Phototherapy utilizing visible light, particularly blue light with a wavelength range of 400–500 nm, has been extensively employed for acne treatment. The key physiological mechanisms activated by blue light involve the generation of reactive oxygen species (ROS) and nitric oxide. These contribute to angiogenesis promotion, anti-inflammatory effects, and direct antimicrobial activity.10 The effectiveness of blue light is contingent upon specific chromophores such as opsins, flavins, porphyrins, and nitrosated proteins. Studies have shown that exposure to blue light leads to the photoexcitation of bacterial porphyrins in C. acnes colonies, resulting in the production of singlet oxygen and subsequent bacterial destruction.1112 Research by Ding et al.13 demonstrated that skin surface lipidomics can reveal a correlation between lipidomic profiles and acne grades in adolescents. Further, significant alterations in skin surface lipids were observed following blue light treatment, indicating potential changes in lipid content and distribution.13 The literature presents some contradictions regarding blue light’s impact on wound healing. A recent study found that low energy densities (< 20 J/cm²) of blue light stimulated various cell types and proteins involved in the healing process by reducing pro-inflammatory cytokines and increasing growth factors. Conversely, high energy densities (20.6–50 J/cm²) were found to significantly inhibit cell proliferation, migration, and metabolism.10 Nakayama et al.14 reported optimal efficacy for blue light treatment when irradiation was administered at 100 mW/cm² for 20 minutes over five consecutive days in a mouse model. Consequently, this treatment protocol could be beneficial for treating acne with high levels of inflammation on a daily basis until improvement is noted.

Red light therapy (620–660 nm) is less effective in activating porphyrins but offers deeper skin penetration, thereby targeting sebaceous glands directly and exerting anti-inflammatory effects through the release of cytokines from macrophages. Subsequently, these cytokines stimulate fibroblast proliferation and the production of growth factors, thereby facilitating wound repair processes.1516 A comparative study by Li et al.17 showed that red and blue light therapies displayed comparable efficacy in treating mild-to-moderate acne vulgaris, particularly inflammatory lesions. Red light therapy had the added advantage of causing fewer adverse reactions than blue light.17 Papageorgiou et al.18 reported an average 76% improvement in inflammatory lesions when treated with a combination of blue and red light, as compared to benzoyl peroxide or blue light alone. Additional research indicates that combined blue and red light LED phototherapy is a safe, effective, and painless treatment for acne lesions.1920

IPL systems operate based on principles similar to lasers: light energy is absorbed by specific target cells containing chromophores within the skin. This energy is then converted into heat, causing damage to the target area. Unlike lasers, IPL systems utilize broadband light (560–1,200 nm) and often employ filters to fine-tune energy output for treating specific areas. This approach enhances penetration without requiring excessive energy levels and allows for the targeting of specific chromophores. The absorption of red and blue light can activate porphyrins, reducing the growth of C. acnes. Additionally, endogenous chromophores in the skin absorb the broad spectrum light emitted by IPL, resulting in damage to the blood vessels supplying the sebaceous glands and consequently reducing gland size and/or function. Barakat et al.21 observed a microscopically significant reduction in inflammation through the downregulation of tumor necrosis factor-α and a reduction in sebaceous gland size in acne vulgaris lesions post-IPL treatment.22 IPL has also proven effective and safe for treating acne-related postinflammatory erythema (PIE) and postinflammatory hyperpigmentation (PIH).23 A prospective study demonstrated that narrow-spectrum vascular filters (530–650 nm and 900–1,200 nm) used in IPL treatment resulted in more effective treatment of PIE, along with greater patient satisfaction and a lower rate of acne relapse, than did broad-spectrum treatment.24

PDT employs photosensitizing agents in conjunction with low-level lasers to induce the rapid formation of ROS. The ROS subsequently triggers cellular apoptosis, necrosis, or immunogenic cell death through lipid peroxidation and DNA damage, as well as induces local immune responses and microvascular damage.2526 PDT offers several advantages and disadvantages for the treatment of skin conditions. Advantages of PDT include: 1) Precise targeting: PDT allows for the selective ablation of abnormal or damaged skin cells without harming adjacent healthy tissues. this selectivity is particularly advantageous for skin condition treatments. 2) Minimally invasive nature: being a generally non-invasive treatment, PDT often results in shorter recovery periods and less scarring. 3) Simultaneous treatment: multiple lesions can be addressed in a single session. However, PDT also has limitations, such as restricted penetration depth, light sensitivity, pain or discomfort during the procedure, the necessity for multiple treatment sessions, and limited accessibility based on geographic location and healthcare resources. The interval between the application of the photosensitizing agent and the initiation of light treatment, termed the “incubation” or “activation” period, may vary according to several factors. These factors include the specific photosensitizing agent employed, the condition under treatment, and the established treatment protocol. Daylight PDT, which forgoes the incubation period and relies on natural sunlight, has been reported as an effective and well-tolerated alternative for acne treatment.27 While the concentration of aminolevulinic acid used in conventional PDT is typically 20%, daylight PDT employs significantly lower concentrations, such as 6% or 1.5%. A split-face clinical trial comparing conventional red-light PDT with daylight PDT found the latter to be equally effective, with fewer adverse effects and shorter downtime.28

PTT is a minimally invasive therapeutic approach that has garnered significant interest in recent years. The technique primarily relies on the activation of photosensitizing agents via electromagnetic radiation, such as radio frequency, microwaves, pulsed lasers in the near-infrared spectrum, or visible light, to convert this energy into heat.

Previous studies have demonstrated the potential efficacy of gold nanoshell-mediated PTT for treating recurrent acne. Advantages of this approach include negligible systemic toxicity, minimal local inflammatory side effects, rapid and efficient reduction in acne severity, and sustained therapeutic benefits due to the targeting of sebaceous glands (Fig. 1). In investigations involving gold nanoshell-mediated PTT, optical imaging identified gold microparticles appearing as hyperreflective columns within hair follicles, a feature absent in the surrounding skin of both healthy participants and acne patients.29 Post-laser exposure analyses, including reflectance confocal microscopy (RCM) and histology, indicated selective perifollicular tissue changes.30 After administering the nanoshells into the follicles and glands, wiping away superficial nanoshells from the skin surface, and exposing the skin to near-infrared laser, these localized nanoshells absorb light, become heated, and induce focal thermolysis of the sebaceous glands. Human clinical studies have confirmed the effectiveness of ultrasonically delivered silica-gold nanoshells in disrupting sebaceous glands without causing collateral skin damage.31 Topically applying gold salt itself directly reduced the activity of the NLRP3 inflammasome in a mouse model, indicating a potential anti-acne effect.32

Interestingly, chronic recurrent acne has been linked to the presence of enlarged facial pores. A recent case report has documented the efficacy and safety of gold nanoshell-mediated PTT as a treatment modality for enlarged facial pores.33

RF technology emits low-frequency electromagnetic waves that generate thermal heat in the dermis, subsequently stimulating collagen production, elastin formation, and neovascularization, all crucial elements in the healing process.34 The therapeutic efficacy of microneedle RF in treating active acne can be attributed to multiple factors.

- Reduction of inflammation: thermal heat generated by RF has been shown to attenuate the inflammation often associated with active acne.35 Inflammation is a critical contributor to the formation and persistence of acne lesions. A study by Hernández-Bule et al.36 demonstrated that RF stimulation led to decreased production of interleukin-8 and RANTES while increasing levels of monocyte chemoattractant protein-1, without notably altering other chemokines such as macrophage inflammatory protein-1.36 Seok et al.37 investigated the effectiveness of IPL, RF, and a combination of both on cultured C. acnes strains using an induced rabbit ear model. They found that RF significantly reduced papule volume, while IPL exhibited an immunomodulatory effect. A synergistic effect was observed when both treatments were applied in combination.

- Regulation of sebaceous glands: RF energy has the potential to modulate the activity of sebaceous glands in the skin, an important consideration in the management of acne. Targeted intervention at the sebaceous gland level is essential for effective treatment, particularly in cases of severe histological inflammation like acne conglobata. In such instances, a unipolar single needle with partial insulation has shown efficacy. The length of the insulation is designed to align with the depth of the sebaceous gland. This approach offers an alternative mechanism for acne improvement, distinct from laser treatments, as supported by clinical literature. A prospective, randomized, controlled clinical trial involving 63 patients with moderate to severe facial acne assessed the effectiveness of a single microneedle RF device. The device demonstrated significantly greater efficacy in reducing acne lesions compared to simple needling, as evaluated through the reduction rate and the number of acne lesions at a 12-week follow-up. Specifically, the mean reduction rate was 20.86 ± 81.37% in the treatment group and −5.13 ± 75.21% in the control group (P = 0.03). Importantly, no serious adverse events were reported.38 Moreover, multi-needle fractional RF devices, commonly used for enhancing dermal conditions like acne scarring and pore treatment, can also be adapted for treating active acne lesions. Effective treatment can be achieved by optimizing parameters such as conduction time, intensity level, and needle depth to establish an appropriate ablative injury zone for the lesion.3839

Given the anatomical distribution of sebaceous glands and water as the primary chromophore, wavelengths in the range of 1,300–1,800 nm have been extensively employed for acne treatment. Among these, the 1,450 nm wavelength has gained recent prominence. Monte Carlo simulations, which model light penetration and heat transfer, indicate that the penetration depth of this wavelength is 435 µm. Furthermore, thermal damage zones have been identified in the upper dermal layer in human studies.40 Paithankar et al.41 found that an infrared 1,450-nm diode laser led to thermal coagulation of the sebaceous lobule and its associated hair follicle by heating the mid-dermis in a rabbit ear model. At fluences lower than or equal to 14 J/cm², the extent of thermal injury and coagulation was less pronounced. Nevertheless, it was posited that the heat generated in the infundibulum and sebaceous lobules led to reduced sebaceous gland activity, which in turn resulted in fewer inflammatory acne lesions.4041 Several small, uncontrolled studies have reported that the 1,450 nm laser yields significant improvements in inflammatory acne, with lesion counts decreasing by 40% to 83%.42434445 Moreover, a substantial long-term clinical remission rate exceeding 70% was observed 12 months post-treatment.42 Politi et al.46 reported that an integrated cooling-vacuum-assisted non-fractional 1,540 nm erbium:glass laser effectively treated 22 patients with mild-to-moderate acne vulgaris. This mid-infrared laser yielded favorable outcomes through its anti-inflammatory effects on acne and induction of neocollagenesis within atrophic scars.46 In studies focused on Asian populations, both inflammatory and non-inflammatory acne lesions showed improvement. Additionally, the technology contributed to reduced sebum secretion and some improvement in skin texture. Notably, PIH, a concern particularly for Asians, was substantially mitigated when employing a brief cooling time combined with a low flow/multi-pass method.47

The laser operating at a 1,726 nm wavelength exhibits spectral selectivity for sebaceous glands due to its narrow bandwidth at the specific absorption ratio peak.48 Goldberg et al.49 evaluated the safety and efficacy of this laser, equipped with contact cooling, in 17 adult patients who had mild-to-severe acne. Relative to baseline measurements, there was a statistically significant reduction in inflammatory lesion counts (ILC) ranging from 52% to 56% over a period of 4–12 weeks. Long-term follow-ups conducted 24 months post-treatment revealed a 97% reduction in ILC.49 A prospective, open-label, single-arm study involving 104 subjects with moderate to severe acne corroborated these findings. The study found that three full-face treatments, each lasting 30 minutes, with the 1,726 nm laser were generally well-tolerated. Progressive post-treatment improvement persisted for at least 26 weeks. At least a 50% reduction in inflammatory acne was observed in 80% of the treatment population, and a 70% reduction in nodule count was noted at the 3-month follow-up visit. While no serious device-related adverse effects such as burns or blisters were reported, some participants did find the treatment to be mildly uncomfortable.50

PDL is primarily employed for the treatment of vascular lesions and rosacea.51 In addition, it has applications in managing hypertrophic scars and keloids due to its ability to stimulate dermal remodeling and collagen synthesis.5051 Recent studies suggest that performing multiple PDL treatments at fluences low enough to prevent purpura may lead to a reduction in inflammatory acne.52 Although earlier literature attributed the effects to a decrease in C. acnes population or sebum secretion, recent insights suggest anti-inflammatory effects and dermal remodeling, facilitated by a significant increase in transforming growth factor (TGF)-β, as more plausible mechanisms.53 Numerous clinical studies have consistently reported not only a reduction in the number of acne lesions but also improvements in acne erythema and scarring alongside active acne.5

The 532 nm KTP laser is predominantly employed for treating telangiectasia and rosacea, as well as various pigmentary disorders, with hemoglobin and melanin acting as the primary chromophores.5455 Recent studies have reported its efficacy in treating active acne, with the proposed mechanisms involving selective photothermolysis of blood vessels and photoactivation of porphyrins against C. acnes and sebaceous glands.56 In studies focused on mild-to-moderate acne, split-face trials have confirmed reductions in both the number of lesions and sebum secretion, although further follow-up studies are warranted.57 This laser technology also holds promise for treating patients with both pigmented lesions and acne or acne scars.

Both microneedling and RF are known to stimulate collagen production in the skin. The MFR device functions by generating RF thermal zones, avoiding epidermal injury in the process.5859 Prior research has demonstrated the transcription and expression of TGF-β persisting for a week following RF treatment. This is accompanied by neocollagenesis, marked by an increased expression of type I and III collagen as well as the upregulation of type I collagen mRNA within the affected tissue.60 The synergistic action of microneedling-induced micro-injuries and RF energy facilitates the skin’s natural wound healing mechanisms. A study by Hernández-Bule et al.36 showed that the electrostimulation facilitated by RF led to the proliferation and/or migration of keratinocytes and fibroblasts. This was achieved through the modulation of intercellular adhesion proteins like β-catenin and E-cadherin, proteins that manage cell-to-substrate adhesion such as vinculin and p-FAK, matrix metalloproteinase-9, and additional proteins that control both processes, including MAP kinases p-p38, p-JUNK, and p-ERK1/2.36 Fusano and Bencini61 examined the in vivo morphological changes in atrophic acne scars following MFR treatment, using RCM and three-dimensional (3D) imaging. They treated a total of 11 patients with atrophic facial acne scars through four monthly MFR sessions. Assessments with 3D imaging and RCM were conducted both at baseline and one month following the final session. The study found that 3D imaging revealed significant improvements in the mean depth of the scars, while RCM showed collagen remodeling and the restoration of a reticular structure.61 A recent randomized, single-treatment, split-face trial involving 15 patients with moderate to severe acne scars compared the efficacy of ablative fractional CO₂ laser (AFL) with microneedle RF. The results suggested that both AFL and microneedle RF were equally effective in improving skin texture affected by acne scars. However, AFL resulted in more noticeable local skin reactions, whereas microneedle RF was associated with greater pain.62 Also, RF combined with IPL is shown to effectively treat moderate to severe acne.63

The 1,540 and 1,550 nm erbium glass lasers are predominantly employed for the treatment of wrinkles, scars, enlarged pores, and diminished skin elasticity by promoting nonablative dermal remodeling and collagen biosynthesis.64 Compared to other lasers that target scarring, this laser technology is less invasive and is often selected for treating acne scars and pores owing to its minimal downtime.65 Although its impact on acne itself remains a subject of debate, certain studies have indicated a decline in acne lesions following 3–5 treatments spaced 3–4 weeks apart.66 Lasers operating at these wavelengths can penetrate deeply into the dermis and modulate sebaceous gland activity through thermocoagulation, providing a theoretical basis for their utility in acne management.67 Given that more than 90% of acne cases are accompanied by some form of scarring, these lasers offer the potential for concurrent improvement of both conditions by tailoring the parameters to individual patients. Hwang et al.68 demonstrated that CO₂ fractional laser is an effective and safe treatment for acne scars and wrinkles in Korean patients. The study showed that skin barrier damage and erythema resolved after treatment, with patients reporting "moderate or greater improvement" and high satisfaction.68

More recently, the use of fractional picosecond lasers has garnered attention. Fractional picosecond laser is known for its non-ablative mechanism to improve acne scars with minimal downtime.69 These lasers facilitate dermal remodeling via the laser-induced optical breakdown mechanism, which generates plasma within the tissue and produces a cavity.70 A study involving 25 patients with acne scars compared the safety and efficacy of fractional picosecond lasers and nonablative fractional lasers. Patients underwent four consecutive treatments at 3-week intervals on one side of their face and were monitored for 8 weeks subsequent to the final treatment. The results indicated that those treated with the fractional picosecond laser demonstrated superior outcomes in both acne scar improvement and overall evaluation by researchers compared to those treated with nonablative fractional lasers. Notably, patients undergoing treatment with the fractional picosecond laser reported greater satisfaction in terms of pore reduction and skin texture enhancement. Histological analyses corroborated these findings, revealing a significant augmentation in collagen, elastic fibers, and the dermal matrix throughout the dermal layer.71

The 1,064 nm wavelength exhibits significant penetration depth, enabling effective heat transfer to the dermal layer while minimizing epidermal damage. This characteristic makes it particularly useful for treating pigmentation disorders and scar tissue.72 Recent studies have also demonstrated its efficacy in treating active acne, noting reductions in sebum secretion and inflammation.73 Various pulse durations—including Q-switched, quasi-long, and long pulses—can be employed to treat acne, and the technique can be augmented by the use of carbon particles for targeted treatment of the sebaceous glands.74 Given that many patients present with multiple skin issues, such as acne, enlarged pores, irregular skin texture, and pigmentation, optimizing treatment parameters can yield simultaneous improvements across these conditions.

Ultrasound has been extensively utilized in treating various skin conditions, such as cutaneous wounds, inflammatory skin disorders, and aesthetic concerns.75 This form of energy targets both dermal and subdermal tissues, inducing thermal injuries that promote collagen remodeling. As a result, ultrasound treatment leads to the lifting and tightening of skin.76 Although limited studies have specifically addressed ultrasound’s efficacy in acne treatment, it is more commonly used as a monitoring device during treatment. Recent preclinical and clinical investigations have, however, pointed to its potential as a therapeutic tool. For example, impulse mode dual-frequency ultrasound operating at 1/3 MHz administered once a week for four weeks demonstrated efficacy and safety in enhancing skin hydration and reducing erythema among acne patients.77 Ultrasound technology has also been employed for transdermal drug delivery, with typical skin penetration enhancements ranging between 1 and 10 folds. Acoustic cavitation serves as the primary mechanism for enhancement in both low-frequency and high-frequency sonophoresis.78 Moreover, ultrasound can function as part of a multimodal approach to treating acne scars.79 Trelles and Martínez-Carpio80 reported that the combination of unipolar fractional ablative RF and ultrasonic dermal injections of bioactive compounds through perforated acoustic pressure microchannels led to a reduction in acne scars. Additionally, keloid and hypertrophic scars, which are common byproducts of the acne healing process, can also be addressed through ultrasound treatment. A recent study demonstrated a significant reduction in fibroblast growth and extracellular matrix deposition without adversely affecting cell viability or adhesion, suggesting these effects were mediated by nonthermal mechanisms. The findings indicate that ultrasound could serve as a beneficial therapeutic approach for scar reduction.