## 5 aPDT Performance in Clinical Studies  
Evidence-based dentistry guides dentists to integrate clinical judgment and the patient's values with the best available evidence. Overall, the existing literature on aPDT performance can be categorized as studies that have a randomized experimental design. For this review, we searched for keywords and subject terms related to randomized clinical studies that evaluated the antibacterial effects of aPDT against endodontic pathogens. Two independent reviewers ([PERSON] and [PERSON]) performed the searches, using PubMed, MEDLINE, SCOPUS, and EMBASE databases. Table 2 and Box 1 demonstrate a summary of the randomized clinical trials investigating the role of aPDT in root canal disinfection. The following search strategy was used: _\"((photodynamic therapies) OR photodynamic OR Photochemotherapy) AND (endodontic* OR (root canal)) AND ((case control) OR (clinical trial) OR (in vivo))\"_. Previously published reviews about this theme were also assessed to look for cross-references about in vivo studies. Grey literature was also reviewed. A total of 205 studies were extracted. After removing the duplicates and reading the abstracts, 27 articles were eligible for full-text evaluation. The inclusion criteria include the randomized clinical trials that used aPDT for endodontic disinfection. Articles with no clear randomization approach or those that used only a light therapy without PS were excluded. After the full-text evaluation, only seven randomized clinical trials were included (Table 1). In a clinical trial by [PERSON] et al., a significant inhibition against _E. faecalis_ and _Candidia albicans_ was reached when aPDT was performed using MB at 50 mg/mL and diode laser (810 nm; 0.2 W power) delivered by a 200 um-diameter end tip [51]. After root canal instrumentation and irrigation, bacterial biofilm samples were taken. Then, in the aPDT group, 0.5 mL of methylene blue was placed inside the canals for 5 min, followed by  
\begin{table}
\begin{tabular}{c c c c c c} \hline \hline
**Author** & **Target Tooth** & **PS** & **Light Parameters** & **Protocol** & **Main Outcome** \\ \hline [PERSON] \(Z\) & Root canal treated molars with periapical lesion & MB (50 mg/mL) & Diode laser (808 nm; 0.2 W) & The PS intracanal application; 5 min + 10 s irradiation & Both aPDT and calcium hydroxide therapies significantly reduced the CFUs counts of _E. faecalis_ and _C. albicans_, with no significant difference between the two approaches. \\ \hline [PERSON] M & Root canal treated molars with periapical lesion but with no existing pain, swelling, or any systematic diseases & TBO (0.1 mg/mL) & Red LED (630 nm; 2-4 mW; 1.2-4.4 J / cm\({}^{2}\)) & The PS intracanal application; 5 min + 60 s irradiation & The microbiological sampling revealed that aPDT could disinfect the canals in a single visit. aPDT was associated with a lower number of colonies compared to the calcium hydroxide group. \\ \hline [PERSON] (2017) [53] & Root canal treated teeth (single root) with apical periodontitis & MB (660 nm; 60 mW; 129 J/cm\({}^{2}\)) & Diode Laser application; 1 min + 2 min irradiation  
10 s irradiation. The canals were irrigated again, and another bacterial sample was taken. In the other group, Ca(OH)\({}_{2}\) was used as an intracanal medicament for seven days, and then another bacterial sample was taken. Both approaches revealed significant inhibition against _E. faecalis_ and _C. albicans_ with no significant difference between them. This report was among the first studies to investigate the effect of aPDT in endodontics in vivo. Similarly, the use of TBO (0.1 mg/mL) to treat molars with periapical infections was also attempted by [PERSON] et al. [52]. The design was similar to the previous study, where aPDT was compared to Ca(OH)\({}_{2}\). However, in this study, the TBO was incubated for 5 min and irradiated for another 1 min with an energy density of 1.2-4.4 J/cm\({}^{2}\) and light intensity of 2.4 mW, using LED light. At the same time, the Ca(OH)\({}_{2}\) was placed for two weeks.