Emerging Role of Photodynamic Therapy in Management of Periodontitis: A Systematic Review

1. Professor and Head, Department of Periodontology, K.M. Shah Dental College and Hospital, Vadodara, Gujarat, India. 2. Postgraduate Student, Department of Periodontology, K.M. Shah Dental College and Hospital, Vadodara, Gujarat, India. 3. Professor, Department of Periodontology, K.M. Shah Dental College and Hospital, Vadodara, Gujarat, India. 4. Reader, Department of Periodontology, K.M. Shah Dental College and Hospital, Vadodara, Gujarat, India.

Abstract

Introduction: Photodynamic Therapy (PDT) presents a non invasive avenue for treating various infections, including periodontal disease, offering an alternative to mechanical methods like scaling and root planing. Concerns about antibiotic resistance have fueled the exploration of PDT as an antimicrobial therapy. PDT combines low-power lasers with photosensitising drugs to eliminate microorganisms through the generation of cytotoxic reactive oxygen species upon light activation.

Aim: To evaluate the scope of PDT and its role in periodontology.

Materials and Methods: A comprehensive electronic search was conducted in major medical databases, including Google Scholar, PubMed, Cochrane Library, Scopus, Web of Science, Embase, and Wiley. A total of 43 studies from 2007 to 2023 were selected, focusing on PDT for the treatment of periodontal disease. The review included Randomised Controlled Trials (RCTs), case-control studies, and cohort studies involving human subjects, using Photosensitisers (PSs) or Indocyanine Green (ICG) for subgingival irrigation in chronic periodontitis patients after scaling and root planing, with follow-ups extending over one month. The outcomes measured were Probing Pocket Depth (PPD), Clinical Attachment Level (CAL), Plaque Index (PI), and Gingival Index (GI).

Results: In present review, after thorough analysis, a total of 21 studies were selected from databases including Google Scholar, PubMed, Cochrane Library, Scopus, Web of Science, Embase, and Wiley. The risk of bias assessment showed high-risk in 1 out of 128 studies (0.59%), low risk in 139 out of 168 studies (82.74%), and unclear risk in 28 out of 168 studies (16.67%). The results indicated significant clinical improvements when PDT was combined with conventional treatments.

Conclusion: The PDT in periodontology showcases varied roles, from antimicrobial action to tissue healing and the promotion of periodontal health. Its efficacy as an adjunctive treatment, especially in challenging cases or against resistant microbes, is evident, accentuated by its non invasive nature and minimal adverse effects, making it an appealing option in periodontal care.

Antibiotic resistance, Microbial infections, Non invasive treatment, Oral health, Photochemical reaction, Photosensitiser drugs

Periodontal diseases are a group of prevalent oral health conditions that affect the supporting structures of teeth, including the gums, periodontal ligament, and alveolar bone (1). These diseases are primarily caused by the accumulation of dental plaque, a complex biofilm comprising bacteria and their by-products, which leads to inflammation, tissue destruction, and potential tooth loss if left untreated. Traditional methods of periodontal therapy involve mechanical scaling and root planing to remove bacterial deposits and promote tissue healing (2). While effective, these approaches may have limitations in sites with difficult access and may not fully address the rising concerns of antibiotic resistance (3).

In recent years, PDT has emerged as a promising non invasive treatment approach for various infections, including periodontal diseases caused by dental plaque (4). PDT utilises low-power lasers with specific wavelengths in combination with PSs drugs to selectively target and destroy microorganisms. The activation of photosensitising compounds by light initiates a photochemical reaction, leading to the production of cytotoxic reactive oxygen species, particularly singlet oxygen, which effectively kills bacteria (5).

The simplicity and high efficacy of bacterial killing with PDT have led to its extensive use as an antimicrobial therapy in various medical fields (6). In periodontology, PDT offers a potential alternative to traditional mechanical methods, with the advantage of addressing concerns about bacterial resistance and providing an adjunct to non-surgical periodontal therapy (7).

The findings from this systematic review will contribute to a better understanding of the potential of PDT in periodontology, its limitations, and areas for further research. With the rising concerns of antibiotic resistance and the need for innovative and effective treatments, exploring PDT’s role in periodontal disease management holds promise for revolutionising the way we approach the treatment of periodontal diseases and combating dental plaque-associated infections.

The present systematic review aimed to comprehensively assess the existing literature on the application of PDT in periodontology. By exploring the current evidence, authors aimed to evaluate the scope of PDT in periodontal disease management, its impact on clinical outcomes, factors affecting its efficacy, and potential safety considerations. Furthermore, authors will identify gaps in the literature and provide insights into future perspectives and recommendations for integrating PDT into clinical practice.

Material and Methods

A comprehensive electronic search was conducted in major medical databases, including PubMed, Embase, and the Cochrane Library, to identify relevant studies published upto the date of this review. The following keywords and Medical Subject Headings (MeSH) terms were used: “Chronic Periodontitis,” “Scaling and Root Planning,” “Non Surgical Periodontal Therapy,” “Subgingival,” and “PDT,” as shown in (Table/Fig 1). After conducting a thorough analysis, duplicates were eliminated based on relevant databases, titles, authors, publication years, and abstracts. For present review article, a meticulous manual screening process was carried out to ensure the removal of duplicates.

Inclusion criteria: Randomised Controlled Trails (RCTs), case-control studies, and cohort studies involving human subjects (both parallel and split-mouth designs) from 2007 to 2023 were included. Studies in which either PSs, ICG, or antimicrobial PDT (aPDT) was used for subgingival irrigation or subgingival application as an adjunct to scaling and root planning in chronic periodontitis patients were considered. Studies reporting outcomes such as probing pocket depth, Clinical Attachment Level (CAL), Plaque Index (PI), Gingival Index (GI), and other correlated outcomes were included.

Exclusion criteria: Animal studies, in-vitro studies, and studies in which patients were under systemic medication that may affect clinical outcomes were excluded. Additionally, studies that did not have proper follow-up and articles published in languages other than English were also excluded. Studies in which interventions were conducted using other antimicrobials were not considered.

In present review article, the included studies were selected from electronic databases covering the past 16 years, specifically from 2007 to 2023. After a complete analysis, duplicate entries were eliminated based on the titles and abstracts of the studies (Table/Fig 2).

Study Procedure

Data assessment: The risk of bias for RCTs was assessed using the Cochrane Collaboration tool and performed with RevMan 2 software (8). Risk of bias was evaluated by two independent reviewers for the RCTs included in the review, and discrepancies were resolved through discussion and consultation with a third reviewer. The domains for risk assessment were graded as high, unclear, or low risk based on selection bias, random sequence generation, allocation concealment, selective reporting, other bias, blinding of participants, blinding of outcome assessment, incomplete outcome data, and overall risk of bias. A study was assessed to have a low overall risk only if, all domains were found to have low risk; it was assessed to have a high overall risk if, one or more of the six domains were found to be at high-risk. An unclear risk assessment was assigned to studies when one or more domains were uncertain, provided none were at high-risk.

Results

Risk of bias: RevMan software version 5.4 was used to analyse the risk of bias in the present study. Authors evaluated individual studies for various domains, including selection bias (creation of a random sequence), performance bias (blinding of cases and staff), attrition bias (incomplete results data), selective reporting (reporting bias), and other biases. Each study was classified as having low risk (+), high-risk (-), or unclear risk (?), as depicted in (Table/Fig 3) (9),(10),(11),(12),(13),(14),(15),(16),(17),(18),(19),(20),(21),(22),(23),(24),(25),(26),(27),(28),(29). The present review of PDT in periodontology consolidated 43 articles into 21 relevant RCTs, as highlighted in (Table/Fig 3), providing a comprehensive summary of findings. Among these studies, the most concerning issues were the inadequacy or absence of randomisation, which resulted in a high-risk for 1 out of 168 trials (0.59%). In contrast, low risk was noted in 139 out of 168 trials (82.74%), and unclear risk was noted in 28 out of 168 trials (16.67%), as represented in (Table/Fig 4).

The assessment of study quality within the pool of 21 included studies was conducted using the Cochrane risk of bias tool, as detailed in (Table/Fig 4) (9),(10),(11),(12),(13),(14),(15),(16),(17),(18),(19),(20),(21),(22),(23),(24),(25),(26),(27),(28),(29). Among the 21 studies, one study showed a high-risk of bias (13), and six of them were found to exhibit an overall unclear risk of bias [9,16,20,21,26,29]. Despite this unclear risk, the quality of these studies was deemed acceptable, suggesting that while they had some methodological limitations, they still provided valuable contributions to the research area.

In contrast, the majority of the studies, specifically 17 out of the 21, demonstrated an overall low risk of bias (9),(10),(11),(12),(13),(14),(15),(16),(17),(18),(19),(20),(21),(22),(23),(24),(25),(26),(27),(28),(29). These studies were recognised for their robust methodology and study design, resulting in a classification of good quality. Their lower risk of bias underscores the reliability and trustworthiness of their findings within the context of the systematic review.

Study characteristics: In the present review, approximately 21 studies were included, which primarily focused on evaluating aPDT alongside traditional methods such as ultrasonic debridement and Scaling and Root Planing (SRP). Thirteen studies specifically compared these approaches, with five studies showing significant improvements in outcomes like Bleeding on Probing (BOP), Probing Pocket Depth (PPD), and Clinical Attachment Level (CAL) gain (17),(19),(21),(22),(26). Two studies reported enhancements in BOP only (14),(20). However, five studies did not find notable differences between aPDT combined with conventional treatments and conventional treatments alone (10),(13),(15),(16),(28).

The aPDT protocols in the trials used various PSs like phenothiazine chlorine, methylene blue, toluidine blue, and Indocyanine Green (ICG). These were incubated for upto five minutes. Different light strategies were employed depending on the PS, with ICG treated at 810 nm and others at 628 to 680 nm. Light power ranged from 2 to 100 mW/cm², with energy levels between 20 and 320 J/cm² (10),(11),(12),(13),(14),(15). Moreover, the integration of ICG as a PS was consistently combined with conventional treatments in the studies, showing clinical improvements. Follow-up durations ranged from seven days to 12 months, allowing for the assessment of both short-term and long-term effects.

Discussion

The systematic review on PDT in periodontology has provided valuable insights into the potential of this innovative treatment approach for managing periodontal diseases caused by dental plaque. This discussion will delve into the key findings, implications, and future perspectives identified in the review, shedding light on the current evidence and its significance in the field of periodontal therapy.

Effectiveness of PDT in periodontal disease management: The review demonstrated that PDT, when used as an adjunct to conventional periodontal treatments, can lead to significant clinical improvements. The ability of PDT to target and kill microorganisms through the generation of cytotoxic reactive oxygen species, particularly singlet oxygen, provides a promising alternative to traditional mechanical approaches for eliminating bacterial deposits (30),(31). These findings suggest that PDT has the potential to enhance the outcomes of non-surgical periodontal therapies and address the limitations of conventional methods in sites with difficult access.

Effectiveness of PDT in various test groups: Similarly, another study introduced a test group infused with probiotics in conjunction with PDT and SRP. The outcomes reported by Patyna M et al., favoured this combination, resulting in significant clinical improvements and a microbiological achievement marked by a substantial reduction of specific pathogens (27).

The review also included two studies that explored the implications of repeated applications of PDT in supportive periodontal therapy. The outcomes of these studies underscored the potential for multiple applications of adjunctive PDT to yield improved clinical results in residual pockets among maintenance patients (11),(12).

Furthermore, a comparison between PDT and antibiotics in the context of scaling and root planing revealed comparable long-term improvements in periodontal parameters for both interventions. Another investigation examined the adjunctive effect of PDT in surgical periodontal therapy, showing significant reductions in probing depth and gains in clinical attachment level for the PDT group. Notably, changes in the subgingival microbiota were consistent across both groups; however, the PDT group exhibited a higher concentration of bacteria associated with periodontal disease at the conclusion of the study (29).

Andersen R et al., and Christodoulides N et al., employed more complex methodologies in their investigations, each characterised by three distinct study arms. One study introduced a supplementary experimental group exclusively undergoing PDT, with three study arms designed to comprehensively investigate the effects of different interventions. Each arm represented a unique aspect, enhancing internal validity and providing insights into the effectiveness of the interventions. In a prior investigation, patients underwent SRP before being randomised into either a no further treatment arm or an adjunctive PDT arm (9),(10).

Variability in study outcomes: While the majority of studies demonstrated favourable outcomes, it is important to acknowledge the variability in the results. Some studies did not observe significant differences between PDT in combination with conventional treatment and conventional treatment alone (10),(13),(15),(16),(28). This variability could be attributed to several factors, including differences in study design, patient populations, PDT protocols, PSs used, and light parameters. These variations highlight the need for standardisation and consistency in future research to obtain more robust and generalisable results.

In the analysis of the 21 studies included in present review, it is noteworthy that one study was identified as having a high-risk of bias, as indicated by the risk of bias assessment tool utilised (13). This finding emphasises the importance of critically evaluating the methodological quality of studies in research synthesis, as studies with a high-risk of bias may introduce substantial uncertainty and potential inaccuracies in the conclusions drawn. Additionally, the discovery that six studies demonstrated an overall unclear risk of bias further underscores the need for transparent reporting and robust methodological approaches in future research endeavours. Addressing and minimising bias in study design, conduct, and reporting are imperative to enhance the reliability and validity of research outcomes, ultimately contributing to evidence-based decision-making in healthcare and clinical practice.

Factors affecting PDT efficacy: The review identified various factors that can influence the efficacy of PDT in periodontal disease management. One crucial aspect is the selection of appropriate PSs and their concentrations. The PSs should possess the following properties: a high binding affinity for the target microorganism, a broad spectrum of action, a low binding affinity for mammalian cells to avoid the risk of photodestruction of host tissues, a low propensity for selecting resistant bacterial strains, a minimal risk of promoting mutagenic processes, and low chemical toxicity (32).

Different PSs exhibit varying levels of bacterial selectivity and activation wavelengths, which can impact the overall effectiveness of PDT. Generally, Gram-positive bacteria are susceptible to photo-inactivation, whereas Gram-negative bacteria are often resistant unless the permeability of their outer membrane is modified. This is connected to the difficulties encountered by PSs in penetrating gram negative bacterial cells. Antimicrobial PSs such as porphyrins, phthalocyanines, and phenothiasines (e.g., methylene blue and toluidine blue O) have been reported to penetrate both gram-positive and gram negative bacteria. The positive charge seems to promote the binding of the PSs to the gram negative bacterial membrane, leading to localised damage and resulting in increased permeability. Hence, toluidine blue O and methylene blue are commonly used in antimicrobial photodynamic therapy (aPDT). The hydrophilicity, low molecular weight, and positive charge of methylene blue facilitate its passage across the porin-protein channels in the gram negative outer bacterial membrane. Methylene blue’s interaction with the anionic lipopolysaccharide macromolecule of gram negative bacteria results in the generation of methylene blue dimers, which participate in the photosensitisation process (32),(33).

Moreover, the choice of light sources and their parameters, including light intensity and exposure time, can also influence the photodynamic reaction (34). Therefore, optimising these parameters is essential for achieving consistent and reproducible outcomes in PDT-based periodontal therapies.

Safety and adverse effects: The safety profile of PDT in periodontology was explored in the review. PDT is generally considered safe, with minimal adverse effects reported in the selected studies (35),(36),(37),(38). However, like any medical procedure, PDT is not entirely devoid of risks. Potential adverse effects may include mild discomfort, tissue sensitivity to light, and transient post-treatment inflammation (39). Nonetheless, the incidence of serious complications is low, indicating that PDT can be considered a safe treatment modality when appropriately administered. Long-term studies with larger sample sizes would be beneficial to further assess the safety and potential long-term effects of PDT in periodontal patients.

Future perspectives and recommendations: The systematic review has highlighted the potential of PDT as a valuable addition to periodontal disease management. However, several avenues for future research and improvements in PDT’s clinical application have been identified. Further investigations are needed to establish the long-term efficacy of PDT and to identify optimal treatment protocols, including the most suitable PSs and light parameters (40). Large-scale randomised controlled trials and comparative studies can provide stronger evidence for the effectiveness of PDT and enable the identification of specific patient populations that may benefit the most from this therapy. Additionally, exploring the use of PDT in combination with other emerging periodontal treatments or technologies may offer further benefits and enhance its efficacy.

Limitation(s)

Studies on PDT in periodontology may vary widely in terms of study designs, patient populations, intervention protocols, and outcome measures, making it challenging to draw direct comparisons or generalise findings and many studies may have short-term follow-up periods, which limits the assessment of the long-term efficacy and safety of PDT in periodontal treatment.

Conclusion

The PDT presents a promising scope in periodontology, showcasing varied roles ranging from antimicrobial action to tissue healing and periodontal health development. Its efficacy as an adjunctive treatment, especially in challenging cases or against resistant microbes, is evident. This is further accentuated by its non invasive nature and minimal adverse effects, making it an appealing option in periodontal care. Despite these advantages, PDT’s full potential remains untapped due to challenges such as protocol standardisation, optimising light sources, and identifying ideal PSs, which necessitates further investigation. Moreover, addressing cost-effectiveness and accessibility concerns is pivotal for the widespread adoption of PDT. In essence, PDT offers a pathway for advancements in periodontal therapy. Ongoing research and trials are vital to unravel its mechanisms, improve protocols, and solidify its role in enhancing periodontal treatment outcomes.

DOI and Others

DOI: 10.7860/JCDR/2024/69286.20255

Date of Submission: Dec 26, 2023
Date of Peer Review: Feb 27, 2024
Date of Acceptance: Aug 22, 2024
Date of Publishing: Nov 01, 2024

Author declaration :
• Financial or Other Competing Interests: None
• Was informed consent obtained from the subjects involved in the study? NA
• For any images presented appropriate consent has been obtained from the subjects. NA

PLAGIARISM CHECKING METHODS:
• Plagiarism X-checker: Dec 27, 2024
• Manual Googling: Feb 29, 2024
• iThenticate Software: Aug 21, 2024 (12%)

Etymology: Author Origin

Emendations : 9