Indocyanine green-mediated antimicrobial photodynamic therapy as an adjunct to non-surgical periodontal treatment: a systematic review and meta-analysis

To the Editor: Chronic periodontitis has been defined as a slowly progressive disease. Scaling and root planning (SRP) provides a satisfactory prognosis in most cases. However, due to the complex anatomy under gingiva, non-surgical periodontal treatment alone is difficult to prevent bacterial plaque recolonization and thoroughly eliminate dental calculus in deep pockets.^[1] In recent years, the efficacy of indocyanine green (ICG)-mediated antimicrobial photodynamic therapy (aPDT) as an adjunct to non-surgical therapy has been explored in some research, but there are no consistent results.

This meta-analysis followed the Cochrane Handbook for Systematic Review of Interventions and the Preferred Reporting Items for Systematic Reviews and Meta-analyses and was registered on PROSPERO with the registration number of CRD42020220606.^[2] A literature search was performed before November 2020 in Cochrane Library, PubMed, and Embase. Reliability was verified by Kappa statistics, assuming that 0.61 was the threshold value. Inclusion criteria were as follows: (1) Research design was randomized controlled trial (RCT), which includes split-mouth design or full-mouth design. (2) The participants who had periodontal diseases were without restrictions in age, gender, ethnicity, or socioeconomic status. According to the American Academy of Periodontology/European Federation of Periodontology classification, periodontal disease was defined as clinical attachment loss (CAL) ≥2 mm at non-adjacent teeth, or CAL ≥3 mm with pocketing >3 mm for at least two teeth.^[3] (3) Types of interventions: ICG-mediated photodynamic therapy as an adjunct to SRP vs. SRP alone. (4) Types of outcomes: the outcomes measured included the probing pocket depth (PPD) and CAL. Exclusion criteria were as follows: (1) Participants had a systematic disease. (2) Patients accepted antibiotic therapy or periodontal treatment within 3 months before the trial. (3) The participants were followed up for <3 months. (4) Medicine or other intervention approach was used in test groups. (5) High-power laser (output power was >1 W) was implemented in the test group.

According to the Cochrane Tool for risk of bias assessment, the methodological quality was estimated. REVMAN 5.4 (Cochrane Collaboration, Cochrane Collaboration, Oxford, England) was utilized to calculate the overall effects in this meta-analysis. Mean difference (MD) and 95% confidence interval (95% CI) as the effect size were applied to describe continuous variables. Heterogeneity was calculated through Q-statistic and I². Because of the moderate insensitivity for Q-statistic, P < 0.1 was deemed to represent significant heterogeneity. When I² < 50%, we used the fixed-effects model. Otherwise, the random-effects model was used to measure the pooled effects. Statistical Z-test was elected for analysis. If P < 0.05, the pooled effects were considered to be statistically different. Sensitivity analysis was conducted to evaluate whether some literatures had a significant effect on overall outcomes. Egger's test was conducted to evaluate the publication bias by STATA 12.0 (Stata Corp LP, College Station, TX, USA).

In this article, the primary outcomes were the PPD reduction and CAL gain at 1 month, 3 months, and 6 months. The secondary outcomes were the changes in plaque index (PI) at 1 month, 3 months, and 6 months.

Seven hundred and twenty-two records were identified by retrieval strategy [Supplementary Figure 1, https://links.lww.com/CM9/B111]. Finally, a total of eight articles were eligible for this meta-analysis (κ = 0.79).^[3-11] All the studies were RCTs and published from 2015 to 2020 [Supplementary Table 1, https://links.lww.com/CM9/B112]. The numbers of participants in every study were different, and 255 patients were enrolled in all trials. Two studies adopted full-mouth design and six studies adopted split-mouth design. For the clinical parameters, all studies adopted the 810 nm laser to irradiate ICG. Eight studies were evaluated for the risk of bias based on the Cochrane Handbook for Systematic Reviews of Interventions (RoB 2). Four studies were classified as having a low risk of bias and three studies as having a moderate risk of bias. One study had a high risk of bias.

Four studies provided data on PPD and CAL and three studies provided the data of PI at 1 month. The PPD had a significant reduction for aPDT + SRP vs. SRP (MD = −1.08, 95% CI [−1.60, −0.55], P < 0.01). The CAL had no significant gain for aPDT + SRP group (MD = −0.81, 95% CI [−1.81, 0.18], P = 0.11). The PI reduction was not significant for aPDT + SRP group (MD = 0, 95% CI [−0.08, 0.07], P = 0.98). PPD and CAL were provided by seven studies at the 3-month follow-up, PI was provided by five studies. A significant reduction with strong evidence for heterogeneity was observed for PPD in aPDT + SRP group vs. SRP group (MD = −0.82, 95% CI [−1.48, −0.16], P = 0.01). The CAL had a significant reduction for aPDT + SRP group (MD = −0.60, 95% CI [−1.15, −0.05], P = 0.03). The difference in PI was not significant (MD = −0.08, 95% CI [−0.13, −0.03], P < 0.01) [Figure 1]. The data were provided by four studies at 6 months. Compared to SRP alone, ICG-mediated aPDT + SRP groups showed a significant reduction in PPD (MD = −0.81, 95% CI [−1.50, −0.12], P < 0.01), CAL (MD = −0.81, 95% CI [−1.08, −0.53], P < 0.01), except PI (MD = −0.27, 95% CI [−0.63, 0.10], P = 0.15). Sensitivity analysis was conducted to confirm the stability of this meta-analysis. A significant difference was not observed by the Egger's test. Therefore, there was no obvious publication bias.

Figure 1: Forest plots of the effects of aPDT + SRP vs. SRP on patients with periondontal diseases in terms of (A) PPD, (B) CAL, and (C) PI at 3 months. aPDT: Antimicrobial photodynamic therapy; CAL: Clinical attachment loss; CI: Confidence interval; MD: Mean difference; PI: Plaque index; PPD: Probing pocket depth; SD: Standard deviation; SRP: Scaling and root planning.

The maximum absorption peak of ICG is 805 to 810 nm, which means that the absorption peak wavelength of ICG can penetrate deeper tissue (6.0–6.5 mm).^[12] As shown above, aPDT + SRP achieved exciting results in the short-term and intermediate-term, it suggested that ICG seemed to be a useful photosensitizer for periodontal treatment. In the present research, MD of PPD reduction kept stable during the period of follow-up. It showed that aPDT + SRP was more effective than SRP alone. On the other hand, clinical attachment had a significant gain at 3 months and 6 months.

This meta-analysis was performed to explore the efficacy of ICG-mediated photodynamic therapy as an adjunct to conventional SRP therapy. The combination of two therapies could improve inflammation, attachment loss, plaque adhesion to a certain extent.

Conflicts of interest

None.