Photodynamic Therapy: Future generation – A Evidenced Literature

INTRODUCTION

A wide range of persistent human fections are due to microbial biofilms. Microorganisms grow in biofilms stuck to a solid surface where they multiply and form micro-colonies embedded in extracellular polymeric matrix which includes water and nutrient channels. Periodontal diseases result from accumulation of subgingival bacterial biofilms on tooth surfaces.

There is reduced susceptibility of these biofilms to 1 antimicrobial agents. The rapidly increasing emergence of antibiotic resistance amongst pathogenic bacteria may bring an end to the period extending for the last 50 years, called the antibiotic era. Bacteria replicate very rapidly and a mutation that helps the microbes survive in the presence of antibiotics will quickly become predominant throughout the microbial 2 population. Although mechanical removal of the periodontal pathogens is the current gold standard of treatment, antibiotics are also known to be effective. However, development of resistance in the target organisms is a problem associated with the use of such drugs. The use of photoactivatable compounds or photosensitizers (PS) to cause photodestruction of oral bacteria has been demonstrated, indicating that photodynamic therapy (PDT) could be a useful alternative to mechanical means as well as antibiotics in eliminating periopathogenic bacteria¹.

Light alone or in combination with chemical compounds has been used for a long time to induce a therapeutic effect. Psoralens and light were used in ancient India, China and 3 Egypt for treatment of vitiligo and psoriasis. Moreover PDT 2 is a treatment modality for cancer and other diseases. Its use as a therapeutic approach is based on previous studies where a specific nontoxic dye PS accumulates preferentially in targeted tissues or organisms. PDT involves delivering visible light of appropriate wavelength to excite PS molecule to excited singlet state. This excited state then may undergo intersystem crossing to the slightly lower energy, but longer lived, triplet state, which may then react further by one of the two pathways known as type I and type II photoprocesses, both of which require oxygen. Type I pathway involves electron-transfer from the PS triplet state with the participation of a substrate to produce radical ions that can then react with oxygen to produce cytotoxic species (superoxide, lipid-derived radicals). Type II pathway involves energy transfer from the PS triplet state to ground-state molecular oxygen (triplet) to produce excited-state singlet oxygen, which can oxidize many biological molecules such as proteins, nucleic acid and lipids, and can lead to cytotoxicity².

Methods

A systematic search was conducted to find articles pertaining to the research question.

Search-Strategy

The following keywords and phrases were used for the search: ™ Periowave , Photodynamic therapy, and Laser in periodontitis / periodontology. Four databases were used to locate relevant articles namely, PubMed (1966-2010), Ovid/Medline (1996-2010), Cochrane (1995-2010) and Google Search which yielded 309, 0, 14 and 1,040 articles respectively. In addition to the electronic databases, textbooks in Periodontology, Journal of Periodontics and expert opinion of a Periodontologistwas consulted.

Measures used to determine relevance of material

Our inclusion criteria involved studies that used some form of laser for treatment, a pre-established diagnosis of periodontitis, invivostudies, all studies had to be randomized controlled trials, and in English. We had a total of 1363 articles and only those articles relevant to our inclusion criteria were selected (Table 1). A total of 32 articles remained which were analyzed and an additional 25 articles were eliminated at the abstract stage based on the previously mentioned criteria. The seven articles that remained were reviewed and subjected to a Checklist to Assess Evidence of Efficacy of Therapy or Prevention. Discussion among the authors was carried out to critically appraise the remaining 7 articles and four articles were unanimously accepted.

RESULTS

There were 4 published clinical trials matching the inclusion criteria using laser for treatment of periodontitis. When viewed as a collective body of evidence they provide conflicting results. In the study done by Qadri et al⁴ , 17 patients in the age group of 35-70 for 6 weeks were studied The results showed a difference in probing depth 4 (PD), gingival index (GI) and plaque index (PI) of test and control groups which favored adjunctive use of the laser with scaling and root planning (SRP) versus SRP alone. Two other studies done by Yilmaz et al and Ambrosini et al ^5,6 reported no difference in PD, bleeding on probing (BOP) and clinical attachment loss (CAL) of test and control groups. Moritz et al⁷ suggested that use of laser as an adjunct to SRP can decrease BOP and PD and bacterial count, however there was an ev idenc e of an inc r e a s e in Ac tinomyc e s Actinomycetemcomitans (AA) count in some patients.

DISCUSSION

Systemic antibiotics have been used as an adjunct to scaling and root planing but there are quite a few disadvantages. First, systemic administration can cause adverse effects such as GIT disturbances and allergic reactions. Second, some antibiotics are taken up by mineralized tissues. Third, patient compliance can be a factor in the ineffectiveness of the therapeutic regimen. Finally, the development of resistant organisms is probably the most serious concern of all⁸. PDT on the other hand does not have any of the aforementioned drawbacks.

Photodynamics involves the application of a dye to the treatment area (the dye is referred to as a photosensitizer because the dye after absorbing the light sensitizes the organisms to visible light inducing damage) then light is applied to the dye which results in the production of free oxygen radicals. These oxygen radicals are cytotoxic and destroy cellular constituents. 

Periowave™ is a photodynamic disinfection system developed byOndineBiopharma Corporation that utilizes low intensity lasers and wavelength specific, light-activated compounds to specifically target and destroy microbial pathogens and reduce the symptoms of disease¹⁰. The photosensitive compounds are topically applied in the gingival sulcus and the laser is used to activate the compounds and complete the disinfection. In November 17, 2005 the first regulatory approval for photodynamic disinfection therapy from Health 9 Canada was announced. Also it received company-wide ISO-13485 certification of quality management standard for medical device companies. Based on the evidence to date, treatment of periodontal diseases using PDT of any type is still considered experimental. Health Canada's approval of Periowave ™ has been deemed by the manufacturing company as a “significant milestone in paving the way for near term revenue generation and longer term growth.”¹⁰ The fact that ™ Health Canada granted a medical license for Periowave for its clinical use and importation of the device in the country may imply positively to its efficacy. Health Canada's Medical Licensing Division is responsible for the grant of licensure to products intended for medical and dental use. “Medical devices are classified into one of Classes I to IV by means of the classification rules set out in Schedule 1, where Class I represents the lowest risk and Class IV represents the highest risk.”¹¹

According to the criteria set forth in Schedule 1, Periowave™ is classified as a Class II medical device. Under the Medical Devices Regulations, manufacturers of Class II devices are not required to submit review information. Instead, they must attest that they have evidence to support the safety and effectiveness requirements of the Regulations which are the 11 following: (a) a description of the medical conditions, purposes and uses for which the device is manufactured, sold or represented; (b) a list of the standards complied with in the manufacture of the device to satisfy the safety and effectiveness requirements; (c) an attestation by a senior official of the manufacturer that the manufacturer has objective evidence to establish that the device meets the safety and effectiveness requirements; (d) an attestation by a senior official of the manufacturer that the device label meets the applicable labeling requirements of these Regulations; (e) in the case of a near patient in vitro diagnostic device, an attestation by a senior official of the manufacturer that investigational testing has been conducted on the device using human subjects representative of the intended users and under conditions similar to the conditions of use; and (f) a copy of a quality system certificate certifying that the quality system under which the device is manufactured satisfies National Standard of Canada CAN/CSA-ISO 13488-98, Quality systems – Medical devices – Particular 6 requirements for the application of ISO 9002, as amended from time to time. It is clear upon reviewing the above conditions that no third-party review is required to be submitted for the granting of licensure but merely an attestation by a senior official of the manufacturer that the device meets the eleven safety and effectiveness requirements laid out in sections 10 to 20. The mere fact that Periowave™ has been approved by Health Canada does not mean much in the perspective of efficacy. Efficacy has to be judged by means of an independent, unbiased, and scientifically proven method such as a double blind randomized control trial. At this moment in time as there are no published studies involving Periowave™ it is quite early to claim against or in the favor of the efficacy of Periowave™ . However, the principle of photodynamics is biologically plausible and the numerous studies done on the principle of photodynamics do show that it might have a certain place as a part of an armamentarium to combat periodontal diseases, especially chronic periodontitis.

CONCLUSION

Based on these articles one must conclude that there is a great need to develop an evidence-based approach to the use of lasers for the treatment of periodontitis. It would be prudent to say that there is insufficient evidence to suggest that PDT is superior to the traditional modalities of periodontal therapy. On a technology assessment table PDT/Periowave™ will be clearly identified as a more costly treatment but with a questionable efficacy. Everything new is not always better so an astute clinician should critically appraise all the literature before making a dramatic change from the current standard of treatment.