An Overview of the Systematic Evidence on the Adjunctive Use of Laser Therapy in Non-surgical Periodontal Treatment

This overview aimed to recapitulate the evidence related to laser application in non-surgical periodontal treatment along with conventional periodontal treatment for optimum clinical practice based on the available systematic reviews (SRs). An advanced literature search in the English language was conducted in the PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), ScienceDirect, and Scopus databases from January 2000 to October 2022. Two independent reviewers screened all the databases and extracted the data in duplicate. The risk of bias in the selected studies was assessed with the Methodological Quality of Systematic Reviews 2 (AMSTAR 2) guideline for SRs. Cohen’s kappa statistics were performed to assess the level of agreement for the assessment of the risk of bias. A total of 556 studies (PubMed = 115, Scopus = 66, ScienceDirect = 298, and MEDLINE = 77) were identified after the initial search using the keywords from different databases. After removing the duplicates and assessing the full manuscripts, a total of 24 studies were selected based on the inclusion criteria for the current overview. A total of three, four, 12, and five systematic reviews were classified as high, moderate, low, and critically low-quality SRs as per the AMSTAR 2 quality assessment tool. Cohen’s Kappa statistics showed perfect (𝛋 =1.000) agreement between the two reviewers. Adjunctive laser therapy along with conventional non-surgical periodontal treatment might be effective in short-term treatment outcomes; however, evidence of long-term effects is still lacking.


Introduction And Background
Periodontitis is an infectious condition caused by inflammatory pathogens [1]. This phenomenon is generally treated with either surgical or non-surgical modalities. Scaling and root planning (SRP) is one of the most common techniques to conduct non-surgical treatment modalities for periodontitis [2,3]. The outcome of SRP is also influenced by patient-related factors such as systemic disease, smoking, and stress [4][5][6]. Other than patient-related factors, sometimes ultrasonic or manual instruments fail to access the furcation area, deep pockets area, and groove, resulting in incomplete removal of detriments [7]. Moreover, unfavorable wounds in periodontal tissue can also be observed after the SRP treatment [8]. Therefore, alternative treatments for periodontitis have been investigated in conjunction with SRP.
A few alternatives, such as local application of antiseptic, antibiotic, and laser (light amplification by stimulated emission of radiation) therapy, were proposed as a supplement or substitute for non-surgical periodontal treatment [9][10][11].
Laser therapy is a non-invasive procedure that is rarely associated with any adverse effects in periodontal treatment. Different types of lasers with diverse wavelengths were commonly studied in the management of periodontitis with SRP [12][13][14]. Diode laser (DL), erbium, chromium-doped: yttrium, scandium, gallium, garnet (Er, Cr: YSGG) laser, neodymium-doped yttrium aluminum garnet (Nd: YAG) laser, erbium-doped: yttrium, aluminum, and garnet (Er: YAG) laser, and carbon dioxide (CO2) laser are the most commonly used as adjunctive non-surgical periodontal treatment [15]. Various independent studies investigated the efficacy of laser therapy in periodontal treatment; however, the outcome was not consistent. Therefore, systematic reviews (SRs) were conducted to distinguish the pooled efficacy of laser therapy in periodontal treatment [16][17][18][19][20].
aids in decision-making [24,25]. Hence, the current study is based on systematic reviews, which are considered the highest level of scientific evidence. This overview of systematic reviews aimed to recapitulate the evidence related to laser application in non-surgical periodontal treatment regarding the optimum clinical practice.

Review
An advanced literature search in the English language was conducted in the PubMed, Medical Literature Analysis and Retrieval System Online (MEDLINE), ScienceDirect, and Scopus databases from January 2000 to October 2022. Two independent reviewers screened all the databases in duplicate using the following keywords: ('periodontitis' OR 'periodontal disease' OR 'non-surgical periodontal treatment' OR 'periodontal treatment') AND ('laser' OR 'laser therapy' OR 'photodynamic therapy') AND ('systematic review' OR 'metaanalysis'). Manual hand searching was also performed from the reference list of the selected studies. All the selected titles and abstracts were managed with the Endnote software (version X9). The overview was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines by Moher et al. [26].
The following inclusion criteria were followed for selecting the studies in this overview: SRs with or without meta-analysis, non-surgical periodontal treatment such as SRP, and application of laser therapy as an adjunct to the periodontal treatment. On the other hand, studies other than SRs, surgical treatment of periodontitis, and adjunctive treatment with antimicrobial photodynamic therapy were excluded from this overview.
The titles and abstracts were screened primarily by two independent reviewers. The full manuscripts were selected if the studies met the inclusion criteria. After removing duplicates, full texts were evaluated by two reviewers who independently listed all the studies to be included in this review ( Figure 1). Both reviewers resolved any disagreements with a discussion regarding finalizing the studies. Both reviewers checked the selected lists of studies. If the final lists by both reviewers did not match, they discussed the reason for the elimination of the study and decided whether to keep it in the final list of selected studies by consensus. The risk of bias in the selected studies was assessed with the Methodological Quality of Systematic Reviews 2 (AMSTAR 2) guideline for SR ( Table 1).

Q1
Did the research questions and inclusion criteria for the review include the components of PICO?
Q2* Did the report of the review contain an explicit statement that the review methods were established prior to the conduct of the review, and did the report justify any significant deviations from the protocol?  Q15* If they performed quantitative synthesis, did the review authors carry out an adequate investigation of publication bias (small study bias) and discuss its likely impact on the results of the review?

Q16
Did the review authors report any potential sources of conflict of interest, including any funding they received for conducting the review? High (no, or one non-critical weakness: the systematic review provides an accurate and comprehensive summary of the results); moderate (more than one non-critical weakness but no critical flaws: the systematic review provides an accurate summary of the results); low (one critical flaw, with or without noncritical weaknesses: the systematic review may not provide an accurate and comprehensive summary of the results); critically low (more than one critical flaw, with or without non-critical weaknesses: the review should not be relied on to provide an accurate and comprehensive summary of the results).
PICO: patient/population, intervention, comparison, and outcomes; AMSTAR 2: Methodological Quality of Systematic Reviews 2 A total of 16 items were used to evaluate the methodological quality of the SR. Each item was scored as 'yes', 'partially yes', 'no', and 'no meta-analyses'. Seven out of 16 items were considered critical domains (item two, item four, item seven, item nine, item 11, item 13, and item 15) ( Table 1). Each study scored as high (no or one non-critical weakness), moderate (more than one non-critical weakness but no critical flaws), low (one critical flaw with or without non-critical weakness), and critically low (more than one critical flaw with or without non-critical weakness). A level of agreement between the two reviewers was achieved. The clinical heterogeneity of the selected SRs was assessed. Based on the similar types of lasers and the followup duration of the periodontal measurements, the clinical effects of adjunctive laser therapy were evaluated.
A total of 556 studies (PubMed = 115, Scopus = 66, ScienceDirect = 298, and MEDLINE = 77) were identified after the initial search using the keywords from different databases. After removing the duplicates and assessing the titles and abstracts, a total of 64 studies were selected for full-text assessment. Two independent reviewers screened and assessed all the full texts and finally selected 24 studies based on the inclusion criteria to be included in the current overview (   The rest of the studies were excluded, and the reasons for exclusion are mentioned in Figure 1.

Risk of bias assessment
The AMSTAR 2 tool was used to evaluate the risk of bias for all selected SRs, and the assessment is presented in Table 3.  [40][41][42][43][44] were classified as critically low-quality studies. Both reviewers used the AMSTAR 2 tool for the selected studies and assessed the quality of the studies.

Synthesis of results
The characteristics of the included SR were described according to the author and year of publication, study design, number of studies included, type of laser, measurements, meta-analysis, follow-up, and conclusion, which are presented in Table 2.
A few primary studies overlapped with the included SR. Hence, no meta-analysis was performed in this overview due to the duplication of information that would provide a biased overview [45]. The clinical effects of adjunctive laser therapy along with SRP are presented in Table 4.  None of the pooled effects of previous SR [21,42] exhibited significant differences between the two groups (laser with SRP and SRP only) with Er: YAG laser in six months and 12 months in periodontal pocket depth (PPD) and clinical attachment level (CAL). One meta-analysis showed a significant difference in favor of adjunctive Yr: YAG laser at the three-month follow-ups in PPD and CAL measurements [42]. One out of three meta-analyses found significant effects of diode lasers at the six-month follow-up in PPD [32]. Meta-analysis on Nd:YAG laser presented mixed outcomes. Roncati M et al. (2014) [40] found a significant improvement in adjunctive laser therapy in PPD, whereas CAL showed no significant difference. On the other hand, Chambrone et al. (2018b) [46] showed the opposite pooled effect.

Discussion
Adjunctive use of laser therapy to SRP in periodontitis did not reveal robust evidence from the previous SRs. Though the use of lasers did not report any side effects, it is important to highlight that most of the studies conducted the comparison in short-term follow-up (≤ six months), which is not enough time to conclude about the effectiveness of the laser. As per the results of the SRs, the laser might be effective as an adjunct with SRP for a short period, yet its effectiveness for a longer period is still questionable.
It needs to be mentioned that this overview was based on the published SRs. Therefore, the data exhibited in the tables were gathered from the included SR and meta-analyses. The current overview did not pay any attention to extracting data from the primary studies.
All the SRs included in this overview were selected for randomized clinical trials (RCTs) as the study design.  [40]. Oftentimes, a retrospective study design provides weak evidence for a systematic review. Moreover, retrospective study design instigates low scores in quality analysis in SRs due to the blinding factor, which is an important assessment parameter in any quality analysis (Alam et al. (2022) [47] and Raposo et al. (2018) [48]). Therefore, RCTs stipulate a more constructive quality of report in an SR [49].
The number of primary studies included in an SR plays a major influence on the outcome of the SR. Out of the 24 studies included, 10 assessed fewer than 10 primary studies. For instance, Sgolastra  [32]. The primary studies usually use one type of laser in their studies, irrespective of the study design. Therefore, it would be better to conduct SR with a specific laser with a specific wavelength, which could provide a constructive outcome for a specific type of laser to be used clinically.
Most of the studies concluded that adjunctive laser therapy with conventional SRP is effective compared to the only SRP treatment, except for a few studies that did not identify any positive effects of additional laser therapy over conventional SRP treatment [43,2,21,30,39,28]. Moreover, few studies claimed that laser therapy showed clinical effectiveness only in short-term follow-up; however, there was no significant benefit in long-term follow-up [8,37,42,36].  [34]. This overview extracted a few homogenous meta-analyses in Table 3 on PPD and CAL. The use of laser compared to SRP increased PPD reduction by -0. 22 [32].
A total of three, four, 12, and five SRs were classified as high, moderate, low, and critically low in the quality analysis by the AMSTAR 2 tool. The AMSTAR tool was first published in 2007 in order to assess the quality of SRs [50]. In 2017, the original AMSTAR tool was revised and modified to AMSTAR 2 for a better reflection of the risk of bias and better alignment of the selected format by Shea et al. (2017) [51]. Using the AMSTAR 2 tool, researchers and clinicians differentiate the high-quality SR from the reviews that were inadequately conducted. Therefore, before conducting an SR, researchers should consider the AMSTAR 2 tool for a better outcome. Moreover, the reviews published after 2017 should have scored higher in the quality assessment, and two SRs, Pawelczyk-Madalińska et al. (2021) [19] and Trombelli et al. (2020) [28], were among the three high-quality SRs in the current overview published after 2017.
Among all the studies that were classified as moderate, none violated any critical assessment (Table 1); however, the most common items that were ignored were items 1 and 10. The number 1 item is based on the participants, intervention, comparison, and outcome (PICO) format for conducting an SR. All the SRs, straightforwardly or subsidiarily, use this format; however, it is imperative to mention it clearly in the SR. On the other hand, item 10 is about the funding. Most of the readers usually ignore the funding part mentioned in the manuscript; nevertheless, it is an important topic, specifically if the study design is an RCT. Therefore, the AMSTAR 2 tool requires this item to be addressed in the SR, though we did not put this item under the critical domain. Most of the studies that were conducted after 2017 usually mentioned the funding item in SR [46, 18-20, 28,34].
According to the AMSTAR 2 tool, only one violation of the critical domain classified any SR as a low-quality study. The majority of the selected SRs in this overview are classified as low-quality SRs. Item 7 and item 15 were the most common critical domains that were not addressed in the respective studies. Item 7 represents the list of exclusion studies, and item 15 signifies publication bias. Previously, excluded studies were just presented with a number; however, the AMSTAR 2 tool recently demonstrated that it could list down the excluded studies with the reasons. Most of the recent studies mentioned the excluded list and explanation either inside the main manuscript or as a supplementary document in the journal. On the other hand, another important factor is publication bias, which lists many SRs as low-quality SR. Analyzing a publication is an important part of a meta-analysis. Many meta-analyses in this current overview were conducted with small numbers of primary studies. Statistical publication bias generally cannot be conducted when the number of included studies is less than 10 [47]. Therefore, many of the included studies did not perform publication bias, which led to low-quality studies. Some of the studies fulfilled all the criteria for the AMSTAR 2 tool except item 15 and dropped into low-quality studies [28,34,35]. -were listed as critically low quality under the AMSTAR 2 tool due to violating more than one critical domain. Items seven, nine, and 10 are the most violated critical domains by these studies. However, all these studies were published before the AMSTAR 2 tool was proposed, except one study by Estrin et al. (2022) [44]; therefore, this overview could not exclude these studies based on the critically low-quality study.
The limitations inherent to this SR include the classification of the detected SR into distinct quality levels ranging from high to severely low based on the AMSTAR 2 assessment tool, which serves as an example of the inherent heterogeneity in methodological quality that systematic reviews as the primary data source involve. The robustness of inferences made from the combined evidence may be impacted by this variability in SR quality. Additionally, even if the AMSTAR 2 guidelines were used to assess the risk of bias in a few particular studies, its accuracy in identifying potential sources of bias might remain subject to concern.
Conclusions Based on this overview, though adjunctive laser therapy showed a superior effect in periodontitis patients in short-term follow-up, the long-term effect is not satisfactory. Therefore, long-term studies for laser application along with conventional periodontal treatment are required before clinically treating periodontitis patients with laser.

Conflicts of interest:
In compliance with the ICMJE uniform disclosure form, all authors declare the following: Payment/services info: All authors have declared that no financial support was received from any organization for the submitted work. Financial relationships: All authors have declared that they have no financial relationships at present or within the previous three years with any organizations that might have an interest in the submitted work. Other relationships: All authors have declared that there are no other relationships or activities that could appear to have influenced the submitted work.