Table 1.

Clinical studies of LED-based antimicrobial photodynamic therapy in the treatment of periodontitis.

Reference	Study Participants (n) Study Design	Groups (n: Sites) Treatment Provided	Follow-Up Findings
Bassir et al., 2013 [41]	CP (16) Split-mouth	SRP + a-PDT (119):   SRP (US/H)   +LED (625–635 nm, 2000 mW/cm2, Fotosan®)   +TB (0.1 mg/mL)     Photosensitizer incubation time: not described     Irradiation time:       10 s (inside) + 10 s (outside the pocket), ×6 (per tooth) SRP + LED (96):   SRP (US/H)   +LED (625–635 nm, 2000 mW/cm2, Fotosan®)     Irradiation time:       10 s (inside) + 10 s (outside the pocket), ×6 (per tooth) SRP + PS (90): SRP (US/H) + TB (0.1 mg/mL) SRP (91): SRP (US/H)	Follow-up: 3 months. Adjunctive treatments (a-PDT, LED, or PS) were repeated 7 and 14 days later. Photoactivation using LED did not show additional effects on clinical parameters (PD, CAL, BOP, PI) compared to SRP alone.
Pulikkotil et al., 2016 [42]	CP (16) Split-mouth	SRP + a-PDT (16):   SRP + LED (628 nm, Fotosan®) + MB     Photosensitizer incubation time: 1 min     Irradiation time: 10 s (inside) + 10 s (outside the pocket) SRP (16): SRP	Follow-up: 3 months. Significantly greater improvement in BOP was seen in the SRP + a-PDT group compared to that in the SRP group after 3 months of treatment. No difference in the quantity of Aa was detected between the groups.
Husejinagic et al., 2019 [43]	Periodontitis (20) Split-mouth, RCT	SRP + a-PDT (20):   SRP (US/H)   +LED (635 nm, 750 mW, PADPLUS) + TB (12.7 µg/mL)     Photosensitizer incubation time: 1 min     Irradiation time: 10 s (inside the pocket), ×6 (per tooth) SRP (20): SRP (US/H)	Follow-up: 3 months. Significant improvements in clinical parameters (PD, CAL, BOP) were shown in both groups, but the test and control groups were comparable. The recolonization of Pg and Td was reduced after adjuvant treatment, but not significantly.
Harmouche et al., 2019 [44]	Periodontitis (28) Split-mouth, RCT	SRP + a-PDT (579):   SRP (US/H)   +LED (625–635 nm, 2000 mW/cm2, Fotosan®)   +TB (0.1 mg/mL)     Photosensitizer incubation time: 1 min     Irradiation time: 10–30 s (inside) + 10 s (outside the pocket)       PDT applications were repeated 7 days and 3 months after SRP. SRP (609): SRP (US/H)	Follow-up: 6 months. Repeated application of a-PDT with SRP significantly improved SRP outcome (PD and BOP) compared to SRP alone. This effect was mainly observed at 6 months in initially deep sites (PD > 6 mm) with BOP.
Mongardini et al., 2014 [45]	CP (30); Residual pockets during SPT Split-mouth	SRP + a-PDT (30):   SRP (H)   +LED (628 nm, 2000 mW/cm2, Fotosan®) + TB (0.1 mg/mL)     Photosensitizer incubation time: 1 min     Irradiation time:       10 s (outside) + 10 s (inside the pocket), ×2 (per tooth) SRP (30): SRP (H)	Follow-up: 1 week. One week after the treatment, the number of sites showing a PD reduction of ≥2 mm was higher in the a-PDT group than in the SRP group. Higher reductions in relative proportions of red complex bacteria were observed in the a-PDT group compared to the SRP group.
Goh et al., 2017 [46]	Periodontitis (27); Residual pockets during SPT Split-mouth, RCT	SRP + a-PDT (36):   SRP (US/H)   +LED (620–640 nm, 2000–4000 mW/cm2, Fotosan®)   +TB (0.1 mg/mL)     Photosensitizer incubation time: not described     Irradiation time: 20 s/site × 2 SRP (36): SRP (US/H)	Follow-up: 6 months. At 3 months after treatment, significantly greater improvements in PD and CAL were observed in the SRP + a-PDT group compared to the SRP group. However, the differences were no longer significant at the 6-month follow-up. Adjunctive a-PDT did not offer additional reduction in the levels of GCF cytokines, including IL-8, IL-6, and TNF-α.
Hormdee et al., 2020 [47]	Periodontitis (12) Split-mouth, RCT	SRP + a-PDT (12):   SRP (US/H)   +LED (420–480 nm, 1000–1200 mW/cm2)   +CUR gel (25 µg/mg)     Photosensitizer incubation time:       none (irradiated immediately)     Irradiation time: 2 min (inside the pocket) per tooth SRP (12): SRP (US/H)	Follow-up: 6 weeks. In the a-PDT group, significant reductions in PD and CAL were observed in the intragroup comparison from the first week up to the fourth week of follow-up. In contrast, a significant reduction in PD was observed after only a week in the SRP group. The quantities of Fn and Pi were recovered in the SRP group, while there was no significant recolonization of these bacteria on PDT sites throughout the 6-week study duration.
Ivanaga et al., 2019 [48]	CP with type 2 DM (23); Residual pockets during SPT Split-mouth, RCT	SRP + a-PDT (88):   SRP (US/H)   +LED (465–485 nm, 100 mW/cm2, InGaN) + CUR (0.1 mg/mL)     Irrigation with CUR for 1 min     Irradiation time: 60 s (outside the pocket) SRP + LED (80)   SRP (US/H)   +LED (465–485 nm, 100 mW/cm2, InGaN),     Irrigation with 1 mL saline solution     Irradiation time: 60 s (outside the pocket) SRP + PS (67): SRP (US/H) + CUR (0.1 mg/mL) SRP (97): SRP (US/H)     Treatment modalities were performed in a total of 332 sites, but only 290 sites were included in the final evaluation.	Follow-up: 6 months. Significant improvements in PD and BOP were shown in all treatment groups; however, the mean values for PD, CAL, GR, BOP, and PI did not differ among the four groups at baseline, 3-, and 6-month follow-ups. Significant CAL gain was found only in the a-PDT and LED groups at 3 months in comparison to baseline data.

CP: chronic periodontitis, SRP: scaling root planing, H: hand scaling, US: ultrasonic scaling, a-PDT: antimicrobial photodynamic therapy, PS: photosensitizer, LED: light-emitting diode, MB: methylene blue, TB: toluidine blue, CUR: curcumin, PD: probing depth, CAL: clinical attachment level, GR: gingival recession, BOP: bleeding on probing, PI: plaque index, GI: gingival index, Aa: Aggregatibacter actinomycetemcomitans, Fn: Fusobacterium nucleatum, Pg: Porphyromonas gingivalis, Pi: Prevotella intermedia, Td: Treponema denticola, GCF: gingival crevicular fluid.