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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


the inability to completely debride root surface in deep periodontal
Periodontitis is a group of inflammatory disease caused by period- pockets and inaccessible furcation defects, incomplete elimination of
ontopathogenic bacteria such as Aggregatibacter actinomycetemcomitans, periopathogenic bacteria and hence recurrence of the disease [6,7]. To
Porphyromonas gingivalis, Treponema denticola and Tannerella forsythia surmount these limitations, certain adjunctive therapies have been
residing in the dental plaque that causes periodontal breakdown and clinically proposed [8–11], mainly the use of systemic or local anti-
eventually tooth loss [1]. Nowadays, periodontal treatment does not biotics/antimicrobial agents (AB) [12,13]. Numerous studies have in-
only involve in arresting the disease progression through reduction of dicated that adjunctive AB may improve clinical periodontal outcomes
total bacterial load, but also in the regeneration of the soft and hard in periodontitis [14]; however, their use is not free of risks as AB may
tissue that have been lost during the disease progression [2–4]. be associated with significant allergy and drug resistance [15], and
Scaling and root planing (SRP) remains a gold standard for non- hence, they should be indicated for certain situations under optimal
surgical periodontal treatment where root surface is debrided with ei- conditions.
ther hand or ultrasonic instruments that facilitates periodontal re- In the last decade, the use of antimicrobial photodynamic therapy
attachment [5]. This therapeutic approach is demanding, nevertheless, (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. Photodiagnosis and Photodynamic Therapy 19 (2017) 86–92

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 2. Material and methods
adjunct to SRP, was demonstrated to enhance periodontal healing
[16,17]. The mechanism of aPDT involves the stimulation of photo- 2.1. Protocol registration and focused PICO question
sensitizer dye molecules by application of laser light of specific wave-
length which excites the dye molecule from ground singlet state to This review was registered at the National Institute for Health
triplet state. These excited triplet state molecules reacts with en- Research PROSPERO, International Prospective Register of Systematic
dogenous oxygen to form cytotoxic singlet oxygen that facilitates bac- Reviews (http://www.crd.york.ac.uk/PROSPERO, registration number:
terial cell destruction [18]. The benefits of aPDT over AB includes in- CRD42017064233). This review was structured in accordance with
stant suppression of causative periopathogenic bacteria, minimum guidelines from ‘Preferred Reporting Items for Systematic Review and
antibiotic resistance, absence of systemic disturbance and undesirable Meta-Analysis’ (PRISMA) [20]. The PICO principle (i.e., “Patients” −
effects on the healthy periodontal tissue [19]. However, the true effi- adults with either chronic or aggressive periodontitis; “Interventions”
cacy of the two treatment modalities i.e., aPDT compared with AB is − PDT plus SRP; “Comparisons” − AB plus SRP; “Outcomes” − PPD
unclear. Therefore, it becomes imperative to compare the efficacy of reduction and CAL gain) was used to develop and address the following
both aPDT and AB as an adjunct to SRP in the treatment of period- focused question: “Does aPDT as an adjunct to SRP yield better clinical
ontitis. Therefore, the objective of this systematic review was to eval- periodontal outcomes than AB therapy as an adjunct to SRP in the
uate whether treatment with aPDT as an adjunct to SRP would promote treatment of periodontal disease?”
superior clinical results (i.e., periodontal probing depth [PPD] reduc-
tion or clinical attachment level [CAL] gain) compared to AB as adjunct 2.2. Search strategy
to SRP in periodontal disease.
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

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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 antimicrobial therapy adjunct to SRP, case series; case reports; animal
of following MeSH (Medical Subject Headings) and free text words were studies; letters to the editor, opinion articles; abstract; review papers
used: ((((photochemotherapy OR photodynamic therapy OR lasers OR and unpublished articles were excluded.
diode OR photosensitizing agents) AND (chronic periodontitis OR period-
ontitis, chronic OR adult periodontitis OR periodontitis, adult OR aggressive 2.4. Screening and selection
periodontitis OR periodontitis, aggressive OR periodontal disease OR al-
veolar bone loss OR attachment loss, periodontal OR periodontal pocket)) Two reviewers (ZA and AH) independently screened titles and ab-
OR ((scaling, dental AND root planing) OR scaling, supragingival OR stracts for eligible papers. Inter-observer’s agreement was assessed by
scaling, root OR scaling, subgingival OR planning, root OR periodontal means of kappa scores. If information relevant to the eligibility criteria
debridement))) AND (agents, antibacterial OR antibacterial agents OR an- was not available in the abstract, or if the title was relevant but the
tibiotics OR bactericides OR anti-infective agents OR antibiotic prophylaxis abstract was not available, the paper was selected for full reading of the
OR amoxicillin OR metronidazole OR doxycycline OR systemic antibiotics). text. Next, full-text papers that fulfilled the eligibility criteria were
Unpublished data were sought by searching a database listing un- identified and included in the review. Reference lists of original studies
published studies (OpenGray). 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
2.3. Selection criteria
therapy, J Periodontol, J Periodontal Res and J Clin Periodontol. Cross
references were also considered. Studies that fulfilled the selection
Screening and assessment of articles was conducted independently
criteria were processed for data extraction. Fig. 1 describes the
by two reviewers (ZA and TH). Any disagreement among the authors
screening process according to PRISMA guidelines [20].
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 2.5. Data extraction
criteria were entailed:
Two reviewers (ZA and TH) performed the data extraction in-
a Study design: Randomized control trials (RCTs), controlled or dependently. The information from the accepted studies was tabulated
comparative clinical trials (CCTs), split-mouth clinical trials, double according to the: study design, demographic characteristics of the
blinded or blinded studies in humans. participants, study groups, their follow-ups, study outcome, laser
b Participants: adult patients (aged ≥18 years) diagnosed with characteristics, type of photosensitizer, assessed periodontal parameters
chronic or aggressive periodontitis with no gender predilection. including; changes in PPD and CAL. Data collected were based on the
c Intervention: subjects allocated to test (aPDT + SRP) versus con- focused question outlined for the present systematic review. The re-
trol group (AB + SRP) with at least 10 patients per group. viewers crosschecked all extracted data. Any disagreement was re-
d Outcome: Periodontal probing depth (PPD) reduction (primary solved by discussion until consensus was reached.
outcome) and clinical attachment level (CAL) gain (secondary out-
come). 2.6. Assessment of risk of bias and quality assessment in included studies
e Language: articles published only in English language.
The present systematic review was conducted using a pre-submis-
In-vitro studies; treatment with laser therapy alone, patients with no 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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Table 3
Clinical periodontal parameters of the included studies.

Investigators PPD (mm) CAL (mm)

Ramos et al. [24] DOXY ± SRP: aPDT ± SRP: DOXY ± SRP: aPDT ± SRP:
Baseline: 4.86 ± 1.39 Baseline: 4.89 ± 0.68 Baseline: 5.53 ± 0.86 Baseline: 5.60 ± 0.68
Follow up: 2.88 ± 0.45* Follow up: 3.47 ± 0.58* Follow up: 3.87 ± 0.52* Follow up: 3.90 ± 0.52*
Al-Zahrani et al. [25] DOXY ± SRP: aPDT ± SRP: DOXY ± SRP: aPDT ± SRP:
Baseline: 3.26 ± 0.45 Baseline: 3.00 ± 0.46 Baseline: 3.9 ± 0.74 Baseline: 4.33 ± 1.15
Follow up: 2.82 ± 0.23* Follow up: 2.55 ± 0.33* Follow up: 3.41 ± 0.43* Follow up: 3.87 ± 1.16*
Arweiler et al. [26] AMOX ± MET ± SRP: aPDT ± SRP: AMOX ± MET ± SRP: aPDT ± SRP:
Baseline: 5.0 ± 0.8 Baseline: 5.1 ± 0.5 Baseline: 5.5 ± 1.1 Baseline: 5.7 ± 0.8
Follow up: 3.2 ± 0.4* Follow up: 4.0 ± 0.8* Follow up: 3.9 ± 1.0* Follow up: 4.7 ± 1.1*
Tabenski et al. [27] MINO ± SRP: aPDT ± SRP: MINO ± SRP: aPDT ± SRP:
Baseline: 9, 8/10§ Baseline: 8, 8/10§ Baseline: 9, 8/10§ Baseline: 10, 8/12§
Follow up: 5, 4/7§ Follow up: 6,5/8§ Follow up: 6,5/7§* Follow up: 8, 6/9§*
Arweiler et al. [28] AMOX ± MET ± SRP: aPDT ± SRP: AMOX ± MET ± SRP: aPDT ± SRP:
Baseline: 5.0 ± 0.8 Baseline: 5.1 ± 0.5 Baseline: 5.5 ± 1.1 Baseline:5.7 ± 0.80
Follow up: 3.0 ± 0.6* 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 studies did not mention anything regarding energy fluence, power
output and optic fibre diameter [25–28]. Four studies [24,26–28] used
All the studies [24–28] used diode lasers. The wavelengths of dif- phenothiazine chloride while one study [25] used methylene blue as
ferent lasers used in the included studies [25–28] ranged between photosensitizer. The frequency of aPDT application ranged from single
660 nm and 670 nm. Power density and duration of irradiation were 75 to four applications in the included studies [24–28] (Table 2).
milliwatts per square centimeters (J cm−2) and 60 s respectively. Four

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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
Fig. 3. Funnel plots for (A) probing depth reduction (B) clinical attachment level gain the clinical outcomes in patients with aggressive periodontitis and not
between aPDT and AB therapy as an adjunct to SRP.
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].
3.5. Main outcome of the studies The presence of blood and high concentration of protein may have an
overall effect on the bactericidal efficacy of phototherapy and hence
All studies [24–28] reporting clinical periodontal parameters clinical outcomes of periodontitis during aPDT [30].
showed that aPDT as an adjunct to SRP was effective in the treatment of It is noteworthy that the included studies [24–28] had a lack of data
periodontitis at follow up. When compared with adjunctive AB, none of pertinent to laser and photosensitizer parameters. Parameters such as
the studies showed additional benefits of aPDT at follow up. Three power density, pre-irradiation time (5–300 s), concentration of photo-
studies [26–28] showed significant improvement in periodontal out- sensitizer and frequency of application either varied considerably or
comes among adjunctive AB as compared to adjunctive aPDT, whereas were not reported in some studies. The frequency of aPDT application
two studies [24,25] showed comparable periodontal outcomes between varied from four applications to just one which could have influenced
adjunctive aPDT and AB at follow up (Table 3). the overall efficacy of aPDT in the studies included [24–28]. Moreover,
Four studies [24–26,28] presented available data to be included in fibre diameter is known to influence the power density and energy
the meta-analysis considering the effects of aPDT and AB on PPD and output during aPDT and can modify the actual amount of energy re-
CAL; one study [27] presented periodontal outcome data using median leased during the process, potentially affecting the antimicrobial effi-
(25/75%) values for aPDT and AB and hence it was excluded from the cacy of aPDT [31]. Therefore, further RCTs with standard laser para-
meta-analysis. Considering the effects of adjunctive aPDT as compared meters are warranted in order to obtain stronger conclusions in this
to AB, a high degree of heterogeneity for PPD (Q value = 23.94, regard.
P < 0.0001, I2 = 87.47%, Fig. 2A) was noticed among both the It is well-recognized that periodontal treatment outcomes are poorer
groups. No significant difference in PPD reduction (WMD = 0.67, 95% in patients with diabetes mellitus patients as compared to non-diabetic
CI = –0.36 to 1.71, p = 0.204) were observed at follow-up between the individuals [32]. Chronic hyperglycemia has been linked with excessive
test and control groups. Considering the effects on CAL, a low degree of formation and build-up of advanced glycation end products (AGEs) in
heterogeneity (Q value = 4.34, P = 0.22, I2 = 31.01%, Fig. 2B) was the body tissues including periodontium [33]. These end products have
noticed among both the groups. The overall mean difference for CAL been reported to impair fibroblastic growth and proliferation and im-
gain between adjunctive aPDT were significant (CAL: WMD = 0.60, pair healing in hyperglycemic patients. Moreover, research indicates
95% CI = 0.25 to 0.95, p = 0.001) at follow-up. that increased proinflammatory cytokines are responsible for increased
periodontal destruction [34,35]. Although Ramos et al. [24] reported

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the levels of certain cytokines (interleukin (IL)-1β, tumor necrosis alone as adjunct to scaling and root planing on gingival crevicular fluid inflammatory
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