Do Lasers Have an Adjunctive Role in Initial Non-Surgical Periodontal Therapy? A Systematic Review

(1) Background: dental lasers have numerous applications for periodontal therapy which include surgical procedures of soft tissue and osseous structures, and non-surgical treatments such as pathogen reduction, removal of surface accretions, and photobiomodulation. The aim of this review was to evaluate the scientific literature to ascertain whether lasers have a beneficial role when used adjunctively in initial non-surgical periodontal therapy. (2) Methods: A PubMed search was performed specifically for randomized clinical trials where a dental laser was used adjunctively for initial periodontal therapy on human patients published from January 2010–April 2020. The first search identified 1294 eligible studies. After additional criteria and filters were applied, 20 manuscripts were included in this review. (3) Results: The chosen manuscripts reported on investigations into initial therapy for patients diagnosed with chronic periodontitis. After periodontal charting, conventional instrumentation such as hand and ultrasonic scaling was performed on all patients in the studies, and then a test group or groups of patients were treated adjunctively with a laser. That adjunctive laser group’s periodontal findings showed various degrees of improved health compared to the group treated with only conventional methods. (4) Conclusion: This systematic review found that 70% of the included studies reported significantly better outcomes in certain clinical parameters, but no improvement in others. The remaining 30% of the manuscripts reported no significant difference in any of the measurements. With consideration to correct parametry, lasers have an adjunctive role in initial non-surgical periodontal therapy.


Introduction
Chronic periodontal disease continues to be a significant health problem that commonly occurs in adults [1]. Certain risk factors including genetics, medical history, and lifestyle also exist that can increase the disease's severity and those factors continue to be discovered [2].
This disease is a multi-factorial, predominately chronic inflammatory process whereby microbial deposits associated with the gingival tissues produce toxins that evoke tissue reaction, loss of bone and gingival support; untreated, it can lead to tooth mobility, migration and loss [3]. Periodontitis is a slowly progressing oral infection of the soft and hard tissues surrounding the teeth. The primary etiology is the presence of pathogens in a biofilm which, when left intact on the gingiva or tooth surface, can lead to soft tissue inflammation. Subsequently, increasing pathogen population can then invade the connective tissue attachment while causing apical migration of the epithelial attachment apparatus with resulting alveolar bone resorption and tooth loss. Treatment always begins with initial periodontal therapy whose purpose is to remove the aforementioned biofilm and calcified deposits, known as calculus. This initial therapy will continue with periodic evaluations to assess the result and is sometimes termed 'Phase 1 therapy' which implies that subsequent surgery (Phase 2) would have to follow if the periodontal infection cannot be reversed [4]. The widely used protocol is known as periodontal debridement [5] and can result in improvement of clinical indices such as decreased probing depths and reduction of inflammation. This non-surgical approach continues to be the hallmark of periodontal therapy [6]. However, it has been known for some time that the debridement is usually incomplete because of the difficult access to some areas of the periodontium [7]; moreover, one study has shown that sonic powered scalers could have little effect on pathogen reduction [8]. The use of systemic or locally delivered anti-infective medications has been utilized to supplement debridement with benefits and limitations [9]. Laser instruments designed specifically for dentistry have been available for about 30 years [10], and various protocols and parameters for periodontal applications have been developed [11]. For the purposes of this manuscript, the term 'laser instruments' or 'laser' is defined as those devices whose indications for use include debridement of the soft tissue side of the pocket. Thus a laser whose only purpose is for photoactivated disinfection and/or photobiomodulation will not be included in this review. While there have been numerous studies showing an additional benefit for laser use, there have been some papers describing no benefit. The purpose of this manuscript was to analyze manuscripts published between January 2010 and April 2020 that feature laser use adjunctive to periodontal debridement in randomized clinical trials. This review will answer the question: can adjunctive use of lasers provide an additional benefit during initial non-surgical therapy for chronic periodontitis when compared to a control group where a laser was not used at a 6-month evaluation?

Search Strategy
An electronic search was conducted between 15 April and 25 April 2020 relating to laser use as an adjunct in non-surgical periodontal therapy. Databases used were PubMed and the Cochrane Library with the following MeSH terms, keywords and their combinations: (Laser OR diode OR Nd:YAG OR Er:YAG OR Er,Cr:YSGG OR CO 2 ) AND (periodontitis OR periodontal) NOT (aPDT OR photodynamic OR PAD OR PDT OR photobiomodulation OR low level OR peri-implantitis OR endodontic OR orthodontic).
After applying the additional filters (published within the last 10 years, clinical trials in humans, and only English language reports), the preliminary number of 1294 articles was further reduced to 61. Titles and abstracts of the above articles were independently screened by four reviewers via application of the following criteria. In case of any disagreements arising, these were satisfactorily resolved by discussions.
Inclusion criteria: After screening and implementation of the eligibility criteria, a total of 20 articles were retained. In accordance with the PRISMA statement [12], details of the selection criteria are presented in Figure 1. After screening and implementation of the eligibility criteria, a total of 20 articles were retained. In accordance with the PRISMA statement [12], details of the selection criteria are presented in Figure  1.

Data Extraction
Having reached a consensus regarding the selection of included articles, the four reviewers involved subsequently extracted data regarding:

Data Extraction
Having reached a consensus regarding the selection of included articles, the four reviewers involved subsequently extracted data regarding: •

Quality Assessment
Following data extraction, articles were further scrutinized by evaluating their risk of bias. The Cochrane Risk of Bias tool [13] was modified according to the requirements of this systematic review.
The risk of bias was determined according to the number of "yes" or "no" responses to the parameters presented below, which were allocated to each study: The risk of bias is determined by the total number of "yes" answers to the above parameters, and hence classified as follows: High risk = 0-4 'yes' answers Moderate risk = 5-7 'yes' answers Low risk = 8-10 'yes' answers

Primary Outcome
The primary goal of this systematic review was to critically appraise the treatment outcome of the adjunctive use of lasers in non-surgical periodontal therapy.

Data Presentation
The evaluation of the included studies is presented in Table 1.

Quality Assessment Presentation
A risk of bias assessment of studies included in this review is presented in Table 2.
In total 11/20 (55%) articles showed a low risk of bias with the following grading: • 10/10 one article [ [20,32] Besides the sufficient description of the laser protocol used, the most common negative answers concerned (a) the power meter used and (b) the sample size calculation and required number included.
Worse results in some of the examined parameters and no significant differences in the rest were shown in 2/20 (10%) [26,27].

Background
The purpose of this manuscript was to analyze, through a systematic review, manuscripts published between 2010 and 2020 that featured laser use adjunctive to periodontal debridement in randomized clinical trials. For purposes of this manuscript, 'adjunctive' was defined when scaling and root planning (SRP) using either ultrasonic driven scalers and/or hand scaling instruments was performed together other treatments such as a laser. Other adjunctive modalities have been developed, such as antimicrobial photodynamic therapy [34] or systemic and locally delivered anti-microbial medications [35] but will not be discussed here.
The term "non-surgical therapy" is defined as a protocol to remove as much calculus as possible to disrupt or eliminate the biofilm and accompanying microbes, and to reduce inflammation contributing to periodontal and peri-implant disease as initial therapy [36]. For several years in the latter part of the 20th century, some non-surgical procedures could have been considered essentially surgical ones, such as gingival curettage and removal of large amounts of root cementum. These two therapies have slowly been de-emphasized [37]. For clarity, surgical periodontal therapy is performed with excisional and incisional instruments, periosteal elevators, chisels, files, and tissue forceps. The site is exposed with a flap, then closed with sutures, and covered with a dressing [38]. Currently, surgery for treatment of chronic periodontitis has been de-emphasized in favor of non-surgical treatment. Many periodontal surgical procedures now include soft tissue and bone grafting to cover exposed roots and augment osseous structures for implant placement [39].
The use of lasers in periodontology can be seen in three areas of treatment: removal of diseased pocket lining epithelium, microbiocidal effect of lasers on pocket organisms and, for certain instruments, the removal of calculus deposits and root surface detoxification. When integrated into a sound approach to pocket reduction, all current dental wavelengths in the photoablative mode have been advocated for the removal of diseased epithelium [40][41][42][43][44][45][46][47]. Additionally, it should be noted that due to the local effects of photothermal laser action, laser treatment should be capable of effectively targeting periodontal tissues infected by bacteria [48,49].
The studies included in this manuscript represent a majority of the dental laser wavelengths; the citations' wavelengths are: 532, 808, 810, 940, 1064, 2780, and 2940 nm. However, those of carbon dioxide (9300-10,600 nm) for which no paper matching our search and inclusion criteria could be found. Table 1 lists the data found in each included manuscript in this review. The criteria of blinded, adequately sized groups, randomization, and statistics/data were fulfilled. Three studies included addition treatment: Dilsiz, et al. [23] and Giannopoulou, et al. [27] who used antimicrobial photodynamic therapy in one group and Lopes, et al. [33] who used a laser as monotherapy. Neither of these methods were part of our inclusion criteria and those groups were not analyzed in this review.
Several other aspects of the data will be discussed.

Group Selection at Baseline
Four groups had a large difference of male and female members of their study group. Sanz-Sanchez, et al. [20]  While the baseline measurements of the clinical parameters that each study measured were similar, we assigned a high rate of bias in the baseline grouping category to them.

Laser Parameters
Each included manuscript listed laser operating parameters. An analysis of those reported parameters will be further explained and scrutinized.

Power
There was a wide variety of how laser parameters were reported. Power parameters were stated in sometimes missing or confusing notations. Ciurescu, et al. [14], and Giannopoulou, et al. indicated a diode laser power parameter without any pulse notations, so the reader has to assume an undescribed continuous wave mode in which case that notation would be both peak and average power. Ciurescu, et al. also utilized two different power settings for the three diode sessions without explanation for the difference.
For gated diode lasers, Saglam, et al. [22], and Dilsiz, et al. indicated power values without specification if it was the peak or average power.
Slot, et al. [26] refers the reader to a previously published study to find any laser parameters. Qadri, et al. [30] uses a water-cooled pulsed Nd:YAG laser (1064 nm,) whose power ' . . . was automatically controlled by the device.' Ciurescu, Abduljabbar, Ustun, Saglam, Dilsiz, and Euzebio-Alves and their colleagues gave the most complete parameter descriptions.
Average power is one useful measurement when comparing clinical outcomes, especially among clinicians whose laser instrument's panel has a power setting display. The parameters of adjunctive laser use for periodontal therapy can be found in the operating manual of the device and should be below those needed for excisional surgery [36].

Power Meter Measurement
Except for Euzebio Alves, et al., no other study measured the actual power emission from the fiber/tip. That manuscript described a mean energy (sic) loss of approximately 20%.
Clinical experience has shown both a loss of transmission of photonic energy with fiber use and variation of that transmission among new fibers. A study of urology fibers confirmed those differences by using a power meter to measure them [50]. It is accepted that fiber construction may be of differing quality or purity [51] and some literature sources do allude to possible power losses along delivery fibers in a range of 5% to 20% [52]. Additional data show that there is a wide variation in the range of transmission for different infrared fibers, and that the loss in most of those fibers is quite high compared with silica fibers [53].
Thus, the output power mentioned the manuscripts is likely to be inaccurate.

Fiber/Tip Size
Most studies reported a numerical tip diameter. Some provided no or minimal detail and/or used the manufacturer's product name. The irradiation time of laser photonic energy greatly influences the amount of tissue temperature necessary to remove diseased tissue and reduce pathogens [36,54]. The range of time listed in the studies included may have had an influence on the results.

Treatment Protocols
The conventional SRP methods in the studies showed some differences. During SRP, Sanz-Sanchez, Dilsiz, Euzebio Alves and their colleagues (for both control and test groups), and Giannopoulou et al. (only for test sites) used only ultrasonic instrumentation.
These differences may not be significant and usually depend on the clinician's skill. However, hand instrumentation does offer an enhanced tactile sense when removing the calculus. Euzebio Alves's addition of this hand instrumentation to only the test group may also have affected the outcomes.
In the following studies, SRP was performed before the adjunctive laser therapy in the same session: Abduljabbar, Magaz, Sanz-Sanchez, Saglam, Slot, Giannopoulou, Qadri, Kelbauskiene, and Lopes and their colleagues, along with Eltas and Orbak [28,29] It is well known that pigmented tissue has a high absorption by these wavelengths [54]. Caution is advised when using these wavelengths that could interact with the dark colored calculus on the root surface and cause thermal damage. Zhou, et al. and Rotundo, et al. used an erbium laser before SRP in the same session, but that laser family can safely remove calculus [36].
Three studies limited the number of teeth in their groups. Euzebio Alves, et al. and Eltas and Orbak [29] performed full mouth SRP but only evaluated one pair of contralateral teeth or one tooth per group, respectively. Lopes, et al. only used 4 sites for the control group (SRP) and the test group (laser + SRP.) This individual tooth study design could have limited significance, since all the patients had generalized periodontitis.
Several manuscripts described therapies spanning more than one session. Ciurescu, et al. listed multiple laser uses: initial treatment with a diode, a diode and Er,Cr:YSGG utilization one week later, and two months later, therapy consisted of a diode laser on all sites and an Er,Cr:YSGG on periodontal pocket depth (PD) ≥4 mm. Celik Kelbauskiene and colleague's therapy was an initial appointment of SRP + laser, followed by an average of two laser appointments, with a week between each visit.
The multiple laser treatments would certainly seem to provide additional benefit, although the results were comparable to single visit therapies.

Gingival Crevicular Fluid Level (GCF) Sampling
Abduljabbar, Ustun, Euzebio Alves (colony forming units (CFU) count), Giannopoulou, Qadri and Lopes and their colleagues as well as Eltas and Orbak [28,29]. noted split-mouth studies with GCF sampling; whereas Saglam, et al. used a parallel group design. Although both methods are acceptable, a question could be raised about the accuracy of split-mouth assaying since the pathogen population could have some similarities on both sides of the mouth.
It is worth noting that subject numbers should be sufficiently high to enable robust statistical analysis [55]. In the aforementioned GCF studies, the group sizes ranged from 19-52. Moreover, two manuscripts only analyzed either one pair of contralateral teeth per patient (Euzebio Alves, et al.), or one tooth per patient (Eltas and Orbak) [29]. Considering the diversity of the flora in periodontal pockets, the addition of microbiologic analysis to conventional protocols should increase the quantification of the effectiveness of dental therapies [56].

Smoking
While smoking has long been reported as one of the etiologic factors in periodontitis [57], Eltas and Orbak [28] reported that the smoker control and test group did not benefit from adjunctive laser use.

Halitosis
Dereci's adjunctive laser treatment showed significant reduction of halitosis, explained by the possible reduction of the volatile sulphur compounds (VSC) producing bacteria. This has some promising clinical application, since it has been reported that oral malodor is a common human attribute and can be an important reason to seek dental care [58].

Follow-Up
A 6-month follow up minimum period was chosen as an inclusion criterion so that evaluation of the clinical outcomes would have more clinical significance, and a few of the studies exceeded that time frame. Dental practitioners always emphasize periodic visits for their patients with susceptibility to periodontal disease to decrease the likelihood of progressive and episodic disease. The American Academy of Periodontology's position paper on periodontal maintenance (PM) states continuing care therapeutic appointments should be performed at intervals of less than six months, with the ideal schedule of PM every three months [59].

General Comments
The periodontal pocket occupies a three-dimensional space with irregular anatomy [60]. For meaningful photonic energy interaction, a careful and complete description of the protocol is necessary [61]. Some authors gave detailed descriptions of the direction and location of the laser emission during the irradiation time, but others did not. There were some explanations of coronal to apical motion, 'sweeping' motion, along with angulations of the tip. Those narratives are even more important when an end-emitting fiber or tip is used [62,63]. For example, Ciurescu described how the laser tip was ' . . . introduced subgingivally to the bottom of the pocket and the laser firing was performed during sight sinusoidal retracting movements . . . until the entire accessible . . . surface was contacted. ' Abduljabbar describes placing ' . . . the fiber into the periodontal pocket almost parallel to the tooth and moving from mesial to distal directions continuously on the buccal and the lingual aspect of the tooth. The fiber was held in a constant motion in contact with the pocket epithelial lining almost parallel to the long axis of the root.' In contrast, Giannopoulou simply states that ' . . . subgingival irradiation was performed with the diode laser for 60 s without any further description of the technique. A few mentioned the need to follow the manufacturer's instructions, but most did not. As a result, any missing information increases the difficulty of reproducing the study and its results.
Some of the studies included only analyzed single rooted teeth, while others treated an entire quadrant which included multi-rooted teeth. As noted, some authors' design had only one tooth. Given the complexity and variations of root anatomy, some of these study results may be criticized as not universally applicable for treatment of periodontitis.

Conclusions
The multi-factorial etiology and multiple treatment options when delivering initial periodontal therapy can offer challenges in attempting to standardize and analyze published papers. This systematic review found that 70% of the included studies [14][15][16][17][19][20][21][22][23][28][29][30][31]33] reported significantly better outcomes in certain clinical parameters, but no improvement in others. The remaining 30% of the manuscripts [18,[24][25][26][27] reported no significant difference in any of the measurements. With consideration of correct parametry, lasers have an adjunctive role in initial non-surgical periodontal therapy. We encourage additional publication of long-term randomized clinical trials to confirm these additional benefits.