Does selective caries removal in combination with antimicrobial photodynamic therapy affect the clinical performance of adhesive restorations of primary or permanent teeth? A systematic review with meta-analysis

Introduction

Minimally invasive dentistry includes early diagnosis, preventive care, and conservative treatment of carious lesions, even when an invasive approach is required, to reduce tooth loss [1]. Previous decade, the caries process was better understood and added to it the improvements in dental materials, have facilitated the provision of more conservative and less invasive treatments [1, 2, 3].

Deep carious lesions are characterized by a penetration depth of three-quarters or more of the internal dentinal thickness [4]. Conservative techniques of caries removal, such as selective caries removal (SCR) [5], and SCR combined with antimicrobial photodynamic therapy (aPDT) [6, 7], have been investigated for the treatment of deep carious lesions. Considerable evidence has proven the efficacy of aPDT. This technique reduces the number of microorganisms [6, 8, 9, 10] preserves pulp vitality and prevents caries progression [11]. In the literature, the success rates of minimally invasive techniques have been reported [3, 12, 13, 14]. The systematics reviews respond to the challenge of an unmanageable amount of information by synthesizing research-based evidence and it is presented as a method to transform the information into an accessible format [15].

Although the effect of aPDT on carious dentin in human models has already been evaluated in vitro studies, there is no knowledge about any chemical and structural changes affecting the remaining dentin surface [16, 17]. Therefore, using a systematic review method this study aimed to evaluate the scientific evidence of the treatment on deep carious lesions using SCR or SCR in combination with aPDT on the clinical performance of adhesive restorations of primary or permanent teeth.

METHOD

RESULTS

Studies identification and studies selection

A flowchart of the studies selection of this systematic review is presented in Fig. 1. Initially, 42 studies were found: 24 on PubMed, 05 in Web of Science, 07 in Scopus, 03 in Cochrane Library, none in LILACS and 03 registered trials were found. No article was included from the manual search, google scholar, grey literature, or personal communication. After exclusion of duplicate studies, 30 studies prevailed. After analyzing the titles and abstracts, 27 studies were excluded, resulting 03 studies eligible.

Fig. 1.Prisma 2020 flow diagram describing the reports, records and studies identification/selection.

Meta-analysis and the certainty of evidence

In terms of treatment, in the experimental (SCR + aPDT) and control groups (SCR), no difference was observed between the groups after 6 months of follow-up (p = 0.78; CI [confidence interval] -0.01-0.09, 0.07)) (Fig. 2). Additionally, no difference was observed after 12 months (p = 0.75; CI −0.02 (−0.12, 0.08)) (Fig. 3).

Fig. 2.Evaluation of the groups according to the number of successful treatments after the 6-month period. CI: confidence interval.

Fig. 3.Evaluation of the groups according to the number of successful treatments after the 12-month period. CI: confidence interval.

In terms of the used photosensitizer (MB), no difference was observed after 6 months (p = 0.76; CI −0.01 (−0.10, 0.07)) (Fig. 4) and 12 months (p = 0.71; CI −0.02 (−0.14, 0.09)) (Fig. 5).

Fig. 4.Evaluation of treatment success taking into account the photosensitizer (methylene blue) after 6-months period. CI: confidence interval.

Fig. 5.Evaluation of treatment success taking into account the photosensitizer (methylene blue) after 12-months period. CI: confidence interval.

This study did not have as many covariables to perform the meta-regression or sensitivity analysis [24]. Publication bias cannot be assessed once there were no subgroup analyses with at least 10 studies included in the meta-analysis [25].

The certainty of the evidence was moderate, since in two studies, the sample sizes were small and could not be considered representative because of the method of sample size calculation used in both articles [8, 10]. In these articles, the assessments were divided in microbiological and clinical stages, and sample calculation was based on microbiological reduction and not on the restorations success rate (Table 5).

Table 5.The certainty of the evidence of studies the treated SCR + aPDT compared to Control (SCR) for deciduous considering the outcomes time of follow-up and photosensitizer.

Certainty assessment	No. of patients	Effect	Certainty
No. of studies	Study design	Risk of bias	Inconsistency	Indirectness	Imprecision	Other considerations	aPDT + SCR	SCR	Relative	Absolute
									(95% CI)	(95% CI)
Evaluation of the groups according to the number of successful treatments after the 6-month period.
3	randomized trials	not serious	not serious	not serious	serious${}^b$	none	60/63 (95.2%)	52/54 (96.3%)	RR −0.02 (−0.11 to 0.07)	982 fewer per 1.000 (from 1.000 fewer to 896 fewer)	$⨁⨁⨁◯$ MODERATE
Evaluation of the groups according to the number of successful treatments after the 12-month period.
2	randomized trials	not serious	not serious	not serious	serious${}^b$	none	47/53 (88.7%)	38/42 (90.5%)	RR −0.04 (−0.17 to 0.09)	941 fewer per 1.000 (from 1.000 fewer to 823 fewer)	$⨁⨁⨁◯$ MODERATE
Evaluation of treatment success taking into account the photosensitizer (methylene blue) after 6-months period
3	randomized trials	not serious	not serious	not serious	serious${}^b$	none	50/53 (94.3%)	52/54 (96.3%)	RR −0.02 (−0.11 to 0.07)	982 fewer per 1.000 (from 1.000 fewer to 896 fewer)	$⨁⨁⨁◯$ MODERATE
Evaluation of treatment success taking into account the photosensitizer (methylene blue) after 12-months period
2	randomized trials	not serious	not serious	not serious	serious${}^b$	none	37/43 (86.0%)	38/42 (90.5%)	RR −0.04 (−0.18 to 0.10)	941 fewer per 1.000 (from 1.000 fewer to 814 fewer)	$⨁⨁⨁◯$ MODERATE
CI: Confidence interval; RR: Risk ratio; aPDT: Antimicrobial photodynamic therapy; SCR: selective caries removal. Explanations: ${}^a$: Small sample size. The sample size of 2 papers were calculated based on the microbiological analysis; ${}^b$: Small sample size.

DISCUSSION

This systematic review detected three randomized clinical studies that investigated the failure of restorations after SCR with aPDT. Of them, two studies performed the clinical observation of a reduction in the number of microorganisms and longitudinal follow-up of restorations [8, 10]. The other randomized clinical trial performed only the follow-up of restorations [23]. Steiner-Oliveira et al. [8] and Faria et al. [23] evaluated SCR in combination with aPDT in longitudinal follow-up (6 and 12 months), but Alves et al. [10] evaluated a period of 6 months only. The 03 studies used primary teeth and no study was found in permanent teeth.

Various in-vitro studies have simulated the use of composite resin bonded to carious dentin using aPDT. One study [16] analyzed the shear bond strength (adhesive bond integrity) of composite resin bonded to carious dentin using aPDT in combination with MB. The lowest bond strength was observed in Group of aPDT on infected dentin. Another in vitro study [17] evaluated the effect of different photosensitizers activated by aPDT on the shear bond strength of composite resin to caries-affected dentin compared to conventional disinfectants such as chlorhexidine. All the tested photosensitizers (MB, curcumin, and indocyanine green) activated by aPDT demonstrated acceptable shear bond strength. Curcumin demonstrated the highest shear bond strength. Therefore, in vivo studies are required to detect changes in dentinal surfaces after aPDT. Hence, it is important to evaluate the longevity of these restorations, as long-term effects of aPDT on the tooth substrate submitted to the procedure in clinical studies have not been analyzed, as proposed in this study. Based on the results of these in vitro studies, we suggest that clinical experiments should be performed to assess the influence of other photosensitizers on restoration longevity.

From the included articles, Steiner-Oliveira et al. [8] followed the restorations to determine the level of clinical and radiographic success as well as the presence of failure in the retention of restorations (the author did not use any specific criteria described in the literature). Alves et al. [10] used the modified USPHS criterion to assess retention, presence of secondary caries, marginal discoloration/adaptation, and color. Faria et al. [23] used the FDI criteria to evaluate the biological, esthetic, and functional properties of the restorations. Therefore, this meta-analysis was performed by comparing the treated groups (with and without aPDT) for restorative failure. Regardless of the method used to detect the restoration failure, all studies evaluated the use of SCR in combination with aPDT.

Although the follow-up period did not influence the treatment groups in the meta-analysis, this duration of clinical follow-up (6 and 12 months) can be considered a limitation in these studies. For deciduous teeth, the follow-up duration was adequate due to its short period on the oral cavity, but long-term follow-up studies are required for permanent teeth. Another point important to highlight is about the diversity of laser or LED light and photosensitizer protocols. In the included studies, the time of irradiation and dose varied. Despite using different parameters in all studies [8, 10, 23], the use of aPDT presented satisfactory restoration retention. However, further studies evaluating the influence of these parameters can be done to evaluate this influence.

Considering the photosensitizer, only one study [8] included two groups with different photosensitizers (MB and TB). Therefore, this meta-analysis basically assessed the use of MB as a photosensitizer. The MB concentration was different in the studies: 0.01% [8, 23] and 0.005% [10]. However, in both studies, the incidence of failure was low. Other photosensitizers, which also lead to a reduction in the microorganisms, are also used with aPDT, as presented in a systematic review [6]. However, more studies are necessary to detect the influence of other photosensitizers on restoration retention.

The certainty of evidence (GRADE) was influenced by the limited sample size of the studies. This was primarily a concern of the two published studies [8, 10]. As highlighted previously, both studies [8, 10] were structured into two stages: microbiological and clinical analyses. Thus, the sample size calculation shown in the articles was based only on microbiological analysis, which may have led to a sample bias. Ideally, the calculation should have been based on studies that detected the clinical efficacy, as performed in other studies [3, 5, 23]. In this way, the sample size would have been more reliable and representative of the expected outcome (clinical efficacy).

This systematic review controlled the risk of bias since it followed on the PRISMA guidelines [18]. The degree of confidence in the results of the review was high. The search was done in several databases. The eligibility criteria, data extraction, risk of bias and GRADE were performed by two researchers. In addition, evaluation instruments established in the literature (risk of bias using the Cochrane Collaboration’s tool and RobotReviewer) assessed the risk of bias in the studies. The limitation of this study would be articles related, because none of them showed negative results; thus, emphasizing that the clinical protocol could have been biased. Considering the number of studies included in the meta-analysis not have any restriction for number. In the literature we found some meta-analysis with just two studies however, more studies mean that the meta-analysis have more power and is more exact and reliable. Despite of it, this review is extremely important, because the results enable future authors to delineate their studies aggregating adequate results and revealing the best possible scientific evidence.

Another limitation that we can point relates to the few studies. The risk of publication bias across studies was also not assessed, as it can be assessed only when at least 10 studies are included in the meta-analysis [24].

Minimal invasive treatment in cavitated or non-cavitated teeth can be considered a rational method for the treatment of caries and should be advocated at public, private, and educational levels. The patient should also be informed of the advantages of these techniques compared to traditional restorative procedures. Currently, the techniques for SCR include the use of Carisolv and atraumatic restorative treatment, and various systematic reviews have proven their effectiveness [12, 14]. SCR is particularly advantageous in deep carious lesions, since it significantly reduces the risk of pulp exposure compared to total caries removal [2, 5]. The use of aPDT as an adjuvant technique can provide a conservative treatment for caries. This is due to its antibacterial property, which provides a virtually total reduction of microorganisms in decayed dentin, where it can be preserved and consequently prevent pulp exposures. Therefore, the association of aPDT with SCR, which completely removes caries from the dentin walls in order to adhere to the restorative material, is suggested as an association that preserves the tooth structure during caries treatment, according to the current principles of minimal intervention dentistry.

The success of the adhesive restoration presented in this review is additional information that indicates that the association of SCR + aPDT techniques can be used successfully in clinical practice, but these results should be interpreted with caution due to the small number of published studies and the moderate certainty of the evidence. To date, several studies have been conducted on primary teeth, but research on permanent teeth must be carried out to delineate the quality and safety of aPDT.

CONCLUSIONS

The meta-analysis observed that the use of aPDT as an adjuvant has a strong potential for clinical use. However, a database of clinical studies is limited presenting moderate certainty of the evidence. Therefore, the resulting conclusions are limited confirmatory and only available for primary teeth at all what leads to limited significance of the information provided by the investigation.

CONFLICT OF INTEREST

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

FUNDING

This study was support by Jovem Cientista Nosso Estado - Fundação de Amparo a pesquisa do Estado do Rio de Janeiro (FAPERJ E-26/202.712/2018) (LAA). LAA and TOF were supported by National Council for Scientific and Technological Development (CNPq). LVF was supported by CAPES program for master degree.

ACKNOWLEDGMENTS

The authors would like to thank the authors for the contribution of available data from their papers.