|Year : 2020 | Volume
| Issue : 2 | Page : 102-108
Photodynamic therapy in the treatment of periodontal diseases: A review
Fatemah AlAhmari1, Lujain Shaikh2, Deema AlDhubaiban2
1 Department of Periodontics and Community Dentistry, King Saud University, Riyadh, Saudi Arabia
2 Saudi Board in Periodontics, Riyadh, Saudi Arabia
|Date of Submission||13-Sep-2018|
|Date of Acceptance||13-Jan-2020|
|Date of Web Publication||28-Mar-2020|
Dr. Fatemah AlAhmari
Dr. Fatemah AlAhmari, Department of Periodontics and Community Dentistry, King Saud University, Riyadh.
Source of Support: None, Conflict of Interest: None
Aim: Periodontal diseases remain a challenging clinical condition and hence existing literature showed no consensus on the best treatment option for disease control. The aim of this review was to provide a comprehensive overview of exciting clinical evidence on the effect of photodynamic therapy (PDT) in the treatment of periodontal diseases. Materials and Method: A literature review was performed using MEDLINE, PubMed, Wiley, ScienceDirect, and Scopus using the terms PDT, periodontal disease, laser, scaling and root planning, chronic periodontitis, and aggressive periodontitis. Results: Of a total of 149 articles appeared from various sources, 147 articles were screened and 36 were related to the research objective. Adjunctive therapy with PDT may promote additional clinical and microbiological outcomes. Conclusion: Little information is available with regard to PDT photosensitizers, wavelength, number of sessions, and duration. Therefore, large randomized control trials with longer follow-up are needed to assess the potential of PDT in the treatment of periodontal disease.
Keywords: Adjunctive Therapy, Aggressive Periodontitis, Chronic Periodontitis, Periodontal Diseases, Photodynamic Therapy
|How to cite this article:|
AlAhmari F, Shaikh L, AlDhubaiban D. Photodynamic therapy in the treatment of periodontal diseases: A review. J Int Oral Health 2020;12:102-8
|How to cite this URL:|
AlAhmari F, Shaikh L, AlDhubaiban D. Photodynamic therapy in the treatment of periodontal diseases: A review. J Int Oral Health [serial online] 2020 [cited 2021 Apr 16];12:102-8. Available from: https://www.jioh.org/text.asp?2020/12/2/102/281487
| Introduction|| |
Periodontitis is an inflammatory disease of the periodontium, which is initiated and perpetuated by bacteria. The main goal of nonsurgical periodontal therapy is reduction of pathogenic bacteria by scaling and root planing (SRP). However, there are some features that limit the access of mechanical debridement such as presence of root curvatures, furcation involvement, and deep pocket. Moreover, some patients have risks such as systemic disease, hereditary factors, and smoking, which are accompanied by persistent infection with particular periodontal pathogenic bacteria., Consequently, recolonization of the periodontal tissues by pathogens is common after treatment.
These problems necessitate other protocols with the aim of potentiating the effects of mechanical therapy. Among these protocols, photodynamic therapy (PDT) has been proposed as an adjunctive approach to nonsurgical periodontal treatment in patients with periodontitis. PDT is a technique that was first used in the treatment of neoplasms. It requires the use of a photosensitizing agent, which is activated by light to destroy bacteria and their by-products.
The aim of this review was to provide a comprehensive overview of exciting evidence on the effectiveness of PDT in the treatment of periodontal diseases.
| Materials and Methods|| |
The electronic databases MEDLINE, PubMed, Wiley, ScienceDirect, and Scopus were searched for available data up to December 2019. A literature search to collect relevant data was performed using the terms PDT, periodontal disease, laser, SRP, chronic periodontitis, and aggressive periodontitis. Randomized control trials (RCTs), clinical trials, and in vivo and in vitro studies in English were included. Review articles, studies on the effect of PDT on periodontal surgery outcome, and per-implant tissues were excluded.
| Results|| |
The search yielded 149 records and 95 full-text articles were independently assessed. Among these 95 articles, 36 articles were included for the review. [Figure 1] shows the flow diagram of the reports that were identified, duplicates removed, screened, excluded, assessed for eligibility, and included in the review. Few studies examined the effect of PDT in the treatment of aggressive periodontitis. Also, limited articles were found on the effect of the frequency of the sessions and the duration of PDT on the treatment outcome.
|Figure 1: Flow diagram showing the number of studies identified, screened, assessed for eligibility, excluded, and included in the literature review|
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| Discussion|| |
Mechanism of photodynamic therapy
PDT requires the use of a light with wavelength ranging from 635 to 690nm, photosensitizing agent, and oxygen inside the cells. There are different photosensitizing agents that are used in periodontal therapy such as methylene blue, phenothiazinium chloride, indocyanine green, and toluidine blue. A molecule of the photosensitizer absorbs a photon of light at its ground state and with the energy of the photon; it goes into the excited state. Part of excited molecule energy emitted as light energy (fluorescence) or as a heat by internal conversion with the lost energy. The remaining energy directs the excited molecule into an excited triplet state by means of intersystem crossing, which includes a change in the electron’s spin. In the presence of oxygen, it generates free radicals and singlet oxygen, which are toxic to the bacteria and will result in irreversible damage to the cytoplasmic membrane of the bacteria and the breakdown of the nucleic acid, which leads to cell death. The destruction of the cell membrane can occur by the inactivation of the transport system and the inhibition of the enzyme activities. Singlet oxygen, which is the major damaging factor in the PDT, is characterized by approximately 100nm of diffusion distance and its half-life is <0.04 µs.
Triplet state molecules can react in two ways: type I and type II photo processes to transfer its energy to molecular oxygen. Type I reaction includes the electron transfer reactions from the triplet state molecule with the involvement of a substrate to generate radical ions that can interact with the oxygen to create cytotoxic species such as lipid-derived radicals, hydroxyl radical, and superoxide. Type II reaction includes the energy transfer from the triplet state photosensitizer molecule to the molecular oxygen at ground state (triplet) to create singlet oxygen at excited state and this can cause cytotoxicity because this excited singlet oxygen can oxidize several biological molecules such as lipids, nucleic acids, and proteins.
There are many parameters influencing photodamage: the light energy influence, light power density, wavelength of light, availability of oxygen and location of the photosensitizer, incubation time, dose, and type. Dual selectivity is known to be the significant characteristic of PDT. The dual selectivity is achieved first by specific binding to target tissue by accomplishing an increased concentration of the photosensitizer and second by restricting the irradiation to a particular volume.,
Photodynamic therapy for the treatment of chronic periodontitis
It has been shown that mechanical treatment alone cannot entirely eliminate the pathogens from periodontal tissues. Moreover, it can only momentarily decrease the bacterial infection and may return to the level before treatment in no more than 2 weeks. The limitations of traditional periodontal therapy led to use of PDT as conjunctive therapy for chronic periodontitis.
The advantage of PDT over other therapies is that it has dual selectivity, which limits the damage to the normal tissues. It is achieved by control of light delivery and increasing the selective accumulation of photosensitizers in the diseased tissues. Moreover, PDT used low-level lasers, which have been found to reduce pain, promote faster healing, and aid in hemostasis.,
Photosensitizers in PDT such as phenothiazines, phthalocyanines, and porphyrins can target both gram-negative and gram-positive recommending that PDT could be helpful in the oral applications, essentially for the periodontal therapy.,, Many researches have shown that periodontal pathogens are susceptible to PDT in biofilms,, and planktonic cultures,,,,,, using safranine O, indocyanine green, hematoporphyrin ester, phthalocyanine, toluidine blue O,, methylene blue-loaded polymeric nanoparticles, and methylene blue., However, other researches have shown that PDT led to partial destruction of periodontal pathogens.,, Data obtained from these studies are presented in [Table 1].
|Table 1: Studies on the application of photodynamic therapy in the treatment of chronic periodontitis|
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Toluidine blue O reacts even in the absence of light with lipopolysaccharides that exist in the gram-negative bacteria cell membrane. When it is exposed to a wavelength of 630nm, it achieves maximal absorption and also photodynamic properties by eliminating several microbes in vitro. Gram-negative bacteria are resistant to several photosensitizing agents that are used in PDT. However, certain microbial species such as oral black-pigmented bacteria consist of naturally existent photosensitizers; hence, they are very susceptible to PDT. It was shown that the light band having wavelength from 380 to 520nm stimulates a threefold decrease in the growth of Prevotella melaninogenica, P. nigrescens, P. intermedia, and Porphyromonas gingivalis in the samples of dental plaque got from the patients with chronic periodontitis. On the basis of these findings, phototherapeutic strategy in which everyday exposure of the visible light would slowly decrease the numbers of black-pigmented bacteria, which would result in a healthy environment from microbial environment.
However, there are many researches evaluating the efficacy of PDT in periodontal therapy that have not shown the superiority of PDT over the traditional treatment. A systemic review and meta-analysis carried out by Azarpazhooh et al. concluded that as an independent therapy or as an adjunct to SRP, PDT was not superior in controlling the chronic periodontitis rather than SRP. Another meta-analysis carried out by Sgolastra et al. recommended that the use of PDT associated with the traditional therapy gives short-term benefits with respect to pocket depth reduction and clinical attachment gain. Also, a systematic review conducted by Chambrone et al. evaluated the efficacy of PDT in the treatment of periodontitis. It showed that PDT may provide similar clinical improvements in pocket depth and clinical attachment loss as compared with conventional periodontal therapy.
Photodynamic therapy for the treatment of aggressive periodontitis
Certain researches on the impact of PDT in the patients with aggressive periodontitis,,,, have shown desirable results for the state of subgingival flora. It has been recommended that both SRP and PDT could be useful in the nonsurgical therapy for the aggressive periodontitis. The report from Moreira et al. showed additional immunological, microbiological, and clinical benefits of PDT in patients with aggressive periodontitis. A systematic review conducted by Chatzopoulos et al. to assess the efficacy and safety of PDT with or without SRP. It was found that PDT may show a beneficial role in the therapy of aggressive periodontitis after repeated applications. Data obtained from these studies are presented in [Table 2].
|Table 2: Studies on the application of photodynamic therapy in the treatment of aggressive periodontitis|
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Until now, no existing evidence was found advocating for PDT to be used as a monotherapy and alternative to SRP for aggressive periodontitis. Some studies reported that PDT did not show additional benefits as compared to SRP alone in the treatment of aggressive periodontitis., In the trial carried out by Moreira et al., PDT was repeated for four sessions, which resulted in a slight benefit in treating the deep pockets in single-rooted teeth. The randomized clinical trial carried out by de Oliveira et al. compared SRP to PDT with a follow-up for 3 months. Both treatment modalities showed similar results in the treatment of aggressive periodontitis. A recent clinical trial showed that usage of PDT as an adjunct to SRP does not lead to any beneficial effects on the investigated clinical and microbiological parameters except for sulcus bleeding index.
Another clinical trial compared SRP plus systemic antibiotics to SRP and PDT with a follow-up for 6 months. The patients in both studies showed improvement; however, SRP and antibiotics group resulted in significantly higher reduction of pocket depth and a lower number of deep pockets as compared to PDT. In a meta-analysis investigating if PDT as an adjuvant therapy to SRP produces similar or better outcomes than SRP alone or associated with systemic antibiotics in the treatment of aggressive periodontitis. We found that SRP is sufficient and adding PDT is not necessary.
All of these trials reported the use of different photosensitizer, laser type, intensity, and wavelength. Hence, it is difficult to arrive at a definitive conclusion as to what could be the result if PDT could have been used as a monotherapy or in combination for aggressive periodontitis based on the available RCTs. Moreover, the studies have very small sample sizes, high level of heterogeneity, and a follow-up period ranging only from 3 to 6 months.
Risk and side effects of photodynamic therapy
There are some undesirable photoallergic and phototoxic side effects with respect to the photodynamic action. The target leaving out the tongue, mucosa, and gingiva has to be stained selectively to avoid the phototoxic reactions. During the d-aminolevulinic acid (ALA)-PDT, there is some discomfort or pain in the illuminated area., This happens when the light exposure begins, reaches the maximum in minutes, then levels out, and then ends up with tissue damage or nerve stimulation because of the reactive oxygen species.
Moreover, the PDT is also associated with risks and side effects related to light energy, photosensitizer, and related photochemical reaction. While using the lasers as the light source for the therapy, there are certain concerns that should be focused and rules that should be followed. Although the power of the laser used in the therapy is low, the patients’ eyes should be protected from the possible accidental irradiation while providing the therapy. The patients, the assistants, and the operators should wear the protective glasses as a precaution in the laser surgery. The protective eyeglasses should be used even if the non-laser light is used due to the high intensity of the light. During the therapy course, as the laser may interact with the tissue, there may be a chance of thermogenesis, which should be controlled and taken care of. It should also be noted that the wavelengths of the diode lasers penetrating deep tissue do not interact with the periodontal tissues inside the tooth crown or pocket fundamentally. Hence, the PDT that uses the low-level diode laser with short irradiation time should not produce any thermogenesis in the root surfaces and gingival tissues or damage of any apparatus at the base of the pockets., Moreover, the thermal changes in the pockets can be reduced with application of photosensitizer solution. However, the long-time irradiation of the laser at the same site may cause lesions on dental pulp, bone, or other deeper tissues.
While using the photosensitizers and exploring the photochemical reactions, it should be known that the PDT can be used in eliminating the targeted periodontal pathogens by avoiding the risks and side effects associated with the application of therapy on the periodontal tissues around. There is yet concern with respect to the long-term and also short-term side effects on the periodontal tissues, even though there are studies proving the safety of the PDT as an adjuvant therapy in association with traditional mechanical therapy in the periodontal tissue in many clinical trials and on animals.,
| Conclusion|| |
The periodontal disease remains a challenging clinical condition. Existing literature showed no consensus on the best treatment option for disease control. Adjunctive therapy with PDT might promote additional clinical and microbiological benefits. Large RCTs with a longer follow-up are needed for proper evaluation of PDT in the treatment of periodontal disease.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Azarpazhooh A, Shah PS, Tenenbaum HC, Goldberg MB. The effect of photodynamic therapy for periodontitis: A systematic review and meta-analysis. J Periodontol 2010;81:4-14.
Umeda M, Takeuchi Y, Noguchi K, Huang Y, Koshy G, Ishikawa I. Effects of nonsurgical periodontal therapy on the microbiota. Periodontol 2000 2004;36:98-120.
Kuo L-C, Polson AM, Kang T. Associations between periodontal diseases and systemic diseases: A review of the inter-relationships and interactions with diabetes, respiratory diseases, cardiovascular diseases and osteoporosis. Public Health 2008;122:417-33.
Grossi SG, Zambon JJ, Ho AW, Koch G, Dunford RG, Machtei EE, et al
. Assessment of risk for periodontal disease. I. Risk indicators for attachment loss. J Periodontol 1994;65:260-7.
Henderson BW, Waldow SM, Mang TS, Potter WR, Malone PB, Dougherty TJ. Tumor destruction and kinetics of tumor cell death in two experimental mouse tumors following photodynamic therapy. Cancer Res 1985;45:572-6.
Wainwright M. Photodynamic antimicrobial chemotherapy (PACT). J Antimicrob Chemother 1998;42:13-28.
Nussbaum EL, Lilge L, Mazzulli T. Effects of 630-, 660-, 810-, and 905-nm laser irradiation delivering radiant exposure of 1 – 50 J / cm 2 on three species of bacteria in vitro
. J Clin Laser Med Surg 2002;20:325-33.
Ochsner M. Photophysical and photobiological processes in the photodynamic therapy of tumours. J Photochem Photobiol B 1997;39:1-18.
Soukos NS, Goodson JM. Photodynamic therapy in the control of oral biofilms. Periodontol 2000 2011;55:143-66.
Konan YN, Gurny R, Allémann E. State of the art in the delivery of photosensitizers for photodynamic therapy. J Photochem Photobiol B 2002;66:89-106.
Athar M, Mukhtar H, Elmets CA, Zaim MT, Lloyd JR, Bickers DR. In situ
evidence for the involvement of superoxide anions in cutaneous porphyrin photosensitization. Biochem Biophys Res Commun 1988;151:1054-9.
Redmond RW, Gamlin JN. A compilation of singlet oxygen yields from biologically relevant molecules. Photochem Photobiol 1999;70:391-475.
Karlsson MR, Diogo Löfgren CI, Jansson HM. The effect of laser therapy as an adjunct to non-surgical periodontal treatment in subjects with chronic periodontitis: A systematic review. J Periodontol 2008;79:2021-8.
Schwarz F, Aoki A, Becker J, Sculean A. Laser application in non-surgical periodontal therapy: A systematic review. J Clin Periodontol 2008;35:29-44.
Passanezi E, Damante CA, de Rezende ML, Greghi SL. Lasers in periodontal therapy. Periodontol 2000 2015;67:268-91.
Sgolastra F, Petrucci A, Severino M, Graziani F, Gatto R, Monaco A. Adjunctive photodynamic therapy to non-surgical treatment of chronic periodontitis: A systematic review and meta-analysis. J Clin Periodontol 2013;40:514-26.
Smiley CJ, Tracy SL, Abt E, Michalowicz BS, John MT, Gunsolley J, et al
. Systematic review and meta-analysis on the nonsurgical treatment of chronic periodontitis by means of scaling and root planing with or without adjuncts. J Am Dent Assoc 2015;146:508-24.e5.
Klepac-Ceraj V, Patel N, Song X, Holewa C, Patel C, Kent R, et al
. Photodynamic effects of methylene blue-loaded polymeric nanoparticles on dental plaque bacteria. Lasers Surg Med 2011;43:600-6.
Voos AC, Kranz S, Tonndorf-Martini S, Voelpel A, Sigusch H, Staudte H, et al
. Photodynamic antimicrobial effect of safranine O on an ex vivo
periodontal biofilm. Lasers Surg Med 2014;46:235-43.
Bhatti M, MacRobert A, Henderson B, Wilson M. Exposure of Porphyromonas gingivalis
to red light in the presence of the light-activated antimicrobial agent toluidine blue decreases membrane fluidity. Curr Microbiol 2002;45:118-22.
Chan Y, Lai CH. Bactericidal effects of different laser wavelengths on periodontopathic germs in photodynamic therapy. Lasers Med Sci 2003;18:51-5.
Matevski D, Weersink R, Tenenbaum HC, Wilson B, Ellen RP, Lépine G. Lethal photosensitization of periodontal pathogens by a red-filtered xenon lamp in vitro
. J Periodontal Res 2003;38:428-35.
Topaloglu N, Gulsoy M, Yuksel S. Antimicrobial photodynamic therapy of resistant bacterial strains by indocyanine green and 809-nm diode laser. Photomed Laser Surg 2013;31:155-62.
Dobson J, Wilson M. Sensitization of oral bacteria in biofilms to killing by light from a low-power laser. Arch Oral Biol 1992;37: 883-7.
Qin Y, Luan X, Bi L, He G, Bai X, Zhou C, et al
. Toluidine blue-mediated photoinactivation of periodontal pathogens from supragingival plaques. Lasers Med Sci 2008;23:49-54.
Soukos NS, Mulholland SE, Socransky SS, Doukas AG. Photodestruction of human dental plaque bacteria: Enhancement of the photodynamic effect by photomechanical waves in an oral biofilm model. Lasers Surg Med 2003;33:161-8.
Müller P, Guggenheim B, Schmidlin PR. Efficacy of gasiform ozone and photodynamic therapy on a multispecies oral biofilm in vitro
. Eur J Oral Sci 2007;115:77-80.
Zeina B, Greenman J, Purcell WM, Das B. Killing of cutaneous microbial species by photodynamic therapy. Br J Dermatol 2001;144:274-8.
Soukos NS, Som S, Abernethy AD, Ruggiero K, Dunham J, Lee C, et al
. Phototargeting oral black-pigmented bacteria. Antimicrob Agents Chemother 2005;49:1391-6.
Chambrone L, Wang HL, Romanos GE. Antimicrobial photodynamic therapy for the treatment of periodontitis and peri-implantitis: An American Academy of Periodontology best evidence review. J Periodontol 2018;89:783-803.
Novaes AB Jr, Schwartz-Filho HO, de Oliveira RR, Feres M, Sato S, Figueiredo LC. Antimicrobial photodynamic therapy in the non-surgical treatment of aggressive periodontitis: Microbiological profile. Lasers Med Sci 2012;27:389-95.
de Oliveira RR, Schwartz-Filho HO, Novaes AB, Garlet GP, de Souza RF, Taba M, et al
. Antimicrobial photodynamic therapy in the non-surgical treatment of aggressive periodontitis: Cytokine profile in gingival crevicular fluid, preliminary results. J Periodontol 2009;80:98-105.
de Oliveira RR, Schwartz-Filho HO, Novaes AB Jr, Taba M Jr. Antimicrobial photodynamic therapy in the non-surgical treatment of aggressive periodontitis: A preliminary randomized controlled clinical study. J Periodontol 2007;78:965-73.
Moreira AL, Novaes AB Jr, Grisi MF, Taba M Jr, Souza SL, Palioto DB, et al
. Antimicrobial photodynamic therapy as an adjunct to non-surgical treatment of aggressive periodontitis: A split-mouth randomized controlled trial. J Periodontol 2015;86:376-86.
Vohra F, Akram Z, Safii SH, Vaithilingam RD, Ghanem A, Sergis K, et al
. Role of antimicrobial photodynamic therapy in the treatment of aggressive periodontitis: A systematic review. Photodiagnosis Photodyn Ther 2016;13:139-47.
Chatzopoulos GS, Doufexi AE. Photodynamic therapy in the treatment of aggressive periodontitis: A systematic review. Med Oral Patol Oral Cir Bucal 2016;21:e192-200.
Souza E, Medeiros AC, Gurgel BC, Sarmento C. Antimicrobial photodynamic therapy in the treatment of aggressive periodontitis: A systematic review and meta-analysis. Lasers Med Sci 2016;31:187-96.
Valenzeno DP, Pooler JP. Phototoxicity: The neglected factor. JAMA 1979;242:453-4.
Chitsazi MT, Shirmohammadi A, Pourabbas R, Abolfazli N, Farhoudi I, Daghigh Azar B, et al
. Clinical and microbiological effects of photodynamic therapy associated with non-surgical treatment in aggressive periodontitis. J Dent Res Dent Clin Dent Prospects 2014;8:153-9.
Borekci T, Meseli SE, Noyan U, Kuru BE, Kuru L. Efficacy of adjunctive photodynamic therapy in the treatment of generalized aggressive periodontitis: A randomized controlled clinical trial. Lasers Surg Med 2019;51:167-75.
Arweiler NB, Pietruska M, Skurska A, Dolińska E, Pietruski JK, Bläs M, et al
. Nonsurgical treatment of aggressive periodontitis with photodynamic therapy or systemic antibiotics. Three-month results of a randomized, prospective, controlled clinical study. Schweiz Monatsschr Zahnmed 2013;123:532-44.
Lui H, Anderson RR. Photodynamic therapy in dermatology: Recent developments. Dermatol Clin 1993;11:1-13.
Kalka K, Merk H, Mukhtar H. Photodynamic therapy in dermatology. J Am Acad Dermatol 2000;42:389-413.
Research, Science and Therapy Committee of the American Academy of Periodontology. Lasers in periodontics. J Periodontol 2002;73:1231-9.
Andersen R, Loebel N, Hammond D, Wilson M. Treatment of periodontal disease by photodisinfection compared to scaling and root planing. J Clin Dent 2007;18:34-8.
Christodoulides N, Nikolidakis D, Chondros P, Becker J, Schwarz F, Rössler R, et al
. Photodynamic therapy as an adjunct to non-surgical periodontal treatment: A randomized, controlled clinical trial. J Periodontol 2008;79:1638-44.
Luan XL, Qin YL, Bi LJ, Hu CY, Zhang ZG, Lin J, et al
. Histological evaluation of the safety of toluidine blue-mediated photosensitization to periodontal tissues in mice. Lasers Med Sci 2009;24:162-6.
[Table 1], [Table 2]
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