Measurement of Radiation and Dosimetric Procedure.pptx
Лікування рефрактерного періодонтиту
1. Original Article
Clinical outcomes of adjunctive indocyanine
green-diode lasers therapy for treating
refractory periodontitis: A randomized
controlled trial with in vitro assessment
Chun-Pin Chiang a,b,c
, Olivia Hsieh d
, Wei-Chiu Tai d
,
Yi-Jane Chen c,d
, Po-Chun Chang c,d,
*
a
Department of Dentistry, Far Eastern Memorial Hospital, New Taipei City, Taiwan
b
Graduate Institute of Oral Biology, School of Dentistry, National Taiwan University, Taipei, Taiwan
c
Department of Dentistry, National Taiwan University Hospital, Taipei, Taiwan
d
Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, Taipei,
Taiwan
Received 28 July 2019; received in revised form 10 August 2019; accepted 20 August 2019
KEYWORDS
Photochemotherapy;
Periodontitis;
Cytokines;
Indocyanine green
Background/purpose: It is still challengeable to treat periodontal pockets refractory to me-
chanical debridement. This study is to evaluate the potential of indocyanine green (ICG)-diode
laser-based photothermal therapy (PTT) for solving this dilemma.
Methods: Bone marrow-derived mesenchymal stem cells (BMSCs) and periodontal ligament
cells (PDLCs) were incubated with phosphate-buffered saline, chlorhexidine, or ICG, non-
irradiated or irradiated with 810-nm diode lasers, and the cell viability was evaluated. Patients
with teeth refractory to mechanical periodontal debridement on different quadrants were re-
cruited. At baseline (T0), all examined teeth received scaling and root planing, and those on
the test quadrant (PTT group) received ICG-diode laser treatment. The outcome was evaluated
using clinical parameters and cytokines in the gingival crevicular fluids at 4e6 weeks (T1) and 6
months (T2).
Results: In ICG-treated cultures, the viability of BMSCs and PDLCs was recovered on day 4, and
laser irradiation inhibited the metabolic activities of BMSCs. 22 patients with 30 control teeth
and 35 PTT-treated teeth were examined. All examined teeth showed modest reductions in
probing pocket depth (PPD), clinical attachment loss (CAL), bleeding upon probing (BOP),
and plaque score at T1 and T2 and significant reductions in IL-1b and MMP-8 at T2. Compared
with controls, BOP was reduced more prominently, IL-1b and MMP-8 were significantly lower,
and reductions in PPD and CAL were slightly greater in the PTT group at T1 (0.05e0.19 mm).
* Corresponding author. Graduate Institute of Clinical Dentistry, School of Dentistry, National Taiwan University, 1 Chang-Te St, Taipei,
100, Taiwan. Fax: þ886 2 2383 1346.
E-mail address: changpc@ntu.edu.tw (P.-C. Chang).
+ MODEL
Please cite this article as: Chiang C-P et al., Clinical outcomes of adjunctive indocyanine green-diode lasers therapy for treating re-
fractory periodontitis: A randomized controlled trial with in vitro assessment, Journal of the Formosan Medical Association, https://
doi.org/10.1016/j.jfma.2019.08.021
https://doi.org/10.1016/j.jfma.2019.08.021
0929-6646/Copyright ª 2019, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an open access article under the CC
BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Available online at www.sciencedirect.com
ScienceDirect
journal homepage: www.jfma-online.com
Journal of the Formosan Medical Association xxx (xxxx) xxx
2. Conclusion: ICG-diode laser-based PTT is compatible to periodontium and assists in faster res-
olution of gingival inflammation in periodontal pockets refractory to mechanical debridement.
Copyright ª 2019, Formosan Medical Association. Published by Elsevier Taiwan LLC. This is an
open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-
nc-nd/4.0/).
Introduction
Subgingival debridement to remove or disrupt subgingival
biofilm has been considered as an integral component of
nonsurgical and surgical periodontal treatments.1
In gen-
eral, 1e3 mm of probing pocket depth (PPD) reduction and
0e2 mm of clinical attachment gain can be achieved.2e4
However, debridement was found to be ineffective in
sites with PPD ! 6 mm, regardless of nonsurgical or surgical
approach.5
Furthermore, sites with a residual PPD ! 6 mm
after treatment exhibited potential risk for future tooth
loss.6
Antibiotics have been used as an adjunct treatment
strategy to resolve sites that are refractory to mechanical
debridement.7
Although clinical improvements could be
observed in some protocols,7,8
bacterial resistance and
drug-associated adverse effect are still issues that need
concern.9,10
Antimicrobial photodynamic therapy (aPDT) has been
developed as a novel adjunct to mechanical periodontal
debridement.11
aPDT generally consists of two compo-
nents, a photosensitizer which can be uptaken by bacteria
and the light irradiation which is used to activate the
photosensitizer to generate singlet oxygen. The singlet
oxygen can target the cellular content to injure cells or
bacteria and is unlikely to develop bacterial resistance.12,13
Clinical studies have demonstrated that adjunct aPDT re-
sults in modest short-term improvement in clinical param-
eters.14,15
A previous meta-analysis reported that aPDT may
provide an additional 0.08e0.44 mm of PPD reduction and
0.43e0.51 mm of clinical attachment gain during the sup-
portive phase compared with mechanical debridement.16
In addition to oxidative attack, indocyanine green (ICG),
an FDA-approved fluorescence perfusion dye and a commonly
used photosensitizer, has been reported to act as a photo-
thermal agent that responds to near-infrared (NIR) laser.17
The hyperthermic condition caused cell injury, and NIR
excitation wavelength allowed deeper light penetration.18
Previous studies have confirmed that ICG with low-level
diode laser inhibited the growth of periodontopathogens,
including Porphyromonas gingivalis, Fusobacterium nuclea-
tum, and Aggregatibacter actinomycetemcomitans.13,19,20
Altogether, ICG with NIR laser irradiation might have
greater efficacy on deep periodontal pockets.
In the present study, we investigated the effect of ICG-
diode lasers (810 nm, within NIR range) on periodontal cells
with regeneration potential. Tang et al. reported that ICG-
NIR laser irradiation can increase the temperature to
>43
C21
and this hyperthermic condition can potentially
influence the subsequent tissue reattachment and repair. A
split-mouth clinical trial was conducted to evaluate the
therapeutic value of ICG-diode lasers in sites that were
refractory to mechanical debridement.
Materials and methods
Ethical approval
This study was conducted in accordance with the Declara-
tion of Helsinki of 1975, and revised in 2000, and ethical
approval was granted by the Institutional Review Board of
the National Taiwan University Hospital (NTUH) under the
protocol no. 201506054RINB for the harvesting of peri-
odontal ligament cells and the protocol no. 201701035MIPA
for the clinical investigation. The clinical investigation has
also been registered on clinicatrials.gov with the identifier
no. NCT03557827.
Diode laser and treatment solutions
A diode laser apparatus (FOX 810, A.R.C. Laser GmbH,
Nurnberg, Germany) with a wavelength of 810 nm and a
maximum power output of 8 W was used. Phosphate-
buffered saline (PBS) was obtained from SigmaeAldrich.
ICG (Emundo, A.R.C. Laser GmbH) was freshly prepared
according to the manufacturer’s instruction chlorhexidine
(CHX) (Corol; Sintong Biotech Co. Ltd., Taoyuan, Taiwan)
was diluted to 0.01% using PBS.
In vitro examination
Immortalized bone marrow-derived mesenchymal stem
cells (BMSCs) were indirectly obtained from Professor Junya
Toguchida, and the establishment and the characterization
of these cell lines have been previously described.22
Pri-
mary periodontal ligament cells (PDLCs) were isolated from
three premolars extracted from young healthy patients for
the purpose of orthodontics as previously described.23
In
brief, the PDL tissue was detached from the root surface,
cut into 1-mm2
chips, and placed in culture dishes for 7e10
days. PDLCs grown from the explants were subcultured for
3e5 passages before examinations.
Both BMSCs and PDLCs were seeded onto 12-well plates
at an initial density of 105
cells/well with culture medium
containing Dulbecco’s modified Eagle’s medium supple-
mented with 100 U/mL of penicillin, 100 mg/mL of strep-
tomycin, and 10% fetal bovine serum. After 24 h, the
culture medium was removed and the plates were washed
twice with PBS. The cultured cells were then treated with
PBS, CHX, or ICG, respectively, for 8 min, and half of the
wells in each group received diode laser irradiation for 20 s
immediately after adding the solution. Laser irradiation
was delivered using a bleaching handpiece at 500 mW
output power continuously under a noncontact mode
(5e10 mm distance between the handpiece and the cell
2 C.-P. Chiang et al.
+ MODEL
Please cite this article as: Chiang C-P et al., Clinical outcomes of adjunctive indocyanine green-diode lasers therapy for treating re-
fractory periodontitis: A randomized controlled trial with in vitro assessment, Journal of the Formosan Medical Association, https://
doi.org/10.1016/j.jfma.2019.08.021
3. layer). The treatment solution was then removed, replaced
with the abovementioned culture medium, and the cells
were incubated for 24 h and 96 h. Then, the cell layers
were examined by Alamar blue and 40
,6-diamidino-2-
phenylindole (DAPI) staining using commercialized kits.
The experiments were independently performed in
triplicate.
Recruitment of participants
The participants were recruited from January 2018 to
October 2018 at the Department of Dentistry, NTUH. The
inclusion criteria were 1) age 20e82 years; 2) being sys-
temically healthy; 3) having at least 20 teeth present; 4)
having completed full mouth periodontal treatment and
being under regular follow-up; 5) having at least one tooth
with !5 mm PPD, !5 mm clinical attachment loss (CAL),
and bleeding upon probing (BOP) in at least two quadrants;
6) no smoking history; 7) no long-term (2 weeks) use of
medications known to affect periodontal or systemic con-
dition; and 8) no antibiotics taken within the past 2 months.
BOP was evaluated using the protocol described by Ainamo
and Bay.24
All eligible subjects were recruited at the
Department of Dentistry, NTUH, and signed informed con-
sent was obtained before participation.
Study design of clinical trial
A paired (split-mouth) study design was used. Photothermal
therapy (PTT) was randomly assigned to the teeth re-
fractory to mechanical debridement of one quadrant of
each participant, and teeth refractory to mechanical
debridement in the other quadrant were served as control.
The allocation of the treatment strategies was based on the
outcome generated by a computer algorithm. The protocols
of PTT described below were applied by a single specialist
who was not involved in the assessment of clinical
parameters.
1. Subgingival scaling was performed using a scaling tip.
2. After 15 min, ICG was directly injected into periodontal
pockets using a 27G blunt needle in the apico-coronal
direction for 60e90 s.
3. Continuous irradiation to periodontal pockets was car-
ried out by a 500-mW diode laser using a bleaching
handpiece with a 5e10 mm distance to the gingival
margin for 10 s (anterior teeth and premolars) or 15 s
(molars).
4. Continuous irradiation to periodontal pockets was car-
ried out by a 200-mW diode laser using a 300-mm bulb
fiber on the gingival margin and a contact mode for 10 s
(anterior teeth and premolars) or 15 s (molars).
5. Continuous irradiation was carried out by a 200-mW
diode laser using a 300-mm bare fiber inserting into
periodontal pockets using a contact mode for 10 s
(anterior teeth and premolars) or 20 s (molars).
6. After 90 s, the ICG was washed off by inserting the
scaling tip into periodontal pockets with copious water
irrigation but without contacting the root surface or the
pocket epithelium for 60 s.
7. The abovementioned procedures were repeated (sec-
ond-round PTT) after 4e7 days.
8. If patients still complained of soreness or spontaneous
bleeding persisting for more than 1 week after the
second-round PTT, a third-round PTT (Steps 1e6) was
performed 2 weeks after the second-round PTT.
The teeth in the control group received none of the
abovementioned procedures except subgingival scaling.
Assessment of clinical parameters
Clinical parameters were assessed at baseline (T0), 4e6
weeks (T1), and 6 months after the last round of PTT (T2).
PPD (the distance from the free gingival margin to the
bottom of periodontal pocket), gingival recession (GR; the
distance from the cementoenamel junction to the free
gingival margin), and clinical attachment loss (CAL; the
distance from the cementoenamel junction to the bottom
of periodontal pocket) were measured at six surfaces of the
teeth using a 10-mm manual periodontal probe (PCP10-SE,
Hu-Friedy Co. Inc., Chicago, IL, USA). Plaque score (PS) was
measured at four surfaces of the teeth.25
Gingival crevicular fluid sampling and biomarker
analysis
Gingival crevicular fluid (GCF) was harvested from all
examined teeth at 2e3 pm using prefabricated paper strips
(Oraflow Inc., Plainview, NY, USA) after removing plaque
and dried by an air springe supragingivally at T0, T1, and
T2. The strips were inserted into the pockets until resis-
tance was noted and were maintained for 30 s. Samples
contaminated with blood were discarded. GCF volume was
measured using a calibrated Periotron 8100 (Oraflow, Inc.).
The GCF sample was eluted in 100 ml PBS for 30 min and
stored at À20
C until subsequent analysis.
Commercially available enzyme-linked immunosorbent
assay (ELISA) kits were used to determine the levels of IL-1b
and MMP-8 in the GCF according to the manufacturer’s in-
structions (Boster Biological Tech., Pleasanton, CA, USA).
The experiments were independently performed in
triplicate.
Statistical analysis
The reduction of CAL in sites with an initial PPD !5 mm and
a CAL !5 mm at 6 months was set as the primary outcome
variable of this study, and the sample size was calculated
by power analysis based on an effect size of 0.40, a Z 0.05,
and 80% power. On the basis of these data, the minimum
number of participants required for this study was calcu-
lated as 15 per treatment group. Considering potential
dropouts and incompliance to treatment instruction, 23
participants per group were enrolled. Because all examined
parameters were not assumed to exhibit a normal distri-
bution, the Wilcoxon signed-rank test was used to evaluate
the differences in the examined parameters between
groups at the same time point, and the Friedman test with
Dunn’s post-test was used to evaluate the differences in the
examined parameters among different time points in the
Photothermal therapy for periodontitis 3
+ MODEL
Please cite this article as: Chiang C-P et al., Clinical outcomes of adjunctive indocyanine green-diode lasers therapy for treating re-
fractory periodontitis: A randomized controlled trial with in vitro assessment, Journal of the Formosan Medical Association, https://
doi.org/10.1016/j.jfma.2019.08.021
4. group receiving the same clinical treatment protocol. Data
were described as mean Æ standard error of the mean in
the bars and line charts and as mean with 5%e95%
percentile in the box and whisker plot. Statistical signifi-
cance was defined as p value 0.05.
Results
Viability of cells
Regarding BMSCs, on day 1, it was found that the number
and metabolic activities of cells reduced significantly in
Groups CHX and ICG compared with Group PBS, and laser
irradiation resulted in a slightly reduced number of BMSCs
in Group PBS (Fig. 1A and B). In Group PBS, the number of
BMSCs increased significantly, and the metabolic activities
of the laser-irradiated specimens resumed to levels similar
to those of specimens without laser irradiation on day 4.
The number and metabolic activities remained low in Group
CHX but increased significantly in Group ICG on day 4.
However, in Group ICG, the metabolic activities were
significantly reduced in the laser-irradiated specimens
compared with those of specimens not exposed to laser
irradiation at both time points (Fig. 1B).
Regarding PDLCs, the number and metabolic activities of
cells increased significantly in Groups PBS and ICG on day 4,
whereas these levels were consistently low in Group CHX
(Fig. 1C and D). There was no obvious difference between
the non-irradiated and irradiated specimens in any viability
parameter of any group at any time point.
Baseline characteristics of participants
A total of 23 participants were recruited, and 1 participant
dropped out at 3 months because she could not comply with
the treatment schedule and was excluded from the study.
Consequently, 22 participants (10 males aged 48e82 years
with a mean age of 59.6 Æ 11.4 years and 12 females aged
43e78 years with a mean age of 60.3 Æ 11.8 years) with a
total of 30 examined teeth receiving the control treatment
and 35 examined teeth receiving PTT were evaluated.
Table 1 lists the baseline characteristics of the examined
sites. All examined teeth exhibited BOP at baseline (T0). In
the PTT group, the mean PPD and CAL were slightly greater,
and PI was slightly lower. The maximal initial PPD and CAL
were significantly greater in the PTT group than in the
control group (p 0.05 for both).
Changes in clinical parameters after treatment
Fig. 2 shows the levels of clinical parameters from T0 to T2.
In general, PPD, CAL, and PS were slightly reduced from T0
Figure 1 The in vitro assessment of IG-diode laser irradiation on oral cells. (A) The DAPI(þ) BMSCs. (B) Viability of BMSCs by
Alamar blue assay. (C) The DAPI(þ) PDLCs. (D) Viability of PDLCs by Alamar blue assay. (Significant differences to the same
irradiation protocol in the same group at different time points: a
p0.05, b
p 0.001; significant differences to Group PBS under
the same irradiation protocol at the same time point: c
p 0.05, d
p 0.01, e
p 0.001; significant differences to the no laser-
irradiated specimens in the same group at the same time point: f
p 0.05, g
p 0.01).
4 C.-P. Chiang et al.
+ MODEL
Please cite this article as: Chiang C-P et al., Clinical outcomes of adjunctive indocyanine green-diode lasers therapy for treating re-
fractory periodontitis: A randomized controlled trial with in vitro assessment, Journal of the Formosan Medical Association, https://
doi.org/10.1016/j.jfma.2019.08.021
5. to T1 and became steady after T1, regardless of treatment
groups. Moreover, in sites with maximal initial PPD or CAL,
the changes in clinical parameters from T0 and T1 were
more obvious in the PTT group than in the control group.
The reduction in the number of BOP-positive teeth at T1
was more obvious in the PTT group than in the control
group. Although the number of BOP-positive teeth
increased at T2, the incidence in the PTT group (14 of 30
teeth) was still lower than that in the control group (22 of
35 teeth).
Fig. 3 illustrates the comparison of changes in clinical
parameters. Although there was no significant difference
between treatment groups, compared with the control
group, PTT treatment resulted in an additional mean PPD
reduction of 0.11 mm and mean CAL reduction of 0.15 mm
from T0 to T1. In sites with maximal initial PPD or CAL, PTT
treatment resulted in an additional mean PPD reduction of
0.05 mm and mean CAL reduction of 0.19 mm from T0 to
T1. The changes from T1 to T2 were not obvious, except for
the changes in GR and CAL in the PTT group. GR showed a
slightly progressive change in the PTT group (an additional
0.17 mm for all sites and an additional 0.33 mm for sites
with initial maximal GR) and consequently resulted in an
additional mean CAL of 0.25 mm in all examined sites and
an additional mean CAL of 0.23 mm in sites with maximal
initial CAL.
Changes in proinflammatory cytokine levels after
treatment
In general, the levels of cytokines were not significantly
different between the control and PTT groups, and MMP-8
level was slightly higher in the PTT group than in the control
group at T0 (Fig. 4A and B). The levels of both MMP-8 and IL-
1b were gradually reduced in the PTT group. At T1, the IL-
1b level was significantly reduced compared to that at T0 in
the PTT group (Fig. 4A). At T2, both IL-1b and MMP-8 levels
were significantly reduced in both the PTT and control
groups (Fig. 4A and B). After normalization with the cyto-
kine levels at T0, as shown in Fig. 4C and D, the reduction in
the levels of IL-1b and MMP-8 was apparently greater in the
PTT group than in the control group. At T1, the levels of
both cytokines were significantly reduced in the PTT group
compared to those in the control group.
Discussion
BOP and residual PPD after traditional periodontal therapy
have been identified as risk markers of periodontitis pro-
gression and tooth loss.6,26
To manage these poorly
responding sites, additional therapeutic intervention is
potentially required. In this study, ICG-diode laser-based
PTT was applied as an antimicrobial adjunct to scaling and
root planing (ScRP) for treating sites refractory to tradi-
tional periodontal therapy. The results showed that most of
the clinical parameters were modestly improved, and the
improvement was sustained for 6 months in both groups,
and PTT appeared to facilitate inflammation resolution by
decreasing the number of BOP-positive teeth. These data
were consistent with a randomized clinical trial conducted
by Chondros et al.27
who used phenothiazine chloride (PC)
with diode laser irradiation, a PDT modality, as an adjunct
to ultrasonic scaling for sites with the PPD ! 4 mm in the
supportive phase. Their results demonstrated that the
number of BOP-positive sites is significantly reduced in the
Table 1 Background characteristics.
Group Control PTT
Participants
(Teeth)
22 (35) 22 (30)
Mean PD 3.35 Æ 0.57 mm 3.59 Æ 0.67 mm
Maximal PD 5.52 Æ 0.98 mm 6.19 Æ 1.33 mm
Mean REC 1.70 Æ 1.03 mm 1.75 Æ 1.02 mm
Maximal REC 0.71 Æ 0.96 mm 0.81 Æ 0.87 mm
Mean CAL 5.05 Æ 0.94 mm 5.34 Æ 0.96 mm
Maximal CAL 7.43 Æ 1.25 mm 8.43 Æ 1.60 mm
PS 64.65 Æ 28.40% 57.58 Æ 29.42%
BOP 100.00% 100.00%
IL-1b 190.9 Æ 118.0 pg/ml 178.2 Æ 108.0 pg/ml
MMP-8 372.8 Æ 712.7 mg/ml 541.9 Æ 864.8 mg/ml
Figure 2 The mean levels of clinical parameters of examined teeth at T0-T2. (A) PPD of all sites and the sites with maximal initial
PPD of each examined tooth. (B) GR of all sites and the sites with maximal initial GR of each examined tooth. (C) CAL of all sites and
the sites with maximal initial CAL of each examined tooth. (D) The percentage of BOP-positive teeth. (E) PS. (Significant difference
between the control and PTT groups at the same point: a
p0.05).
Photothermal therapy for periodontitis 5
+ MODEL
Please cite this article as: Chiang C-P et al., Clinical outcomes of adjunctive indocyanine green-diode lasers therapy for treating re-
fractory periodontitis: A randomized controlled trial with in vitro assessment, Journal of the Formosan Medical Association, https://
doi.org/10.1016/j.jfma.2019.08.021
6. PDT groups at both 3 and 6 months. Petelin et al. also re-
ported a similar outcome using adjunct PC-diode laser-
based PDT modality during initial periodontal therapy.28
The beneficial effect of resolving gingival inflammation,
as reported by these studies, was associated with the
reduction in subgingival periodontopathogens. ICG-diode
lasers (PTT modality) also demonstrated bactericidal ef-
fects equivalent to those of PDT modality.19,29
Although
microbial dynamics was not investigated in the present
study, inflammatory biomarkers, including IL-1b and MMP-8
in the GCF, were monitored, and the results showed that
both cytokine levels were significantly reduced at T1
(Fig. 4). Altogether, the data obtained in this study confirm
that the adjunctive ICG-diode laser PTT modality can
accelerate the resolution of gingival inflammation in the
examined sites.
The frequency of PDT or PTT treatment has been dis-
cussed in previous studies, and it appears that a single
application may not be sufficient to provide additional
benefit to ScRP. Thus, multiple PDT/PTT applications are
proposed.30
Although the benefit of multiple PDT/PTT ap-
plications has not yet been confirmed, in the present study,
two sessions of PTT were conducted. The first session of
PTT (on day 0) was conducted after ScRP to ensure the
complete clearance of periodontopathogens. Therefore, as
the colonization of periodontopathogens was resumed and
exceeded the baseline level within 7 days,31
a second ses-
sion of PTT was applied to prevent further microbial
recolonization. Furthermore, this study also demonstrated
that the metabolic activities of ICG-treated BMSCs were
reduced after diode laser irradiation (Fig. 1B). This phe-
nomenon could be related to the temperature elevation
induced by ICG-NIR irradiation.21
As reported by Goyal and
Ta, febrile temperature stress (40
C) had a negative in-
fluence on the viability of MSCs, and the characteristics
(surface antigens and signaling transduction) were there-
fore retained.32
Because ICG-NIR was not directly applied
on bone surfaces or BMSCs, subgingival PTT application
Figure 3 The change of clinical parameters of all sites of examined teeth (left panels in the micrograph) and sites with maximal
initial value of each examined tooth (right panels in the micrograph) in the intervals of T1-T0, T2-T0, and T2-T1. (A) PPD. (B) GR.
(C) CAL. The plus signs indicate the means of the clinical parameters.
Figure 4 The levels of cytokines of examined teeth at T0-T2. (AeB) The mean levels of (A) IL-1b and (B) MMP-8 at T0-T2. (CeD)
The mean levels of (C) IL-1b and (D) MMP-8 at T1 and T2 after normalization with the levels at T0 in each examined tooth. The plus
signs indicate the means of the normalized cytokines. (Significant differences to the level at T0 in the control group: a
p0.05,
b
p 0.01; significant differences to the level at T0 in the PTT group: c
p 0.05, d
p 0.001; significant difference between the
control and PTT groups at the same point: e
p 0.05).
6 C.-P. Chiang et al.
+ MODEL
Please cite this article as: Chiang C-P et al., Clinical outcomes of adjunctive indocyanine green-diode lasers therapy for treating re-
fractory periodontitis: A randomized controlled trial with in vitro assessment, Journal of the Formosan Medical Association, https://
doi.org/10.1016/j.jfma.2019.08.021
7. could still be considered as an acceptable option for clinical
periodontal treatment.
One study compared the antimicrobial efficiency among
PTT, metronidazole gel, and chlorhexidine gel in vitro and
reported that all these modalities significantly reduced the
bacterial load, but the effect was less prominent by PTT.19
Nevertheless, there are still certain advantages of using
PTT for treating periodontitis. First, the bactericidal effect
of PTT is exerted through oxidative attack, and bacterial
resistance is unlikely to develop compared with antibiotic
treatment.13
Second, as shown in Fig. 1, cytotoxicity to oral
cells by PTT was significantly less prominent compared to
that by CHX. Moreover, the major clinical drawbacks asso-
ciated with CHX, including the change in taste and tooth
staining, were absent in the case of PTT.19
In addition,
because a deeper penetration is achievable, PTT may pro-
vide additional benefit at sites with difficult access (e.g.,
deep furcation involvement, deep pockets, great root
concavities, and developmental grooves).
Notwithstanding the limitations, our study has demon-
strated that PTT using ICG and diode lasers is compatible to
the periodontal apparatus and assists in faster resolution of
gingival inflammation in periodontal pockets refractory to
mechanical debridement. Therefore, PTT may be recom-
mended as an adjunct during the maintenance phase of
periodontal treatment.
Conflicts of interest
All authors declare no conflicts of interest related to this
article.
Acknowledgements
The authors acknowledge the support from A.R.C. Laser
GmbH (Nurnberg, Germany) and Evermed Co., Ltd (New
Taipei City, Taiwan) for providing and maintaining ICG and
diode lasers. The study was supported by a research grant
(106-N3615) from NTUH.
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Please cite this article as: Chiang C-P et al., Clinical outcomes of adjunctive indocyanine green-diode lasers therapy for treating re-
fractory periodontitis: A randomized controlled trial with in vitro assessment, Journal of the Formosan Medical Association, https://
doi.org/10.1016/j.jfma.2019.08.021