Photodiagnosis and Photodynamic Therapy 19 (2017) 86–92

Contents lists available at ScienceDirect

Photodiagnosis and Photodynamic Therapy

journal homepage: www.elsevier.com/locate/pdpdt

Review

Efficacy of photodynamic therapy versus antibiotics as an adjunct to scaling MARK

and root planing in the treatment of periodontitis: A systematic review and
meta-analysis
⁎
Zohaib Akrama, , Tahira Hydera, Nawwaf Al-Hamoudib, Munerah Saleh Binshabaibc,
Shatha Subhi Alharthic, Ayesha Hanifa
a
Department of Periodontology, Faculty of Dentistry, Ziauddin University, Karachi, Pakistan
b
Department of Periodontics and Community Dentistry, King Saud University, Riyadh, Saudi Arabia
c
Department of Periodontology, College of Dentistry, Princess Nourah Bint Abdulrahman University, Riyadh, Saudi Arabia

A R T I C L E I N F O A B S T R A C T

Keywords: Background: To determine whether treatment with antimicrobial photodynamic therapy (aPDT) as an adjunct to
Photodynamic therapy scaling and root planing (SRP) yield better clinical periodontal outcomes than antibiotics (AB) as adjunct to SRP
Antibiotics in periodontitis.
Scaling and root planing Methods: Electronic searches were conducted in databases (MEDLINE, PubMed, EMBASE, SCOPUS, Cochrane
Periodontitis
Central Register of Controlled Trials and Cochrane Oral Health Group Trials Register databases) up to and
Review literature as topic
Meta-analysis
including April 2017.
Results: Five randomized trials were included. All studies used the combined approach aPDT + SRP and AB
+ SRP in the test and control group respectively. The follow up period ranged from 12 to 48 weeks. All studies
used diode lasers. The wavelengths, power density and duration of irradiation used were 670 nanometre, 75
milliwatts per square centimeters and 60 s respectively. None of the studies showed additional benefits of aPDT
at follow up. Considering the effects of adjunctive aPDT as compared to AB, a high degree of heterogeneity for
periodontal probing depth (PPD) (p < 0.0001, I2 = 87.47%) was noticed among both the groups. Meta-analysis
showed significant clinical attachment level (CAL) gain (WMD = 0.60, 95% CI = 0.25 to 0.95, p = 0.001), and
not PPD reduction (WMD = 0.67, 95% CI = –0.36 to 1.71, p = 0.204) for aPDT as compared to AB at follow up.
Conclusion: It remains debatable whether aPDT is more effective as compared to adjunctive AB in the treatment
of periodontitis, given that the scientific evidence is weak. Precautions must be exercised when interpreting the
results of this study due to the small sample size and high heterogeneity among studies.

1. Introduction it is associated with several physical limitations, mainly related with

Periodontitis is a group of inflammatory disease caused by period-
ontopathogenic bacteria such as Aggregatibacter actinomycetemcomitans,
Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia
residing in the dental plaque that causes periodontal breakdown and
eventually tooth loss [1]. Nowadays, periodontal treatment does not
only involve in arresting the disease progression through reduction of
total bacterial load, but also in the regeneration of the soft and hard
tissue that have been lost during the disease progression [2–4].
Scaling and root planing (SRP) remains a gold standard for non-
surgical periodontal treatment where root surface is debrided with ei-
ther hand or ultrasonic instruments that facilitates periodontal re-
attachment [5]. This therapeutic approach is demanding, nevertheless,
the inability to completely debride root surface in deep periodontal
pockets and inaccessible furcation defects, incomplete elimination of
periopathogenic bacteria and hence recurrence of the disease [6,7]. To
surmount these limitations, certain adjunctive therapies have been
clinically proposed [8–11], mainly the use of systemic or local anti-
biotics/antimicrobial agents (AB) [12,13]. Numerous studies have in-
dicated that adjunctive AB may improve clinical periodontal outcomes
in periodontitis [14]; however, their use is not free of risks as AB may
be associated with significant allergy and drug resistance [15], and
hence, they should be indicated for certain situations under optimal
conditions.
In the last decade, the use of antimicrobial photodynamic therapy
(aPDT) has occupied part of the dialogue within dentistry due to several

⁎
Corresponding author at: Department of Periodontology, Faculty of Dentistry, University of Malaya, Kuala Lumpur 50603, Malaysia.
E-mail address: drzohaibakram@gmail.com (Z. Akram).

http://dx.doi.org/10.1016/j.pdpdt.2017.05.007
Received 24 April 2017; Received in revised form 2 May 2017; Accepted 9 May 2017
Available online 11 May 2017
1572-1000/ © 2017 Elsevier B.V. All rights reserved.
Z. Akram et al.
Fig 1. PRISMA flow diagram for studies retrieved through the searching and selection process.
proposed advantages. In the arena of periodontology, aPDT use as an
adjunct to SRP, was demonstrated to enhance periodontal healing
[16,17]. The mechanism of aPDT involves the stimulation of photo-
sensitizer dye molecules by application of laser light of specific wave-
length which excites the dye molecule from ground singlet state to
triplet state. These excited triplet state molecules reacts with en-
dogenous oxygen to form cytotoxic singlet oxygen that facilitates bac-
terial cell destruction [18]. The benefits of aPDT over AB includes in-
stant suppression of causative periopathogenic bacteria, minimum
antibiotic resistance, absence of systemic disturbance and undesirable
effects on the healthy periodontal tissue [19]. However, the true effi-
cacy of the two treatment modalities i.e., aPDT compared with AB is
unclear. Therefore, it becomes imperative to compare the efficacy of
both aPDT and AB as an adjunct to SRP in the treatment of period-
ontitis. Therefore, the objective of this systematic review was to eval-
uate whether treatment with aPDT as an adjunct to SRP would promote
superior clinical results (i.e., periodontal probing depth [PPD] reduc-
tion or clinical attachment level [CAL] gain) compared to AB as adjunct
to SRP in periodontal disease.
87
Photodiagnosis and Photodynamic Therapy 19 (2017) 86–92
2. Material and methods
2.1. Protocol registration and focused PICO question
This review was registered at the National Institute for Health
Research PROSPERO, International Prospective Register of Systematic
Reviews (http://www.crd.york.ac.uk/PROSPERO, registration number:
CRD42017064233). This review was structured in accordance with
guidelines from ‘Preferred Reporting Items for Systematic Review and
Meta-Analysis’ (PRISMA) [20]. The PICO principle (i.e., “Patients” −
adults with either chronic or aggressive periodontitis; “Interventions”
− PDT plus SRP; “Comparisons” − AB plus SRP; “Outcomes” − PPD
reduction and CAL gain) was used to develop and address the following
focused question: “Does aPDT as an adjunct to SRP yield better clinical
periodontal outcomes than AB therapy as an adjunct to SRP in the
treatment of periodontal disease?”
2.2. Search strategy
Electronic and manual literature searches were conducted in the
databases (MEDLINE, PubMed, EMBASE, Science direct, SCOPUS,
Cochrane Central Register of Controlled Trials and Cochrane Oral
Health Group Trials Register) up to and including April 2017 for articles
Z. Akram et al. Photodiagnosis and Photodynamic Therapy 19 (2017) 86–92

Table 1
General characteristics of included studies.

Investigators, Study Mean age in Female (%) Systemic Periodontitis diagnostic Study groups Follow-up Study outcome
Country design years diseases/ criteria (weeks)
(range) Smokers
Test (n) Control (n)

Ramos et al. [24], RCT aPDT: 48.9 53 Included/ CP; ≥1 site with PPD aPDT + SRP DOXY + SRP Up to 12 Improvements in clinical
Brazil DOXY: 49.3 Excluded ≥5 mm on each (15) (15) periodontal outcomes were
(40–70) quadrant and two teeth comparable for both groups
with CAL ≥6 mm at follow-up
Al-Zahrani et al. RCT aPDT: 51.9 55 Included/ CP; CAL ≥3 mm at aPDT + SRP DOXY + SRP Up to 12 Improvements in clinical
[25], Saudi DOXY: 51.4 Included ≥30% of sites (14) (15) periodontal outcomes were
Arabia (35–77) comparable for both groups
at follow-up
Arweiler et al. RCT aPDT: 37.4 66 Excluded/ AgP; at least 3 sites with aPDT + SRP AMOX/ Up to 12 Clinical periodontal outcomes
[26], Poland AMOX Excluded PPD ≥6 mm (17) MET + SRP were significantly better for
+ MET: (18) control group as compared to
34.7 test at follow up
(23–55)
Tabenski et al. RCT aPDT: NA 46 Excluded/ CP; 4 teeth with PPD aPDT + SRP MINO + SRP Up to 48 Clinical periodontal outcomes
[27], Germany MINO: NA Included ≥6 mm (15) (15) were significantly better for
(NA) control group as compared to
test at follow up
Arweiler et al. RCT aPDT: 37.3 66 Excluded/ AgP; at least 3 sites with aPDT + SRP AMOX/ Up to 24 Clinical periodontal outcomes
[28], Poland AMOX Excluded PPD ≥6 mm (17) MET + SRP were significantly better for
+ MET: (18) control group as compared to
34.7 test at follow up
(23–55)

RCT; randomized clinical trial, CP; chronic periodontitis, AgP; aggressive periodontitis, PPD; Periodontal pocket depth, CAL; clinical attachment loss, DOXY; doxycycline, MINO; local
minocycline, AMOX; amoxicillin, MET; metronidazole, aPDT; antibacterial photodynamic therapy, NA; not available, SRP; scaling and root planning.

addressing the focused question. For the PubMed library, combinations
of following MeSH (Medical Subject Headings) and free text words were
used: ((((photochemotherapy OR photodynamic therapy OR lasers OR
diode OR photosensitizing agents) AND (chronic periodontitis OR period-
ontitis, chronic OR adult periodontitis OR periodontitis, adult OR aggressive
periodontitis OR periodontitis, aggressive OR periodontal disease OR al-
veolar bone loss OR attachment loss, periodontal OR periodontal pocket))
OR ((scaling, dental AND root planing) OR scaling, supragingival OR
scaling, root OR scaling, subgingival OR planning, root OR periodontal
debridement))) AND (agents, antibacterial OR antibacterial agents OR an-
tibiotics OR bactericides OR anti-infective agents OR antibiotic prophylaxis
OR amoxicillin OR metronidazole OR doxycycline OR systemic antibiotics).
Unpublished data were sought by searching a database listing un-
published studies (OpenGray).
2.3. Selection criteria
Screening and assessment of articles was conducted independently
by two reviewers (ZA and TH). Any disagreement among the authors
regarding study selection or exclusion was resolved through discussion
and/or by consulting a third reviewer (AH). Studies, which did not
fulfill the inclusion criteria, were excluded. The following eligibility
criteria were entailed:
a Study design: Randomized control trials (RCTs), controlled or
comparative clinical trials (CCTs), split-mouth clinical trials, double
blinded or blinded studies in humans.
b Participants: adult patients (aged ≥18 years) diagnosed with
chronic or aggressive periodontitis with no gender predilection.
c Intervention: subjects allocated to test (aPDT + SRP) versus con-
trol group (AB + SRP) with at least 10 patients per group.
d Outcome: Periodontal probing depth (PPD) reduction (primary
outcome) and clinical attachment level (CAL) gain (secondary out-
come).
e Language: articles published only in English language.
In-vitro studies; treatment with laser therapy alone, patients with no
antimicrobial therapy adjunct to SRP, case series; case reports; animal
studies; letters to the editor, opinion articles; abstract; review papers
and unpublished articles were excluded.
2.4. Screening and selection
Two reviewers (ZA and AH) independently screened titles and ab-
stracts for eligible papers. Inter-observer’s agreement was assessed by
means of kappa scores. If information relevant to the eligibility criteria
was not available in the abstract, or if the title was relevant but the
abstract was not available, the paper was selected for full reading of the
text. Next, full-text papers that fulfilled the eligibility criteria were
identified and included in the review. Reference lists of original studies
were hand searched to identify articles that could have been missed
during the electronic search. Manual searching of the following journals
was performed: Lasers Med Sci, Photodiagnosis and Photodynamic
therapy, J Periodontol, J Periodontal Res and J Clin Periodontol. Cross
references were also considered. Studies that fulfilled the selection
criteria were processed for data extraction. Fig. 1 describes the
screening process according to PRISMA guidelines [20].
2.5. Data extraction
Two reviewers (ZA and TH) performed the data extraction in-
dependently. The information from the accepted studies was tabulated
according to the: study design, demographic characteristics of the
participants, study groups, their follow-ups, study outcome, laser
characteristics, type of photosensitizer, assessed periodontal parameters
including; changes in PPD and CAL. Data collected were based on the
focused question outlined for the present systematic review. The re-
viewers crosschecked all extracted data. Any disagreement was re-
solved by discussion until consensus was reached.
2.6. Assessment of risk of bias and quality assessment in included studies
The present systematic review was conducted using a pre-submis-
sion checklist based on the revised recommendations of the

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Z. Akram et al. Photodiagnosis and Photodynamic Therapy 19 (2017) 86–92

PS; photosensitizer, PTC; phenothiazine chloride, MB; methylene blue, NA; not available, aPDT; antibacterial photodynamic therapy, nm; nanometers, J cm−2; joules per square centimeters, mW; milliwatts, mW cm−2; milliwatts per square
Consolidated Standards of Reporting Trials statement [21]. The risk of
Frequency of aPDT bias was estimated for each selected RCT based on the Cochrane
Handbook for Systematic Reviews of Interventions [22]: 1) low risk of
bias (when all criteria were met); 2) high risk of bias (when ≥1 cri-
application

terion was not met); and 3) unclear (when ≥1 criterion was partially
met).
4

2
Concentration of PS

2.7. Data synthesis

10 mg/mL

Meta-analyses were conducted separately for each of the primary

0.01%

(PPD), and secondary outcomes (CAL). Heterogeneity among the in-

NA

NA

NA

cluded studies for each outcome was assessed using the Q-statistic and
I2 statistic [23]. Forest plots were computed reporting weighted mean
Pre-irradiation time

difference (WMD) of outcomes and 95% confidence intervals (CI). The

pooled effect was considered significant if p-value was < 0.05. Data
unsuitable for quantitative analysis were assessed descriptively. Funnel
(seconds)

plots were generated to evaluate publication bias in the metaanalyses.

5–10
300

180

180

180

All above statistical analyses were carried out by a specialized statistical

software (MedCalc Software- B-8400 Ostend v 15.11.04, Belgium).
Types of

PTC

PTC

PTC

PTC
MB
PS

3. Results
diameter (mm)

3.1. Study selection

Optic fibre

A total of 63 study titles and abstracts were initially identified in the

0.06

following databases: MEDLINE (n = 5), PubMed (n = 21), EMBASE

NA

NA

NA

NA

(n = 15), Science direct (n = 18), SCOPUS (n = 1), Cochrane Central

irradiation (seconds)

Register of Controlled Trials and Cochrane Oral Health Group Trials

Register (n = 1). After removal of the duplicates, 61 articles were
identified. Fifty-one records were excluded as irrelevant to the focus
Duration of

question (k score for inter-assessor agreement at initial screening

kappa = 0.94). A total of 10 papers were selected for full-text reading.
Of these 10 studies, 5 studies were further excluded. After the final
60

60

60

60

60

stage of selection, 5 studies [24–28] were included and processed for

data extraction (k score for inter-assessor agreement at full-text elig-
Power density

ibility kappa = 1 [100% agreement]). Fig. 1 shows the study identifi-

(mW cm−2)

cation flow chart according to PRISMA [20] with the reasons for ex-
clusion of articles.
NA

NA

NA
28

75
Power output

3.2. General characteristics of included studies

(mW)

Five RCTs [24–28] were included in this review. The studies were
NA

NA

NA

NA
70

carried out in Brazil [24], Saudi Arabia [25], Germany [27] and Poland
[26,28]. In all studies [24–28], number of participants ranged between
16.72 per tooth
Energy fluence

29 and 35 individuals with mean age ranging between 34.7 and 51.9
years. All studies [24–28] reported the percentage of female partici-
(J cm−2)

pants, which ranged between 53% and 83%. Smokers were included in
NA

NA

NA

NA

two studies [25,27] while two studies [24,25] included subjects with
Laser and photosensitizer parameters of included studies.

diabetes mellitus. Three studies [24,25,27] included subjects with

Wavelength (nm)

chronic periodontitis while two studies [26,28] included patients with

aggressive periodontitis. All studies [24–28] used the combined ap-
proach aPDT + SRP in the test group and AB + SRP in the control
centimeters, mg/mL; milligram per milliliter.
670

660

670

660

group. In all studies [24–28], the follow-up period ranged from 12 to 48

NA

weeks (Table 1).

Type of

Diode

Diode

Diode

Diode

Diode
laser

laser

laser

laser

laser

laser

3.3. Quality of the clinical studies

Tabenski et al. [27]
Arweiler et al. [26]

Arweiler et al. [28]

All the five studies were RCTs [24–28]. All studies [24–28] pre-
Ramos et al. [24]

Al-Zahrani et al.

sented appropriate sample size calculation, randomization, statistical

Investigators

analysis and description of losses. The masking of assessor(s) [25–28]

[25]

and methods of allocation concealment [25,26,28] was inadequate in

Table 2

the included studies. The risk of bias was considered low in one study
[24] and unclear in four RCTs assessed [25–28] (Table 4).

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Z. Akram et al. Photodiagnosis and Photodynamic Therapy 19 (2017) 86–92

Table 3
Clinical periodontal parameters of the included studies.

Investigators PPD (mm) CAL (mm)

Ramos et al. [24] DOXY ± SRP:
Baseline: 4.86 ± 1.39
Follow up: 2.88 ± 0.45*
Al-Zahrani et al. [25] DOXY ± SRP:
Baseline: 3.26 ± 0.45
Follow up: 2.82 ± 0.23*
Arweiler et al. [26] AMOX ± MET ± SRP:
Baseline: 5.0 ± 0.8
Follow up: 3.2 ± 0.4*
Tabenski et al. [27] MINO ± SRP:
Baseline: 9, 8/10§
Follow up: 5, 4/7§
Arweiler et al. [28] AMOX ± MET ± SRP:
Baseline: 5.0 ± 0.8
Follow up: 3.0 ± 0.6*
aPDT ± SRP: DOXY ± SRP: aPDT ± SRP:
Baseline: 4.89 ± 0.68 Baseline: 5.53 ± 0.86 Baseline: 5.60 ± 0.68
Follow up: 3.47 ± 0.58* Follow up: 3.87 ± 0.52* Follow up: 3.90 ± 0.52*
aPDT ± SRP: DOXY ± SRP: aPDT ± SRP:
Baseline: 3.00 ± 0.46 Baseline: 3.9 ± 0.74 Baseline: 4.33 ± 1.15
Follow up: 2.55 ± 0.33* Follow up: 3.41 ± 0.43* Follow up: 3.87 ± 1.16*
aPDT ± SRP: AMOX ± MET ± SRP: aPDT ± SRP:
Baseline: 5.1 ± 0.5 Baseline: 5.5 ± 1.1 Baseline: 5.7 ± 0.8
Follow up: 4.0 ± 0.8* Follow up: 3.9 ± 1.0* Follow up: 4.7 ± 1.1*
aPDT ± SRP: MINO ± SRP: aPDT ± SRP:
Baseline: 8, 8/10§ Baseline: 9, 8/10§ Baseline: 10, 8/12§
Follow up: 6,5/8§ Follow up: 6,5/7§* Follow up: 8, 6/9§*
aPDT ± SRP: AMOX ± MET ± SRP: aPDT ± SRP:
Baseline: 5.1 ± 0.5 Baseline: 5.5 ± 1.1 Baseline:5.7 ± 0.80
Follow up: 3.9 ± 0.8* Follow up: 3.6 ± 0.9 Follow up: 4.7 ± 1.1*

PPD: periodontal pocket depth, CAL; clinical attachment loss, PI; plaque index, BOP; bleeding on probing, NA; not available, SRP; scaling and root planing, aPDT: antimicrobial
photodynamic therapy, DOXY: doxycycline, AMOX: amoxicillin, MET: metronidazole, MINO: minocycline.
§
Median, 25/75%.
* Significant difference from baseline to follow-up.

Table 4
Evaluation of bias risk in the included studies.

Investigators Sample size Allocation Randomization Losses (withdrawals/ Masking of Appropriate statistical Estimated risk of
calculation concealment dropouts) assessor(s) analysis bias

Ramos et al. [24] 2 2 2 1 2 2 Low

Al-Zahrani et al. 2 1 2 1 1 2 Unclear
[25]
Arweiler et al. [26] 2 1 2 1 1 2 Unclear
Tabenski et al. [27] 2 2 2 1 1 2 Unclear
Arweiler et al. [28] 2 1 2 1 1 2 Unclear

Fig. 2. Meta-analysis of included studies reporting (A) probing depth reduction (B) clinical attachment level gain between aPDT and AB therapy as an adjunct to SRP.

3.4. Laser and photosensitizer parameters of the included studies
All the studies [24–28] used diode lasers. The wavelengths of dif-
ferent lasers used in the included studies [25–28] ranged between
660 nm and 670 nm. Power density and duration of irradiation were 75
milliwatts per square centimeters (J cm−2) and 60 s respectively. Four
studies did not mention anything regarding energy fluence, power
output and optic fibre diameter [25–28]. Four studies [24,26–28] used
phenothiazine chloride while one study [25] used methylene blue as
photosensitizer. The frequency of aPDT application ranged from single
to four applications in the included studies [24–28] (Table 2).

90
Z. Akram et al.
Fig. 3. Funnel plots for (A) probing depth reduction (B) clinical attachment level gain
between aPDT and AB therapy as an adjunct to SRP.
3.5. Main outcome of the studies
All studies [24–28] reporting clinical periodontal parameters
showed that aPDT as an adjunct to SRP was effective in the treatment of
periodontitis at follow up. When compared with adjunctive AB, none of
the studies showed additional benefits of aPDT at follow up. Three
studies [26–28] showed significant improvement in periodontal out-
comes among adjunctive AB as compared to adjunctive aPDT, whereas
two studies [24,25] showed comparable periodontal outcomes between
adjunctive aPDT and AB at follow up (Table 3).
Four studies [24–26,28] presented available data to be included in
the meta-analysis considering the effects of aPDT and AB on PPD and
CAL; one study [27] presented periodontal outcome data using median
(25/75%) values for aPDT and AB and hence it was excluded from the
meta-analysis. Considering the effects of adjunctive aPDT as compared
to AB, a high degree of heterogeneity for PPD (Q value = 23.94,
P < 0.0001, I2 = 87.47%, Fig. 2A) was noticed among both the
groups. No significant difference in PPD reduction (WMD = 0.67, 95%
CI = –0.36 to 1.71, p = 0.204) were observed at follow-up between the
test and control groups. Considering the effects on CAL, a low degree of
heterogeneity (Q value = 4.34, P = 0.22, I2 = 31.01%, Fig. 2B) was
noticed among both the groups. The overall mean difference for CAL
gain between adjunctive aPDT were significant (CAL: WMD = 0.60,
95% CI = 0.25 to 0.95, p = 0.001) at follow-up.
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Photodiagnosis and Photodynamic Therapy 19 (2017) 86–92
3.6. Publication bias
Funnel plot for PPD appeared asymmetrical, suggesting significant
publication bias regarding PPD reduction at follow-up. Only in the
funnel plot of CAL gain at follow-up that most studies were in the
confidence area and demonstrated certain symmetry (Fig. 3A and B).
3.7. Occurrence of adverse effects/complications associated with
photodynamic therapy
None of the included studies [24–28] reported the occurrence of
adverse effects/complications associated with tested aPDT protocols.
4. Discussion
The present systematic review was based on the hypothesis that
aPDT as an adjunct to SRP promotes superior clinical outcomes than AB
as an adjunct to SRP in the treatment of periodontitis. All the studies
[24–28] included in the present systematic review showed that aPDT
improved clinical outcomes in periodontal disease patients. When
compared with adjunctive AB, none of the studies showed additional
benefits of aPDT as compared to AB.
There were several inconsistencies observed among the included
studies [24–28] such as forms of periodontitis studied and presence or
absence of blood. The inclusion of periodontitis forms differed among
the included studies [24–28]. Two [26,28] out of five studies [24–28]
included patients with aggressive periodontitis and showed significant
improvement with adjunctive AB therapy and not with adjunctive
aPDT. Results from recent systematic review by Akram et al. [8]
showed that the antimicrobial effect of aPDT as an adjunct to SRP
against Aggregatibacter actinomycetemcomitans in aggressive period-
ontitis is arguable. Furthermore, evidence suggests that the use of
combination AB therapy (Amoxicillin and Metronidazole) as an adjunct
to SRP in patients with aggressive periodontitis leads to significant re-
duction in deep pockets and gain in attachment loss [29]. It can be seen
from the two studies [26,28] that patients treated with adjunctive AB
with SRP showed favorable periodontal outcomes. It may therefore be
tempting to speculate that the use of combination AB may have favored
the clinical outcomes in patients with aggressive periodontitis and not
with aPDT. Moreover, the presence or absence of blood in the period-
ontal pocket was not reported in any of the included studies [24–28].
The presence of blood and high concentration of protein may have an
overall effect on the bactericidal efficacy of phototherapy and hence
clinical outcomes of periodontitis during aPDT [30].
It is noteworthy that the included studies [24–28] had a lack of data
pertinent to laser and photosensitizer parameters. Parameters such as
power density, pre-irradiation time (5–300 s), concentration of photo-
sensitizer and frequency of application either varied considerably or
were not reported in some studies. The frequency of aPDT application
varied from four applications to just one which could have influenced
the overall efficacy of aPDT in the studies included [24–28]. Moreover,
fibre diameter is known to influence the power density and energy
output during aPDT and can modify the actual amount of energy re-
leased during the process, potentially affecting the antimicrobial effi-
cacy of aPDT [31]. Therefore, further RCTs with standard laser para-
meters are warranted in order to obtain stronger conclusions in this
regard.
It is well-recognized that periodontal treatment outcomes are poorer
in patients with diabetes mellitus patients as compared to non-diabetic
individuals [32]. Chronic hyperglycemia has been linked with excessive
formation and build-up of advanced glycation end products (AGEs) in
the body tissues including periodontium [33]. These end products have
been reported to impair fibroblastic growth and proliferation and im-
pair healing in hyperglycemic patients. Moreover, research indicates
that increased proinflammatory cytokines are responsible for increased
periodontal destruction [34,35]. Although Ramos et al. [24] reported
Z. Akram et al.
the levels of certain cytokines (interleukin (IL)-1β, tumor necrosis
factor-alpha and transforming growth factor-beta) that promote peri-
odontal destruction, it may be due to other increased proinflammatory
cytokines (such as IL-6 and several matrix metalloproteinase) that may
have given comparable periodontal outcomes between adjunctive aPDT
and AB in the studies [24,25]. Two studies [25,27] included smokers in
their clinical trial. It is well recognized that cigarette smoking is a risk
factor for the outcomes of periodontal treatment [36]. All these po-
tential concerns should be evaluated with caution when interpreting
the results of the present study. Therefore, further clinical trials with
strict inclusion and exclusion criteria should be undertaken for allowing
a more precise assessment of the efficacy of adjunctive aPDT and AB in
the treatment of periodontitis.
The main limitation of the present systematic review and meta-
analysis was the small number of included studies in the qualitative and
quantitative analysis of periodontal outcomes. Furthermore a short
follow up period with short sample size was reported in the included
studies [24–28]. These methodologic shortcomings should be con-
sidered when analyzing the findings as the reported data were highly
heterogeneous and most of the included studies were categorized with
‘unclear’ degree of bias. The present systematic review does not seem to
support the hypothesis that a PDT promotes superior periodontal out-
comes as compared to adjunctive AB in the treatment of periodontitis.
However, because the roles of important prognostic factors remain to
be analyzed and further RCTs are needed, it is difficult to give re-
commendations for clinicians at this stage.
5. Conclusion
It remains debatable whether aPDT as an adjunct to SRP promotes
superior clinical efficacy as compared to AB in the treatment of peri-
odontal disease, given that the available evidence is insufficient.
Precautions must be exercised when interpreting the results of this
study owing to the small sample size and high heterogeneity among
studies. Therefore, more randomized clinical trials with standard laser
parameters and long follow up periods are required in order to obtain
stronger conclusions in this regard.
Conflict of interest statement
The authors declare that they have no conflict of interest and all
authors have read and approved the final draft.
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