Novel Approaches of Indocyanine Green and aPDT in the Treatment of Periodontitis: A Narrative Review

Abstract

In recent years, increasing attention has been given to adjunctive therapies aimed at improving clinical outcomes in periodontal treatment. Among these, antimicrobial photodynamic therapy (aPDT) using the photosensitizer indocyanine green (ICG) has shown great promise. Objective: This narrative review seeks to summarize the existing evidence from randomized controlled trials, systematic reviews, and in vitro and in vivo studies on the use of antimicrobial photodynamic therapy with indocyanine green (ICG) as a photosensitizer, as well as the emerging approach of double-light aPDT with ICG, in the treatment of periodontitis. Materials and Methods: PubMed, Web of Science, and Cochrane Library databases were searched to find relevant articles regarding the topic. The articles were published in English between the years 2015 and 2025. The search used keywords such as (“indocyanine green” AND “antimicrobial photodynamic therapy” AND (“efficiency” OR “efficacy” OR “effect”) AND (“periodont*” OR “gingivitis” OR “gingival” OR “gum”). The articles chosen were required to evaluate the treatment outcomes of periodontitis with ICG-aPDT. Conclusions: ICG-aPDT represents an effective adjunct treatment in periodontal therapy. It can non-invasively target biofilms and minimize systemic action. It makes this technique an attractive adjunct in modern periodontology practice. This narrative review shows that ICG-aPDT can be integrated into comprehensive periodontal care as an adjunct measure promoting tissue healing. However, more high-quality clinical trials are needed to develop standardized protocols and demonstrate long-lasting benefits.

1. Introduction

Periodontitis is a chronic, multifactorial inflammatory condition linked to dysbiotic plaque biofilms and marked by the progressive breakdown of the tooth-supporting structures, affecting about 20–50% of people worldwide [1]. It affects the supporting structures of the teeth, including the gingiva, periodontal ligament, and alveolar bone. In susceptible individuals, this bacterial plaque triggers an inflammatory response that can lead to tissue destruction and, if untreated, tooth loss [2]. Periodontal disease affects oral health and can influence the pathogenesis of many systemic diseases and quality of life. The literature has also linked periodontitis to a range of other health problems, including diabetes, heart conditions, rheumatoid arthritis, and respiratory diseases [3]. Mental health struggles and complications during pregnancy have also been implicated [3]. These co-occurring conditions, like periodontitis itself, significantly affect the quality of life of those who experience them.

Clinically proven initial non-surgical periodontal therapy primarily consists of eliminating perio-pathogens by debridement of the root surface, disrupting biofilm (scaling and root planing (SRP)), which, in combination with the patient’s carefully performed oral hygiene at home, in most cases, generally results in favorable long-term treatment outcomes [1]. Despite this, the success of periodontal treatment appears to depend on multiple factors, such as genetics, systemic diseases, smoking status, complicated root anatomy, furcation and intrabony defects, and the presence of microorganism reservoirs persisting in the cementum, dentinal tubules, and soft tissue [4]. However, mechanical debridement alone may not eliminate all causative microorganisms, and the use of adjunctive agents has been considered to enhance outcomes of non-surgical periodontal therapy (NSPT) [5]. Systemic and local antibiotics demonstrated high clinical effectiveness, but their use is limited due to the potential risks of side effects and the development of antibiotic resistance, which remains a growing global concern [6]. The gold standard of periodontal antimicrobial treatment, chlorhexidine, also has side effects: it stains teeth, causes taste disturbances, and may exert cytotoxic effects on fibroblasts of mucosal tissues [7]. Therefore, its use is generally restricted to short-term applications.

Antimicrobial photodynamic therapy (aPDT) is an alternative adjunctive periodontal treatment modality that has been investigated since 1992, yielding controversial data on treatment outcomes [8]. Many studies have assessed the effect of aPDT in the context of different types of lasers, photosensitizing agents, and heterogeneous protocols, and treatment has been applied only once or twice over a short observation period [8]. However, current evidence suggests positive effects obtained with photosensitizer indocyanine green (ICG), which might be more effective than previously reviewed agents [9].

Indocyanine green is a water-soluble photosensitizing dye used in aPDT, composed of a lipophilic core and exhibiting fluorescent properties. It has been widely applied in liver function tests, oncology, and ophthalmology, and is frequently used in soft tissue surgery [10]. ICG is unique because it can contribute to both photodynamic (PDT) and photothermal (PTT—photothermal therapy) effects. Recently, ICG has gained increased interest in dentistry due to its excellent tissue penetration and strong absorption peak near the 810 nm wavelength of diode lasers, which, in contrast to conventional photosensitizers, is higher and predominantly photothermal—approximately 85% of the absorbed energy can be converted into heat [11]. Another key property of ICG is its ability to generate efficient reactive oxygen species (ROS), particularly singlet oxygen, supporting its role as a potentially beneficial agent for aPDT [12]. The ability of ICG to exert antibacterial effects through multiple mechanisms is considered advantageous, especially since the thermal antibacterial effect could be beneficial in deep periodontal pockets where oxygen availability is limited.

Moreover, some evidence suggests that treatment may be more effective in studies that have used repetitive aPDT [13]. This method has been associated with better therapeutic results, possibly due to the cumulative effect of repeated exposure, which may allow for prolonged antibacterial activity. In addition, repeated application of aPDT might improve the overall penetration of the photosensitizer, resulting in better exposure to bacterial cells and more effective pathogen elimination. As a result, many studies suggest that the repetitive use of aPDT could contribute to improved clinical results in various medical and dental applications [14,15,16]. In a recent split-mouth randomized clinical trial, Nie and co-authors reported that “repeated aPDT showed a more powerful effect than single aPDT” [16]. Due to the continuous activity in the bacterial biofilm, a series of photodynamic therapy sessions may be superior to a single procedure and could potentially help more effectively control the recolonization of pathogenic microorganisms and maintain better periodontal health.

This review aims to provide a summary of randomized controlled trials, in vitro and in vivo studies, as well as the conclusions of systematic reviews and meta-analyses on the use of aPDT in combination with ICG as a photosensitizing agent, with a particular focus on the application of the dual-light approach in the treatment of periodontitis.

2. Materials and Methods

A search for information was carried out in electronic databases. PubMed, Web of Science, and Cochrane Library were included, covering the period from 2015 to 1 April 2025 (Figure 1). Keywords were used, such as (“indocyanine green” AND “antimicrobial photodynamic therapy” AND (“efficiency” OR “efficacy” OR “effect”) AND (“periodont*” OR “gingivitis” OR “gingival” OR “gum”)). Additionally, a manual search of the literature and the bibliographies of key systematic reviews was performed to reduce the risk of missing relevant studies (Figure 1).

The search was filtered to include randomized controlled trials (RCTs), systematic reviews, meta-analyses, in vitro and in vivo studies, and publications in English from the past ten years. Data were extracted into RefWorks Citation Manager by one reviewer (RS) and double-checked by another (IMP). All disagreements were resolved through mutual discussion. The retrieved documents were reviewed to identify relevant references. Multiple publications from the same study were linked together and treated as a single study for data extraction. The initial electronic search revealed a total of 159 articles, of which 51 were rejected as duplicates. After reviewing the titles and the abstracts, a further 64 articles were filtered as irrelevant. Eligibility was assessed for 44 reports, of which 3 were rejected as irrelevant to periodontitis, 1 because full text was not available, 5 because of inadequate study design, 3 studies related to surgical periodontal treatment, and 2 studies that investigated periodontitis in association with systemic diseases. Four additional articles were identified during the manual search and assessed as eligible. Finally, a total of 34 articles were included in this review (Figure 1).

3. ICG Photosensitizer in aPDT Treatment of Periodontitis

ICG has wide applications in dentistry due to its non-toxicity, non-ionizing properties, ease of handling, and rapid elimination. Another advantage is that ICG does not cause green staining in tooth surfaces and dental restorative materials [17]. ICG-assisted antimicrobial photodynamic therapy (aPDT) has been investigated as an adjunctive treatment for periodontitis, utilizing either laser or novel LED light activation methods.

The results of in vitro studies and in vivo randomized clinical trials (RCTs) suggest that adjunctive aPDT may improve periodontitis treatment outcomes when ICG is used as the photosensitizer [18,19,20,21,22,23,24,25,26,27,28,29,30,31]. In total, eight in vitro studies were included in this analysis, evaluating the effects of ICG-mediated aPDT either on periodontopathogenic microorganisms [24,25,26,27,28] or on human gingival fibroblast cells [29,30,31]. The RCTs compared ICG-aPDT with laser or LED activation as the test intervention against scaling and root planing (SRP) as the control (

Table 1. Characteristics of included RCTs investigating ICG-assisted aPDT in the treatment of periodontitis.

Study (Year)	Sample Size	Study Design	Test Group	Control Group	Follow-Up
Sethi et al., 2019 [23]	30	Split-mouth	ICG-aPDT + SRP	SRP alone	3 months
Sukumar et al., 2020 [20]	40	Split-mouth	ICG-aPDT + SRP	SRP alone	6 months
Joshi et al., 2020 [19]	50	Parallel	ICG-aPDT + SRP	SRP alone	3 months
Karmakar et al., 2021 [18]	20	Split-mouth	ICG-aPDT + SRP	SRP alone	3 months
Wadhwa et al., 2021 [22]	40	Parallel	ICG-aPDT + SRP	SRP alone	6 months
Annunziata et al., 2023 [21]	40	Split-mouth	ICG-aPDT + SRP	SRP alone	6 months

). RCT studies used ICG-aPDT with laser or LED light as the test group, and scaling and root planing (SRP) as the control (Table 1). Four out of the six included RCTs employed a split-mouth design.

3.1. Effect of Laser-Assisted aPDT with ICG on Human Gingival Fibroblast Cells

After receiving antimicrobial photodynamic therapy (aPDT), microbial cells in the biofilm structure may produce and/or release soluble biofilm-derived effectors (BDEs), which can influence the biology of host cells within the surrounding microenvironment. Peeridogaheh and co-authors investigated the effects of BDEs released by Aggregatibacter actinomycetemcomitans following exposure to sublethal doses of ICG-mediated aPDT on human gingival fibroblasts (HGFs), focusing on cytokine production [29]. They found that an irradiation time of 1 min with an energy density of 31.2 J/cm² using an 810 nm diode laser represented the maximal sublethal dose. The corresponding maximal sublethal dose of ICG-PDT was 20.15 μM ICG at the same fluence of 31.2 J/cm². Tissue repair processes were enhanced following the inactivation of pro-inflammatory cytokines and chemokines by the bacterial conditioned medium (BCM) derived from ICG–PDT-treated A. actinomycetemcomitans.

Moreover, regenerative processes in the periodontium were stimulated by increased concentrations of TGF-β and bFGF, which were induced by the products of ICG-PDT applied to Aggregatibacter actinomycetemcomitans [29]. Pourhajibagher et al. (2016) reported a reduction in cell viability correlated with prolonged laser exposure and decreasing ICG concentrations. Specifically, when PDT was performed with 500 µg/mL of ICG, followed by a 30 s irradiation, a 1 min interval, and a subsequent 30 s laser application, cell survival rates were significantly reduced, being statistically lower than in other experimental groups (p < 0.01) [31]. Pourhajibagher et al. (2020) reported that using ICG at concentrations of 1000 μg/mL or higher is recommended to achieve optimal antimicrobial effects in PDT while minimizing the apoptosis induction in human cells [30]. Consequently, a precise understanding of the photosensitizer concentration and irradiation duration is crucial to prevent cellular toxicity.

Such insights are essential for establishing PDT as a potential alternative to conventional antimicrobial treatments for periodontal diseases. These studies highlight the importance of carefully selecting the photosensitizer concentration and illumination parameters to achieve the desired therapeutic effect without causing harm to the host cells.

3.2. Antibacterial Effect of Laser-Assisted aPDT: In Vitro and In Vivo Data

The reviewed studies demonstrate that laser-assisted antimicrobial photodynamic therapy (aPDT) is an effective method for reducing microbial viability in vitro and improving treatment outcomes for oral infections (Appendix A). Pourhajibagher et al. reported that using 1000 μg/mL of ICG combined with diode laser irradiation for 1 min produced significant and near-significant reductions in the viability of A. actinomycetemcomitans when using ICG-aPDT [24,25]. Other studies have reported that photodynamic therapy with ICG combined with 810 nm laser irradiation was effective in significantly eradicating P. gingivalis and L. acidophilus [27,28].

Also, ICG has demonstrated efficacy in vitro against highly aggressive periodontopathogens, including Porphyromonas gingivalis [32]. Fekrazad et al. showed that aPDT using indocyanine green significantly reduced Candida albicans colony counts, indicating its promising antifungal potential [28]. Evidence from randomized controlled trials (RCTs) indicates the significant antimicrobial efficacy of ICG-mediated aPDT against a wide range of periodontal bacteria, including, but not limited to, Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Tannerella forsythia, Fusobacterium nucleatum, and Treponema denticola [20,21,23]. Four studies, with sample sizes ranging from 20 [18] to 59 participants [19], investigated the effects of ICG-aPDT on specific bacterial species [18,20,21,23]. Despite some variability among studies, a consistent finding was that adjunctive ICG-aPDT significantly reduced microbial counts over observation periods ranging from 3 to 6 months [20,21,23]. An interesting observation was the pronounced effectiveness of antibacterial aPDT against Gram-positive bacteria, such as Streptococci, possibly due to their lack of the catalase enzyme, which renders them more susceptible to the reactive oxygen species (ROS) in the treatment, leading to their elimination [20].

In vitro and in vivo studies have demonstrated that laser-assisted aPDT significantly reduces the colony-forming units of key pathogens involved in oral biofilms, including Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans.

3.3. Clinical Outcomes of Laser-Assisted ICG-aPDT in Periodontitis Treatment

The reviewed randomized controlled trials showed that adjunctive indocyanine green-based photodynamic therapy significantly reduced periodontal pocket depth compared with scaling and root planing (SRP) alone, with follow-up periods ranging from 3 to 6 months [18,19,20,21,22,23] (Appendix B), (Appendix C). The studies employed varying protocols to standardize probing pocket depth (PPD) assessment. For example, Joshi et al. inserted the probe parallel to the long axis of the tooth to measure the PPD, recording measurements at the two deepest sites per single-rooted tooth in both the test and control groups, with the ICG-aPDT group showing a greater reduction compared to the SRP alone [19]. Sukumar et al. reported that the ICG-aPDT group exhibited a significant reduction in pocket depth in comparison to the control group [20].

Regarding bleeding on probing (BOP), Wadhwa et al. found no difference between groups at baseline; however, a significant reduction was observed in the ICG-aPDT group after 3 months (p = 0.01) and 6 months (p < 0.001) [22]. Joshi et al. [19], Sukumar et al. [20], and Karmakar et al. [18] did not include BOP values in their final analysis (Appendix B). However, Sethi et al. determined a statistically significant reduction in percentage-based BOP in the test group at 3-month post-treatment [23]. In the study by Annunziata et al., BOP was defined as the percentage of sites that showed bleeding within 10 s of probing (%). These results were also statistically significantly better in the ICG-aPDT group [21].

Clinical attachment level (CAL)—defined as the distance from the cementoenamel junction to the base of the periodontal pocket—was measured in all the studies. An increase in CAL was observed in studies with follow-up periods at 3–6 months, showing statistically significant improvements [18,19,20,21,22,23] (Appendix B). These results suggest that ICG-aPDT has the potential to be an effective adjunctive treatment modality for periodontal diseases, although longer-duration clinical studies are needed to confirm these findings.

3.4. Antimicrobial Effects of Novel Dual-Light aPDT

Previously, aPDT treatment was used and investigated exclusively in clinical settings. However, rapid advancements in light-emitting diode (LED) technology have enabled the development of new personal devices for light-based applications at home, allowing patients to perform aPDT treatment themselves on a more frequent basis [14]. The light produced by LEDs reduces the risks associated with laser light, such as eye damage and thermal injury to tissues. In addition, the advantage of LED light is that it allows for higher cumulative light exposure compared to laser devices, as it can be used daily [33].

“Lumoral” is a CE-certified medical device that features an intraoral mouthguard applicator integrated with an LED dual-lighting system (Koite Health LTD, Espoo, Finland) [33]. The device is intended to be used as an adjunct to regular personal dental hygiene procedures, such as tooth brushing, interdental brushing, and flossing [34]. The device works through two different mechanisms. An 810 nm near-infrared (NIR) light component that activates indocyanine green (ICG) adhered to bacteria, resulting in a thermoactive effect combined with the release of reactive oxygen species, and a 405 nm antibacterial blue light (aBL) that is absorbed by porphyrins and flavins in bacterial cells [33]. In addition, NIR light is believed to exert a positive effect on periodontal tissue health due to its photobiomodulatory properties [35]. This effect is explained by the fact that NIR light is absorbed by cytochrome-c oxidase, the main mitochondrial enzyme in cells, which leads to increased adenosine triphosphate (ATP) production and cellular bioenergetics. Furthermore, the biomodulatory properties of the low-level laser therapy may facilitate cell metabolism and proliferation, which accelerates the healing and regeneration process of inflamed periodontal structures [35]. The antibacterial effect of dual-light therapy, integrating antimicrobial photodynamic therapy (aPDT) and antibacterial blue light (aBL), has been shown in several preclinical studies in vitro [36,37,38] and in clinical studies [33,39,40,41].

3.4.1. Evaluation of the Results of In Vitro Assessment

We identified three studies investigating the antibacterial effects of antimicrobial blue light (aBL) and NIR light-based aPDT on biofilms of Streptococcus mutans, Staphylococcus aureus, and Streptococcus oralis [36,37,38].

Nikinmaa and co-authors investigated the effects of single-wavelength aBL or aPDT on Streptococcus mutans biofilm. In a one-day biofilm, dual-light aPDT was significantly more effective than either aBL or aPDT applied separately; although, both methods demonstrated a bactericidal effect. In a four-day biofilm, aPDT and dual-light aPDT were more effective than aBL alone [39]. Notably, in experiments with four- and fourteen-day-old biofilms, where light application was repeated daily using the same wavelengths, increased S. mutans viability and enhanced biofilm adaptation were observed when the light modalities were applied separately. In contrast, synchronous application of aBL light with aPDT effectively inhibited biofilm adaptation and significantly enhanced the long-term antibacterial effect [39]. Another study investigated the effects of dual-light aPDT on Staphylococcus aureus biofilms [37]. The methodology involved varying relative proportions of light wavelengths, either simultaneous application of aBL and aPDT or their separate use, with indocyanine green (ICG) as the photosensitizer at energy doses of 100 or 200 J/cm². Biofilms aged 1, 3, or 6 days were analyzed. The results demonstrated that the long-term bactericidal effect of dual-light aPDT on S. aureus biofilms was superior to that of 405 nm aBL or 810 nm aPDT applied individually. A relatively higher proportion of aBL significantly enhanced the antibacterial effect, particularly with repeated applications. The optimal antibacterial outcome on biofilms was observed when the relative amount of aBL proportion exceeded 50%. The authors suggested that dual-light aPDT could be an alternative to topical or systemically applied antibacterial agents [37].

3.4.2. Clinical Evaluation of Dual-Light ICG aPDT in the Reduction in Dental Plaque

In vitro findings were supported by a clinical study evaluating the effects of indocyanine green-assisted and dual-light activated aPDT on dental plaque reduction [39]. Nikinmaa et al. conducted a randomized split-mouth trial to assess the impact of dual-light aPDT combined with ICG on dental plaque formation. Following scaling and root planing, participants were instructed to refrain from brushing their maxillary teeth for four days during which the treatment was applied daily. The study demonstrated that plaque accumulation on aPDT-treated premolars (35.1%) was significantly lower compared to controls (42.5%). A reduction trend in MMP-8 levels in gingival crevicular fluid (GCF) was observed in the aPDT group, indicating decreased inflammation. Additionally, treatment resulted in a reduction in pathogenic bacteria, such as Streptococcus, Acinetobacter, Capnocytophaga, and Rothia, and an increase in beneficial species, such as Neisseria and Haemophilus in plaque samples [39].

3.5. Investigations of the Clinical Effectiveness of Dual-Light aPDT in the Treatment of Periodontitis

The effectiveness of dual-light aPDT has recently been investigated as an adjunctive non-surgical treatment for periodontitis. Although the number of published studies remains limited, and some involve small sample sizes [33,41], the findings are promising and indicate potential for dual-light aPDT as a supportive therapy to non-surgical periodontal treatment (NSPT).

Notable findings were reported by Pakarinen and co-authors, who investigated patients with stage I–III periodontitis. This study evaluated the effectiveness of daily dual-light aPDT use in a home setting. Participants were randomized to receive NSPT combined with dual-light aPDT treatment or NSPT alone. The interim results from 51 patients indicated that adjunctive application of dual-light aPDT with ICG significantly enhanced the outcomes of NSPT in reducing inflammation and improving oral hygiene. Patients in the test demonstrated a significant reduction in the visible plaque index and exhibited substantially lower bleeding on probing reduction in deep pockets. Notably, 92% of patients in the test group experienced reductions, compared to 63% in the control group (p = 0.02) [33]. There were no serious adverse events related to the device; minor issues reported included discomfort due to warmth and excessive salivation [33]. As only interim results of the study have been published to date, further analyses with extended follow-up periods are needed to confirm the reproducibility of these findings and better define the long-term benefits of this treatment approach.

Similar positive effects were shown in a pilot study on peri-implant tissues, suggesting that the repeated use of dual-light aPDT could help to reduce microbial pathogens and lower the inflammation, particularly by decreasing the inflammatory marker MMP-8 in peri-implant sulcular fluid around dental implants [14]. Further studies in larger populations are needed to evaluate the long-term results.

4. Discussion

4.1. Laser-Assisted and Dual-Light ICG Antibacterial Photodynamic Therapy (aPDT)

This narrative review summarizes the preclinical and clinical evidence of ICG-antimicrobial photodynamic therapy for periodontal treatment. Indocyanine green (ICG), when activated by an 810 nm diode laser, exhibits strong light absorption and deep tissue penetration. This process generates reactive oxygen species (ROS) and induces photothermal effects, causing bacterial cell destruction. These dual mechanisms enhance the antibacterial action, particularly against key oral pathogens such as Porphyromonas gingivalis and Aggregatibacter actinomycetemcomitans, as confirmed by in vitro and in vivo studies [18,19,20,21,22,23,24,25,26,27,28,29,30,31]. Several clinical trials report that adjunctive use of laser-activated ICG-aPDT with scaling and root planing leads to better outcomes in periodontal treatment, including reductions in probing pocket depth, bleeding on probing, and pathogenic microbial load, as well as gains in clinical attachment levels [24,25,26,27,28]. These enhancements are largely attributed to the ability of the technology to deliver concentrated photonic energy to subgingival regions, areas where conventional antimicrobial agents often exhibit limited efficacy.

Repeated administration of ICG-aPDT has been shown to produce more robust and sustained clinical and microbiological improvements compared to single-session protocols. Studies by Nie et al. and Pakarinen et al. underscore the importance of long-term antimicrobial effects, which are more pronounced with multiple treatment sessions [16,33]. Nevertheless, more long-term clinical studies are needed to confirm its safety and sustained efficacy. A critical factor influencing the efficacy of this treatment modality is the precise regulation of both the photosensitizer concentration and the parameters of laser light exposure. Careful calibration of these variables is essential to ensure effective eradication of the target microorganisms while minimizing potential damage to the surrounding host tissues [29,30,31]. Salvo et al. also indicated in their article that the available evidence on adjunctive use of lasers and aPDT is limited due to the low number of controlled studies and the heterogeneity of study designs. After 6 months, a high variability in clinical outcomes was observed, and patient-reported benefits have not yet been confirmed [8].

More recently, a dual-light aPDT approach—combining ICG- based therapy with antibacterial blue light (aBL)—has gained attention. This method not only increases ROS generation but also inhibits bacterial adaptation mechanisms. Dual-light therapy has demonstrated superior effectiveness in disrupting mature biofilms and maintaining a healthier oral microbiota. In Streptococcus mutans, dual-light aPDT has been shown to activate heat-sensitive genes such as grpE, dnaK, and fruR, while aBL alone modulates expression of gtfB, brp, smu630, and comDE, enhancing bacterial susceptibility to oxidative stress [38,42].

Dual-light ICG-assisted antibacterial photodynamic therapy, combining antibacterial blue light and near-infrared light, appears to offer distinct advantages over conventional mouthwashes. Unlike chemical agents such as chlorhexidine, which are associated with the development of bacterial resistance and mucosal side effects [43], aPDT relies on non-specific ROS production, making the development of bacterial resistance highly unlikely [38]. Moreover, initial studies suggest that dual-light aPDT preserves oral microbiome balance without causing tissue damage [14]. Nevertheless, further research is needed to confirm whether it is superior and more effective in antibacterial action than conventional antibacterial photodynamic therapy.

Inflammation of periodontal tissues is initiated by the activity of bacterial biofilm and the host immune response. Thus, the success of periodontitis treatment highly depends on infection control. Although Streptococci are not directly related to periodontitis etiopathogenesis, they participate in the early stages of dental biofilm formation [44]. Therefore, the potential benefit of aPDT lies in its ability to inhibit early biofilm development and prevent further maturation, which is essential for periodontitis pathogenesis. In vitro studies suggest that mature biofilms are more sensitive to dual light when the relative proportion of aBL is higher [38]. However, while aBL tissue penetration is limited, NIR light penetrates deeper into the mucosal tissue. Therefore, reducing the NIR light fraction may limit overexposure, which could otherwise interfere with the photobiomodulation effect [45].

Patients with periodontitis require lifelong, ongoing anti-infective therapy [46], and dual-light aPDT may be advantageous due to the possibility of daily, sustained home use. While repetitive procedures may provide greater benefit than single in-office sessions, current evidence-based guidelines advise against adjunctive aPDT at 660–670 nm or 800–900 nm [46,47]. Although the 2020 recommendations did not suggest photodynamic therapy (PDT) as an adjunctive method to conventional periodontitis treatment, more recent studies have reported promising results. This opens the possibility of considering PDT as a potential therapeutic approach; however, the available evidence requires critical appraisal, and further well-designed, high-quality studies are needed to assess its effectiveness reliably [46,48]. Further long-term studies are therefore needed to clarify its clinical relevance and safety.

4.2. Strengths and Limitations

The findings of this review should be interpreted with some limitations in mind. The heterogeneity of studies—concerning photosensitizer concentration, light source parameters (wavelength, energy density), and treatment frequency—makes it difficult to establish standardized clinical protocols. The evidence is limited due to heterogeneity studies, small sample sizes, and short follow-up periods (typically up to 6 months). Long-term outcomes, patient adherence to at-home treatment regimens, and cost-effectiveness analyses have not been comprehensively studied to date.

Despite the limitations, this review was conducted using a comprehensive methodology, carefully selecting studies based on their relevance and the specificity of their analysis. A diverse range of studies was included to capture a range of perspectives and outcomes, acknowledging the potential for selection bias in this review.

4.3. Future Directions

Although photodynamic therapy is a promising antimicrobial treatment method, several challenges need to be addressed before it can be widely adopted. The lack of standardized treatment protocols across studies is the primary obstacle to comparing them. The situation is further complicated by differences in light delivery systems and dosimetry, which hinder the reproducibility of studies. In addition, there is a lack of long-term clinical trials evaluating the long-term efficacy of aPDT.

Future studies should aim to define treatment parameters, such as light wavelength, energy dose, exposure time, and photosensitizer concentration, to ensure both safety and efficacy. Additional research could explore the cumulative effects of repeated aPDT applications on oral biofilm and their impacts on periopathogens, such as Porphyromonas gingivalis, Tannerella forsythia, and Treponema denticola. Furthermore, studies may investigate changes in periodontal inflammation markers after aPDT therapy to better understand the host immune response at the molecular level. Finally, randomized controlled long-term clinical trials with large sample sizes are needed to further confirm the efficacy of LED-based dual light ICG-aPDT for repeated home use.

5. Conclusions

This review highlights the potential of ICG-based aPDT as an adjunctive approach to the conservative treatment of periodontitis. Evidence from small clinical studies indicates that conventional ICG aPDT may provide short-term clinical and microbiological improvements when applied following standard mechanical scaling. However, the heterogeneity of treatment parameters—including wavelength, dose, exposure time, and frequency of sessions—limits the certainty of these findings, underscoring the need for adequately powered randomized controlled trials with at least 6–12 months of follow-up. In parallel, dual-light ICG aPDT protocols have demonstrated promising antibacterial activity against periodontal pathogens and potential benefits in reducing dental plaque formation. Preliminary data suggest that this modality may contribute not only to improved short-term outcomes but also to the prevention of clinical signs of periodontitis. Nevertheless, the current body of evidence remains insufficient to establish optimal treatment frequency, long-term efficacy, and safety. Well-designed randomized controlled trials are therefore required to validate these promising findings and to refine treatment protocols.