Combined Fractional CO_₂ and Pulsed Dye Laser Therapy for Scar Treatment: A Systematic Review and Meta-analysis

Abstract

Background:

Pathological scars, particularly hypertrophic and keloid types, often pose significant cosmetic and functional challenges. Although fractional CO₂ lasers and pulsed dye lasers have individually shown promise in scar treatment, their combined efficacy remains underexplored.

Methods:

Following preferred reporting items for systematic reviews and meta-analyses guidelines and registered in PROSPERO (CRD42024619973), a comprehensive search across 6 databases identified studies involving patients treated with combined fractional CO₂ laser and pulsed dye laser for scars of various etiologies. Inclusion criteria focused on clinical outcomes such as scar thickness, vascularity, pliability, and pigmentation, assessed via validated tools such as the Vancouver Scar Scale, Patient and Observer Scar Assessment Scale, and Observer Scar Assessment Scale. Nine studies, involving a total of 247 patients, were included. Meta-analyses were performed using a random-effects model.

Results:

The combination therapy significantly improved scar appearance across multiple scales. The pooled mean differences were −18.09 for the Patient and Observer Scar Assessment Scale, −19.44 for the Observer Scar Assessment Scale, and −3.80 for the Vancouver Scar Scale, all of which were statistically significant (P < 0.0001). Improvements were consistent across pigmentation, vascularity, texture, and patient satisfaction, with minimal adverse effects reported. Heterogeneity was high, but it did not impact the direction of the findings.

Conclusions:

Combining fractional CO₂ and pulsed dye lasers offers superior outcomes in scar remodeling compared with monotherapy, improving both functional and aesthetic aspects with a favorable safety profile. Future studies should focus on standardizing treatment protocols and exploring long-term outcomes to optimize clinical use.

Takeaways

Question: Can combining fractional CO₂ laser and pulsed dye laser improve scar appearance more effectively than monotherapy?

Findings: This systematic review and meta-analysis included 9 studies (randomized controlled trials, prospective studies, and retrospective studies) involving 247 patients. It showed that combination therapy significantly improved scar characteristics—such as pigmentation, vascularity, pliability, and texture—based on Vancouver Scar Scale, Patient and Observer Scar Assessment Scale, and Observer Scar Assessment Scale scores, with high patient satisfaction and minimal adverse events.

Meaning: Dual-laser therapy using CO₂ and pulsed dye laser offers a safe and effective option for enhancing scar remodeling, outperforming monotherapy in both clinical and patient-reported outcomes.

INTRODUCTION

Scars are a common result of tissue injury, reflecting a complex wound-healing response.¹ Pathological scars, particularly hypertrophic scars (HTSs), occur in 32%–94% of burn and trauma cases and often cause significant morbidity.^2,3 Though not life-threatening, scars can lead to itching, pain, and contractures that impair mobility, while also affecting psychological well-being, body image, and self-esteem.^3–5

Pathological scarring arises from excessive collagen deposition, dysregulated healing cascades, and impaired tissue remodeling.⁶ Despite advances in management, optimizing both function and appearance remains difficult, especially in refractory cases.^7,8 Conventional treatments—pressure garments, silicone-based agents, medications, and surgical excision—often yield inconsistent outcomes, highlighting the need for more effective strategies.⁹

Laser technologies have shown promise in scar treatment, with fractional CO₂ lasers (FCLs) and pulsed dye lasers (PDLs) offering distinct benefits.¹⁰ FCL promotes collagen remodeling via controlled microthermal injury, improving texture and depth, whereas PDL targets vascular abnormalities, reducing erythema and hypervascularity for better cosmetic outcomes.^11,12

Although both modalities are effective individually for hypertrophic, atrophic, and postsurgical scars, their combined use remains underinvestigated. Given their complementary mechanisms, dual FCL–PDL therapy may provide synergistic benefits, especially for scars with both structural and vascular components.^12,13

However, few studies have systematically evaluated this approach. This review aimed to assess the clinical effectiveness of combined FCL and PDL therapy in scar management by synthesizing current evidence and identifying knowledge gaps. The findings may help shape future protocols and improve both functional and aesthetic outcomes in patients with complex scars.

METHODS

This systematic review was registered in PROSPERO (CRD42024619973) and followed preferred reporting items for systematic reviews and meta-analyses guidelines.^14,15 Studies were included if they (1) involved patients with scars of various causes; (2) used a combined fractional CO₂ and PDL treatment; (3) measured outcomes such as scar size, thickness, redness, and pliability; and (4) included a control group (eg, monotherapy, placebo, or no treatment). The exclusion criteria were (1) use of other laser combinations; (2) absence of a control group; (3) irrelevant populations/interventions or missing relevant outcomes; (4) unavailable full text; (5) non-English publications; (6) review articles, case reports, letters, editorials, or conference abstracts; and (7) animal or in vitro studies.

A comprehensive search was conducted across PubMed, CENTRAL, MEDLINE, ScienceDirect, Web of Science, and Google Scholar for studies published up to December 2024. The search combined keywords and MeSH terms, including “fractional CO2 laser,” “pulsed dye laser,” “scars,” and “combination treatment.” A total of 875 articles were identified and screened using Rayyan software.¹⁶ After removing 150 duplicates, 725 titles/abstracts were reviewed; 705 were excluded, and 20 full texts were assessed. Nine studies met the inclusion criteria; 4 qualified for meta-analysis (Fig. 1).^17–25

Fig. 1.

PRISMA flowchart of the included studies, demonstrating the selection of studies for inclusion in the present meta-analysis. PRISMA, preferred reporting items for systematic reviews and meta-analyses. “*” indicates the databases and registers from which records were identified, while “**” denotes records excluded during the screening stage.

Two authors (A.K.B., M.A.A.) independently extracted data using a standardized Excel-based form. Extracted variables included study characteristics (eg, author, year, country, journal, design, sample size, scar type), treatment details (eg, laser settings, number of sessions), outcomes (eg, scar improvement via validated scales such as the Vancouver Scar Scale [VSS] and visual analog scale), and reported adverse effects (eg, erythema, hyperpigmentation, hypopigmentation, scarring). Discrepancies were resolved by consensus or consulting the first author.

Scar outcomes were assessed using validated tools. The VSS evaluates vascularity, pigmentation, pliability, and height.²⁶ The Patient and Observer Scar Assessment Scale (POSAS) combines clinician and patient ratings of color, thickness, pliability, and symptoms such as pain and itchiness. The Observer Scar Assessment Scale (OSAS) is the clinician-only POSAS subscale.²⁷ The Global Assessment Score (GAS) provides an overall rating of improvement (0–4 scale).²⁸

Meta-analysis was performed in RStudio (v2024.09.1) using R (v4.4.2) and R Markdown (v2.29). Mean differences (MDs), standard errors, and 95% confidence intervals (CIs) were calculated to assess treatment effects. A DerSimonian–Laird random-effects model with inverse-variance weighting was used due to expected heterogeneity.

Heterogeneity was quantified using the I² statistic and interpreted according to Cochrane guidelines: 0%–40% (unimportant), 30%–60% (moderate), and 50%–90% (substantial). Leave-one-out sensitivity analyses were conducted using the “dmetar” package. Funnel plots were visually examined for publication bias.

Risk of bias was assessed independently by 2 authors (F.A.A., M.A.A.) using tools based on study design. For randomized controlled trials (RCTs), the Cochrane Risk of Bias Tool evaluated sequence generation, allocation concealment, blinding, incomplete data, selective reporting, and other bias domains as shown in Table 1.²⁹ For nonrandomized studies, the Newcastle-Ottawa Scale was used, scoring selection (4 points), comparability (2 points), and outcome (3 points), for a total of 9 points. Studies scoring 7–9 were low risk; 5–6, moderate; and less than 5, high risk, as shown in Table 2.³⁰

Table 1.

RoB Assessment for Included RCTs Using the RoB 2 Tool

Study ID	Bias Arising From the Randomization Process	Bias Due to Deviations From Intended Interventions	Bias Due to Missing Outcome Data	Bias in Measurement of the Outcome	Bias in Selection of the Reported Result	Overall RoB
Kivi et al, 202417	Low risk	Some concerns	Low risk	Some concerns	Low risk	Low risk
Cooper et al19	Some concerns	Low risk	Low risk	Some concerns	Low risk	Some concerns
Safra et al21	Moderate risk	High risk	High risk	Low risk	Moderate risk	High risk (to be repeated)
Ouyang et al22	Unclear	Low risk	Low risk	Low risk	Low risk	Low risk
Naeini et al23	Unclear	Low risk	High risk	Unclear risk	Low risk	Low risk

RoB, risk of bias.

Table 2.

Risk of Bias Assessment for Retrospective and Prospective Studies Using the Newcastle-Ottawa Scale

Study ID	Selection				Comparability	Outcome			Quality Score	Risk of Bias (7–9: Low; 5–6: Moderate; 0–4: High)
	Q1	Q2	Q3	Q4	Q5	Q6	Q7	Q8
Liu et al18	1 point	0 points	1 point	1 point	0 points	1 point	1 point	1 point	6 points	Moderate
Matuszczak et al20	1 point	0 points	1 point	1 point	0 points	1 point	1 point	1 point	6 points	Moderate
Bonan et al24	1 point	0 points	1 point	1 point	1 point	1 point	1 point	0 points	6 points	Moderate
Alster et al25	1 point	1 point	1 point	1 point	1 point	1 point	1 point	1 point	8 points	Low

Selection: Q1. Representativeness of the exposure cohort? Q2. Selection of the nonexposure cohort? Q3. Ascertainment of exposure? Q4. Demonstration that the outcome of interest was not present at the start of the study? Comparability: Q5. Comparability of cohort on the basis of the design or analysis? Outcome: Q6. Assessment of outcome? Q7. Was follow-up long enough for outcomes to occur? Q8. Adequacy of follow-up of cohorts?

RESULTS

Search Results and Study Selection

The initial search yielded 875 results. After screening titles, abstracts, and full texts, 9 studies were included in the systematic review, and 4 were eligible for meta-analysis (Fig. 1).^17–25

Risk of Bias

Risk of bias ranged from low to high across the included studies. Among RCTs, Kivi et al¹⁷ and Cooper et al¹⁹ showed low risk, indicating sound methodology. In contrast, Safra et al²¹ had moderate to high risk, mainly due to unclear randomization procedures, although outcome measurement remained at low risk, using validated tools and blinded assessors. Ouyang et al²² and Naeini et al²³ showed variable risk of bias due to inconsistent randomization and intervention execution, as shown in Table 1.

For prospective studies by Matuszczak et al,²⁰ Bonan et al,²⁴ and Alster et al,²⁵ risk of bias was not clearly addressed but seemed mixed, requiring cautious interpretation. The retrospective study by Liu et al¹⁸ added to overall risk concerns due to the inherent limitations of observational designs, as shown in Table 2.

Studies Characteristics

The 9 studies included 247 patients aged 1–67 years. Male patients comprised 101 (54.89%), as shown in Table 3. Studies originated from the United States, China, Poland, Italy, Egypt, Iran, and Israel, with the United States and China contributing 2 each. Fitzpatrick skin types II–IV were most common. Most studies used combined fractional CO₂ and PDL therapy, with control groups receiving monotherapy or other interventions. Some demographic or treatment details were unreported.

Table 3.

Characteristics of Included Studies and Patients

First Authors, Year	Country	Study Design	Groups		No. Patients	Demographic
			Intervention Group	Control Group		Age	Sex	Skin Type
Kivi, 202417	Iran	RCT	NR	NR	20	11–63 y (23.35 ± 4.59 y)	Male: 4; female: 16	NR
Liu, 202318	China	Retrospective	NR	NR	60	≤14 y (2.95 ± 1.50 y)	Male: 38; female: 22	NR
Cooper, 202219	United States	RCT	NR	NR	25	18–65 y (29 y)	Male: 19; female: 6	NR
Matuszczak, 202120	Poland	Prospective study	25	0	25	22 mo to 17 y (6.40 ± 1.72)	NR	Skin phototype III
Safra, 201921	Israel	RCT	18 (treatment of half of the scar)	18 (treatment of half of the scar)	18	34–67 y (51 ± 11.3 y)	NR	Type II: 10 (55.6%); type III: 6 (33.3%); type IV: 1 (5.6%)
Ouyang, 201822	China	RCT	28	28	56	3–51 y (NR)	Male: 35; female: 21	NR
Naeini, 201423	Iran	RCT	3 (treatment of part of the lesions)	3 (treatment of part of the lesions)	3	NR (31.2 ± 11.5)	Male: 0; female: 3	Fitzpatrick skin types III–IV
Bonan, 201324	Cairo	Cohort study	20	0	20	NR	NR	Fitzpatrick types II and III
Alster, 199825	United States	Prospective study	20 (treatment of half of the scar)	20 (treatment of half of the scar)	20	16–55 y (37 y)	Male: 5; female: 15	Skin phototypes I and II

NR, not reported by the study authors.

Scar Characteristics

Scar characteristics varied across studies, including type, etiology, size, number, maturity, color, and location, as provided in Supplemental Digital Content 1. (See table, Supplemental Digital Content 1, which displays the scar characteristics, https://links.lww.com/PRSGO/E653.) Kivi et al¹⁷ reported hypertrophic and keloid scars from fire and gas injuries, mostly on limbs. Liu et al¹⁸ observed HTSs from burns and scalds, averaging 107.53 cm², mainly on the face and neck. Bonan et al²⁴ distinguished keloids by greater variability in maturity, whereas Matuszczak et al²⁰ emphasized the presence of red and purple scar hues. These findings highlight the heterogeneity of scars by cause, location, and demographics.

Interventional Methods Used

Across the included studies, protocols for fractional CO₂ and PDL varied widely in session number (single versus multisession) and spacing (weeks to months), as well as in pass count, dwell/pulse duration, density/fluence, and spacing/spot size, as shown in Table 4. For FCL, regimens ranged from conservative single-pass resurfacing to staged protocols using higher settings, longer dwell times, and broader coverage. For PDL, programs spanned from one-off treatments using modest parameters to serial sessions with longer pulses, higher fluences, and larger spot sizes delivered at regular intervals. Overall, parameter selection was tailored to scar characteristics and tolerance, yielding heterogeneous but broadly comparable approaches to scar optimization.^{17,18,21,24,25}

Table 4.

Interventional Methods Used

Study	PDL Parameters	Fractional CO2 Laser Parameters	Treatment Protocols and Follow-up
Kivi et al17	595 nm, 6.5 J/cm², 0.5-ms duration, 7-mm spot size	10,600 nm, 12 J/cm², stack of 2, 800-ms dwell, 900-mm² space	Up to 3 sessions, 40 d apart
Liu et al18	595 nm, 6.0–12.0 J/cm², 7-mm diameter, 1.5- to 3.0-ms pulse widths	10,600 nm, 30.0–50.0 mJ, 300 Hz, 5% density	PDL monthly for 4 mo; CO2 every 3 mo
Cooper et al19	0.45 ms, 5.25 J/s	300 Hz, 15 mJ, 15% density	3 episodes of treatment, 4–6 wk apart, follow-up more than 3–6 mo
Matuszczak et al20	595 nm, 6.86 J/cm2 (SD, 1.10; range: 5–10 J/cm2)	10,600 nm AFCL; mean energy: 75.12 mJ (SD, 1.88; range: 54–80 mJ)	4 treatment sessions at 68-wk intervals
Safra et al21	7-mm spot size, 0.45—ms pulse, 4–6 mJ/cm²	10,600 nm, 12.5–17.5 mJ, 5% density	3 sessions, 1-mo intervals
Ouyang et al22	1.5–3 ms, 7–15 J/cm2, 7-mm spot size	595 nm; energy: 30–50 mJ; frequency: 300 Hz; density 5%; scan shape and spot size were determined by the shape and the area of the scar	1–3 mo
Naeini et al23	585 nm, 5–7 J/cm2, duration of 0.5 ms, 7–mm spot size	10,600 nm, CO2 tube; output energy: 140 mJ; duration: 20–9540 μ	2–3 sessions 2/3 wk apart; follow-up every other week for 2 mo
Bonan et al24	595 nm, 6.0–6.5 J/cm², 10-mm spot size, 0.5-ms duration	10,600 nm, 15 Ws/session, 500-μm spacing, 0.7- to 1-ms dwell	4 PDL sessions (4–6 wk apart), 2 CO2 sessions
Alster et al25	585 nm, 6.5 J/cm², confluent nonoverlapping spots	3-mm spot, 500-mJ energy, 7-W power, 2 passes	Single session; follow-up at 1, 2, 6, and 12 wk

AFCL, Ablative Fractional CO₂ Laser.

Interventional Outcomes

The combined use of fractional CO₂ and PDL demonstrated notable effectiveness in improving scar characteristics, as evidenced by multiple validated assessment tools. The VSS revealed significant improvements in appearance, with Kivi et al¹⁷ reporting a 25.55% ± 14.59% reduction, whereas Bonan et al²⁴ observed a decrease in VSS scores from 7.13 ± 0.99 to 1.63 ± 0.74 during 6 months. Similarly, the POSAS reflected positive outcomes; Liu et al¹⁸ documented a significant drop in observer scores from 39.62 ± 1.17 to 11.73 ± 0.84 (P < 0.001), and Safra et al²¹ reported a reduction from 19.10 ± 3.47 to 8.11 ± 1.75. Alster et al²⁵ further supported these findings through GAS, demonstrating an improvement from 1.0 in the first week to 3.2 by week 12 (P < 0.001).

In addition to these primary outcomes, several studies reported improvements in pigmentation, vascularity, and pliability. Patient satisfaction was consistently high across studies, with Liu et al¹⁸ noting a satisfaction rate of 96.67%, reflecting both cosmetic and functional enhancements. Adverse events were minimal and transient, including erythema, purpura, irritation, pruritus, scabbing, blistering, crusting, and postinflammatory hyperpigmentation. Most resolved spontaneously within days, whereas pigmentary changes were managed with topical treatments such as hydroquinone. Importantly, no severe or long-term complications were reported, confirming the favorable safety and tolerability of the combined laser therapy, as shown in Table 5.

Table 5.

Interventional Outcomes

Study	Primary Outcome Measures	Assessment Tools and Results	Adverse Events
Kivi et al17	Improved VSS score (25.55% ± 14.59%); better results in immature scars	VSS, patient satisfaction	None reported
Liu et al18	POSAS scores improved significantly (observer: 39.62–11.73)	POSAS; parent satisfaction rate 96.67%	Rash, pigment deposition, blister (all resolved with treatment)
Cooper et al19	Improved POSAS scores (except in hypertrophic burn did not show a significant decrease)	POSAS	None reported
Matuszczak et al20	Improved VSS scores (9.20–4.04, P = 0.000), and POSAS scores (28.83–14.26, P = 0.000)	VSS and POSAS	None reported
Safra et al21	Improved OSAS scores (19.10–8.11, treated versus untreated areas)	OSAS, PSAS	Local irritation, erythema, purpura (all resolved spontaneously)
Ouyang et al22	Improved VSS scores (total VSS 3.50 ± 1.48)	VSS	None reported
Naeini et al23	Improved mean surface area (P = 0.03), the dermatologist-assessed improvement score was 6.68 ± 0.77	Dermatologist-assessed improvement score, and mean surface area before and after treatment modalities	Postinflammatory hyperpigmentation
Bonan et al24	Significant improvement in modified VSS scores (7.13–1.63)	Modified VSS, cutaneous multispectral analyzer	Erythema and scabbing (resolved within 1 wk)
Alster et al25	Significant GAS improvement (1.0–3.2, P < 0.001)	GAS; erythema reduction	Posttreatment purpura and crusting

Meta-analysis

Due to substantial heterogeneity, all meta-analyses used a DerSimonian–Laird random-effects model. I² ranged from 90% to 99.8%, driven by differences in populations, scar types, protocols, and follow-up. Leave-one-out tests did not resolve heterogeneity. Although pooled results favored combination therapy, findings require cautious interpretation.

POSAS Change

The pooled analysis revealed a statistically significant MD in POSAS scores following combined fractional CO₂ and PDL treatment, with a reduction of –18.09 (95% CI, –35.07 to –1.11; P < 0.0001), as shown in (Fig. 2). Sensitivity analysis revealed substantial heterogeneity among the included studies (I² = 99.8%). A leave-one-out test excluding Liu et al¹⁸ reduced heterogeneity slightly (I² = 97%), but it did not resolve the issue (Fig. 3). The funnel plot for POSAS change is presented in Figure 4.

Fig. 2.

Forest plot of the POSAS outcome, showing the pooled analysis and illustrating the MD in POSAS scores following combined fractional CO₂ and PDL treatment.

Fig. 3.

Sensitivity test of the POSAS outcome, presenting heterogeneity among the included studies.

Fig. 4.

Funnel plot of the POSAS outcome, demonstrating publication bias among the included studies.

OSAS Change

The pooled MD in OSAS scores was –19.44 (95% CI, –36.05 to –2.83; P < 0.0001), indicating significant improvement posttreatment (Fig. 5). Substantial heterogeneity was noted (I² = 99.7%). The funnel plot for the change in OSAS is shown in Figure 6.

Fig. 5.

Forest plot of the OSAS change outcome, showing the pooled analysis and illustrating the MD in OSAS of posttreatment status after CO₂ and PDL procedures.

Fig. 6.

Funnel plot of the OSAS change outcome, demonstrating publication bias among the included studies.

VSS Change

The pooled analysis demonstrated a significant reduction in VSS scores, with an MD of –3.80 (95% CI, –6.57 to –1.03; P < 0.0001), as shown in Figure 7. Heterogeneity among the included studies was high (I² = 99.0%). A leave-one-out sensitivity analysis excluding Bonan et al²⁴ reduced heterogeneity to an I² of 90% but did not eliminate it (Fig. 8). The funnel plot for VSS change is presented in Figure 9.

Fig. 7.

Forest plot of the VSS change outcome, showing the pooled analysis and illustrating the MD in OSAS of posttreatment scar appearance after CO₂ and PDL procedures.

Fig. 8.

Sensitivity test of the VSS change outcome, presenting heterogeneity among the included studies.

Fig. 9.

Funnel plot of the VSS change outcome, demonstrating publication bias among the included studies.

DISCUSSION

This systematic review and meta-analysis provides strong evidence supporting the efficacy of combining fractional CO₂ and PDL for scar treatment. Pooled data revealed significant improvements across validated assessment tools, with mean reductions of –18.09 in POSAS, –19.44 in OSAS, and –3.80 in VSS scores (all P < 0.0001). These findings highlight the synergistic effects of dual-laser therapy, which addresses both vascular and structural components of scars. FCLs induce dermal remodeling via controlled microthermal injury, whereas PDL selectively targets the vascularity of erythematous scars. Together, they promote scar maturation and yield superior outcomes compared with monotherapy.^31–33

A review of the included studies suggests that scar subtype impacts the response to combination therapy. Most of the studies focused on patients with HTSs,^18,22,25 and 1 trial on immature HTSs yielded the best results, suggesting that treating earlier may be beneficial.¹⁸ Two studies examined both HTSs and keloids, reporting that most of the improvement was observed in immature scars.^17,24 Overall, HTSs, particularly immature scars, seem to have greater success with combination therapy. However, because relatively few studies stratified outcomes by scar subtype, further research is needed to confirm these trends and to establish more personalized treatment recommendations in clinical practice.

Multiple studies within this review reinforce these results. Kivi et al¹⁷ and Bonan et al²⁴ reported significant VSS reductions, whereas Liu et al¹⁸ and Safra et al²¹ showed marked improvements in POSAS scores. Alster et al²⁵ documented enhanced GAS, and Liu et al¹⁸ reported a 96.67% patient satisfaction rate, reflecting both clinical efficacy and real-world acceptability. Compared with previous analyses, such as that by Tian et al,³³ our study offers a broader dataset (9 studies, 247 patients versus 7 studies, 189 patients), additional outcome measures (including OSAS), and deeper stratification by scar type, anatomical site, and treatment protocol. Moreover, we evaluated histological changes and patient-reported tolerability—dimensions not captured in the work by Tian et al³³—making this study a more comprehensive contribution to the literature.

Although standalone therapies with fractional CO₂ or PDL lasers have been shown to be effective, the combined approach seems to provide enhanced and more consistent results. For example, Radmanesh et al³⁴ found similar outcomes with monotherapy, but our findings suggest superior results with dual-laser therapy, especially in early-stage scars.³⁴ Supporting the biological plausibility of this approach, Chen et al³⁵ demonstrated that combination therapy reduces fibroblast density and improves collagen alignment, with these histological benefits being most pronounced in immature scars—suggesting an optimal intervention window.

The high statistical heterogeneity observed across all meta-analyses (I² ≥ 90%) indicates considerable variability among included studies, likely due to differences in scar types, laser parameters, session intervals, patient age, skin type, or follow-up duration. Leave-one-out sensitivity analyses did not resolve this variability. Additionally, asymmetry in funnel plots (Figs. 4, 6, 9) suggests the possibility of publication bias, potentially arising from the underreporting of smaller or negative studies. Taken together, these factors limit the generalizability of the findings and underscore the need for standardized protocols, consistent outcome reporting, and cautious interpretation of pooled data. Future subgroup analyses stratified by scar type or treatment parameters could help clarify these differences and provide more precise estimates of treatment effects.

Publication bias is another important consideration in interpreting our findings. Although funnel plots were generated, their interpretability is limited due to the small number of studies included in each meta-analysis. Visual asymmetry was observed, suggesting that smaller studies with null or negative results may be underrepresented in the literature. This selective publication of positive findings can exaggerate the pooled treatment effect and limit the generalizability of our conclusions. Furthermore, the predominance of single-center studies from limited geographic regions may increase the risk of reporting bias. Although we attempted to mitigate this by conducting a comprehensive multidatabase search, the possibility of unpublished or non-English negative-outcome studies remains. Future research should prioritize trial registration, transparent reporting of both positive and negative outcomes, and the inclusion of multicenter datasets to reduce the impact of publication bias on evidence synthesis.

Another key limitation of this meta-analysis is the lack of protocol standardization among included studies. Marked variability was observed in laser parameters, session intervals, and patient- or scar-related factors, which complicates direct comparison and limits reproducibility. Nonetheless, consistent patterns emerged that may guide future standardization: FCLs showed optimal results with multiple sessions spaced 4–8 weeks apart and higher energy for thicker scars, whereas conservative protocols were preferred in darker skin types. PDLs were typically adjusted to vascularity, and combined CO₂–PDL therapy yielded the most favorable outcomes when tailored to scar subtype. These findings underscore the need for international consensus and standardized frameworks defining core treatment parameters while allowing individualized adjustments.

Despite including 9 studies, the overall sample size remains modest, potentially limiting generalizability across age groups, Fitzpatrick skin types, and scar etiologies. Larger, multicenter studies with diverse populations are needed to enhance statistical power and external validity. Another variable among studies is treatment timing. Some support early intervention (<6 mo), whereas others show benefits even in mature scars, suggesting that future trials should incorporate better stratification and patient-specific planning.³⁶ Additionally, although effective in Fitzpatrick types II–IV, postinflammatory hyperpigmentation remains a concern in darker skin tones. Tailored laser settings and diligent aftercare are essential to minimize these effects.³⁷

Another important limitation is that not all included studies directly compared dual therapy with monotherapy, which limits the strength of comparative conclusions. Most trials also reported only short-term outcomes, providing limited insight into the durability of results, recurrence, or late adverse effects. Future RCTs should directly assess CO₂–PDL combination therapy against each monotherapy arm, with extended follow-up to evaluate long-term efficacy and safety. Additionally, emerging evidence suggests potential benefits of combined laser therapy in other scar types—such as postsurgical and acne scars—due to shared vascular and fibrotic features, warranting targeted investigation in these subgroups.

In summary, this review supports a multimodal, patient-centered approach to scar management. By targeting both vascularity and structure, fractional CO₂ combined with PDL therapy enhances functional and aesthetic outcomes. Its favorable safety profile—with mostly mild, self-limited adverse events—further supports its clinical utility. This dual-laser strategy represents a promising advancement in evidence-based scar treatment and deserves further exploration in well-designed, large-scale clinical trials.

CONCLUSIONS

This meta-analysis confirms the clinical efficacy of combining fractional CO₂ and PDLs for treating hypertrophic and keloid scars. The dual-laser approach significantly improved POSAS, OSAS, and VSS scores, with minimal adverse effects and high patient satisfaction. By addressing both dermal remodeling and vascular components, this therapy provides comprehensive improvement across multiple scar dimensions.

Despite variations in protocols and populations, the consistent outcomes support its role as a preferred modality. Future research should aim to standardize laser parameters, optimize treatment schedules, and evaluate long-term efficacy in diverse populations. Preliminary evidence also indicates potential benefits in other scar types, such as postsurgical and acne scars, warranting further targeted trials. Incorporating additional modalities, such as erbium-doped yttrium aluminum garnet lasers or adjunctive therapies, may enhance outcomes further.³⁸ Until more data are available, current evidence strongly supports adopting combination laser therapy as an effective, integrative approach to scar management.

DISCLOSURE

The authors have no financial interest to declare in relation to the content of this article.