Phototherapy for Acne Vulgaris: Strategies and Clinical Applications in Sebum Modulation,Inflammation Control,and Scar Management

Abstract

Background:

Acne vulgaris is a chronic inflammatory skin disease, and photo-based therapies have been adopted as noninvasive alternatives to pharmacological treatment.

Objective:

To systematically evaluate the therapeutic strategies and biological mechanisms of photo-based therapies in the management of acne vulgaris, focusing on sebum modulation, inflammation control, and the treatment of acne sequelae to inform phenotype-oriented clinical decision-making.

Methods:

Following PRISMA 2020 guidelines, a systematic search was conducted in PubMed and Web of Science for studies published between 2005 and 2025. From an initial 2,218 records, 64 articles comprising 42 clinical trials and 22 experimental studies were selected for inclusion based on their focus on the efficacy, safety, and molecular mechanisms of light-emitting diodes (LED), intense pulsed light (IPL), laser systems, and photodynamic therapy (PDT).

Results:

Analysis revealed that photo-based modalities target acne through three primary pathways: 1. Sebum Modulation: Aminolevulinic acid (ALA)-PDT demonstrates superior, durable efficacy in moderate-to-severe acne by inducing sebocyte apoptosis and downregulating lipogenesis via the PI3K/Akt/mTOR and OLR1–Wnt/β-catenin pathways. 2. Inflammation Control: Blue and red light (LED) and IPL provide gradual anti-inflammatory effects suitable for mild-to-moderate acne by reducing C. acnes colonization and modulating cytokines such as TGF-β1, IL-10, and TNF-α. 3. Tissue Remodeling: For acne sequelae, fractional CO2 and picosecond lasers promote collagen remodeling to improve atrophic scars, while vascular-targeted lasers (PDL, Nd:YAG) and IPL effectively reduce post-inflammatory erythema (PAE) and hyperpigmentation (PIH).

Conclusions:

Photo-based therapies are phenotype-specific rather than interchangeable. Strategies targeting sebaceous activity and inflammation are central to treating active lesions, while tissue-remodeling interventions are most effective for managing sequelae. This review establishes a strategy-oriented framework that supports personalized, evidence-based treatment planning in routine clinical practice.

Keywords

acne vulgaris phototherapy clinical efficacy sebum modulation acne sequelae

Introduction

Acne vulgaris is one of the most prevalent chronic inflammatory skin disorders worldwide, affecting adolescents and adults across diverse age groups.¹ Clinically, acne manifests as a spectrum of noninflammatory and inflammatory lesions, including comedones, papules, pustules, nodules, and cysts, frequently accompanied by postinflammatory erythema, hyperpigmentation, and permanent scarring.^2–4 Beyond its visible cutaneous features, acne imposes a substantial psychological and social burden, contributing to anxiety, depression, and impaired quality of life.⁵ Despite its high prevalence and clinical significance, effective long-term management of acne remains challenging.^1,6 The pathogenesis of acne is multifactorial and involves four interrelated processes: excessive sebum production and altered lipid composition, follicular hyperkeratinization, colonization by Cutibacterium acnes, and dysregulated innate and adaptive immune responses.^7–9 These mechanisms interact dynamically within the pilosebaceous unit, generating a proinflammatory microenvironment that drives lesion initiation, persistence, and progression.^10–14 There is a growing impact of acne on the global population with a persistent rise in the burden of acne vulgaris; thus, the more targeted interventions to manage the condition effectively are needed.¹⁵

Currently, the common clinical treatments for acne include topical medication, oral medications, and physical therapies. Although these approaches have shown certain efficacy in clinical practice, there still exist limitations.^16,17 Some therapies show limited efficacy for scarring acne or postinflammatory erythema, and certain patients exhibit poor response to conventional drug treatments or experience high recurrence rates.¹⁰ In recent years, photo-based therapies have emerged as noninvasive and increasingly utilized alternatives or adjuncts in acne management, which include light-emitting diode (LED) therapy, intense pulsed light (IPL), various laser systems, and photodynamic therapy (PDT). By delivering specific wavelengths and energy profiles to cutaneous targets, photo-based therapies can selectively influence microbial viability, sebaceous gland function, inflammatory signaling, and dermal remodeling. As a result, these approaches have been applied not only to active inflammatory acne but also to acne-related sequelae such as postinflammatory erythema, hyperpigmentation, and atrophic scarring.^18,19

Despite their growing clinical adoption, the role of photo-based therapies in acne treatment remains heterogeneous and, in some contexts, poorly defined. Reported clinical outcomes vary substantially across modalities, treatment parameters, and patient populations. While certain approaches demonstrate modest benefits suitable for maintenance or adjunctive use, others particularly PDT-based strategies have shown more pronounced and durable efficacy in selected patient groups, albeit with higher treatment-related burden. Importantly, many existing studies emphasize mechanistic or technical aspects of light-based interventions without systematically integrating these findings with comparative clinical efficacy and therapeutic positioning.^20,21 Therefore, a comprehensive and clinically oriented review of photo-based acne therapies is warranted. In this review, we summarize the fundamental mechanisms by which major photo-based modalities interact with key pathogenic pathways in acne, including sebum metabolism, inflammatory regulation, and tissue remodeling. Beyond mechanistic insights, we critically evaluate and compare their clinical efficacy, durability, and limitations across different acne phenotypes. By integrating molecular mechanisms with comparative clinical outcomes, this review establishes a phenotype-driven framework that clarifies the therapeutic positioning of major photo-based modalities, thereby supporting rational and evidence-informed decision-making in acne management.

Categories of Photo-Based Devices

Common physical modalities applied in acne treatment are generally divided into three categories: LED-based phototherapy (including low-level-laser therapy [LLLT]), laser therapy, and IPL. These modalities employ different regions of the electromagnetic spectrum. LED and laser devices typically operate within the visible light (VL) and near-infrared (IR) ranges, whereas IPL covers a broader spectrum from visible to near-IR. Ultraviolet (UV) radiation is usually excluded in clinical practice due to its DNA-damaging potential.²² VL (380–750 nm) occupies the portion of the electromagnetic spectrum detectable by the human eye, while UV (200–400 nm) and IR (700 nm–1 mm) radiation lie beyond this range. In dermatologic applications, visible and near-IR wavelengths—particularly blue (400–500 nm) and red (625–700 nm) light—are of primary therapeutic relevance.^23–29 These physical distinctions provide the technical basis for subsequent biological effects; however, their clinical relevance ultimately depends on how each modality interacts with dominant pathogenic mechanisms in acne.

Method

The bibliographic search followed a predefined Systematic Review (SR) protocol and strictly adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) 2020 guidelines (Figure 1), which ensures full transparency in the article selection process.

Fig. 1.

PRISMA diagram according to Bibliographic Search. PRISMA, Preferred Reporting Items for Systematic Reviews and Meta-Analyses.

Literature search strategy

The bibliographic search adhered to a predefined SR protocol and strictly complied with the PRISMA 2020 guidelines (Figure 1), which provides a standardized checklist to ensure full transparency in the literature selection process.

Searches were conducted in PubMed and Web of Science databases during 3–10 September 2025 (standardized date format). The following search terms and combinations were used (unified uppercase “OR”, defined abbreviations for clarity):

(Acne vulgaris OR acne) AND (phototherapy) AND (sebum OR sebaceous gland OR pilosebaceous follicle);

(Acne vulgaris OR acne) AND (phototherapy) AND (inflammatory);

(Acne vulgaris OR acne) AND photobiomodulation AND ((LLLT OR Low-Level Light Therapy) OR (LED OR Light-Emitting Diode) OR (blue light) OR (red light)) AND (mechanism OR effect);

(Acne vulgaris OR acne) AND (IPL OR Intense Pulsed Light OR PDT OR Photodynamic Therapy) AND (mechanism OR effect);

(Acne vulgaris OR acne) AND (laser) AND (PIH OR Post-Inflammatory Hyperpigmentation OR PAE OR Post-Acne Erythema).

Following the database search, titles and abstracts of retrieved records were independently screened by two independent reviewers (Xinyi Ren and Lan Ge) against the predefined inclusion/exclusion criteria. Disagreements regarding eligibility were resolved through consensus with a third independent reviewer (Zhiqiang Song); no arbitrary decisions were made.

Literature selection process

•

Initial search results: A total of 2218 records were retrieved (PubMed: 1441; Web of Science: 777);

•

Duplicate removal: 672 duplicates excluded via EndNote, leaving 1546 unique records;

•

Title/abstract screening: Independently conducted by two reviewers (Xinyi Ren and Lan Ge) against inclusion/exclusion criteria. A total of 1441 records were excluded (main reasons: irrelevant topic [n = 1113], nonoriginal studies [n = 297], and non-English [n = 31]). Disagreements on 29 records were resolved by consensus with a third reviewer (Zhiqiang Song), resulting in 105 records for full-text screening;

•

Full-text screening: 41 records excluded (main reasons: lack of primary data [n = 18], irrelevant dermatological condition [n = 10], incomplete therapy data [n = 10], noncompliant study design [n = 6]);

•

Final inclusion: 64 articles were included in the review.

The inclusion and exclusion criteria

Inclusion criteria: 1

Studies published between 2005 and 2025;

Original research, including clinical trials (randomized or nonrandomized), in vitro/in vivo experimental studies, or mechanistic investigations;

Studies explicitly assessing the efficacy, safety, or biological mechanisms of photo-based therapies for acne vulgaris.

Exclusion criteria: 1

Nonoriginal studies (e.g., meta-analyses, narrative reviews, case reports, editorials, letters to the editor, and conference abstracts);

Studies focusing on dermatological conditions other than acne vulgaris;

Studies lacking accessible primary clinical data or mechanistic insights (e.g., purely descriptive reviews without original data);

Non-English language articles;

Duplicate publications or studies with overlapping patient cohorts/data.

Therapeutic Strategies and Mechanisms of Phototherapy in Acne

Acne vulgaris is a multifactorial inflammatory skin disorder in which clinical manifestations arise from excessive sebum production, follicular obstruction, microbial imbalance, and dysregulated immune responses.³⁰ Accordingly, therapeutic strategies are most meaningfully defined by their dominant clinical effects rather than isolated pathogenic mechanisms. Photo-based therapies exert therapeutic benefits by targeting key treatment outcomes, including the reduction of sebaceous activity, modulation of inflammatory responses, restoration of cutaneous microbial balance, and regulation of tissue remodeling. Through a combination of thermal effects, photobiomodulation, and photochemical reactions, these interventions contribute to acne control, improvement of inflammatory lesions, attenuation of fibrotic scar formation, and promotion of collagen neogenesis and skin homeostasis.^24,31,32

Modulation of sebum metabolism

Excessive sebum production, altered glandular structure and lipid composition, and aggravated hyperkeratinization of the pilosebaceous unit lead to the formation of comedones and further promote bacterial colonization.^8,33–35 Light-based therapies have been shown to improve acne by reducing sebum secretion and sebaceous gland volume, regulating sebocyte proliferation and differentiation, and preventing follicular hyperkeratinization, thereby improving overall sebum metabolism.^36–40 Among current photo-based modalities, PDT has been most extensively investigated for its ability to directly suppress sebaceous gland activity and lipid synthesis, whereas nonthermal light-based therapies primarily exert regulatory rather than destructive effects on sebocyte function.^41–45

PDT exerts multiple biological effects beyond the direct phototoxic destruction of sebocytes and C. acnes. The cytotoxicity of reactive oxygen species (ROS) generated during PDT induces oxidative stress, mitochondrial dysfunction, and subsequent apoptosis or autophagy in sebocytes and inflammatory cells.^46,47 The most commonly used topical photosensitizers (PSs) are 5-aminolevulinic acid (5-ALA) and methyl aminolevulinate (MAL), which are enzymatically converted within mitochondria to protoporphyrin IX (PpIX). Upon light activation, PpIX produces cytotoxic ROS that trigger cell apoptosis and necrosis.^48–50 Beyond direct cytotoxicity, increasing evidence indicates that ALA-PDT modulates key lipid metabolic pathways, providing a mechanistic basis for its sustained sebosuppressive effects observed clinically. The 5-ALA-PDT could induce ROS production and regulate the activity of mammalian target of rapamycin (mTOR). Liu and Tuo et al.^51,52 first demonstrated that ALA-PDT suppressed the growth of SZ95 human sebocytes via the mTOR–p70 S6K (T389) signaling pathway and reduced lipogenesis through mTOR–SREBP-1/PPARγ signaling. They further identified the upstream regulation of this cascade as the Akt/Erk-mTOR-p70 S6K pathway. In sebocyte lipogenesis, activation of sterol regulatory element-binding protein 1 (SREBP-1) is tightly regulated by the phosphatidylinositol 3-kinase/Akt/mTORC1 pathway. Yang et al.⁵³ treated primary human sebocytes and sebaceous glands of golden hamsters with or without ALA-PDT and showed that ALA-PDT suppressed lipid secretion while activating the AMPK pathway and downregulating SREBP-1 expression in vitro, elucidating a complementary AMPK/SREBP-1-mediated mechanism for lipid suppression. Jiang et al.⁵⁴ further demonstrated that ALA-PDT inhibited sebocyte proliferation and lipid metabolism by downregulating lipid synthesis-related proteins, including SREBP-1, fatty acid synthase (FAS), and stearoyl-CoA desaturase 1 (SCD-1), through induction of mitochondrial and oxidative stress (Fig. 2). Yan et al.⁵⁵ extended these findings by showing that ALA-PDT significantly reduced lipogenesis in an acne-like mouse model and immortalized human sebocytes via upregulation of oxidized low-density lipoprotein receptor 1 (OLR1), which suppressed the SREBP1-FAS axis and involved activation of the OLR1–Wnt/β-catenin pathway. Collectively, these studies indicate that ALA-PDT exerts a deep and multilevel inhibition of sebocyte lipid synthesis, which may account for its superior and durable clinical efficacy in inflammatory acne characterized by excessive sebum production. Based on the observed reduction in lipid production following ALA-PDT, Wu et al.⁵⁶ further investigated its effects in acne patients, animal models, and cell cultures using red light irradiation (630 ± 5 nm) after topical application of 5% freshly prepared 5-ALA cream. Their results confirmed the inhibitory effect of ALA-PDT on lipid production and identified suppression of protein kinase B (Akt) signaling, leading to Jun D proto-oncogene (JunD) activation and enhanced nuclear receptor subfamily 4 group A member 1 (NR4A1) transcription, as an additional mechanism contributing to sebosuppression. These mechanistic insights provide a coherent explanation for the sustained reduction of inflammatory lesions and sebaceous gland activity reported in clinical PDT studies.

FIG. 2.

ALA-PDT reduced sebocyte proliferation and lipid synthesis by inducing mitochondrial stress and oxidative stress. Adapted under a Creative Commons Attribution 4.0 International License. ALA, aminolevulinic acid; PDT, photodynamic therapy.

In addition to PDT, other light-based modalities have also been shown to influence sebum metabolism. Jung et al.⁵⁷ examined the effects of LED irradiation on sebaceous lipid production in human sebocytes and demonstrated that blue light inhibited sebocyte proliferation in a dose-dependent manner, while red light downregulated lipid production, suggesting their potential utility in acne management through nondestructive modulation of sebocyte activity. Ding et al.⁵⁸ further analyzed changes in skin surface lipid composition before and after blue light treatment using lipidomic approaches and physiological measurements, revealing alterations in relative lipid content and redistribution of lipid components. In contrast to PDT, these nonthermal light-based therapies primarily induce regulatory rather than ablative effects on sebaceous glands, which is consistent with their modest but favorable clinical efficacy in mild acne and their suitability for adjunctive or maintenance therapy rather than for severe disease.

Regulation of the inflammatory microenvironment

Abnormal sebum metabolism generates an anaerobic microenvironment that facilitates bacterial proliferation. The resulting dysbiosis of the skin microbiota perturbs innate immune signaling pathways, including peroxisome proliferator-activated receptors (PPAR) and interferon (IFN) cascades, as well as activation of tumor necrosis factor-α (TNF-α), interleukins (ILs), Toll-like receptors (TLRs), and matrix metalloproteinases (MMPs). These alterations collectively drive immune dysregulation, epithelial barrier dysfunction, and pathogenic microbial overgrowth, thereby contributing to the pathogenesis of acne.^31,59,60 Both environmental and genetic factors contribute to interindividual variability in inflammatory responses, with distinct strains of C. acnes eliciting divergent immune outcomes. Acne-associated strains predominantly induce proinflammatory cytokines, including IFN-γ and IL-17, whereas health-associated commensal strains stimulate the production of anti-inflammatory cytokines such as IL-10.^61–65 Therefore, acne pathogenesis reflects a complex interplay between innate and adaptive immune responses shaped by microbial diversity and host susceptibility. Modulation of this inflammatory microenvironment represents a central therapeutic target of photo-based acne treatments. Phototherapy modalities including LED, IPL, and laser systems can influence inflammatory cell activity and bacterial behavior, thereby contributing to restoration of immune homeostasis within the pilosebaceous unit.^30,66–69

IPL has demonstrated notable clinical efficacy in inflammatory acne.^70–75 Previous studies suggest that intense pulsed light exerts anti-inflammatory effects by reducing C. acnes burden, attenuating bacterium-induced cytokine release, targeting both inflammatory components and sebaceous glands, and potentially inhibiting inflammatory cell migration through vascular effects.^30,76–79 Clinically, these mechanisms translate into a measurable reduction in inflammatory papules and pustules, particularly in patients with mild-to-moderate inflammatory acne. Byun et al.⁸⁰ reported that ALA-IPL PDT reduced TGF-β1 and increased IL-10 expression in cultured fibroblasts, suggesting that induction of IL-10 contributes to the anti-inflammatory effects of PDT in inflammatory dermatoses. Ali et al.⁸¹ further demonstrated that IPL treatment upregulated the TGF-β1/Smad3 signaling pathway in perilesional biopsies from patients with mild-to-moderate inflammatory acne vulgaris. Barakat et al.⁸² observed a significant decrease in the density of inflammatory infiltrates in skin biopsies from 24 acne patients following 6 sessions of IPL therapy (Fig. 3A). Similarly, Fan et al.⁸³ reported that levels of TNF-α and MMP-2 correlated with acne severity and were significantly reduced after 420 nm IPL treatment in an animal model, indicating both clinical and histological improvement. Seok et al.⁸⁴ further noted increased TGF-β expression and a slight, nonsignificant increase in PPAR-γ expression in a rabbit ear acne model following IPL exposure, suggesting an immunomodulatory mechanism involving elevated TGF-β, decreased TNF-α, and enhanced PPAR-γ signaling (Fig. 3B). Liu et al.⁸⁵ investigated the effects of IPL on the skin microbiota and epidermal barrier in patients with mild-to-moderate acne treated over 12 weeks and observed a reduction in the relative abundance of Staphylococcus epidermidis, while C. acnes levels remained largely unchanged, concluding that IPL contributes to microbial rebalancing and lesion improvement. In contrast to the relatively gradual anti-inflammatory effects of IPL, PDT induces a more complex immune response. Liu et al.⁸⁶ examined ALA-PDT in patients with severe acne using transcriptome microarray analysis and identified upregulation of multiple inflammation-related genes, including TREM1 and PTGS2. In a C. acnes induced acne-like mouse model, subsequent co-culture experiments revealed that prostaglandin E₂ (PGE₂) secreted by ALA-PDT-treated HaCaT keratinocytes promoted THP-1 macrophage M1 polarization via the COX-2/PGE₂/TLR4/TREM1 axis, thereby amplifying inflammatory signaling.

FIG. 3.

Regulation of the inflammatory microenvironment. (A) Clinical evaluation of acne vulgaris patients in response to IPL. Representative photographs of face (a–d) before (a, c) and after IPL (b, d). Adapted with permission under the terms of the Creative Commons Attribution License, (B) TNF-α(i) and MMP-2(ii) expression. (a) Control group A. (b) Propionibacterium acnes-injected group C. (c) Group D after six treatments. Adapted with permission under Creative Commons Attribution-NonCommercial- NoDerivs License. IPL, intense pulsed light; MMP, matrix metalloproteinase.

Importantly, this transient amplification of inflammatory pathways does not necessarily indicate treatment failure; rather, it may represent an integral component of PDT-mediated lesion clearance and subsequent clinical remission. Such bidirectional immunomodulation may help explain both the superior efficacy and the higher short-term adverse reactions associated with PDT in severe inflammatory acne. Increasing evidence has also demonstrated the beneficial effects of blue light therapy in acne vulgaris. The predominant hypothesis is that blue light reduces follicular colonization of C. acnes, potentially through activation of endogenous bacterial porphyrins. When blue and red light are applied in combination, a synergistic dual-action effect is achieved: blue light selectively eliminates C. acnes, while red light penetrates more deeply to suppress inflammation and promote tissue repair. Clinically, this combination approach is associated with moderate but consistent reductions in inflammatory lesions and favorable tolerability. Reported clinical data indicate that combined blue and red light therapy can reduce inflammatory acne by approximately 60–70%.^68,87 Taken together, LED- and IPL-based therapies primarily exert gradual and repeatable anti-inflammatory effects suitable for mild-to-moderate inflammatory acne, whereas PDT induces a more profound and complex immune response that is particularly effective in severe disease, albeit with increased treatment-related burden.

Management of acne sequelae

Inflammatory acne triggers a complex wound-healing process characterized by an imbalance between extracellular matrix degradation and collagen synthesis. This dysregulation leads to either excessive or insufficient collagen deposition, resulting in hypertrophic scars, keloids, or atrophic scars.^32,88–91

The inflammatory cascade associated with acne has also been hypothesized to stimulate angiogenesis and melanogenesis, which underlie the development of postacne erythema (PAE) and postinflammatory hyperpigmentation (PIH).⁹² Unlike active inflammatory acne, these sequelae primarily reflect disordered tissue repair, vascular remodeling, and pigmentary dysregulation rather than ongoing microbial or sebaceous pathology. PAE is thought to result from the release of inflammatory cytokines such as IL-6 and TNF-α, which induce dilatation of superficial dermal microcapillaries during the healing phase. Additionally, erythrocyte aggregation within dilated capillaries contributes to the persistent erythematous appearance.⁹³ PIH, by contrast, represents a hypermelanotic response to cutaneous inflammation, characterized by melanocyte proliferation and hyperactivity, leading to excessive or irregular melanin synthesis and dispersion. Acne-related PIH typically involves the epidermal layer, where melanocytes transfer melanin granules to neighboring keratinocytes.^94,95 Light-based therapies used in acne management can be broadly categorized according to their predominant biological targets rather than purely physical parameters. Blue and red light primarily exert antimicrobial and anti-inflammatory effects through activation of endogenous porphyrins and photobiomodulation. PDT targets sebaceous glands via PS-mediated ROS generation, resulting in sustained suppression of lipid production. Vascular-targeted modalities, including pulsed dye laser (PDL) and selected IPL settings, selectively act on hemoglobin to reduce PAE. Fractional laser systems induce controlled dermal injury and photobiomodulation to promote collagen remodeling and scar improvement.⁹⁶

Phototherapeutic improvement of acne scars

Fractional ablative CO₂ laser has been established as an effective treatment for acne scars by promoting skin resurfacing and connective tissue restructuring through controlled thermal injury. Fractional photothermolysis generates microscopic zones of thermal damage within the epidermis and dermis, stimulating collagen remodeling and fibroblast activation while preserving surrounding tissue. The retention of viable keratinocytes facilitates rapid re-epithelialization, often within 48 h, without permanent disruption of the epidermal barrier.^97–100

Scarcella et al.⁹⁹ evaluated the efficacy and safety of a novel CO₂ laser system characterized by narrow and deep ablation columns using histological analysis of ex vivo sheep skin and a clinical study involving 20 patients with Fitzpatrick skin types II–IV and atrophic acne scars. Histological examination revealed well-defined microablation columns and coagulated collagen microzones extending from the epidermis into the papillary and reticular dermis, supporting the structural basis for scar remodeling.

Beyond photothermal ablation, laser-induced photobiomodulation contributes significantly to tissue repair and regeneration. Specific wavelengths of light penetrate the epidermis and dermis, activating molecular pathways that enhance collagen synthesis, promote keratinocyte migration, and stimulate growth factor secretion, thereby accelerating wound healing and restoring skin integrity.^101,102 Nowak et al.¹⁰³ proposed that super-pulsed CO₂ laser irradiation modulates wound healing by increasing basic fibroblast growth factor (b-FGF) secretion while suppressing TGF-β1 expression. This dual regulation promotes cellular proliferation while preventing excessive fibrosis and aberrant collagen deposition. Supporting these findings, animal and in vivo studies have demonstrated that tissue concentrations and temporal dynamics of TGF-β1 and b-FGF critically influence the quality of laser-induced tissue regeneration.¹⁰⁴ Prignano et al.¹⁰⁵ further demonstrated that fractional CO₂ laser treatment induces a distinct cytokine release profile that differs from conventional wound injury, with dynamic temporal changes in growth factor secretion. These findings highlight the importance of controlled cytokine orchestration in achieving functional scar remodeling rather than indiscriminate tissue repair. Other fractional laser systems, including argon lasers, Er:YAG (2940 nm) lasers, and picosecond Nd:YAG (1064 nm) lasers, have also been applied clinically for acne scar treatment. Although many studies primarily report clinical outcomes rather than detailed molecular mechanisms,¹⁰⁶ available evidence supports their efficacy and safety. Sannino et al.¹⁰⁷ demonstrated significant clinical improvement in atrophic acne scars among Asian patients treated with fractional Q-switched 1064 nm Nd:YAG laser. Similarly, Hamblin et al.¹⁰⁸ reported favorable outcomes using a 755 nm picosecond Alexandrite laser in patients with acne scars and PAE. Pan et al.¹⁰⁹ retrospectively evaluated combined ultra-pulse and fractional CO₂ laser therapy in 103 patients, observing improvements in scar depth, contour, and texture with minimal adverse effects. Similarly, Odrzywolek et al.¹¹⁰ further confirmed that 1550 nm fractional erbium-glass laser treatment improved skin density and texture using quantitative imaging assessments.

Collectively, these findings indicate that fractional and picosecond laser systems are particularly effective for structural remodeling of acne scars, primarily through controlled photothermal injury and photobiomodulation rather than antimicrobial or sebosuppressive mechanisms.

Phototherapeutic improvement of PAE and PIH

Effective therapeutic options for PAE and PIH include PDL, Q-switched 1064 nm Nd:YAG laser, IPL, and other nonablative laser modalities.¹¹¹ In general, light-based therapies alleviate acne-associated PIH by accelerating epidermal turnover and promoting re-epithelialization with newly formed, less pigmented keratinocytes.⁹⁴ PDL is the most widely used laser modality for treating PAE, owing to its selective targeting of oxyhemoglobin within superficial dermal vessels. Photothermal coagulation induced by PDL leads to vascular remodeling and reduction of erythema. In addition to its vascular effects, PDL exerts anti-inflammatory actions by upregulating TGF-β1 and modulating local cytokine expression. Photochemical activation of endogenous porphyrins by red light further contributes to selective photodestruction of C. acnes and hyperactive sebaceous glands, while enhancing local immune regulation.^93,112

Nd:YAG lasers exert therapeutic effects on acne-related vascular and pigmentary lesions through multiple mechanisms, including selective photothermolysis of dermal vessels, modulation of inflammatory cytokines, and regulation of TLR-2 signaling.¹¹¹ The Q-switched Nd:YAG laser, particularly in large-spot, low-fluence 1064 nm mode, induces subcellular photomechanical fragmentation of melanosomes and hemoglobin with minimal epidermal damage, owing to its deep dermal penetration and lower melanin absorption. Clinically, this modality has been validated in the treatment of melasma, acquired dermal melanosis, and photoaging. Importantly, its combined ability to suppress vascular inflammation via TGF-β upregulation and to target erythrocyte-laden microcapillaries renders it particularly suitable for persistent PAE, in which prolonged microvascular dilation plays a central role.¹¹³

IPL also demonstrates therapeutic benefits for acne scars, inflammatory lesions, and PIH. By emitting broad-spectrum, noncoherent light (400–1200 nm), IPL selectively heats melanin and hemoglobin in the epidermis and superficial dermis, followed by phagocytic clearance of damaged chromophores. Concurrently, IPL stimulates dermal fibroblasts, enhances collagen VI and TGF-β1 expression, and promotes collagen and elastin synthesis, thereby improving dermal structure and texture.¹¹⁴ By selecting appropriate cut-off filters, IPL can be tailored to target specific chromophores, enabling effective treatment of vascular and pigmentary lesions with minimal adverse effects.^87,115 A refined form of IPL, delicate pulsed light, further narrows the wavelength range to 500–600 nm, increasing vascular selectivity and improving outcomes in superficial erythematous lesions, while also contributing to sebaceous regulation and inflammation reduction.¹¹³

Taken together, light-based modalities for PAE and PIH primarily act through vascular and pigmentary targeting rather than direct acne control and are best applied during the postinflammatory or recovery phase of acne management. To facilitate clinical interpretation within a strategy-oriented framework, representative clinical studies are summarized in Table 1. The studies are organized according to dominant therapeutic strategies, including sebum modulation, regulation of the inflammatory microenvironment, and management of acne sequelae. For each study, key elements such as treatment modality, study design, patient characteristics, treatment parameters, and principal clinical outcomes are presented to enable structured comparison of efficacy profiles across different pathogenic targets. This synthesis aims to integrate clinical evidence with the underlying therapeutic strategies discussed above.

Table 1.

Representative Clinical Studies of Photo-Based Therapeutic Strategies in Acne Vulgaris

Therapy strategies	Modality	Study period	Study group	Treatment parameters	Research aims	Treatment efficacy	Ref
Improve sebum metabolism	IPL (broadband light)	2017–2018	25 patients with enlarged facial pores	10–12 J/cm², 20–25 ms; 5 treatments, 2-week intervals	Evaluate IPL efficacy on facial pore size and sebum secretion	Safe but only mildly effective: no statistically significant difference in pore count reduction between treated and untreated sides at 2-month follow-up (p = 0.606)	¹¹⁶
Improve sebum metabolism	785 nm LLLT	2021	27 patients with mild-to-severe acne	80 mW/cm², 10 min/session; 6 sessions, 2-week intervals	Assess LLLT effects on acne lesions and sebum production	Significant reduction in both inflammatory and non-inflammatory lesion counts (p < 0.01). Significant decrease in sebum secretion	¹¹⁷
Regulate inflammatory microenvironment	MAL-PDT red light	2021	33 patients with mild-to-severe acne	20 J/cm², 5 min 14 s; 1–2-week intervals	Compare anti-inflammatory efficacy of MAL-PDT vs. red light alone	Inflammatory lesions reduced by 74% (2 treatments) and 85% (4 treatments). The new regimen (MAL-1.5 h incubation, 20 J/cm²) is effective	¹¹⁸
	1450 nm diode laser	2019–2020	20 patients with inflammatory acne	14–18 J/cm², 6 mm spot size, 1 Hz, 210 ms; 3 sessions, 4–6-week intervals	To comprehensively investigate efficacy using objective (VISIA) and subjective (CGI-I, PGI-I) assessments.	Significant improvement in VISIA porphyrin and red area scores. Clinician (CGI-I) assessment showed significant improvement (p = 0.001)	¹¹⁹
	IPL	2018–2020	23 patients with acne vulgaris	A dual-band filter, 11–13 J/cm², 4.0–5.0 ms; 5 sessions, 2-week intervals	Evaluate the efficacy and safety of dual-band IPL for facial acne	Significant reduction in papules, pustules, comedones, and melanin index (p < 0.05)	¹²⁰
	ALA-PDT	2019	11 patients with severe facial acne	36–50 J/cm² 40 mW/cm², 18 min; 3 sessions, 2-week intervals	To compare the microbiome in pilosebaceous units before and after ALA-PDT via metagenomics	Significantly reduced the relative abundance of C. acnes	¹²¹
	1726 nm Laser	2023	104 subjects with moderate-to-severe acne (Fitzpatrick skin types II–VI)	20.5 J/cm² and 22.8 J/cm², 50 ms, 3.1 mm laser spot size following pre-cooling 1 s delay; 3 sessions, 3-week intervals	Assess the tolerability and therapeutic outcomes across skin types	50% improvement in inflammatory acne in 79.8% subjects, and the sebaceous gland effect produced durable, progressive improvement	¹²²
Ameliorate acne scar, PAE, or PIH	IPL	2020–2021	60 patients with PAE/PIH	640 nm (8–12 J/cm², 30–35 ms), 590 nm (8–12 J/cm², 15–20 ms) 560 nm (6–10 J/cm², 12–15 ms); 3–7 sessions, 4–6-week intervals	To evaluate the efficacy and safety of IPL for acne-related PIE and PIH	81.7% of patients showed complete/partial clearance. Significant improvement in CADI, EAS, and VISIA red/brown spot counts (p < 0.01)	⁸⁷
	577 nm pro-yellow laser	2017–2019	40 patients with acne sequelae	22 J/cm², single session	Evaluate the efficacy and safety of pro-yellow laser for postacne erythema and scarring	77.5% of patients had good to excellent improvement in erythema. Mild to moderate improvement in atrophic scars	¹²³
	577 nm High-power optically pumped semiconductor laser (HOPSL)	2020	21 patients with PAE	12–15 J/cm², 30 ms, 1 mm spot size; 3 sessions, 1-month intervals	Evaluate the efficacy and safety of 577 nm HOPSL for PAE	Laser-treated sides showed significant reduction in Erythema Index vs. control	¹²⁴
	1550 nm Erbium glass laser	2025	20 patients with mild-to-moderate atrophic acne scars	2.8 ms impulse duration 30–35 mJ pulse, 70 µm beam size, and a spot area of 0.0038 mm²; 2 sessions, 1-month interval	Assess scar improvement efficacy using gray-level co-occurrence matrix (GLCM) image analysis	GLCM analysis showed significant posttreatment reduction in contrast and increase in homogeneity (p < 0.05)	¹²⁵
	1064 nm Nd: YAG laser	2021	19 subjects with moderate-to-severe acne	8 J/cm², 300 µs; 6.6 sessions on average, 2-week intervals	Evaluate safety and efficacy for active acne	Significant reduction in AGSS scores (p = 1.63E-05)	¹²⁶
	FxPico + IPL	2021	17 patients with atrophic acne scar and PIE	IPL (560 or 590 nm filter, 15–19 J/cm², 3.5–4.0 ms, 1 pass). Fractional picosecond laser (1064 nm, 1.5–2.5 mJ/microbeam, 450 ps, spot size of 6 mm, 6 Hz, 3–4 passes); 5 sessions, 4-week intervals	Evaluate the efficacy and safety of combination therapy for atrophic scar with PIE	FxPico + IPL side showed significant ECCA score improvement and greater pore count reduction vs. IPL alone (p < 0.05)	¹²⁷
	Pulsed 1064-nm Nd:YAG laser	2024	23 subjects with mild-to-severe facial acne	650 µs; 5 treatments at 2-week intervals	Evaluate the efficacy and tolerability of a 650-microsecond, pulsed 1064-nm Nd:YAG laser therapy for mild-to-severe facial acne vulgaris	Median lesion count reduction was 48.15% after 1 treatment, 83.72% after 3 treatments, and 86.67% at 90-day follow-up	¹²⁸

ALA, aminolevulinic acid; IPL, intense pulsed light; LLLT, low-level-laser therapy; MAL, methyl aminolevulinate; PAE, postacne erythema; PDT, photodynamic therapy; PIH, postinflammatory hyperpigmentation.

To facilitate clinical interpretation within a strategy-oriented framework, representative clinical studies are summarized in Table 1. The studies are organized according to dominant therapeutic strategies, including sebum modulation, regulation of the inflammatory microenvironment, and management of acne sequelae. For each study, key elements such as treatment modality, study design, patient characteristics, treatment parameters, and principal clinical outcomes are presented to enable structured comparison of efficacy profiles across different pathogenic targets. This synthesis aims to integrate clinical evidence with the underlying therapeutic strategies discussed above.

Building upon this strategy-based evidence, Table 2 further translates these findings into phenotype-oriented clinical recommendations. Acne presentations are categorized according to predominant pathogenic features, and corresponding phototherapy modalities, representative treatment parameters, evidence levels, and practical considerations are outlined. This structured summary is intended to bridge mechanistic rationale and clinical evidence with individualized treatment planning in routine practice.

Table 2.

Phenotype-Based Phototherapy Recommendations for Acne Vulgaris

Acne phenotype	Dominant pathogenic features	Preferred phototherapy modalities	Recommended parameters	Evidence level (GRADE)	Clinical notes
Sebum-excess phenotype	Increased sebum secretion, enlarged pores, comedonal acne	IPL, LLLT (red/blue light), diode laser (1450 nm)	IPL: 10–12 J/cm², 20–25 ms; 6–8 treatments (2-week intervals)	1B (moderate certainty)	Avoid high fluence in seborrheic skin; combine with oil-control skincare
Inflammation-dominant phenotype	Papules, pustules, nodular acne; C. acnes overgrowth	MAL-PDT/ALA-PDT, red light (630–660 nm), diode laser (1064 nm)	ALA-PDT: 36–50 J/cm², 18 min; 3–4 treatments (3-week intervals)	1A (high certainty)	Pretreat with antibiotics for severe inflammation; monitor for posttreatment erythema
Scar/PIH/PAE-predominant phenotype	Atrophic scars, postinflammatory hyperpigmentation/erythema	Fractional laser (Er:YAG/CO2), IPL (560–640 nm), FxPico laser	Fractional Er:YAG: 30–35 mJ/pulse, 70 µm beam; 3–5 treatments (4-week intervals)	1B (moderate certainty)	PIH-prone skin: prioritize IPL (lower downtime); scar revision may require combined therapies
Mixed phenotype (sebum + inflammation + scar)	Coexistence of above features	Sequential therapy: PDT → Fractional laser → IPL	PDT (3 treatments) → Fractional laser (2 treatments) → IPL (3 treatments); 2–4-week intervals between modalities	2A (low-moderate certainty)	Individualize sequence based on dominant phenotype; monitor skin barrier function

Conclusion and Outlook

Acne vulgaris is a multifactorial inflammatory skin disorder in which dysregulated sebum metabolism, immune activation, microbial imbalance, and impaired tissue repair collectively shape disease course and long-term outcomes. Within this context, photo-based therapies should be conceptualized as therapeutic strategies targeting specific pathological processes, rather than as interchangeable device-based interventions. The effective clinical application of photo-based strategies relies on appropriate alignment between therapeutic goals and disease phenotype. Strategies targeting sebaceous activity and inflammatory dysregulation primarily address active acne lesions, whereas strategies focused on tissue repair and remodeling are more relevant to acne sequelae. Importantly, the role of photo-based therapies is increasingly extending beyond standalone interventions toward integration within broader treatment frameworks.

Taken together, photo-based therapies should be regarded as phenotype-specific rather than interchangeable options within acne management. Future development of photo-based acne management is likely to emphasize personalized and precision-oriented approaches, in which treatment strategies and parameters are tailored according to individual biological characteristics and clinical presentation. In addition, optimization of combination and sequential treatment strategies, as well as the growing use of home-based and maintenance phototherapy, may further enhance long-term disease control while reducing treatment burden. Continued evaluation of long-term efficacy, safety, cost-effectiveness, and patient-reported outcomes will be essential to support evidence-based and patient-centered clinical decision-making.

Authors’ Contributions

X.R.: Writing—review and editing, writing—original draft, methodology, and investigation. L.G.: Methodology and investigation. Z.S.: Supervision, funding acquisition, conceptualization, methodology, and investigation.

Footnotes

Author Disclosure Statement

There are no potential conflicts of interest.

Funding Information

This work was supported by the Chongqing Medical Leading Talents Project (YXLJ202411).

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