|Year : 2020 | Volume
| Issue : 4 | Page : 146-154
Clinical and microbiological evaluation of antimicrobial photodynamic therapy as an adjunctive nonsurgical modality in patients with periodontitis: a randomized controlled trial
Yasser M El Makaky BDS, MSC, PhD 1, Hany K Shalaby2
1 Department of Oral Medicine and Periodontology, Faculty of Dentistry, Tanta University, Tanta, Egypt
2 Department of Periodontology and Oral Medicine, Faculty of Dentistry, Suez Canal University, Suez Canal, Egypt
|Date of Submission||23-Feb-2020|
|Date of Acceptance||19-Apr-2020|
|Date of Web Publication||22-Jan-2021|
Yasser M El Makaky
Department of Oral Medicine and Periodontology, Faculty of Dentistry, Tanta University, PO Box 2898, Tanta 43353
Source of Support: None, Conflict of Interest: None
Photodynamic therapy (PDT) was utilized in the dentistry field as an adjunctive process to traditional mechanical debridement in periodontitis patients. This study aimed to assess the clinical and microbiological impacts of PDT as an additional modality in individuals having periodontitis.
Patients and methods
A prospective, parallel-arm, controlled trial was applied on 30 (16 males and 14 females) nonsmoker, systemically healthy participants with periodontitis. Patients were randomly allocated into a control group (n = 15) who received scaling and root planing (SRP) solely or to the test group (n = 15) which was treated by PDT plus SRP. Gingival index, probing depth, plaque index, and clinical attachment level were monitored at baseline and on 1, 3, and 6 months. Subgingival plaque samples were taken and evaluated for the number and percent of sites positive for Porphyromonas gingivalis, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and Treponema denticola at baseline and on 1, 3, and 6 months.
All periodontal variables and microbial parameters decreased significantly in all study populations after both treatment approaches (P ≤ 0.05). The inter groups comparison showed significantly better results in the test group than the control group concerning periodontal pathogens reduction and periodontal parameters improvement (P ≤ 0.05).
PDT combined with traditional SRP could provide significant beneficial impacts on the studied periodontal and microbiological parameters compared to SRP solely.
Keywords: nonsurgical therapy, periodontitis, photodynamic therapy, randomized controlled trial
|How to cite this article:|
El Makaky YM, Shalaby HK. Clinical and microbiological evaluation of antimicrobial photodynamic therapy as an adjunctive nonsurgical modality in patients with periodontitis: a randomized controlled trial. Tanta Dent J 2020;17:146-54
|How to cite this URL:|
El Makaky YM, Shalaby HK. Clinical and microbiological evaluation of antimicrobial photodynamic therapy as an adjunctive nonsurgical modality in patients with periodontitis: a randomized controlled trial. Tanta Dent J [serial online] 2020 [cited 2021 Oct 16];17:146-54. Available from: http://www.tmj.eg.net/text.asp?2020/17/4/146/307806
| Introduction|| |
Periodontitis is defined as an inflammatory disorder that affects dental soft tissues, manifested by periodontal pocketing and progressive destruction of periodontal supporting tissues. If left untreated, tooth loss and significantly negative impact on the life quality will be the outcomes of this disease. In the United States, the prevalence of severe periodontitis was about 8.5% while that for moderate periodontitis was 30.0%. In chronic periodontitis, the colonization of dental biofilm by numerous bacterial species plays a main role in the initiation and development of this disease. The nonsurgical periodontal therapy (NSPT), chiefly comprised of scaling and root planing (SRP), directs to stop this disease through mechanical removal of calculus and bacterial products from sub and supragingival areas around the root surface. In patients with chronic periodontitis, SRP is considered a gold standard technique for periodontal treatment because it has been evidenced to be both a successful and safe therapeutic method.
SRP by either hand instruments and/or ultrasonic scalers also represents the most popular nonsurgical option for periodontal therapy. However, SRP only is predominantly incapable to eradicate periodontal pathogens and their toxic products completely from areas such as furcation, concavities and curvature of the root, and deep pockets where there are difficulties to perform the mechanical debridement. Following further assessment, the surgical periodontal technique may be essential to remove the residual etiological factors. Therefore, the utilizing of antimicrobial photodynamic therapy (PDT) and lasers as adjunctive approaches to nonsurgical mechanical debridement singly have been progressively assessed. Recently, numerous types of lasers have become displayed commercially as an adjunctive modality in the field of periodontal therapy. All lasers types possess a thermal influence on the dental soft tissues, resulting in a clot of the inflamed sulcular epithelium as well as a reduction in the number of pathogens in the periodontal pockets.
The PDT requires the complex reactions between three various components, namely low-intensity laser light (mostly diode laser), molecule oxygen, and photosensitizer (such as methylene blue and toluidine blue). When irradiated by low-intensity laser light with a certain wavelength, the photosensitizer can be activated and excited to the higher-energy triplet condition. The interaction between the molecule oxygen and the triggered photosensitizer results in the liberation of substances such as free radicals and highly reactive oxygen, which are cytotoxic for many periodontal pathogens. PDT is considered a promising alternative option for the treatment of periodontitis because of its bactericidal influence against periodontal pathogens. However, to be suggested for clinical uses, adjunctive use of any sort of lasers and PDT to NSPT must yield safe and predictable results superior to those produced by mechanical instrumentation only.
Salvi et al., concluded that the available evidence on the efficiency of PDT and laser as an adjunctive modality in periodontal therapy is limited because of a restricted number of controlled clinical trials. The hypothesis of this controlled trial was that 635 nm wavelength. Diode laser and PDT combined with SRP may produce more effective clinical and bacteriological outcomes than SRP alone. Therefore, this trial aimed to evaluate the impact of Diode laser and PDT as an adjunctive therapeutic method in NSPT among patients with periodontitis.
| Patients and methods|| |
Patients and study design
A prospective, parallel-arm, single-blinded, randomized, controlled study with 6 months follow-up period was designed based on a statement of Consolidation Standards of Reporting Trials (CONSORT). The study population consisted of 30 systemically healthy participants (16 males and 14 females) with periodontitis between 30 and 45 years of age with a mean of 37.5 years who were selected from the Department of Periodontology, Faculty of Dentistry, and Suez Canal University from February 2018 to December 2018. All participants were informed about all the steps of procedures that were performed in the study, they accepted participation in the study, and signed written informed consents before recruitment. This trial was done following guidelines accepted by the Declaration of Helsinki (2013) for studies covering human patients. All study populations were known that they could terminate their participation at any time of the study without consequences.
Patients were eligible when they fulfilled the next inclusion criteria: (a) at minimal one site with pocket depths (PD) more than or equal to 4 mm in at least two permanent teeth with bleeding on probing in each quadrant; (b) presence of at least 16 permanent teeth; (c) no history of either periodontal therapy or systemic antibiotic in the last 6 months; and (d) in good general health. Possible study entrants were excluded if they (a) were pregnant or breastfeeding; (b) were current or former smoker; or (c) had systemic disorders that could impact the study outcomes, such as diabetes.
A new classification of periodontitis was used for diagnosis of periodontitis, as following; grade A; stages I, II, or III; and generalized or localized. A periapical radiograph was used to ensure the diagnosis in each patient.
Eligible patients were randomly categorized into two groups utilizing a 1: 1 allocation ratio. Control group: receiving oral hygiene instructions (OHI) and SRP; and test group: receiving OHI, SRP, and PDT. Randomization was achieved via tossing a coin. Closed opaque envelopes were utilized for allocation hiding and opened just prior to the interventions and the details of the sequences were anonymous to the patients.
Sample size computation
In this study, the primary outcome was a change in the mean values of clinical attachment level (CAL) between study groups. According a total sample size of 24 participants was computed to detect a significant difference of 0.5 mm in CAL between studied groups with a SD of 0.6 mm at 80% statistical power and 5% type I error on a two-sided hypothesis test. In this trial, considering a probable dropout rate throughout the follow-up periods, the total count of patients was 30.
Seven days after supra-gingival scaling and OHI, all participants in both groups were recalled to gather baseline clinical data. After that, patients received the allocated periodontal therapy comprised of full-mouth SRP in a single 2-h session utilizing an ultrasonic scaler (Cavitron; Dentsply, New York, New York, USA) and Gracey curettes (Hu-Friedy, Chicago, Illinois, USA). Local anesthesia was injected only if needed. This allocated intervention was done by the same specialist for all study participants. SRP procedures were stopped when the periodontist was confirmed that the root surfaces became thoroughly debrided as evaluated by a sharp-ended probe. OHI was provided at each treatment and follow-up visit, again based on individual requirements.
For the test group, following the full mouth SRP, a 635 nm wavelength diode laser (Lasotronix, 0.5–500 Piaseczno, Poland) at a radiation power of 200 mW was used with a 0.01% methylene blue photosensitizer which was applied with a blunt needle at the base of the periodontal pocket and incubated in place for 1 min, followed by distilled water irrigation to eliminate any excess. The dye-filled pocket was irradiated by the laser using a flexible tip applicator [Figure 1] (200 μm diameter) for 60 s. The PDT protocol was done two times, once after SRP and another after 2 weeks by the same trained periodontist [Figure 2].
The clinical assessments were done by a single calibrated investigator utilizing a graduated North Carolina probe (Hu-Friedy) at baseline (before NSPT and PDT), 1, 3, and 6 months postoperatively. The calibration for pressure was done prior to the periodontal probing. The reliability of the investigator was evaluated for periodontal measurements on 10 participants just before the initiation of the study. The correlation coefficient of the agreement for CAL was 0.95 while for PD it was 0.92.
The clinical periodontal assessment included gauging of PD, assessing of plaque index (PI), determination of cementoenamel junction to measure CAL, and gingival index (GI). After excluding third molars, the clinical outcomes such as PD, GI, and CAL were monitored at six sites for each tooth. PI per tooth was assessed on a scale from 0 to 3.
Gingival crevicular fluid collection
Gingival crevicular fluid (GCF) samples were taken before the measurement of periodontal variables to prevent blood contamination, mechanical irritation, and stimulation of GCF. After isolation of sample sites by cotton rolls, plaque in the supragingival area was eliminated and sampling areas were dried using an air syringe to decrease any contamination with saliva and plaque. Paper strips (Periopaper; Oraflow, Amityville, New York, USA) were gently introduced into the gingival sulcus until mild resistance was detected and were stayed in site for 30 s. Thereafter, they were transferred to 1.5 ml sterile Eppendorf tubes and saved at −80°C till analyzed. Strips polluted with blood were discarded. GCF samples were taken at baseline, 1, 3, and 6 months after the allocated intervention in both study groups.
An extraction DNA commercially available kit (QiaAmp DNA mini kit; Hilden, Germany) was utilized to isolate DNA from subgingival samples, depending on the manufacturer's guidelines. A real-time PCR (TaqMan Applied Biosystem, California, USA) was used for bacterial identification and quantification. Probes and oligonucleotide primers were chosen according to species-specific highly conserved areas from the 16 S rRNA gene for the following species: Porphyromonas gingivalis, Tannerella forsythia, Aggregatibacter actinomycetemcomitans, and Treponema denticola. Cloning procedures were done to perform a quantitative assay as formerly described by Rodrigues et al., to gain positive plasmid controls for these species. From each plasmid control, 10 folds of dilutions were run serially in triplicate to get a standard curve. Negative controls, samples, and plasmid standard controls were run in triplicate, in a reaction blend (20 μl), containing: 0.5 μl of the reverse and forward primers, 10 μl of Taqman FAST PCR, 6.5 μl of sterilized free water-DNAase, 2 μl DNA sample, and 0.5 μl of probe. The amplification was done by a 7500 fast real-time PCR utilizing the following cycles: one cycle for 20 s at 95°C, and 40 cycles for 3 s at 95°C and for 30 s at 60°C.
Changes in the mean values of CAL between studied groups following intervention procedures were the primary outcome. While, secondary outcomes were the level of periodontal pathogens, GI, PD, and PI.
In this controlled trial, each variable value was expressed as mean and SD. Version 18.0 SPSS statistical package was utilized for data analyses. The Kolmogorov–Smirnov normality test was used to normally distribute all outcome values. Study variables between the studied groups were compared utilizing Student's t test. The comparisons at different follow-up periods within each treatment group were carried out by using one-way analysis of variance and then post-hoc Tukey. The significance level was detected at P value less than or equal to 0.05.
| Results|| |
A 6-month controlled clinical trial was implemented on 30 participants. No patients observed any complications or discomfort regarding this study. All study populations returned till the end of the study period. The microbiological and periodontal parameters (GI, PI, CAL, and PD) were evaluated prior to treatment (baseline), and at 1, 3, and 6 months after the treatment in both groups.
The clinical results
Baseline findings of periodontal parameters were displayed in [Table 1]. There were no significant differences between the study groups regarding PI, GI, PD, and CAL (all P > 0.05). The means of PI among studied groups were exhibited in [Table 2]. Within the groups, there were significant decreases in the mean values of PI from the baseline measurements in both groups. In addition, the differences between the test and control group at 1, 3, and 6 months were statistically significant (all P < 0.05).
|Table 1: Means values of the periodontal parameters at baseline in both groups|
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[Table 3] shows changes in GI between and within the study groups at different follow-up visits. All Patients showed a significant reduction regarding GI from baseline to 1, 3, and 6 months after periodontal therapy (all P < 0.05). It has been found that the differences between the two studied groups at 1, 3, and 6 months were statistically significant. Within the test group, the mean value of PD was significantly decreased from the baseline measurement to the subsequent follow-up periods. The same observation was recorded in patients within the control group. Besides, the differences between both study groups concerning PD were significant at 1, 3, and 6 months (all P < 0.05) [Table 4]. The changes in mean values of CAL within study groups from baseline to 1, 3, and 6 months displayed similar trends with a significant reduction as PD. Also, intergroup differences in this trial regarding CAL at 1, 3, and 6 months were statistically significant [Table 5].
|Table 5: The changes of clinical attachment level in all patients at the different follow-up periods|
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At baseline, no significant differences were recorded between the study groups concerning the number and percent of positive sites for the four studied periodontal pathogens (all P > 0.05). However, these differences reached a significant level at 3 and 6 months follow-up periods. All participants in this study were 100% positive for T. denticola, P. gingivalis, and T. forsythia. While the prevalence of A. actinomycetemcomitans among patients within the test and control was 40 and 33.3% respectively [Table 6].
|Table 6: Comparison of number and percentage of positive sites for the studied periodontal pathogens among study groups|
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[Table 7] showed that within both study groups the number and percent of positive sites for T. denticola, P. gingivalis, and T. forsythia were significantly decreased at 1, 3, and 6 months when compared with baseline findings. Concerning A. actinomycetemcomitans within both groups, there was significant reduction in the number of sites infected with A. actinomycetemcomitans at 6 months follow-up visit in comparison with baseline data.
|Table 7: Distribution of number and percentage of positive sites for the studied periodontal pathogens within study groups at all follow-up periods|
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| Discussion|| |
PDT is a sort of phototherapy comprised of the use of photosensitizers, light, and reactive oxygen molecules resulting in cell death. PDT can kill microbial cells like viruses, fungi, and bacteria. It is extremely predicted that utilizing PDT as an adjunct procedure to NSPT has considerable effect in periodontal therapy, because NSPT only might not be able to eradicate all periodontopathogens completely. Following SRP, T. forsythia and A. actinomycetemcomitans were shown to stay in periodontal pockets. Immediately or even shortly after SRP, bacterial recolonization in the subgingival areas is expected; it is indicated that the periodontal maintenance is important to avoid a return to baseline levels of pathogens.
In the current study, antimicrobial medications were not utilized to avoid the interference of their adjunctive effect with the trial outcomes. This is in accordance with Pulikkotil et al., who investigated the efficiency of a PDT as an additional technique to SRP for the treatment of periodontitis.
This randomized controlled trial assessed the impact of PDT application in two doses as an adjunct to SRP in patients having periodontitis via clinical and microbiological examination. Concerning PD and CAL, the clinical findings showed significant improvements in patients treated with the composite technique of PDT + SRP compared to those receiving SRP alone. This was in agreement with Corrêa et al., who designed a split-mouth clinical trial to study the effect of PDT combined with NSPT and demonstrated greater CAL gain and PD reduction in sites managed by this combined method (PDT + SRP) in comparison with control sites that were treated with SRP singly. Thus, the application of PDT accompanying SRP could be indicated for the treatment of periodontitis, as supported by former studies,. In consistent with this, other researches have concluded that sites treated with mechanical debridement and PDT achieved significantly better results regarding both PD and CAL compared with traditional SRP in chronic periodontitis.
In accordance with this, Azarpazhooh et al., formulated a systematic review that included five clinical trials to study the success of PDT in the elementary therapy of chronic periodontitis as a monotherapy in comparison with mechanical debridement singly, and with a composite therapy (PDT+SRP). The authors revealed that this composite technique achieved more CAL gains than the other therapeutic modalities utilized as monotherapy, concluding that this therapeutic approach (PDT+SRP) indicated potential benefits in CAL gain.
However, these encouraging outcomes exhibited in the present study regarding PD and CAL when PDT was utilized as adjunctive therapy were not observed in other studies. Borekci et al., applied a 625–635 nm LED source with 1000 mW output power, intensity of 2000 mW/cm2, and 0.1 mg/ml toluidine blue as a photosensitizer in the test group for treatment of generalized aggressive periodontitis. They observed that there were no significant differences between test and control groups in terms of PD and CAL. In accordance with this, Christodoulides et al., used a 670 nm diode laser with 75 mW power output, and photosensitizer (phenothiazine chloride), also failed to display promising findings concerning CAL and PD following PDT application combined with NSPT in initial periodontal treatment.
In the current controlled trial, PDT was carried out after thorough subgingival and supragingival SRP. This is according to Sculean et al., who emphasized the importance of subgingival removal of microbial plaque in the eradication of periodontal infection. The presence of proteins resulted from gingival fluid and saliva or the hemorrhage during PDT implementation may decrease the antibacterial effects of the photosensitizer. These environmental situations may play an important role in the antibacterial properties of PDT. Because of microbial complex cell wall composition, the penetration power of the photosensitizer into the microorganisms directly affects the efficiency of PDT. Moreover, the microbial extracellular polysaccharide matrix from dental plaque can form a physical barrier against photo activation.
The observations of this study regarding GI and PI showed a significant benefit which was achieved by the additional use of PDT to the traditional treatment of periodontitis. Similar findings were showed in previous studies; Betsy et al., assessed the effects of PDT as an additional modality in the treatment of chronic periodontitis and revealed significant improvements in GI and bleeding index within the test group in the short term; Borekci et al., demonstrated that the sulcus bleeding index was significantly lower within the test group (PDT + SRP) than the control group (SRP) after 63 days. These observations proposed that using of PDT as an additional to NSPT, has an extra positive impact on gingival bleeding; Al Rifaiy et al., investigated the benefits of adjunctive PDT in decreasing peri-implant inflammation in participants using electronic cigarettes. A significant reduction in PI was observed at 12 weeks in the group I (test) in comparison with group II (control). Chondros et al., and Cappuyns et al., observed a significant reduction in bleeding on probing in the test group when compared with a control group after implementation of PDT in a single dose along with ultrasonic/hand instrumentation. This marked reduction in bleeding on probing could be caused by the positive influence of PDT on the inflammatory pathways or immune response and require further exploration. Following PDT, with improved treatment results in affected patients, could lead to the detection of other nonbacterial explanation for the action of PDT.
In contrast to our outcomes, Chitsazi et al., stated that there was no difference between the studied groups regarding gingival inflammatory parameters in a trial assessing the success of the additional application of PDT to SRP in patients with aggressive periodontitis. While Chitsazi et al., applied ultrasonic scaler only, in the present trial both hand instruments and ultrasonic were utilized together. In a split-mouth trial designed by de Oliveira et al., concerning gingival inflammation, no significant difference was detected between both groups following the single-dose application of PDT. Lui et al., found no significant difference between studied groups at 3 months after using combined PDT and NSPT for the treatment of individuals with chronic periodontitis regarding PI.
In this trial, the number and percent of positive sites for A. actinomycetemcomitans, T. denticola, P. gingivalis, and T. forsythia were assessed in the plaque samples. Both therapeutic approaches being used in this trial resulted in significant reduction in the number and percent of positive sites for all studied periodontal pathogens at 6 months. However, the complete eradication of these microorganisms was not possible even from the areas supposed to be clinically healthy following treatment. In line with this, the microbiological outcomes of a study by Borekci et al., revealed that the levels of P. intermedia, A. actinomycetemcomitans, T. denticola, T. forsythia, and P. gingivalis in plaque samples decreased significantly following the treatment in both groups without any significant changes concerning the periodontopathogen levels between the two groups regardless that the reduction was more distinct within the test group. On the other hand, our microbiological findings showed a significantly greater reduction in the number and percent of infected sites with studied pathogens in the test group as compared with the control group. This is in accordance with Cappuyns et al., who evaluated the success of PDT on the treatment of residual pockets and reported better outcomes of reduction in T. denticola, T. forsythia, and P. gingivalis after 14 days in PDT group, also Theodoro et al., demonstrated a greater reduction in levels of all bacteria in sites that were treated by PDT adjunctive to SRP after 180 days. Conversely, Christodoulides et al., studied the microbiological impact of SRP plus a single dose PDT and SRP solely in the management of periodontal pockets, they reported insignificant differences in the levels of the assessed bacteria, including P. gingivalis and A. actinomycetemcomitans at 3 and 6 months when comparing these two therapeutic modalities.
The current trial has various limitations that merit investigations. First, study outcomes were not comprehensive. If inflammatory and immunological parameters had been evaluated at the same time with the clinical variables and microbiological profiles, the study findings might be more convincing. Second, the numbers of studied periodontal pathogens are relatively limited. Third, in this trial, laser parameters differed from those that commonly utilized in clinical studies. Therefore, the heterogeneity of results may occur in comparing with these studies
| Conclusion|| |
Within the limits of this trial, the clinical and microbiological findings exhibited that the utilizing of two sessions PDT as an adjunct to SRP provided significant benefits regarding clinical parameters (PD, CAL, PI, and GI) and periodontal pathogens reduction in patients with periodontitis.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2], [Table 3], [Table 4], [Table 5], [Table 6], [Table 7]