(0.0±0.5mm),andin
overbite
(0.7±0.9mm)
-Mod
erateto
severe
anterio
rcrow
ding
canbe
successfully
correctedwith
Invisalign®
-Wellp
redictableresolutio
nof
lower
anterio
rcrow
ding
isachieved
byprotrusion
ofanterio
rteeth(i.e.,
enlargem
entof
theanterio
rarch
leng
th)
-In
gene
ral,theachieved
tooth
movem
entwas
inaccordance
with
thepred
ictedmovem
ent
forallp
aram
eters,except
for
overbite
Kriege
ret
al.[36]
(2011)
Retrosp.
Accuracyof
Invisalign®
treatm
entsin
the
anterio
rtoothregion
.Firstresults
Accuracy
Differen
cesbe
tweentheinitial
andfinalactualmod
elsfro
mthe
initialandfinalvirtualC
linChe
ck®
mod
elsaftertreatm
entwith
Invisalign
-Electron
icde
ntalcaliper
tomeasure
pre-
andpo
st-
treatm
entmod
els
-ToothM
easure®to
measure
the
ClinChe
ck®
-Exam
ined
parameters:overjet,
overbite,and
dentalmidline
shift
-Slight
deviations
inoverjet
(0.1±0.3mm),overbite
(0.3±0.4mm),andde
ntal
midlinede
viation(0.1±0.4mm)
betw
eeninitialactualandvirtual
mod
els
-Larger
deviations
inoverjet
(0.4±0.7mm),overbite
(0.9±0.9mm),andde
ntal
-Accep
tableaccuracy
ofInvisalign®
techno
logy
durin
gcompu
terized
transfer
ofmalaligne
dteethinto
the
ClinChe
ck®presen
tatio
n.-Toothcorrectio
nsin
the
verticalplaneweremore
difficultto
achieve.
-Overcorrectionin
thefinal
Papadimitriou et al. Progress in Orthodontics (2018) 19:37 Page 16 of 24
Table
2Overview
oftheresults,outcomes,and
conclusion
sof
theinclud
edstud
ies(Con
tinued)
Autho
r,year,
design
Title
Subject
grou
pOutcomeassessed
Metho
dof
outcom
eassessmen
tResults
Con
clusions
midlineshift
(0.4±0.5mm)
betw
eenfinalactualandvirtual
mod
els
ClinChe
ck®,case
refinem
entat
treatm
enten
dor
additio
nal
measures(e.g.,ho
rizon
tal
beveledattachmen
tsor
verticalelastics)aresugg
ested
tomeetindividu
alized
therapeutic
goals,espe
ciallyin
verticalcorrectio
ns
Kuncio
etal.[37]
(2007)
Retrosp.
InvisalignandTradition
alOrtho
donticTreatm
ent
PostretentionOutcomes
comparedusingthe
American
Boardof
Ortho
donticsObjective
Grading
System
Invisalign
vs.fixed
appliances
(retention)
Post-retentio
ntreatm
entou
tcom
esinpatientstreatedwith
Invisalign
andthosetreatedwith
tradition
alfixed
appliances
-ABO
-OGSanalysison
pano
ramic
radiog
raph
sandde
ntalcasts
-Investigated
parameters:total
alignm
ent,Mxanterio
rand
posterioralignm
ent,Mnanterio
randpo
sterioralignm
ent,
marginalridge
s,b-linclination,
occlusalcontacts,occlusalrelations,
overjet,interproximalcontacts,root
angulations
-Evaluatio
nafterappliance
removal(T1)
andat
apo
st-
retention(T2)
(3yearsafter
applianceremoval).
-Efficacyin
retentionin
comparison
toEssixretainer
afterfixed
appliances
-Po
st-reten
tionworsening
oftotalalignm
entandMnanterio
ralignm
entforbo
thgrou
ps-Highe
rpo
st-reten
tionchange
sin
totalalignm
ent(ABO
-OGS
score)
forInvisalignpatients
(−2.9±1.6)
than
patients
treatedwith
fixed
appliances
(−1.4±1.2)
-Po
st-reten
tionworsening
ofMx
anterioralignm
entintheInvisalign
grou
pon
ly.
Greater
relapsein
theInvisalign®
grou
pforthisob
servation
perio
d(app
roximately3years)
forInvisalignthan
forfixed
appliancegrou
p
Djeuet
al.[38]
(2005)
Retrosp.
Outcomeassessmen
tof
Invisalignandtradition
alorthod
ontic
treatm
ent
comparedwith
the
American
Boardof
Ortho
donticsob
jective
gradingsystem
Invisalign
vs.fixed
appliances
Treatm
entou
tcom
eof
Invisalign
comparedto
conven
tionalfixed
appliancetreatm
ent
-Pretreatmen
trecords(den
tal
castsandlateralcep
halogram
s)assessed
with
theDI
(measuremen
ts:overjet,
overbite,anteriorop
enbite,
lateralo
penbite,crowding
,occlusion,lingu
alpo
sterior
crossbite,b
uccalp
osterio
rcrossbite,cep
halometrics,and
othe
r)-Po
sttreatm
entrecords(den
tal
castsandpano
ramic
radiog
raph
s)scored
byABO
-OGS(m
easuremen
ts:alignm
ent,
marginalridge
s,b-linclination,
occlusalcontacts,occlusal
relatio
ns,overjet,interproximal
contacts,roo
tangu
latio
n)
-Lower
OGSpassingrate
for
Invisalign®
(27.1%
)than
that
for
fixed
appliances
-Invisalign®
scores
were
sign
ificantlylower
than
fixed
appliancescores
forb-linclin-
ation,occlusalcontacts,occlusal
relatio
nships,and
overjet(P
<0.05)
-Invisalign®
OGSscores
negativelycorrelated
toinitial
overjet,occlusion,andbu
ccal
posteriorcrossibite
-Treatm
entdu
ratio
non
average
4mon
thsshorterwith
Invisalign®
than
with
fixed
appliances
(P<0.05)
-Treatm
entresults
offixed
appliances
aresupe
riorto
thoseof
Invisalign®
(13OGS
pointson
average)
-Redu
cedability
ofInvisalignto
correctlargeA-P
discrepancies
andocclusalcontacts
Prospect.,prospe
ctive,Retrosp.,retrospective,DId
iscrep
ancy
inde
x,AB
OAmerican
Boardof
Ortho
dontics,OGSObjectiv
eGrading
System
,Mxmaxilla(ormaxillary),M
nman
dible(orman
dibu
lar),N
Sno
tstatisticallysign
ificant,
b-lb
uccolingu
al
Papadimitriou et al. Progress in Orthodontics (2018) 19:37 Page 17 of 24
Table
3Qualityassessmen
tof
theinclud
edRC
Tstud
ies
Autho
r-year
ofpu
blication
Stud
yde
sign
Sequ
ence
gene
ratio
n(selectio
nbias)
Allocatio
nconcealm
ent
(selectio
nbias)
Blinding
ofparticipants
andpe
rson
nel
(perform
ance
bias)
Blinding
ofou
tcom
eassessors(detectio
nbias)
Incompleteou
tcom
edata
(attritionbias)
Selectiverepo
rting
(repo
rtingbias)
Other
sourcesof
bias
Overall
risk
Hen
nessyet
al.
[18]
(2016)
RCT
Aj:Low
risk
Sfj:Alth
ough
not
explicitlystated
,sequ
ence
gene
ratio
nisvery
likelydu
eto
referenceof
rand
ompicking
upof
sealed
opaque
envelope
s
Aj:Low
risk
Sfj:Sealed
opaque,
envelope
s
Aj:Low
risk
Sfj:Incompleteblinding
,bu
tthereview
authors
judg
ethat
theou
tcom
eisno
tlikelyto
beinfluen
cedby
lack
ofblinding
Aj:Low
risk
Sfj:Noblinding
ofou
tcom
eassessmen
t,bu
tthereview
authorsjudg
ethat
theou
tcom
emeasuremen
tisno
tlikelyto
beinfluen
cedby
lack
ofblinding
Aj:Low
risk
Sfj:Missing
outcom
edata
balanced
innu
mbe
rsacross
interven
tiongrou
ps,
with
similarreason
sfor
missing
data
across
grou
ps
Aj:Low
risk
Sfj:Thestud
yprotocol
isavailableandallo
fthestud
y’spre-
specified
outcom
esthat
areof
interestin
thereview
have
been
repo
rted
inthepre-
specified
way
Aj:Low
risk
Sfj:Thestud
yappe
ars
tobe
freeof
othe
rsourcesof
bias
Low
Liet
al.[19]
(2015)
RCT
Aj:Low
risk
Sfj:Use
ofa
compu
terrand
omnu
mbe
rge
nerator
Aj:Low
risk
Sfj:Sequ
entially
numbe
red,
opaque,sealed
envelope
s
Aj:Low
risk
Sfj:Blinding
ensuredand
unlikelythat
the
blinding
couldhave
been
broken
Aj:Low
risk
Sfj:Blinding
ofou
tcom
eassessmen
ten
suredandun
likely
that
theblinding
couldhave
been
broken
Aj:Low
risk
Sfj:Nomissing
outcom
edata
Aj:Low
risk
Sfj:Thestud
yprotocol
isavailableandallo
fthestud
y’spre-
specified
outcom
esthat
areof
interestin
thereview
have
been
repo
rted
inthepre-
specified
way
Aj:Low
risk
Sfj:Thestud
yappe
ars
tobe
freeof
othe
rsourcesof
bias
Low
Bollenet
al.
[20]
(2003)
RCT
Aj:Low
risk
Sfj:Referenceto
arand
omnu
mbe
rlist
Aj:Low
risk
Sfj:Rand
omization
sche
dulebased
onalistof
rand
omnu
mbe
rspe
rform
edby
acalibrated
investigator,
unaw
areof
the
treatm
entplan
Aj:Low
risk
Sfj:Incompleteblinding
,bu
tthereview
authors
judg
ethat
theou
tcom
eisno
tlikelyto
beinfluen
cedby
lack
ofblinding
Aj:Low
risk
Sfj:Noblinding
ofou
tcom
eassessmen
t,bu
tthereview
authorsjudg
ethat
theou
tcom
emeasuremen
tisno
tlikelyto
beinfluen
cedby
lack
ofblinding
Aj:Low
risk
Sfj:Missing
outcom
edata
balanced
innu
mbe
rsacross
interven
tiongrou
ps,
with
similarreason
sfor
missing
data
across
grou
ps
Aj:Low
risk
Sfj:Thestud
yprotocol
isavailableandallo
fthestud
y’spre-
specified
outcom
esthat
areof
interestin
thereview
have
been
repo
rted
inthepre-
specified
way
Aj:Low
risk
Sfj:Thestud
yappe
ars
tobe
freeof
othe
rsourcesof
bias
Low
Aj:au
thors’judg
men
t,Sfjsup
portforjudg
men
t
Papadimitriou et al. Progress in Orthodontics (2018) 19:37 Page 18 of 24
include any diagnostic reliability and reproducibility tests(Table 4).
Qualitative synthesis of the included studiesStudy settingsAn overview of the experimental design of the includedstudies is presented in Table 1. Eight studies [5, 21, 22,24, 30, 34–36] used patients’ virtual ClinCheck® modelsof the predicted tooth movement as control group,aided by ToothMeasure® [5, 21, 22, 24, 34–36] or Geo-magic Qualify [30], in order to investigate the treat-ment’s efficacy. More specifically, the extent that the
initial and final actual models were different from theinitial and final virtual models after treatment was eval-uated. However, two of them had similar samples andoutcomes with two other studies, namely [5] with [24,35] with [36]. We decided not to exclude any of thesestudies, since additional information was provided.Seven studies [18, 19, 23, 28, 33, 37, 38] comparedtreatment outcome of Invisalign® orthodontic treatmentwith that of conventional fixed appliances. At last, fourstudies [20, 25, 29, 32] compared Invisalign® groups toeach other, while one study [31] did not have any con-trol or comparison group.
Table 4 Quality assessment of the included prospective and retrospective studies
Author-year of publication Study design anddefined control group
Adequately definedpatient material
Defined diagnosisand end points
Diagnostic reliability andreproducibility tests
Blinded outcomeassessment
Overallrisk
Solano-Mendoza et al. [21](2016)
+(prospective)
+ + + − Moderate
Buschang et al. [26](2015)
+(prospective)
+ + + − Moderate
Castroflorio et al. [22](2013)
+(prospective)
− − − − High
Pavoni et al. [23](2011)
+(prospective)
+ + + − Moderate
Kravitz et al. [5](2009)
+(prospective)
+ + − − High
Kravitz et al. [24](2008)
+(prospective)
+ + − − High
Baldwin et al. [27](2008)
-(prospective,uncontrolled)
+ − + + High
Vlaskalic and Boyd [25](2002)
+(prospective)
+ − − − High
Gu et al. [28](2017)
+(retrospective)
+ + + + Moderate
Khosravi et al. [29](2017)
+(retrospective)
+ + + − Moderate
Houle et al. [30](2016)
+(retrospective)
+ + + − Moderate
Ravera et al. [31] (2016) +(retrospective)
+ + + + Moderate
Duncan et al. [32](2015)
+(retrospective)
+ + + − Moderate
Grünheid et al. [33](2015)
+(retrospective)
+ + + + Moderate
Simon et al. [34](2014)
+(retrospective)
+ + − − High
Krieger et al. [35](2012)
+(retrospective)
+ + + − Moderate
Krieger et al. [36](2011)
+(retrospective)
+ + + − Moderate
Kuncio et al. [37](2007)
+(retrospective)
+ + + + Moderate
Djeu et al. [38](2005)
+(retrospective)
+ + + − Moderate
Papadimitriou et al. Progress in Orthodontics (2018) 19:37 Page 19 of 24
All studies tested mainly non-growing patients, andmost of them included patients of an average age of30 years [5, 19–21, 29–31, 34–38]. Non-extractioncases were used as study samples in nine studies [18,28–33, 37, 38]. Treatment duration differed among andwithin studies, as expected according to malocclusionseverity and the implemented intervention. Six studies[18, 22, 29, 34–36] did not report on treatment dur-ation. Finally, only one study [37] reportedpost-retention treatment outcomes by comparing theinduced changes in patients treated with Invisalign®with those treated with traditional fixed appliances. Theevaluation was conducted at a maximum post-retentiontime of 3 years after appliance removal, with all the pa-tients undergoing at least 1 year of retention.
Clinical findingsTable 2 gives an overview of the results of the includedstudies regarding clinical parameters, grouped in the fol-lowing three subject categories.
A. Accuracy The accuracy of Invisalign® was reportedin nine studies [5, 21, 22, 24, 26, 30, 34–36], where itwas evaluated as the deviation between the achievedand the planned tooth movements. The findings amongstudies were varying ranging from sufficient accuracy inresolving anterior crowding [35, 36] and distalizingmaxillary molars [34] to contradictory findings in upperincisor root control [22, 34] and to inadequacies inbodily expansion of the maxillary posterior teeth [21,26, 30], canine [5, 24] and premolar [34] rotationalmovements, extrusion of maxillary incisors5, and inoverbite control [35, 36].
B. Invisalign® vs traditional fixed appliances Sevenstudies [18, 19, 23, 28, 33, 37, 38] compared Invisa-lign® orthodontic treatment outcomes to that of con-ventional fixed appliances. A recent RCT study [18]found no significant difference in the amount of man-dibular incisor proclination produced by Invisalign®and fixed labial appliances in mild crowding cases,supported by a retrospective study [23], which alsoconcluded that treatment duration in these cases wassimilar for the two methods, though Invisalign wasnot so successful in root alignment. Gu et al. [28] re-ported similar outcomes, but shorter duration withInvisalign, for mild to moderate malocclusions.However, worse performance of Invisalign was notedin more severe cases, a finding also supported byDjeu et al. [38]. In the same line, in a RCT study, Liet al. [19] concluded that both therapeutic approachescan succeed in class I adult extraction cases, thoughInvisalign required more time and was less able to
correct bucco-lingual inclination and occlusal con-tacts. The latter findings are also in agreement withthose of two retrospective studies [33, 38].Differences between the two methods in
post-retention alterations were investigated in oneretrospective moderate risk of bias study [37]. Greaterrelapse was found 1–3 years posttreatment after Invi-salign® treatment compared to conventional orthodon-tic therapy with fixed appliances.
C. Invisalign groups only In an early exploratory study,Vlaskalic and Boyd [25] concluded that Invisalign® maybe more beneficial for patients in the permanent denti-tion with mild to moderate malocclusions after carefultreatment planning. Another early exploratory RCTstudy [20] also concluded that non-extraction treatmentof milder malocclusions has greater chances to be suc-cessfully treated by Invisalign.Three recent retrospective studies also tested vari-
ous Invisalign groups. One showed the moderate abil-ity of Invisalign to manage overbite [29]. Morespecifically, normal overbite was well maintained, butdeep bite was partially corrected, through mandibularincisor proclination. Open bite was also partially cor-rected, but mainly through incisor extrusion. On theother hand, a second study [31] reported the abilityof Invisalign to bodily distalize maxillary molars inadult nonextraction mild class II cases (≤ ½ cusp),with no changes in facial height. Finally, a third study[32] showed the ability of Invisalign to correct mildto moderate crowding nonextraction cases withoutcausing significant changes in the mandibular incisorposition and inclination. On the contrary, suchchanges (protrusion and proclination) were inducedin cases with severe crowding (≥ 6 mm).The Grading of Recommendations Assessment,
Development and Evaluation (GRADE) [16] was im-plemented to assess the overall quality of evidence forthe studies included in this review and for outcomesthat were assessed by two or more studies. GRADEtables illustrate the outcomes that were assessed bytwo or more studies (Additional file 1, 2, and 3).
Quantitative synthesis of the included studiesThe lack of standardized protocols impeded a validinterpretation of the actual results through pooled es-timates. Substantial differences in the implementedinterventions, participants’ characteristics (age andgender distribution), treatment duration, and investi-gated outcomes indicated significant methodologicalheterogeneity. Therefore, a meta-analysis was notfeasible.
Papadimitriou et al. Progress in Orthodontics (2018) 19:37 Page 20 of 24
DiscussionIn order to successfully deliver orthodontic treatment,clinicians need to carefully plan an appropriate thera-peutic approach based on the current scientific evi-dence. Although this is not the only determiningfactor for the final decision, as clinical experience andpatient’s opinion also play an important role, thisinformation needs to be taken into consideration toassess the possibilities and limitations of each treat-ment modality.With regard to Invisalign®, to date, there are four sys-
tematic reviews available, pertaining to clinical effectsof the system [12–15], with one of them [14] evaluatingperiodontal health issues. Given the limited availableevidence in certain earlier attempts [12, 15] and theevaluation of the effectiveness of Invisalign® under thewider spectrum of clear aligners [13, 15], strong con-clusions regarding the investigated clinical efficiency ofthe Invisalign® system were not feasible. This ambientobscurity on a highly increasing treatment approachwas the reason to perform a systematic search of theliterature and assess the available scientific evidencewith respect to the clinical outcomes of the Invisalign®orthodontic treatment. Due to the relatively unexploredtopic, an attempt was made to conduct the presentsystematic review to a high standard, in order tominimize any chance of bias, but also include all theavailable information.Indeed, a considerable number of studies were
included in this review, though only three of themwere RCTs [18–20], with low risk of bias. From theremaining 19 studies, 8 were of prospective [5, 21–27] and 11 of retrospective design [28–38] with mod-erate [21, 23, 26, 28–38] or high [5, 22, 24, 25, 27,34] risk of bias. Thus, since it was difficult to assessthe outcomes and reach safe results and conclusions,a strict methodology in both the data extraction andquality analysis was attempted. The methodologicalquality of the retrieved studies was thoroughly evalu-ated and a qualitative synthesis of the results wasperformed.Considerable differences in participants’ characteris-
tics, types of interventions, reporting of clinical out-comes, and treatment’s duration was evident, thus,preventing the implementation of a meta-analysis.More specifically, the number of patients recruitedranged from 6 [22] to 152 [19], which indicates astrong methodological difference among the studyprotocols and in strength of the stated results.Concerning the age of the patients that underwenttreatment with Invisalign®, it varied between 13 [34]and 61 [30] years, with all studies primarily includingnon-growing patients, most of them having an aver-age age of 30 years [5, 19–21, 29–31, 34–38], and
most of them with moderate [21, 29–31, 35–38] andhigh [5, 34] risk of bias. This reveals a strong lack ofinformation for growing individuals and indicates thatInvisalign® is at present a preferred treatment optionfor late adolescent and adult patients, who usuallyhave higher esthetic demands.With regard to the outcome measures, measure-
ments in pre- and post-treatment records were made.The records included the following: actual or/anddigital dental casts [5, 19–23, 25, 28, 30, 32, 35–38],panoramic radiographs [25, 37, 38], lateral cephalo-grams [18, 19, 25, 29, 31, 32, 38], CBCTs [33], andphotographs [19, 20, 25, 38]. The discrepancy index(DI) and the peer assessment rating index (PAR) wereused in the pre-treatment records to assess the initialseverity of malocclusion [5, 19, 28, 38]. The AmericanBoard of Orthodontics – Objective-grading system(ABO-OGS) was used in three studies [5, 19, 38] tosystematically grade both pre- and post-treatment re-cords evaluating various clinical parameters. Tooth-Measure®, which is the Invisalign®’s proprietarysuperimposition software, was also used to make mea-surements on 3D dental models, including the initialand final ClinCheck® virtual models [5, 24, 35, 36].As for the overall treatment duration, there were
different completion criteria and varying outcomesamong and within studies. When compared to con-ventional appliances, the Invisalign® system showedsignificantly shorter treatment duration in three stud-ies [28, 33, 38], while no difference was reported inanother study [23]. All these studies evaluated nonex-traction treatment of mild to moderate malocclusionsand scored as moderate risk of bias. On the contrary,one study on extraction treatment reported longerduration for Invisalign treatment [19], with low riskof bias. Thus, it seems that Invisalign might treatfaster mild nonextraction cases, but it requires moretime than fixed appliance treatment for more com-plex cases.Substantial variation in the investigated clinical out-
comes was noted among studies. The majority ofthem focused on the accuracy of Invisalign® or itscomparison to conventional fixed appliances. The firstwas found sufficient when certain malocclusion fea-tures, such as overjet or anterior arch length discrep-ancy, were tested [35, 36] or for maxillary molardistalization [34]. The efficacy on maxillary molar dis-talization (≤½ cusp) was also supported by anotherclinical study [31]. However, important limitationswere reported for bodily expansion of the maxillaryposterior teeth [21, 30], canine [5, 24] and premolar[34] rotational movements, extrusion of maxillary in-cisors 5, and in overbite control [35, 36]. All of thesereferred studies scored as moderate according to
Papadimitriou et al. Progress in Orthodontics (2018) 19:37 Page 21 of 24
Bondemark scoring system [17]. Based on these find-ings, the use of additional attachments or overcorrec-tions was commonly suggested in the literature forthese types of movement. As for the comparison tofixed appliances, from studies with moderate [23, 28]to low [18] risk of bias, it seems that Invisalign per-forms well in mild to moderate non-extraction cases[18, 23, 28], but it cannot equally succeed in moredifficult cases, including extraction cases [19, 27, 28,33, 38]. Teeth inclinations and occlusal contacts seemto be among the major limitations of Invisalign [19,33, 38], most of them judged as moderate [23, 33, 38]risk of bias and only two with low [18, 19]. Theresults from studies that included only different Invi-salign groups are in agreement with the abovemen-tioned findings [20, 25, 29, 32].In addition, only one study [37], graded as moder-
ate, included a post-treatment observational periodinvestigating the stability of treatment outcomes withInvisalign®, indicating a general lack of informationwith regard to retention. Although the amount ofevidence is limited, this study showed more relapse inthe Invisalign cases, as compared to fixed appliancetreatment, that might be attributed to the inadequa-cies in obtaining certain bodily movements and solidocclusal contacts.Overall, evidence was of moderate quality. Apart
from the three RCTs [18–20], where a low risk of biaswas considered, the remaining prospective and retro-spective studies were graded as moderate [21, 23, 26,28–38] or high [5, 22, 24, 25, 27, 34] risk of bias. Thestudies’ review showed high amount of heterogeneity interms of methodology and outcome reporting thatimpeded a valid interpretation of the actual resultsthrough pooled estimates. However, there was substan-tial consistency among researchers that the Invisalign®system is a viable alternative to conventional ortho-dontic therapy in correcting mild to moderate maloc-clusions, without extractions. Moreover, when thetreatment is carefully planned, Invisalign® aligners cansafely straighten dental arches in terms of leveling andderotating the teeth, except for canines and premolars.Finally, crown tipping can be easily performed. On theother hand, important limitations include arch expan-sion through bodily tooth movements, extraction spaceclosure, corrections of occlusal contacts, and largerantero-posterior and vertical discrepancies.All things considered, it is evident that more
high-quality research of prospective design with re-spect to the clinical outcomes of Invisalign® needs tobe carried out in the future. A standardized method-ology including control samples would be valuable inobtaining comparative results with conventional ap-proaches. Furthermore, though more than half of the
studies included in the present review have been pub-lished in the last 5 years (range 2012–2017), the find-ings of the review should be interpreted with somecaution; the continuous improvement of the Invisalignsystem (especially in 2013 with SmartTrack® material)[39] may not allow for direct synthesis and validcomparisons between older studies with the most re-cent ones, as the inclusion of data from different iter-ations of Invisalign material may become a factor ofbias. This is, of course, a major consideration whensynthesis of studies’ results for clinical evidence isconcerned, in an era that software, scanners, and 3Dprinter costs are more affordable and potentialin-house printing of aligners is rapidly growing. Lastbut not least, the long-term effectiveness pertainingto retention outcomes also needs further investigation,whereas complete lack of evidence is evident forgrowing patients.
ConclusionsDespite the fact that orthodontic treatment with Invisa-lign® is a widely used treatment option, apart fromnon-extraction treatment of mild to moderate malocclu-sions of non-growing patients, no clear recommenda-tions about other indications of the system can be made,based on solid scientific evidence.Although this review included a considerable num-
ber of studies, treatment outcomes need to be inter-preted with caution due to the high heterogeneity.Further research with parallel arm RCTs or well-designedprospective trials are needed to form robust clinical rec-ommendations for a wide spectrum of malocclusions andfor growing patients.Albeit the existing limitations, the following conclu-
sions were made, based on the available evidence:
� Invisalign might treat faster mild non-extractioncases, but it requires more time than fixed appliancetreatment for more complex cases.
� Invisalign® aligners can safely straighten dentalarches in terms of leveling and derotating the teeth(except for canines and premolars, where a smallinadequacy was reported). Crown tipping can beeasily performed.
� Teeth inclinations and occlusal contacts seem to beamong the limitations of Invisalign®, when accuracyof planned movements achieved with aligners isconcerned.
� Use of additional-novel attachments might be moreeffective for various types of movement, such asbodily expansion of the maxillary posterior teeth,canine and premolar rotational movements, extrusionof maxillary incisors, and in overbite control.
Papadimitriou et al. Progress in Orthodontics (2018) 19:37 Page 22 of 24
Additional files
Additional file 1: GRADE Working Group grades of evidence. Summaryof findings: Invisalign compared in groups of different treatmentmodalities or divergent severity of crowding. (DOCX 16 kb)
Additional file 2: GRADE Working Group grades of evidence. Summaryof findings: Accuracy of treatment result. (DOCX 16 kb)
Additional file 3: GRADE Working Group grades of evidence. Summary offindings: Invisalign compared to fixed appliances in adults. (DOCX 16 kb)
AbbreviationsABO-OGS: American Board of Orthodontics – Objective-grading system;GRADE: Grading of Recommendations Assessment, Development andEvaluation; RCT: Randomized clinical trial
Protocol and registrationThe protocol was not registered prior to the study. This study was notregistered in any publicly assessable database.
Availability of data and materialsAll data generated or analyzed during this study are included in this publishedarticle [and its supplementary information files].
Authors’ contributionsThe first two authors (AP and SM) performed data extraction independentlyand in duplicate. Disagreements were resolved by discussion or the involvementof two collaborators (third author and last author: NG and DK). All authors readand approved the final manuscript.
Ethics approval and consent to participateEthical approval was not required.
Consent for publicationNot applicable.
Competing interestsThe authors declare that they have no competing interest.
Publisher’s NoteSpringer Nature remains neutral with regard to jurisdictional claims inpublished maps and institutional affiliations.
Author details1Department of Orthodontics and Dentofacial Orthopedics, 251 Hellenic AirForce General Hospital, P. Kanellopoulou 3, 11525 Athens, Greece.2Department of Orthodontics, University Hospital Ghent P8, University of
Ghent, C. Heymanslaan 10, B-9000 Ghent, Belgium. 3Department ofOrthodontics and Dentofacial Orthopedics, University of Bern, Freiburgstrasse7, CH-3010 Bern, Switzerland.
Received: 29 June 2018 Accepted: 27 July 2018
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AppendixTable 5 Search strategy, Medline via PubMed, 28 August 2017
1. invisalign 158
2. invisalign [tiab] 158
3. clear aligner 48
4. aligner* AND orthodont* 181
5. ortho caps 5
6. orthocaps 1
7. invisible AND orthodont* 69
8. removable AND aligner 33
9. esthetic AND splint AND orthodont* 75
10. transparent* AND orthodont* 63
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