QUINTESSENCE INTERNATIONAL | volume 51 • number 9 • October 2020696
Improving oral health: a short-term split-mouth randomized clinical trial revealing the superiority of resin infiltration over remineralization of white spot lesionsAhmed Youssef/Mohamed Farid, PhD/Mohamed Zayed, PhD/Edward Lynch, PhD/
Mohammad K. Alam, PhD/Andrej M. Kielbassa, Prof Dr med dent Dr h c
Objectives: To evaluate masking effects of resin infiltration on
labial white spot lesions (WSL), by comparing the latter with a
remineralization approach (using hydroxyapatite and fluor-
ides) and conventional oral care (using fluoride-free tooth-
paste). Method and materials: Fifteen patients with at least
three WSL were enrolled for a within-person randomized con-
trolled trial, thus allowing for intrapersonal comparisons. Each
WSL per tooth in every patient was randomly assigned to one
of the following groups. Group 1: lesions were resin-infiltrated
with Icon (RI; DMG); Group 2: Remin Pro (RP; VOCO) was used
as remineralizing agent; and Group 3 (control): affected teeth
were brushed with Complete Care toothpaste (CC; Himalaya).
RP and CC were applied by means of a polishing brush, using a
low-speed handpiece (5 min), and these procedures were re-
peated chairside thrice daily for 7 consecutive days. Digital
photographs were captured before and after lesion treatment
under standardized conditions. The CIE L*a*b* color system
was used to analyze the optical outcome, and intrapersonal
color differences were statistically evaluated. Results: Com-
pared to RP and CC, RI showed prompt and subjectively satis-
factory color improvements, and this was primarily driven by L*
and b* shifts. Statistical analysis of the objective color differ-
ences (ΔE*) between the three groups revealed significant difEE -ff
ferences for RI vs RP (P = .029), RI vs CC (P < .001), and RP vs CC
(P = .001). Conclusion: Resin infiltration is considered a
time-effective treatment option for esthetically camouflaging
WSL, while RP and CC failed to improve lesion appearance and
oral health in the current short-term trial. (Quintessence Int
2020;51:696–709; doi: 10.3290/j.qi.a45104)
Key words: dental health, enamel caries, health care quality, improvement of oral health, remineralization, resin infiltration,
white spot lesion
From a cariologic point of view, white spot lesions (WSL) on
smooth surfaces of teeth occur as a consequence of undis-
turbed and prolonged biofilm accumulation with a concomi-
tant acid production, thus resulting in subsurface enamel
demineralization. The latter is characterized by a mineral disso-
lution frequently starting at the prism cores; ongoing acid
attacks will result in increasing mineral loss (of mainly calcium
phosphates) at the interprismatic areas and from the prism
peripheries, thus leading to an increased subsurface porous
volume of the WSL without macro-cavitation.1 Along with
organic debris,2 yeasts,3 and bacteria,4,5 these increased porosi-
ties may be filled either with water or air, both showing refrac-
tive indices (1.33 and 1.00, respectively) differing from sound
enamel (1.62); thus, reduced refractive indexes do alter optical
properties, and indicate mineral loss with initial and advanced
enamel lesions with intact surfaces.6 Previous experiments
have led to the development of a low-viscous resin being able
to infiltrate these lesions, to occlude the porous volume, and to
build a 3D network consisting of the infiltrant resin enwrapping
the demineralized enamel remnants.1,7,8
Since the first report revealing the clinical feasibility of
masking WSL by means of this Infiltration concept,1 several
RESTORATIVE DENTISTRY
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Youssef et al
case series,9-11 clinical efficacy (non-randomized) studies,12-17
and randomized controlled trials (RCTs)18-28 have confirmed
that using Icon (DMG) frequently will result in clinically satisfac-
tory alterations of these initially demineralized and esthetically
disfiguring lesions, usually revealing a milky or chalky appear-
ance. However, whitish opacities of labial enamel surfaces are
not only the result of demineralization; fluorosis, hypomineral-
ization/hypomaturation, and enamel hypoplasia are consid-
ered developmental malformations or maturation distur-
bances, and are responsible for mineral-deficient changes or
nonmineralized opacities considered treatable with resin infil-
tration (as has been shown with previous case series and
RCT).12,29,30 These camouflaging effects are mainly due to the
favorable refractive index of the resin infiltrant (1.51);31,32 the
partially dissolved enamel crystals will be enwrapped by the
non-filled, low-viscosity, and light-polymerizable resin, thus
closing the pores,33 forming an enamel hybrid layer,34 and lead-
ing to a decreased light-scattering of the infiltrated lesion.32
There is no doubt that a thorough and patient-centered,
individual determination of the respective etiology is consid-
ered mandatory to successfully manage these mineral-defi-
cient areas; this must include lesion width and lesion depth.35
Any treatment decision of the dental professional must meet
the patients’ expectations, and it seems obvious that the latter
frequently aim for both tissue preservation and esthetic
improvement. From a medical perspective, it seems clear that
with true WSL the demineralization process has to be arrested
(or even reversed),36 to prevent any progress of these lesions;
indeed, regular brushing and professional tooth cleaning have
been shown to be effective for preventing any progress of WSL
on labial surfaces in the long run.18
Hence, with already existing WSL, a wide variety of thera-
peutic options is available, ranging from antiseptics and topi-
cally applied fluorides to microabrasion.37 Notwithstanding, a
clear and indisputable ranking of the various available treat-
ments according to their efficacy has not been elaborated so
far,38 even if an expert panel convened by the American Dental
Association Council on Scientific Affairs and the Center for Evi-
dence-Based Dentistry has prioritized either acidulated phos-
phate fluoride gels (1.23%) with moderate certainty, or sodium
fluoride varnish (5%) with low certainty for the treatment of
noncavitated caries lesions on facial or lingual surfaces.39 This
has recently been corroborated by means of a network
meta-analysis.40 Surprisingly, resin infiltration has been recom-
mended for proximal surfaces (thus following the original idea
of the infiltration concept1,41), while no reference to resin infil-
tration was made with regard to labial smooth surfaces.39,40
From laboratory studies, it is known that with regard to pro-
viding esthetic improvements of WSL resin infiltration is more
effective than fluorides or alternative remineralizing agents.42-44
However, while some authors have concluded that there is a
lack of clinical evidence to sufficiently support either reminer-
alizing or camouflaging strategies in managing postorthodon-
tic WSL,45,46 others clearly have stated that resin infiltration
using triethylene glycol dimethacrylate (TEGDMA) might
enhance the esthetic improvement of these lesions, even with
moderate- to high-caries-risk individuals (like patients with
fixed orthodontic appliances).18
To overcome these uncertainties documented in the litera-
ture, the current study aimed to provide a reliable basis for
treatment decisions with WSL. The treatment approach using
resin infiltration by means of the commercially available prod-
uct Icon (DMG) was compared to an established remineralizing
agent (Remin Pro, VOCO; based on a watery cream containing
hydroxyapatite, fluorides, and xylitol) recommended for treat-
ment of WSL.47,48 A herbal toothpaste (Complete Care, Hima-
laya), known to positively affect salivary glucose levels, salivary
pH,49 and with a documented anti-plaque efficacy,50 was used
as a non-fluoride control without active properties promoting
remineralization.
The objectives of the present split-mouth RCT were to clini-
cally evaluate the short-term effects of these treatment
approaches by using standardized digital photography, and the
CIE (Commission Internationale de l’Éclairage) L*a*b* color sys-
tem was utilized to assess and to compare the esthetic improve-
ments, with the difference in color (ΔE*) as the primary outcome EE
(and with ΔL*, Δa*, and Δb* as the subanalytical points of inter-
ests). With the background presented above, the null hypothe-
sis (H0) assumed that all treatment regimens were equally effec-
tive with regard to esthetic improvement of WSL, and this was
tested against the alternative hypothesis (H1) of a difference.
Method and materials
Sample size estimation
The sample size estimation for the present split-mouth RCT was
based on recently published laboratory31,43 and clinical stud-
ies19 having investigated perceived color differences (CIE L*a*b*
ΔE*) of initially demineralized enamel (WSL) and resin infilEE -
trated WSL. Thus, pre- and posttreatment ΔE* values ranging EE
from 16.1 (± 5.0) to 2.0 (± 1.3),19,31,43 respectively, were used to
carefully assess the standard deviations (SDs) of the within-per-
son differences (μ1 − μ2), thereby following previous recom-
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RESTORATIVE DENTISTRY
mendations.51 Considering a type I error risk of .05 (α) and a
90% power (1 − γ) to detect a true difference, and taking into
account an estimated sample loss of at least 30%,52 a total of 45
treatment sites (or 15 patients contributing three comparable
WSL) was specified.
Ethical considerations and participation consent
Prior to the start of the study, full ethical approval of the study
protocol was obtained from the Ethical Committee of the Minia
University/Faculty of Dentistry (vote number 255/2018; date of
approval 12 June 2019). Treatments were performed in accor-
dance with the Code of Ethics of the World Medical Association
(Declaration of Helsinki, 7th revision/version 2013) for experi-
ments involving humans. The CONSORT (http://www.con-
sort-statement.org) and SQUIRE 2.0 statements (http://www.
squire-statement.org) for reporting of RCTs were followed.
From October 2019 to January 2020, a total of 25 participants
attending the outpatient Clinic of Restorative and Orthodontic
Dentistry at the University of Minia (study setting location)
were screened for eligibility (Fig 1). All participants were pro-
vided with a full explanation of the study (including objectives,
risks, and benefits), and written informed consent was obtained
from each patient to voluntarily take part.
Outcome measures
The primary outcome of the current investigation was the
amount of lesion color change in terms of ΔE*, from the white EE
opaque perception to a natural color mimicking the sound sur-
rounding enamel. Failure was defined as no or only low color
improvement after WSL management. Color measurements of
L*, a*, and b* values before and after the various treatments
were done, and changes of lightness (ΔL*, black/white) as well
Fig 1 Study flowchart (CONSORT).
1
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Youssef et al
as those of the opposing-color axes Δa* (green/magenta) and
Δb* (blue/yellow) were assessed as secondary outcome mea-
sures, and were collected as means and SDs.
Patient eligibility
The main inclusion criteria were patients with (at least) three
noncavitated, post-orthodontic WSL, located on smooth surfaces
of maxillary or mandibular permanent teeth, and comparable in
size, opacity, and whitish appearance. Further aspects were: ■ age (a range from 15 to 30 years of age was determined) ■ good general health (absence of disease/no handicaps, to
ensure oral care at home) ■ preserved pulp vitality of the teeth to be included as deter-
mined by clinical and radiographic observations (to control
for internal discolorations) ■ finished orthodontic therapy ■ consolidated oral care on a daily basis ■ agreement by patient and parents (or guardians) to partic-
ipate in the study.
Patients with periodontal diseases (periodontal pockets or den-
tal mobility) or radiologically identified pathologies (periapical
radiolucencies) were not considered eligible. Teeth revealing
any kind of restorations were excluded from the current study.
Moreover, any kind of previous or planned WSL treatment was
considered as an exclusion criterion.
Enrollment of patients and concealment of allocation
In total, three patients refused to take part in the investigation,
and seven potential participants did not meet the inclusion cri-
teria; in all cases, a regular treatment was administered to these
patients. Finally, 15 patients suffering from post-orthodontic
WSL and, meeting the inclusion criteria, were enrolled for the
present split-mouth RCT. All participants were of legal age, and
signed their consent forms (no written consent from the par-
ents/guardians was necessary). A flowchart describing the par-
ticipants’ enrollment is given in Fig 1.
Due to the nature of the present study design, this trial
could not be blinded. Thus, to reduce any selection bias, an ade-
quate allocation concealment of the lesions had to be assured,
and randomization of the three scheduled treatments was per-
formed within the three studied sites of each patient (but not
within the patients). With multiple eligible lesions, a standard-
ized process was stipulated to single out the study lesions, and
WSL were preferably selected according to (1) comparable
lesion widths, (2) similar tooth types (incisors or canines), and
(3) neighboring lesions. Due to the short-term character of the
current trial, no interim analysis or early termination was
planned, and no monitoring or audits were scheduled.
In Group 1 (RI), the lesions were resin infiltrated (Icon,
DMG), whereas the lesions of Group 2 (RP) were actively
treated using a remineralizing agent (Remin Pro, VOCO);
lesions of Group 3 (CC) received a nonremineralizing tooth-
paste (Complete Care, Himalaya), and served as control
(Table 1). Using a computer-generated and concealed block
randomization allocation sequence (www.randomization.
com; patient #1 RP-CC-RI; #2 RI-CC-RP; #3 RI-RP-CC, and so
on), both a strict running order and a uniform distribution of
the intervention modes were guaranteed. This way, the vari-
ous treatments were randomly assigned to the lesions, with
the first therapeutic approach allocated to the lowest number
of the included tooth (according to the Universal Tooth Num-
bering System).
Table 1 Materials (including their main compositions and manufacturers) used in the various study groups of the current investigation
Study group Material Composition Manufacturer
Group 1 (RI) Icon Icon Etch: hydrochloric acid, pyrogenic silicic acid, surface-active substances
DMG
Icon dry: 99% ethanol
Icon infiltrant: methacrylate-based resin matrix, initiator
Group 2 (RP) Remin Pro Water-based cream containing hydroxyapatite (calcium and phosphate), fluoride (1,450 ppm), and xylitol
Voco
Group 3 (CC) Complete Care Extracts from pomegranate, neem bark, Indian gum arabictree’s fresh twigs, bishop’s weed, five-leaved chaste tree, false black pepper, triphala
Himalaya
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Interventions
With each new patient, the next sealed envelope containing
the allocation sequence was opened. In Group 1, resin infiltra-
tion (Icon vestibular, DMG) of WSL was accomplished according
to the manufacturer’s instructions. Briefly, after rubber dam
isolation and cleaning, the etching (Icon Etch, 2 minutes; DMG)
and drying steps using air and alcohol (Icon-Dry, 30 seconds;
DMG) were assured, and the lesion was controlled. Then, the
resin (Icon-Infiltrant, 3 minutes; DMG) was applied to the lesion
twice, and each step was completed by a sufficient polymeriza-
tion (> 800 mW/cm2, 60 seconds; Elipar FreeLight, 3M Espe).
Remin Pro was used as a remineralizing agent for the WSL
of Group 2. This cream containing fluoridated hydroxyapatite
was applied chairside on the enamel surfaces using a polishing
brush (Jiffy Composite Polishing Brush, Ultradent Products;
DURAtec 2068D, KaVo) and a low-speed handpiece for 5 min-
utes. These procedures were repeated three times per day for 7
consecutive days.
The WSL of Group 3 were treated in a similar way, but using
the herbal toothpaste (Complete Care). Again, the dentifrice
was applied with a low-speed polishing brush (Jiffy Composite
Polishing Brush; DURAtec 2068D) for 5 minutes. This procedure
was repeated three times per day, and was continued for 7 con-
secutive days (Fig 1). Moreover, detailed oral hygiene instruc-
tions were given to the patients, along with a manual tooth-
brush (Oral-B PRO-EXPERT CrossAction, Procter & Gamble), a
nonprescription fluoride-free toothpaste (Parodontax Classic,
GlaxoSmithKline), and dental floss (Oral-B Glide Floss, Procter &
Gamble). Compliance was tested by questions about the home
care practices at the follow-up visit. All patients were motivated
by the resin infiltration approach (and showed some curiosity
with the teeth to be remineralized).
Color measurement
Digital photographs were captured under fixed conditions using
a digital camera (Nikon D7200, Nikon), equipped with a macro
lens (Rokkor-X, 100 mm, Minolta) and a macro ring flash (ML-150,
GODOX Photo Equipment) placed at a standard focal distance
from the patient.16 All intraoral photographs were taken with
fixed camera settings after configuring the white balance, using
the same focal length (50), shutter speed (1/200), flashlight
exposure time (1/64), and sensor adjustment (ISO 200), to ensure
reproducible conditions. With these standard settings matching
the operator distance, three standardized color patches were
measured, and L*a*b* values were compared (R2 > .98).
The participating patients were photographed in a dark-
ened room to remove any room light variables. To eliminate
and to standardize all possible interferences of the background
contrast, lip/cheek retractors (DynaFlex) were used. Before cap-
turing the images in large RAW format to preserve the quality
of the photographs, tooth surfaces were dried to avoid any
influence of moisture on the WSL appearance. Images were
taken before starting (T1) and after the end of the treatments
(T2, after 7 days). To evaluate the digital images, a graphics edi-
tor (Photoshop CS5, Adobe) was used to convert the digital
images (RAW format) to TIFF format with 16-bits image resolu-
tion. CIE L*a*b* color system was used to analyze the optical
results. Demineralized WSL were outlined and analyzed by the
same investigator (AY) on the same computer screen (S2719H
Dell 27 Monitor, Dell Technologies).
2a 2b
Figs 2a and 2b (a) Preoperative view of a study participant. Clearly visible is the whitish appearance of the labial surfaces. (b) Postoperativeview, 1 week after treatment. The maxillary lateral incisor has been resin infiltrated, while the canine has been treated with Remin Pro.
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Youssef et al
This way it was ensured that there were no incomplete out-
come data, and any attrition bias could be avoided. Although
blinding was not possible, this shortcoming was considered
surmountable (or even negligible), since the primary outcome
(ΔE*) was an exclusively computer-based result, thus beingEE
affected neither by subjective inter- and intra-examiner differ-
ences,53,54 nor by measurement bias.
Statistical analysis
Lightness and color data (L*a*b* values) of the respective WSL
were recorded and entered into Excel sheets (Microsoft). Color
changes between T1 and T2 were calculated from the ΔL*, Δa*,
and Δb* values, and was expressed as ΔE* for each group. StatEE -
istical analysis was performed using SPSS for Windows (version
19.0, SPSS, IBM). To determine statistically significant differ-
ences between the three independent groups, the nonpara-
metric Kruskal-Wallis H-test (“one-way ANOVA on ranks”) was
used. To clarify which specific means were significantly differ-
ent from the others, pairwise calculations between the groups
were computed using Dunn post-hoc test for multiple compar-
isons. With all statistical comparisons, a significance level of 5%
(α = .05) was adopted, and this level indicated differences con-
sidered unlikely to have arisen by chance.
Results
In total, 15 patients (8 women, 7 men; mean ± SD age 23 ±
3.3 years) participated in the current investigation. All patients
suffered from post-orthodontic WSL, and orthodontic therapy
had been successfully finalized (mean duration between com-
pletion of orthodontic treatment and start of the study was
4 ± 2.5 months). Mainly maxillary teeth were treated (15 out
the 45 lesions were mandibular teeth). No patient was lost in
this trial, and no adverse events were observed.
Subjective outcome (patients’ and operator’s appraisal)
At baseline, all WSL showed subjectively perceived color dis-
similarities compared with the surrounding sound enamel, and
all patients complained of the detrimental appearance of those
WSL. As a basic outcome, resin infiltration resulted in subjective
satisfaction of all patients, even if not all lesions could be com-
pletely masked from the operator’s perspective. This has been
confirmed with the objective CIE L*a*b* evaluation. However,
while 10 lesions from Group 1 (RI) revealed decreased color dif-ff
ferences and complete camouflaging outcomes of WSL (com-
pared to the preoperative condition and compared to adjoin-
ing normal enamel), three teeth showed a partial (but still
satisfactory) masking only, and two infiltrated lesions were not
rated satisfactory by the operator. In contrast, teeth from Group
2 (RP) and Group 3 (CC) revealed an insignificant improvement
of color, rated clearly inferior to that of the resin infiltration
group (Fig 2). All patients voted for resin infiltration of their
non-altered teeth.
Lightness values (L*)
With a mean L* value of 86.49 ± 4.63, baseline values of Group 1
(RI) were comparable with Group 2 (RP; L* = 87.97 ± 4.01) and
Group 3 (CC; L* = 88.45 ± 2.73) (P > .05). With Group 1 (RI), mean
Table 2 L*) between the various study groups according to CIE L*a*b* results before and after WSL treatments
ΔL* Group 1 (RI) (n = 15) Group 2 (RP) (n = 15) Group 3 (CC) (n = 15) H-test P
Minimum 12.74 3.90 1.07NA
Maximum −1.08 −0.70 −0.09
Mean ± SD 7.07 ± 3.70 2.10 ± 0.79 −0.54 ± 0.31 45.311* < .001*
Median (IQR) 7.39 (9.86 to 3.29) −2.21 (2.47 to 1.76) −0.49 (0.81 to 0.25) NA
Group differences P1
= .047*; P2
< .001*; P3
< .001* NA
Lightness of color (L* = 0 = darkest black, and L* = 100 = brightest white); IQR, interquartile range; NA, not applicable; P1
= Group 1 vs Group 2; P2
= Group 1 vs Group 3; P3
= Group 2 vs Group 3 (Dunn test).
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RESTORATIVE DENTISTRY
lightness decreased to 79.56 ± 6.01 after resin infiltration, while
the values of Group 2 (RP; 86.07 ± 3.93) and Group 3 (CC;
87.91 ± 2.66) remained unaffected after their respective treat-
ments. Intergroup comparisons revealed significant differences
between the three groups (Table 2); with a mean ΔL* value of
7.07 ± 3.70, the effects of resins infiltration in Group 1 (RI) were
considerably increased if compared to Group 2 (RP; ΔL* = 2.10 ±
0.79) and Group 3 (CC; −0.54 ± 0.31). Thus, the disappearance of
the whitish WSL was strongly influenced by the L* component.
Magenta-green range (a* channel)
Mean baseline a* values were low, but negative (Group 1 [RI],
a* = −2.08 ± 3.16; Group 2 [RP], a* = −0.60 ± 1.88; and Group 3
[CC], a* = −0.08 ± 2.32), thus indicating some negligible propor-
tions of the green component (P > .05). Posttreatment inter-
group comparisons revealed nonsignificant differences (P > .05)
between Group 2 (RP; Δa* = 0.21 ± 0.80) and Group 3 (CC;
Δa* = −0.06 ± 0.43), again not revealing any treatment effects,
and emphasizing a neutral outcome. In contrast, a more pro-
nounced effect was observed with Group 1 (RI; Δa* = 2.15 ±
1.92); these means indicated a slight shift to the red compo-
nent, and this was significantly different (P < .05) both from
Group 2 (RP) and from Group 3 (CC) (Table 3).
Yellow-blue axis (b* value)
Baseline comparability could also be observed with regard to
the b* values of the various groups (Group 1 [RI], b* = −1.87 ±
3.40; Group 2 [RP], b* = 2.31 ± 5.21; and Group 3 [CC], b* =
−5.11 ± 2.21). Posttreatment effects again were negligible
(P > .05) between Group 2 (RP; Δb* = 0.88 ± 1.47) and Group 3
(CC; Δb* = 0.11 ± 0.53), thus indicating neither considerable
yellow nor major blue shifts. However, these groups both dif-ff
fered significantly (P < .05) from Group 1 (RI; Δb* = 7.70 ± 4.76),
and these increased means revealed a strong tendency towards
yellow, thus again approximating the surrounding sound
enamel well (Table 4).
Perceived difference in color (ΔE*)
With a ΔE* value exceeding 3.7, the perceived color differenceEE
between pre and post resin infiltration with the lesions of
Group 1 (RI) was clearly observable by the naked eye (Table 5).
In contrast, Group 2 (RP; ΔE*EE = 2.80 ± 0.84) and Group 3 (CC;
0.88 ± 0.28) revealed subperceptible color changes, thus indi-
cating failed treatment effects from a clinical perspective. Inter-
group comparisons are given with Table 5, and means ± SD of
Group 1 (RI) differed significantly from the other groups
(P < .05). With three daily applications of Remin Pro provided
over 7 days, ΔE* values of Group 2 (RP) and Group 3 (CC) difEE -ff
fered significantly (P = .001) at the end of this study.
Discussion
The present investigation aimed to document the instant out-
come of a split-mouth efficacy RCT on the optical effects of WSL
infiltrated with resin. A balanced randomization protocol
assigning the respective teeth of the patients ensured that
selection and allocation bias could be minimized, even if the
basic conditions for inclusion of participants was considered
selective per se. The implemented intra-personal study design
aimed at precise comparisons of lesion behavior within the
same patient (serving as his/her own control), and allowed for a
stringent removal of inter-subject variability from the observed
treatment effects as the main advantage, thus ensuring an
increase of the statistical efficiency. This set-up usually requires
approximately half of the patients if compared to a parallel-arm
trial with the same power,51,55 and it should be stressed that no
systematic differences regarding the outcome of intervention
could be derived from split-mouth and parallel-group RCT.56
However, intra-subject designs encompass some uncertainty
with regard to contamination between sites, in particular, since
assessment of the extent of carry-across effects in a split-mouth
trial would not seem possible; in the present investigation, this
risk of bias was eliminated by strictly treating the tooth surfaces
assigned by the randomization scheme. While Group 1 (RI) would
not seem critical with this respect, some diffusion of fluorides
from Group 2 (RP) cannot be ruled out. It is known, however, that
Remin Pro has only negligible effects on tooth color.57 Thus, no
carry-over effect was to be expected in this regard; most proba-
bly due to the short-term observation, mean ΔE* was 2.80EE ± 0.84
in Group 2, and this was neither significant nor clinically observ-
able. Notwithstanding, an influence of remineralization (trig-
gered by the ingredients,47,48 and by the nonfluoride home care)
should have affected all (study) teeth in a comparable way, and
from the outcome it seems clear that this theoretically conceiv-
able effect is negligible. In Group 3 (CC), a herbal dentifrice con-
taining pomegranate, neem, and ayurvedic triphala was used. By
releasing tannins, polyphenols, and astringents, these ingredi-
ents have shown antimicrobial effects.49,58 Consequently, some
clinical effects on biofilm growth (but not on remineralization)
have been described, and this toothpaste served as a control with
placebo characteristics,50 and without any possible response bias.
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Youssef et al
Finally, split-mouth trials are considered at risk of bias when
finding matching sites is impossible in subjects; this risk could
be avoided with the present study, since all lesions treated were
considered comparable with respect to age and size. Due to the
intrinsic characteristics of the current study, blinding was not
possible, both with the patients and with the operators, thus
increasing the performance bias. However, even if a good cor-
relation between visual (subjective) and spectrophotometric
(objective) evaluation has been described,12 the current set-up
used a standardized computer-based shade determination, thus
eliminating any additional observer bias due to possible mis-
judgment, and allowing for a significantly more reproducible
and objective evaluation than with solely visual assessments.53,54
In this manner, demonstrating the generalizable outcome
benefit of Group 1 (RI) over the remineralization intervention of
Group 2 (RP) and the control Group 3 (CC) became possible with
the current explanatory RCT. By assessing the visually perceived
color difference, it was found that the color of lesions consider-
ably improved in Group 1 after resin infiltration (see Fig 2), and
the altered lesion appearance was clinically recognizable
Table 3 a* (value changes from green to magenta) between the various study groups according to CIE L*a*b*results before and after WSL treatments
Δa* Group 1 (RI) (n = 15) Group 2 (RP) (n = 15) Group 3 (CC) (n = 15) H-test P
Minimum 1.65 −0.96 −0.99NA
Maximum 5.36 1.81 0.49
Mean ± SD 2.15 ± 1.92 0.21 ± 0.80 −0.06 ± 0.43 22.221* < .001*
Median (IQR) 1.76 (0.90 to 4.07) −0.01 (0.21 to 0.50) −0.07 (0.27 to 0.20) NA
Group differences P1
< .001*; P2
< .001*; P3
= .464 NA
Values of the green/magenta coordinate (a*; negative values indicate green, and positive values indicate red/magenta); NA, not applicable; P1
= Group 1 vs Group 2; P2
= Group 1 vs Group 3; P3
= Group 2 vs Group 3 (Dunn test).
Table 4 b*) between the various study groups according to CIE L*a*b* results before and after WSL treatments
Δb* Group 1 (RI) (n = 15) Group 2 (RP) (n = 15) Group 3 (CC) (n = 15) H-test P
Minimum −0.26 −2.74 −1.05NA
Maximum 14.18 2.89 0.85
Mean ± SD 7.70 ± 4.76 0.88 ± 1.47 0.11 ± 0.53 21.635* < .001*
Median (IQR) 8.44 (4.81 to 11.82) 0.68 (0.02 to 2.29) 0.15 (0.01 to 0.51) NA
Group differences P1
= .012*; P2
< .001*; P3
= .116 NA
Changes of color coordinate b*, representing blueness (negative) or yellowness (positive direction); IQR, interquartile range; NA, not applicable; P1
= Group 1 vs Group 2; P2
= Group 1 vs Group 3;P
3= Group 2 vs Group 3 (Dunn test).
Table 5 E* ) between the various study groups according to CIE EE L*a*b* results before and after WSL treatments
ΔE* Group 1 (RI) (n = 15) Group 2 (RP) (n = 15) Group 3 (CC) (n = 15) H-test P
Minimum 2.97 1.27 0.36NA
Maximum 19.68 4.53 1.37
Mean (± SD) 11.29 ± 5.05 2.80 ± 0.84 0.88 ± 0.28 49.352* < .001*
Median (IQR) 12.90 (8.20 to 14.81) 2.76 (2.20 to 3.51) 0.96 (0.68 to 1.04) NA
Group differences P1
= .029*; P2
< .001*; P3
= .001* NA
Perceived difference in color (ΔE*), calculated as [(ΔE L*)2 + (Δa*)2 + (Δb*)2]½; IQR, interquartile range; NA, not applicable; P1
= Group 1 vs Group 2; P2
= Group 1 vs Group 3; P1
= Group 2 vs Group 3 (Dunn test).
QUINTESSENCE INTERNATIONAL | volume 51 • number 9 • October 2020704
RESTORATIVE DENTISTRY
(ΔE*EE > 3.7). Moreover, final outcome of resin infiltration was sig-
nificantly different from the other treatment groups (see Table 5).
Thus, the null hypothesis stating that with regard to any esthetic
improvements of the studied WSL there would be no difference
between the various treatment regimens was rejected. The
dense polymer network,59 completely occluding the porous
enamel surface,33,60,61 and primarily consisting of a TEGDMA/
enamel hybrid layer,34 successfully masked the incipient lesions.
However, measurement of color improvement as provided with
the present outcome would seem to prove treatment success
only, and must be classified as a surrogate outcome, but should
not be compared to clinical endpoints in terms of true remineral-
ization. Surrogate endpoints, however, are useful tools to detect
potential success or failure of treatment, and may allow for early
treatment decisions, in particular when preservation of healthy
conditions is considered mandatory.
The current investigation applied the CIE L*a*b* color space
to measure the color differences. This standard system employs
a lightness value (L*, light to dark) as well as the two color chan-
nels a* (green-to-red component) and b* (blue-to-yellow com-
ponent). Usually, WSL are characterized by increased opacity,
and loss of normal translucency of the enamel due to absorp-
tion and light-scattering (at the roughened surface and within
the porous lesion) is the main esthetic problem. With the resin
infiltrated WSL, all three values used to describe the color index
of the treated lesions changed significantly in the present
study, with ΔL* and Δb* revealing the most prominent differ-
ences (see Tables 2 and 4). This supports the outcome of a
recent paper which showed that the resinous infiltrant itself
displayed comparably high ΔL* values, even after accelerated
aging or bleaching, thus confirming that the infiltration regi-
men is visualized as a lightening procedure.59,61 Due to the
inherent material properties, slight color changes should be
expected over time, with Δb* accounting for the visual alter-
ations.59 In laboratory studies, however, no changes have been
observed, and infiltrated lesions proved stable; untreated
lesions, however, revealed clear alterations over time.43,44,62 This
indeed would be in accordance with clinical reports that
showed a satisfactory optical durability over 6 months20,26 and
1 year;1,9,14,25 even after longer observation periods (lasting up
to 4 years) of exposure to the oral environment, neither the
color of the resin infiltrated WSL nor their esthetic camouflage
was altered.21,22,63
This esthetic effect has been confirmed, with the present
investigation having shown esthetically improved resin infil-
trated WSL (Group 1). Moreover, the nonfavorable results
observed with Group 2 (RP) obviously are in accordance with
previous clinical trials showing significant differences between
resin infiltrated WSL and other study groups. From a cariologic
point of view, resin infiltration (along with additional regular
fluoride varnish treatments) has revealed a clearly superior out-
come with significantly more arrested lesions (if compared to
fluoride varnish treatment alone) in an RCT treating facial
smooth surfaces of primary teeth.24 While resin infiltration
turned out to be superior if compared to microabrasion,19 other
RCT using actively supported remineralization regimens by
means of fluoride varnishes clearly have favored the infiltration
approach, both from an esthetic and from a clinico-medical
perspective.18,22,23,28 The patient preferences revealed in the
present study would seem to confirm these observations.
In contrast, reduced esthetic improvements have been
observed with Group 3 (CC; control) as well, and this corrobo-
rated two independent RCTs26,27 revealing a significant super-
iority of the infiltration concept over nontreated controls; the
latter were also been infiltrated with Icon after 6 months (as
part of an agreement with the patients), so no longer compar-
isons were possible.21 When considering these aspects, a closer
look into the natural fate of WSL on smooth surfaces might
seem helpful. The pioneering Backer Dirks study has shown
that 51% of early smooth surface WSL disappeared (while 36%
kept stable) after 7 years,64 and similar observations have been
published by other authors, again with predominantly stable
(and low progressing) lesion numbers.65,66 From previous clin-
ical investigations, it would seem clear that neither daily brush-
ing with various fluoride toothpastes67 nor an additional use of
highly concentrated fluoride gels (on a weekly basis)68 would
significantly alter (long-existing) WSL size or appearance over
periods of 6 months. After appreciating the outcome of infil-
trated teeth, the present patients enquired about (while some
even insisted on) treating the other lesions the same way; thus,
for ethical reasons, the current study was not prolonged, and
this was comparable to a previous RCT.21
As discussed above, post-orthodontic WSL only gradually
reduce in size69 (or even regress in some cases70) within the first
few years, and this will not be influenced by using low-level
fluoride formulations of mouthrinse and toothpaste.69 Conse-
quently, Backer Dirks64 assumed, that “The disappearance of
white opaque spots can take place by remineralization or sur-
face abrasion, or both.” Indeed, WSL are characterized by a
reduced mineral content resulting in a decreased microhard-
ness, and, thus, a gradual regression as a result of surface abra-
sion of WSL (if compared to sound enamel) has been observed
clinically;71 similarly, a significant surface substance loss of WSL
after brushing either with acidic or with abrasive oral care prod-
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Youssef et al
ucts could be confirmed in highly standardized, laboratory
experiments.72 It should be noted that a considerable increase
of enamel surface roughness has been reported after the use of
acidulated phosphate fluorides, thus indicating a weakened
substrate, susceptible to abrasion.73 In contrast, a recently pub-
lished systematic review compiling the previous studies on
surface microhardness of resin-infiltrated WSL has revealed a
considerable increase.74 These effects are coupled with a
decrease in roughness of demineralized and infiltrated enamel
surfaces,33,60 and with an initially reduced microbial adhe-
sion,75,76 thus presenting an elevated protection against demin-
eralization if compared to nontreated WSL, and an increased
resistance to the challenges of mechanical abrasion.77
It should be emphasized that fluoride treatment is not con-
sidered capable of elevating microhardness by a comparable
extent,78,79 and, accordingly, highly concentrated fluoride gels
or lacquers (supplemental to daily tooth brushing) failed to
completely remineralize and mask WSL to an esthetically
acceptable dentofacial appearance within reasonable time
periods.48,80-83 Consequently, systematic reviews have indicated
a predominantly modest effect not considered clinically rele-
vant to support the effectiveness of an enduring camouflaging
treatment of these WSL.38,46,84,85 Thus, it seems clear that a treat-
ment renunciation (like in Group 3 [CC] of the present study)
would not have the capacity for any beneficial change, since
even in the case of well-maintained mouth hygiene many
(severe) post-orthodontic WSL will not regain their pretreat-
ment level for up to 12 years after debracketing,86 while other
cases would reveal either surface abrasion or cavitation.64,66 It
should be borne in mind, however, that resin infiltration has
been introduced as a preventive regimen, with the main inten-
tion to stop or reduce progression of WSL.1
In the past, some insecurity and confusion has been created
on when to infiltrate WSL, and this has been documented in
personal communications as well as in the scientific litera-
ture.9,27,87 This mainly refers to recommendations aiming to infil-
trate WSL as soon as possible after the removal of fixed ortho-
dontic treatment,9 to avoid any surface breakdown, or to
hamper any occlusion of the tiny pores of the latter. In contrast,
others have recommended an elapse time of even more than
3 months, to wait for a spontaneous recovery.17,19 While the
pseudointact surface layer has a varying thickness of some
40 μm and a mineral content of up to 82 vol%,72 these values
may vary, in particular with arrested and inactive lesions reveal-
ing a smooth and shiny surface (indicating some precipitation
of minerals within the pores of the pseudointact surface layer).
However, from the literature it seems clear that lesions up to
1 year old will be successfully infiltrated.27,88 In these cases, and
this is comparable to resin infiltration of fluorotic or otherwise
hypomineralized teeth,12,22,89 it may become mandatory to
tailor conditioning times (up to several minutes)25,26 and to
increase infiltration times90 and/or frequencies,91 depending on
the lesion history and characteristics;30,91 consequently, the
required dental competence is high, and some well deliberated
and substantiated deviation from the manufacturer’s routinely
propagated protocol would seem advisable in all cases requir-
ing a personalization of the intervention.
Accordingly, in the present study, some teeth of Group 1 (RI)
needed prolonged drying and several applications of the resin-
ous infiltrant to mask the lesion completely, while other lesions
showed a well-pronounced and subjectively satisfactory, but
objectively only partial color improvement after a treatment
sequence following the protocol. This is in concordance with
previous studies also having reported non-complete infiltra-
tion effects in some cases.15,17,22,26 Possible reasons would seem
manifold, but longevity as well as depth and width of lesions,26
along with microorganisms3-5 and external and salivary pro-
teins and lipids2 (occluding both the lesion surface and the
porous lesion volume) have to be considered as primary causes,
at least with patients not suffering from hyposalivation.92
Therefore, a thorough cleaning procedure, along with a depro-
teinization treatment of the lesions by chemically dissolving
organic debris is strongly recommended,93 and this should be
applied prior to etching. Finally, water content also has to be
taken into account, and lesion dryness has to be assured with
utmost care.60 All these aspects must be taken into consider-
ation, and it should be clear that in some reported cases the
clinicians might have missed adopting the desired practice
effectively; thus, a well-developed treatment regimen must
cover not only the option of whether the resin infiltration
would have an effect, but also how to ensure the latter.
It should be emphasized that the chemistry of the resinous
infiltrant differs from former infiltration attempts, and, as has
been shown with the introductory papers on the infiltration
concept,1,7,8 allows for multiple combination therapies. With an
increasing popularity, infiltration treatment has been success-
fully combined with conventional adhesives and composite
resins to improve fissure sealing,94 to restore cavities,1,95 or to
bond orthodontically,96 and other approaches like internal tun-
nel restorations (including internal and external infiltration)97 of
proximal lesions have been introduced. Additionally, supple-
mental applications (like treatment of developmental defects,
or combinations with bleaching approaches30,90) have consider-
ably expanded the initially proposed indications.
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RESTORATIVE DENTISTRY
As has been elucidated above, post-orthodontic WSL have
to be considered as a long-lasting cariologic problem,86 even if
the demineralization process can be interrupted and some
repair is possible, in particular with mild lesions.20,83 From a
medical perspective, it seems clear that arrested and inactive
lesions do not necessitate any interventions, and progression
to cavitated caries should not be a concern with regularly
implemented oral hygiene;27 however, these lesions may
change to brown spots during remineralization, due to ingress
of colorants from exogenous sources, and these changes will
be even more unpleasant if compared to the chalky appear-
ance of WSL. Not astonishingly, patients suffering from the
compromised esthetics call for a clinically relevant (and at best
optically perfect) harmonization of their whitish spots, and this
will not be swiftly and satisfactorily achieved by exclusively fol-
lowing the published recommendations for using either acidu-
lated phosphate fluoride gels (1.23%) or sodium fluoride var-
nish (5%).39,40 Meanwhile, a considerable number of clinical
studies9-28 published in the past decade has provided a con-
vincing data basis for a valid estimate of the long-term durabil-
ity of the resin infiltration approach as an enduring esthetic
improvement,25 arresting the caries process.98
In contrast, various systematic reviews have repeatedly indi-
cated a lack of reliable evidence to support camouflaging or rem-
ineralizing strategies for smooth surface WSL,38,45,46,84,85,87,89,99 again
and again paraphrasing that “there would be a need for long-
term studies to confirm the effectiveness.” This should not be
excoriated from a scientific point of view. However, each of the
studies included in the various systematic reviews do comple-
ment and add some specific value to each other (even if all the
studies have some shortcomings to a certain extent, as does the
present one), thus providing validation and additional under-
standing of the masking effect of resin infiltration. It should be
remembered that the latter is of paramount importance for most
patients, in particular since the caries-arresting resin infiltration
may be successfully combined with a substantial caries remin-
eralization program;36 preferably, regular fluoride varnish appli-
cations should be used.24 Thus, with the accumulated knowledge
and the respective medico-ethical considerations in mind, fur-
ther long-term comparative investigations would not seem enti-
tled anymore.87 In other words, how many patients would be
willing to wait for several-year studies, in particular in those cases
with a significant treatment decision? Patients will favor the most
convenient therapeutic approach; beyond that, the micro-inva-
sive resin infiltration not only is considered a simple treatment
regimen, but also has gained an essential position in dentistry,
and, thus, clearly contributes to improved health care.
With the acceptable clinical and esthetic outcomes of resin
infiltration, a recovery of the patients’ self-esteem seems possi-
ble35 within one highly effective treatment session.12,28,35 By
complementing the concept of minimum intervention den-
tistry,1 the therapeutic benefits of resin infiltration as discussed
above should considerably decrease both long term (re-)
restorative needs and costs,36 and this is considered clinically
relevant, in particular when promoting patient-centered treat-
ment decisions in oral health care. With the available body of
literature in mind, it is not surprising that the infiltration con-
cept has recently been labeled as “gold standard,”20 and others
have recommended resin infiltration as a viable option99 and an
alternative to fluoride treatment of incipient lesions,23 in partic-
ular if these lesions are deemed not to regress naturally.27
Conclusion
From the current RCT identifying color differences by means of
the CIE L*a*b* color coordinates, it is concluded that WSL neces-
sitating a treatment decision will not be satisfactorily redressed
by brushing with a herbal (non-fluoride) toothpaste. When
applying remineralizing agents on a daily basis, an only minor
and clinically irrelevant improvement should be expected
within the short-term period of 1 week. In contrast, resin infiltra-
tion of WSL reveals a significant increase in luminance (ΔL*),
along with a shift in the blue/yellow axis towards yellow (Δb*),
thus resulting in favorable perceived total color alterations (ΔE*). EE
This color-neutralizing impact (if compared to the adjacent
sound enamel) contributes to the camouflaging effect of resin
infiltration, along with mimicking a natural recovery of WSL.
Together with the well-known strengthening of the demineral-
ized enamel, resin infiltration of WSL is considered a prob-
lem-solving regimen, clearly promoting dental and oral health.
Acknowledgments
The authors thank Dr Shereen Osama (Department of Restora-
tive Dentistry, Outpatients Clinics, Ministry of Health, Alexandria.
Egypt) for her clinical assistance. This investigator-driven RCT
was supported by the authors and their respective institutions
only, without any external funding. The manufacturer of the resin
infiltrant (DMG, Hamburg, Germany) has licensed international
patents for the infiltration technique for caries lesions; these pat-
ents are held by Charité - Universitätsmedizin Berlin (Germany),
with Andrej M. Kielbassa being appointed as inventor and receiv-
ing royalties. The authors declare no potential conflict of interest
with respect to authorship and/or publication of this trial.
QUINTESSENCE INTERNATIONAL | volume 51 • number 9 • October 2020 707
Youssef et al
References
1. Kielbassa AM, Müller J, Gernhardt CR.Closing the gap between oral hygiene and minimally invasive dentistry: a review on the resin infiltration technique of incipient (proximal) enamel lesions. Quintessence Int2009;40:663–681.
2. de Holanda Ferreira DA, Aires CP, De Figueiredo RC, de Sousa FB. High amount of organic matter during caries formation re-duces remineralization and resin infiltration of enamel caries. Caries Res 2018;52:580–587.
3. Parolo CC, Maltz M. Microbial contami-nation of noncavitated caries lesions: a scan-ning electron microscopic study. Caries Res2006;40:536–541.
4. Mejàre I, Brännström M. Deep bacterial penetration of early proximal caries lesionsin young human premolars. ASDC J Dent Child 1985;52:103–107.
5. Seppä L, Alakuijala P, Karvonen I. A scan-ning electron microscopic study of bacterialpenetration of human enamel in incipientcaries. Arch Oral Biol 1985;30:595–598.
6. Hariri I, Sadr A, Nakashima S, Shimada Y,Tagami J, Sumi Y. Estimation of the enameland dentin mineral content from the refrac-tive index. Caries Res 2013;47:18–26.
7. Kielbassa AM, Ulrich I, Treven L, MuellerJ. An updated review on the resin infiltrationtechnique on incipient proximal enamel lesions. Med Evol 2010;16:3–15.
8. Paris S, Meyer-Lueckel H, Kielbassa AM. Resin infiltration of natural caries lesions. J Dent Res 2007;86:662–666.
9. Lo Giudice R, Lipari F, Puleio F, et al.Spectrophotometric evaluation of enamel color variation using infiltration resin treat-ment of white spot lesions at one yearfollow-up. Dent J (Basel) 2020;8:35.
10. Muthuvel P, Ganapathy A, Subramaniam MK, Revankar VD. Erosion infiltration tech-nique: a novel alternative for maskingenamel white spot lesion. J Pharm Bioallied Sci 2017;9:S289–S291.
11. Gugnani N, Pandit IK, Goyal V, GugnaniS, Sharma J, Dogra S. Esthetic improvement of white spot lesions and non-pitted fluor-osis using resin infiltration technique: seriesof four clinical cases. J Indian Soc Pedod Prev Dent 2014;32:176–180.
12. Mazur M, Westland S, Guerra F, et al.Objective and subjective aesthetic perfor-mance of Icon treatment for enamel hypo-mineralization lesions in young adolescents: a retrospective single center study. J Dent 2018;68:104–108.
13. Feng C, Liu R, Zhao Q, Chu X. [Effect of infiltration resin on the color masking of labial enamel white spot lesions]. Hua Xi Kou Qiang Yi Xue Za Zhi (West China J Stomatol)2013;31:597–599.
14. Feng CH, Chu XY. [Efficacy of one year treatment of icon infiltration resin onpost-orthodontic white spots]. Beijing DaXue Xue Bao Yi Xue Ban (J Peking Univ Health Sci) 2013;45:40–43.
15. Tirlet G, Chabouis HF, Attal JP. Infiltration, a new therapy for masking enamel white spots: a 19-month follow-up case series. Eur J Esthet Dent 2013;8:180–190.
16. Hammad SM, El Banna M, El Zayat I, Mohsen MA. Effect of resin infiltration onwhite spot lesions after debonding ortho-dontic brackets. Am J Dent 2012;25:3–8.
17. Kim S, Kim EY, Jeong TS, Kim JW. Theevaluation of resin infiltration for maskinglabial enamel white spot lesions. Int J Paedi-atr Dent 2011;21:241–248.
18. Gözetici B, Öztürk-Bozkurt F, Toz-Akalın T. Comparative evaluation of resin infiltrationand remineralisation of noncavitated smooth surface caries lesions: 6-month re-sults. Oral Health Prev Dent 2019;17:99–106.
19. Gu X, Yang L, Yang D, et al. Esthetic im-provements of postorthodontic white-spotlesions treated with resin infiltration and microabrasion: a split-mouth, randomizedclinical trial. Angle Orthod 2019;89:372–377.
20. Kannan A, Padmanabhan S. Compara-tive evaluation of Icon resin infiltration and Clinpro XT varnish on colour and fluores-cence changes of white spot lesions: a randomized controlled trial. Prog Orthod2019; 20:23.
21. Knösel M, Eckstein A, Helms HJ. Long-term follow-up of camouflage effects follow-ing resin infiltration of post orthodonticwhite-spot lesions in vivo. Angle Orthod2019; 89:33–39.
22. Çiftçi ZZ, Hanimeli S, Karayilmaz H, Güngör OE. The efficacy of resin infiltrate on the treatment of white spot lesions and developmental opacities. Niger J Clin Pract2018;21:1444–1449.
23. Giray FE, Durhan MA, Haznedaroglu E,Durmus B, Kalyoncu IO, Tanboga I. Resin infiltration technique and fluoride varnish onwhite spot lesions in children: preliminaryfindings of a randomized clinical trial. Niger J Clin Pract 2018;21:1564–1569.
24. Turska-Szybka A, Gozdowski D, Mierzwińska-Nastalska E, Olczak-Kowalczyk D. Randomised clinical trial on resin infiltra-tion and fluoride varnish vs fluoride varnishtreatment only of smooth-surface early caries lesions in deciduous teeth. Oral Health Prev Dent 2016;14:485–491.
25. Eckstein A, Helms HJ, Knösel M. Camouflage effects following resin infiltra-tion of postorthodontic white-spot lesions in vivo: one-year follow-up. Angle Orthod2015;85:374–380.
26. Knösel M, Eckstein A, Helms HJ. Durability of esthetic improvement follow-ing Icon resin infiltration of multibracket-in-duced white spot lesions compared with no therapy over 6 months: a single-center, split-mouth, randomized clinical trial. Am J Orthod Dentofacial Orthop 2013;144:86–96.
27. Senestraro SV, Crowe JJ, Wang M, et al. Minimally invasive resin infiltration of arrested white-spot lesions: a randomized clinical trial. J Am Dent Assoc 2013;144: 997–1005.
28. Wang L, Jian J, Lu H-F. [Efficiency of resin infiltration versus fluoride varnish for treatment of post-orthodontic white spot lesions]. Zhongguo Zuzhi Gongcheng Yanjiu (Chin J Tissue Eng Res) 2013;17:5303–5308.
29. Khanna R, Chandra A, Singh RK. Quan-titative evaluation of masking effect of resininfiltration on developmental defects of enamel. Quintessence Int 2020;51:448–455.
30. Gugnani N, Pandit IK, Gupta M, Gugnani S, Soni S, Goyal V. Comparativeevaluation of esthetic changes in nonpitted fluorosis stains when treated with resin infil-tration, in-office bleaching, and combination therapies. J Esthet Restor Dent 2017;29:317–324.
31. Hallgren K, Akyalcin S, English J, Tufekçi E, Paravina RD. Color properties of deminer-alized enamel surfaces treated with a resin infiltration system. J Esthet Restor Dent2016;28:339–346.
32. Min JH, Inaba D, Kwon HK, Chung JH, Kim BI. Evaluation of penetration effect of resin infiltrant using optical coherence to-mography. J Dent 2015;43:720–725.
33. Yazkan B, Ermiş RB. Effect of resin infil-tration and microabrasion on the microhard-ness, surface roughness and morphology of incipient carious lesions. Acta Odontol Scand 2018;76:473–481.
34. Perdigão J. Resin infiltration of enamel white spot lesions: an ultramorphological analysis. J Esthet Restor Dent 2020;32:317–324.
35. Muñoz MA, Arana-Gordillo LA, Gomes GM, et al. Alternative esthetic managementof fluorosis and hypoplasia stains: blending effect obtained with resin infiltration tech-niques. J Esthet Restor Dent 2013;25:32–39.
36. Manoharan V, Arun Kumar S, Aru-mugam SB, Anand V, Krishnamoorthy S,Methippara JJ. Is resin infiltration a microin-vasive approach to white lesions of calcified tooth structures? A systemic review. Int J Clin Pediatr Dent 2019;12:53–58.
37. Khoroushi M, Kachuie M. Preventionand treatment of white spot lesions in ortho-dontic patients. Contemp Clin Dent 2017;8:11–19.
QUINTESSENCE INTERNATIONAL | volume 51 • number 9 • October 2020708
RESTORATIVE DENTISTRY
38. Höchli D, Hersberger-Zurfluh M, Papageorgiou SN, Eliades T. Interventions fororthodontically induced white spot lesions: a systematic review and meta-analysis. Eur J Orthod 2017;39:122–133.39. Slayton RL, Urquhart O, Araujo MWB, et al. Evidence-based clinical practice guide-line on nonrestorative treatments for carious lesions: a report from the American Dental Association. J Am Dent Assoc 2018;149:837–849.e819.40. Urquhart O, Tampi MP, Pilcher L, et al.Nonrestorative treatments for caries: system-atic review and network meta-analysis. J Dent Res 2019;98:14–26.41. Paris S, Meyer-Lueckel H, Cölfen H, Kielbassa AM. Resin infiltration of artificial enamel caries lesions with experimental light curing resins. Dent Mater J 2007;26:582–588.42. Prasada KL, Penta PK, Ramya KM. Spectrophotometric evaluation of whitespot lesion treatment using novel resin infiltration material (Icon). J Conserv Dent2018;21:531–535.43. Yuan H, Li J, Chen L, Cheng L, CannonRD, Mei L. Esthetic comparison of white-spotlesion treatment modalities using spectrom-etry and fluorescence. Angle Orthod2014;84:343–349.44. Rocha Gomes Torres C, Borges AB, Torres LM, Gomes IS, de Oliveira RS. Effect of caries infiltration technique and fluoride therapy on the colour masking of white spot lesions. J Dent 2011;39:202–207.45. Borges AB, Caneppele TM, Masterson D, Maia LC. Is resin infiltration an effective esthetic treatment for enamel developmentdefects and white spot lesions? A systematicreview. J Dent 2017;56:11–18.46. Sonesson M, Bergstrand F, Gizani S, Twetman S. Management of post-orthodon-tic white spot lesions: an updated systematicreview. Eur J Orthod 2017;39:116–121.47. Heravi F, Ahrari F, Tanbakuchi B. Effec-tiveness of MI Paste Plus and Remin Pro on remineralization and color improvement of postorthodontic white spot lesions. Dent ResJ (Isfahan) 2018;15:95–103.48. Ebrahimi M, Mehrabkhani M, Ahrari F, Parisay I, Jahantigh M. The effects of threeremineralizing agents on regression of whitespot lesions in children: a two-week, sin-gle-blind, randomized clinical trial. J Clin Exp Dent 2017;9:e641–e648.49. Khairnar MR, Dodamani AS, KaribasappaGN, Naik RG, Deshmukh MA. Efficacy of herbal toothpastes on salivary pH and salivary glucose – a preliminary study. J Ayurveda Integr Med 2017;8:3–6.50. Ramesh MV, Kumar PG, AllamaprabhuCR, et al. Evaluation of dentifrices of comple-mentary and alternative medicinal systemson plaque formation and gingivitis: a ran-domized controlled clinical trial. J Clin ExpDent 2020;12:e227–e234.
51. Pandis N. Sample calculation for split-mouth designs. Am J Orthod Dentofacial Orthop 2012;141:818–819.52. Zanatta RF, da Silva TM, Esper MÂ, et al.Guidelines for conducting split-mouth clin-ical studies in restorative dentistry. Braz DentSci 2017;20:530.53. Kielbassa AM, Beheim-SchwarzbachNJ, Neumann K, Zantner C. In vitro compari-son of visual and computer-aided pre- and post-tooth shade determination using vari-ous home bleaching procedures. J ProsthetDent 2009;101:92–100.54. Derdilopoulou FV, Zantner C, Neu-mann K, Kielbassa AM. Evaluation of visualand spectrophotometric shade analyses: a clinical comparison of 3758 teeth. Int J Prost-hodont 2007;20:414–416.55. Zhu H, Zhang S, Ahn C. Sample sizeconsiderations for split-mouth design. StatMethods Med Res 2017;26:2543–2551.56. Smaïl-Faugeron V, Fron-Chabouis H,Courson F, Durieux P. Comparison of inter-vention effects in split-mouth and parallel-arm randomized controlled trials: a meta-ep-idemiological study. BMC Med Res Methodol 2014;14:64.57. Malekipour M, Norouzi Z, Shahlaei S.Effect of remineralizing agents on tooth color after home bleaching. Front Dent2019;16:158–165.58. Kankariya AR, Patel AR, Kunte SS. The effect of different concentrations of watersoluble azadirachtin (neem metabolite) on Streptococcus mutans compared with chlor-hexidine. J Indian Soc Pedod Prev Dent2016;34:105–110.59. Chen M, Li J-Z, Zuo Q-L, Liu C, Jiang H, Du M-Q. Accelerated aging effects on color, microhardness and microstructure of ICONresin infiltration. Eur Rev Med Pharmacol Sci 2019;23:7722–7731.60. El Meligy OA, Alamoudi NM, Ibrahim ST, Felemban OM, Al-Tuwirqi AA. Effect of resin infiltration application on early prox-imal caries lesions in vitro (epub ahead of print, 1 May 2020). J Dent Sci 2020 doi: 10.1016/j.jds.2020.04.005.61. Horuztepe SA, Başeren M. Effect of resin infiltration on the color and microhard-ness of bleached white-spot lesions in bovine enamel (an in vitro study). J Esthet Restor Dent 2017;29:378–385.62. Zhao X, Ren YF. Surface properties and color stability of resin-infiltrated enamel lesions. Oper Dent 2016;41:617–626.63. Cazzolla AP, De Franco AR, Lacaita M,Lacarbonara V. Efficacy of 4-year treatment of icon infiltration resin on postorthodontic white spot lesions. BMJ Case Rep 2018;bcr2018225639.64. Backer Dirks O. Posteruptive changes indental enamel. J Dent Res 1966;45:503–511.
65. Brown JP, Amaechi BT, Bader JD, et al. The dynamic behavior of the early dental caries lesion in caries-active adults and impli-cations. Community Dent Oral Epidemiol 2015;43:208–216.
66. Ferreira Zandoná A, Santiago E, EckertGJ, et al. The natural history of dental caries lesions: a 4-year observational study. J DentRes 2012;91:841–846.
67. Zantner C, Martus P, Kielbassa AM. Clinical monitoring of the effect of fluorides on long-existing white spot lesions. Acta Odontol Scand 2006;64:115–122.
68. Karlsson L, Lindgren LE, Trollsås K, Angmar-Månsson B, Tranæus S. Effect of supplementary amine fluoride gel in caries- active adolescents. A clinical QLF study. Acta Odontol Scand 2007;65:284–291.
69. Willmot DR. White lesions after ortho-dontic treatment: does low fluoride make a difference? J Orthod 2004;31:235–242.
70. Beerens MW, Boekitwetan F, van der Veen MH, ten Cate JM. White spot lesions after orthodontic treatment assessed by clinical photographs and by quantitative light-induced fluorescence imaging; a retrospective study. Acta Odontol Scand 2015;73:441–446.
71. Årtun J, Thylstrup A. A 3-year clinical and SEM study of surface changes of carious enamel lesions after inactivation. Am J Or-thod Dentofacial Orthop 1989;95:327–333.
72. Kielbassa AM, Gillmann L, Zantner C,Meyer-Lueckel H, Hellwig E, Schulte-Mönting J. Profilometric and microradiographic stud-ies on the effects of toothpaste and acidicgel abrasivity on sound and demineralizedbovine dental enamel. Caries Res 2005;39:380–386.
73. Dionysopoulos D, Koliniotou-KoumpiaE. Effect of acidulated phosphate fluoride gel on the surface of dental nanocomposite re-storative materials. J Nano Res 2018;51:1–12.
74. Zakizade M, Davoudi A, Sadeghian S,Naseri F, Shirban F, Iravani S. Effect of resininfiltration technique on improving surface hardness of enamel lesions; a systematic review and meta-analysis. J Evid Based Dent Pract 2020 20:101405.
75. Tawakoli PN, Attin T, Mohn D. Oral biofilm and caries-infiltrant interactions on enamel. J Dent 2016;48:40–45.
76. Arslan S, Zorba YO, Atalay MA, et al. Effect of resin infiltration on enamel surface properties and Streptococcus mutans adhe-sion to artificial enamel lesions. Dent Mater J 2015;34:25–30.
77. Neres ÉY, Moda MD, Chiba EK, Briso A, Pessan JP, Fagundes TC. Microhardness androughness of infiltrated white spot lesionssubmitted to different challenges. Oper Dent 2017;42:428–435.
QUINTESSENCE INTERNATIONAL | volume 51 • number 9 • October 2020 709
Youssef et al
78. Liu Y, Deng H, Tang L, Zhang Z. [Effect of resin infiltration on microhardness of artificialcaries lesions]. Zhonghua Kou Qiang Yi XueZa Zhi (Chin J Stomatol) 2015;50:737–741.
79. Torres CR, Rosa PC, Ferreira NS, BorgesAB. Effect of caries infiltration technique and fluoride therapy on microhardness of enamel carious lesions. Oper Dent 2012;37: 363–369.
80. He T, Li X, Dong Y, et al. Comparative assessment of fluoride varnish and fluoridefilm for remineralization of postorthodontic white spot lesions in adolescents and adultsover a 6-month period: A single-center, ran-domized controlled clinical trial. Am J Or-thod Dentofacial Orthop 2016;149:810–819.
81. Singh S, Singh SP, Goyal A, Utreja AK,Jena AK. Effects of various remineralizingagents on the outcome of post-orthodontic white spot lesions (WSLs): a clinical trial. ProgOrthod 2016;17:25.
82. Huang GJ, Roloff-Chiang B, Mills BE, et al. Effectiveness of MI Paste Plus and Previ-Dent fluoride varnish for treatment of white spot lesions: a randomized controlled trial. Am J Orthod Dentofacial Orthop2013;143:31–41.
83. Du M, Cheng N, Tai B, Jiang H, Li J, BianZ. Randomized controlled trial on fluoride varnish application for treatment of whitespot lesion after fixed orthodontic treat-ment. Clin Oral Investig 2012;16:463–468.
84. Fernández-Ferrer L, Vicente-Ruíz M, García-Sanz V, et al. Enamel remineralizationtherapies for treating postorthodontic white-spot lesions: a systematic review. J AmDent Assoc 2018;149:778–786.e772.
85. Chen H, Liu X, Dai J, Jiang Z, Guo T, Ding Y. Effect of remineralizing agents onwhite spot lesions after orthodontic treat-ment: a systematic review. Am J Orthod Den-tofacial Orthop 2013;143:376–382.e373.
86. Shungin D, Olsson AI, Persson M. Orthodontic treatment-related white spotlesions: a 14-year prospective quantitativefollow-up, including bonding material as-sessment. Am J Orthod Dentofacial Orthop2010;138:136.e131–138.
87. Abdullah Z, John J. Minimally invasivetreatment of white spot lesions – a system-atic review. Oral Health Prev Dent 2016;14:197–205.
88. Neuhaus KW, Graf M, Lussi A, Katsaros C.Late infiltration of post-orthodontic white spot lesions. J Orofac Orthop 2010;71:442–447.
89. Di Giovanni T, Eliades T, PapageorgiouSN. Interventions for dental fluorosis: a sys-tematic review. J Esthet Restor Dent 2018;30: 502–508.
90. Shahroom NSB, Mani G, Ramakrishnan M. Interventions in management of dentalfluorosis, an endemic disease: a systematicreview. J Family Med Prim Care 2019;8:3108–3113.
91. Abbas BA, Marzouk ES, Zaher AR. Treatment of various degrees of white spotlesions using resin infiltration – in vitro study. Prog Orthod 2018;19:27.
92. Tschoppe P, Wolgin M, Pischon N, Kielbassa AM. Etiologic factors of hyposaliva-tion and consequences for oral health. Quintessence Int 2010;41:321–333.
93. Ulrich I, Mueller J, Wolgin M, Frank W,Kielbassa AM. Tridimensional surface rough-ness analysis after resin infiltration of (depro-teinized) natural subsurface carious lesions. Clin Oral Investig 2015;19:1473–1483.
94. Kielbassa AM, Ulrich I, Schmidl R,Schüller C, Frank W, Werth VD. Resin infiltra-tion of deproteinised natural occlusal sub-surface lesions improves initial quality of fissure sealing. Int J Oral Sci 2017;9:117–124.
95. Borges AB, Abu Hasna A, Matuda AGN, et al. Adhesive systems effect over bondstrength of resin-infiltrated and de-/reminer-alized enamel. F1000Res 2019;8:1743.
96. Anicic MS, Goracci C, Juloski J, Miletic I,Mestrovic S. The influence of resin infiltration pretreatment on orthodontic bonding to demineralized human enamel. Appl Sci 2020;10:3619.
97. Kielbassa AM, Leimer MR, Hartmann J, Harm S, Pasztorek M, Ulrich IB. Ex vivo inves-tigation on internal tunnel approach/internal resin infiltration and external nanosil-ver-modified resin infiltration of proximalcaries exceeding into dentin. PLoS One2020;15:e0228249.
98. Faghihian R, Shirani M, Tarrahi MJ,Zakizade M. Efficacy of the resin infiltrationtechnique in preventing initial caries pro-gression: a systematic review and meta-analysis. Pediatr Dent 2019;41:88–94.
99. Ferreira JD, Flor-Ribeiro MD, Marchi GM, Pazinatto FB. The use of resinous infiltrants for the management of incipient carious lesions: a literature review. J Health Sci 2019;21:358–364.
Ahmed Youssef
Ahmed Youssef PhD candidate, Department of Restorative Den-tistry, Faculty of Dentistry, Minia University, Minia, Egypt
Mohamed Farid Professor, Department of Restorative Dentistry,Cairo University, Cairo, Egypt
Mohamed Zayed Assistant Professor, Department of RestorativeDentistry, Faculty of Dentistry, Minia University, Minia, Egypt
Edward Lynch Adjunct Professor, University of Nevada, Las Vegas,NV, USA; and Honorary Professor, De Montford University, Leicester, UK
Mohammad K. Alam Associate Professor, Department of Preventive Dentistry, College of Dentistry, Jouf University, Aljouf, KSA
Andrej M. Kielbassa Professor and Head, Centre for OperativeDentistry, Periodontology, and Endodontology, University of Den-tal Medicine and Oral Health, Danube Private University (DPU),Krems, Austria
Correspondence: Prof Dr Dr h c Andrej M. Kielbassa, Centre for Operative Dentistry, Periodontology, and Endodontology, University of Dental Medicine and Oral Health, Danube Private University (DPU), Steiner Landstraße 124, A – 3500 Krems, Austria. Email: [email protected]