CO₂ laser treatment for scars after cleft lip surgery: a systematic review and meta-analysis

Abstract

Background

Current studies are controversial on the optimal treatment of postoperative scar treatment by cleft lip. Our objective is to elucidate the therapeutic effect of CO₂ laser on postoperative cleft lip scar treatment.

Methods

A systematic review was performed and reported according to Preferred Reporting Items for Systematic Reviews and Meta-Analyses. We searched five electronic databases (EMBASE, PubMed, Web of Science, Cochrane Library and CNKI, from their inceptions until August 8, 2023) and independently assessed the methodological quality and bias risk of the included studies by two investigators using the Cochrane Handbook for Systematic Reviews. Quality assessment of the certainty of evidence was performed based on the Grading of Recommendations Assessment, Development, and Evaluation guidelines. Weighted mean difference of Vancouver Scar Scale were calculated to conduct meta-analysis by Stata statistical software version 14. We also estimated the pool sensitivity as well as testing the possibility of publication bias.

Results

Five studies were included in this meta-analysis involving 255 subjects. Meta-analysis showed that compared with the control group, CO₂ laser was more effective in treating post-cleft lip scars (WMD = 4.39, 95%CI = 0.54–8.23; Five studies with 255 participants; Low evidentiary certainty, I² = 99.4%).

Conclusions

Patients treated with CO₂ laser therapy for postoperative cleft lip scar treatment tend to have a significant therapeutic effect especially in the early stages.

Trial registration

identifier CRD42023397042 (18/02/2023) [https://www.crd.york.ac.uk/prospero/].

Supplementary Information

The online version contains supplementary material available at 10.1186/s12903-024-05205-6.

Background

Cleft lip and/or palate, as one of the most common congenital deformities affecting the oral-facial area, has been widely concerned in the world [1, 2]. There are two forms of cleft lip and/or palate, syndromic and non-syndromic Cleft lip and/or palate [3], both of which are multifactorial in most cases [4]. According to a meta-analysis published in 2022, the prevalence of cleft lip in every 1000 live births was 0.3 (95% CI: 0.26–0.34) [4]. Although these structural abnormalities can lead to a variety of adverse consequences which may persist into adulthood, including impaired speech, appearance problems, poor mental health and exorbitant economic costs [5–7], they still can be surgically repaired in areas where care is available [6]. Timely and accurate surgical treatment including plastic surgery and oral-maxillofacial surgery [8] as well as special postoperative care is of great significance for children with cleft lip and/or palate [9]. Regrettably, the mechanical tension caused by inevitable facial muscle movements (such as crying and sucking) has an adverse effect on postoperative wound healing, leading to enlarged scars and long-term development that can affect the patients’ physical and mental health [10, 11].

So far, great progress has been made in the treatment of scar after cleft lip surgery. However, these methods all have their limitations [12–14]. The effectiveness of pressure garments and scar massage is largely influenced by patient compliance [15]. Limited tissue availability, possibility of malformation recurrence, difficulty in predicting absorption degree, and risk of infection are the drawbacks of secondary surgery [16]. Drug injection may lead to drug diffusion to adjacent tissues and have no additional benefits in terms of scar pigmentation, vascularity, pliability, or height [17, 18]. Silicone therapy has shown side effects including rash and skin rupture, and there are safety hazards of foreign body ingestion or inhalation [19]. Autologous fat transplantation inevitably involves fat absorption and may require secondary surgery, especially in adults [20]. Apart from that, postoperative scar treatment for cleft lip always requires a multimodal approach to achieve good results [21]. In a word, we need to summarize and explore the effects of more treatment methods for better clinical application.

At present, laser use has become part of the gold standard of treatment as an effective adjuvant in multimodal therapy for pathologic scarring caused by surgery [22]. Among them, CO₂ laser resurfacing technology has been the primary treatment for facial scars since it was introduced in the mid-1990s [23, 24]. Since 2018, multiple clinical studies on CO₂ laser treatment of postoperative scars on cleft lip have been published, most of which believe that it is safe and effective, and will bring high patient satisfaction. Especially, the improvement in flexibility is more evident [11, 21, 25–27]. The CO₂ laser causes skin damage by removing variable parts of the epidermal layer and dermis and associated residual heating [28, 29], making the scars after wound healing blurry and closer to the color and texture of the surrounding normal skin [26]. Epithelial lesions can occur 24 h after treatment, which can reduce the probability of complications and shorten the recovery time [30]. It is relatively safe and effective, and has less damage to the skin [31]. However, the real objective and subjective benefits of CO₂ laser treatment of cleft lip scar are still not supported by sufficient data. Therefore, we conducted this meta-analysis to evaluate the efficacy of CO₂ laser treatment for postoperative cleft lip scar.

Methods

Protocol and registration

This systematic review was conducted according to the Meta-analysis of Observational Studies in Epidemiology guidelines [32] and the Preferred Reporting Items for Systematic Reviews and Meta-Analyses standard (PRISMA) [33]. After the initial screening stage, it was registered in PROSPERO (CRD42023397042) [https://www.crd.york.ac.uk/prospero/] and we raised our research question of this meta-analysis: Is CO₂ laser therapy effective in the management of cleft lip scar?

Eligibility criteria

PICOS model was used to set the inclusion and exclusion criteria:

1. P (patient/ participants): subjects with cleft lip who have undergone cleft lip surgery with good general condition and no infection in scar area. Subjects with a history of keloid scars and laser therapy before the study were excluded;

2. I (intervention/exposure): CO₂ laser therapy;

3. C (comparison/control): Conventional therapy or no therapy;

4. O (outcome): Scar treatment index (Vancouver Scar Scale (VSS));

5. S (study design): Randomized controlled trial (RCT).

Information sources and search strategy

We searched five electronic databases (PubMed, EMBASE, Web of Science, Cochrane Library and CNKI) from their inceptions until August 8, 2023 to investigate the therapeutic effect of CO₂ laser on postoperative scar of cleft lip. We identified all related datasets and search for articles more comprehensively and our search strategies were shown in Supplemental Table 1.

Study selection and data collection

All retrieved studies were assessed by two reviewers independently (XP and HC) based on inclusion/exclusion criteria. When the titles and abstracts might meet the inclusion criteria, the full texts were analyzed for further evaluation. Any differences between the two reviewers (XP and HC) were resolved through consensus, otherwise a third reviewer (ZZ) would be required to participate.

After identifying the studies which met the criteria, we extracted the following information: (1) study characteristics (author/s, year of publication, country, characteristics of participants); (2) types of laser therapy; (3) time of intervention; (4) outcome indicator; (5) follow-up time; (6) type of cleft and so on.

Risk of bias and applicability assessment

The standard form score (VSS) was used to extract outcome data from eligible studies in duplicate. The methodological qualities and bias risk of the included studies were independently assessed by two investigators according to Cochrane Handbook for Systematic Reviews (http://www.cochranelibrary.com/). The results can be used for reference in the quality of evidence grading. Apart from that, the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines were used for rating the quality of evidence [34]. The degree of the evidence certainty is high, moderate, low or very low. RCT studies are downgraded according to the following pre-specified criteria: risk of bias, inconsistency, indirectness, imprecision and other considerations [34]. Two reviewers (XP and ZY) independently perform these two tasks, otherwise a third reviewer (ZZ) would be required to participate.

Data synthesis

The Stata statistical software version 14 was used to assess the weighted mean difference (WMD) and corresponding 95% CIs across the studies for systematic review and meta-analysis intuitively to generate forest plots. A random-effects model was used considering the heterogeneity among the included studies. Cochran’s Q test was used to assess the heterogeneity of included studies. If the p-value was lower than 0.1, the I² statistic was used to quantify the statistical heterogeneity. Respectively, values ≤ 50% and ≥ 50% were classified as less and substantial heterogeneity [35]. Sensitivity analyses were carried to evaluate the robustness of meta-analysis conclusions. The Egger’s test was also used to test the possibility of publication bias. P-values were two-sided, and the significance level was set at 0.05.

Results

Literature search and study characteristics

An electronic search identified 166 articles in PubMed, EMBASE, Web of Science, Cochrane Library and CNKI. After that, the titles and abstracts of all the articles were reviewed and led to 14 articles waiting for further evaluation. Finally, only 5 articles were selected according to the inclusion criteria after the process of full text evaluation of these 14 articles, which means there are 255 participants included in our meta-analysis (Fig. 1).

Fig. 1.

Flow diagram of study selection

A total of 5 studies have explored the efficacy of CO₂ laser in the treatment of postoperative scar of cleft lip, and their specific characteristics are shown in Table 1. The studies were mainly conducted in China and Egypt, all of which were randomized controlled trials (RCTs). There were 178 laser treated scars and 120 untreated/placebo treated scars. In this meta-analysis, scar width, VSS and visual analog scale (VAS) were the main influencing factors. 5 reported VSS scores, 2 reported VAS scores, 1 reported scar width. Except for VSS, there is too little research on other outcome variables to conduct meta-analysis. Three studies used fractional CO₂ laser as the experimental group, while 2 studies used lattice CO₂ laser combined with other lasers to treat scars. The protocol of laser treatment for postoperative scar of cleft lip were shown in Supplemental Table 2. After that, we evaluated the quality of 5 studies in Table 2. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) guidelines assessment is shown in Supplemental Table 3.

Table 1.

Characteristics of the included studies

Source	Chi et al. 2023 [11]	Hao et al. 2022 [25]	Shadad et al. 2021 [21]	Li et ql. 2019 [26]	Aida et al. 2018 [27]
Country	China	China	Egypt	China	Egypt
Age, years	-	10–26 years	-	3 months- 8 years	15–20 years
Sex (Male/Female)	-	6/31	-	31/19	3/3
Participant (Study/Control)	30/12	37	80/40	25/25	6
Laser	CO2 fractional laser	CO2 fractional laser and pulsed laser	CO2 fractional laser	Lattice CO2 laser and intense pulsed light	CO2 fractional laser
Time of intervention	1/3/6 months after the operation	Several years after the operation	3 weeks after the operation; 3 months after the operation	2 weeks after the operation	1 month after operation
Outcome indicator	VSS	VSS	VSS/VAS/ width	VSS	VSS/VAS
Follow-up Time	6 months	6 ~ 12 months	6 months	12 months	6 months
Type of cleft (study)/(control)	postsurgical scarring after second cleft lip treatment	Unilateral/ bilateral	-	Bilateral/Unilateral/ Complete/ Incomplete	Unilateral/ bilateral
Cleft palate and/or cleft alveolar	Unspecified	Unspecified	Unspecified	Unspecified	Unspecified

VSS: Vancouver Scar Scale; VAS: Visual Analog Scale

Table 2.

Assessment of Study Quality

Source	Adequate Sequence Generation	Allocation Concealment	Blinding	Incomplete Outcome Data Addressed	Free of Selective Reporting	Free of Other Bias	Description of Other Bias
Chi et al. 2023 [11]	Unclear	Yes	Yes	Yes	Yes	Yes	-
Hao et al. 2022 [25]	Unclear	Unclear	Yes	Yes	Yes	Yes	-
Shadad et al. 2021 [21]	Unclear	Unclear	Yes	Yes	Yes	Yes	-
Li et ql. 2019 [52]	Unclear	Unclear	Yes	Yes	Yes	Yes	-
Aida et al. 2018 [53]	Unclear	Unclear	Yes	Yes	Yes	Yes	-

Scar assessment

In the meta-analysis of these 5 studies, the random effects model was selected due to the significant heterogeneity. The results of meta-analysis showed that compared with the control group, CO₂ laser therapy had a more positive therapeutic effect on postoperative scar of cleft lip (WMD = 4.39, 95%CI = 0.54–8.23; Five studies with 255 participants; Low evidentiary certainty, I² = 99.4%) (Fig. 2). The heterogeneity was high but due to the small number of studies included and the small sample size, we were not able to conduct subgroup analyses to determine the sources of heterogeneity and further evaluate these studies.

Fig. 2.

Forest plot for the effect of laser therapy on postoperative scar of cleft lip. WMD, weighted mean difference. CI, confidence interval

Shadad et al. also evaluated the scar width and found that the scar width after laser treatment was 2.84 ± 0.68, compared to the control group of 3.27 ± 0.48, indicating a significantly lower evaluation of scar width [21]. However, due to the fact that the other four studies did not use scar width as an indicator for evaluation, meta-analysis could not be conducted. In addition, a significant improvement in lip scars can be observed through VAS. The score after laser treatment was significantly higher (40.35 ± 5.51) compared to anti scar cream (30.40 ± 5.22) [21].

As for the timing of treatment, 3 studies tend to treat scar at the early stage [11, 21, 27]. Chi et al. found that during the follow-up period, VSS scores initiated with CO₂ laser therapy 1 month postoperatively (1.8 ± 0.6) were significantly lower than those at 3 months (3.3 ± 1.0) and 6 months (4.4 ± 0.9) postoperatively [11]. Shadad et al. reached the similar conclusion by dividing the treatment group into two groups: laser treatment starting at 3 weeks postoperatively and 3 months postoperatively. The results showed that patients who started treatment at 3 weeks postoperatively had significantly lower VSS scores (1.92 ± 0.88) than those started treatment at 3 months postoperatively (3.70 ± 1.11) [21].

In short, there is scar thickening accompanied by redness and itching after cleft lip surgery, which has been immediately tightened after laser treatment in dark red on the surface, with uniform punctate white to yellowish skin gasification. Perhaps during the treatment process, some patients may feel uncomfortable due to burning or pain, but the appearance of the scar after treatment has been greatly improved with reduced volume and thickness, and the scar becoming softer and flatter.

Sensitivity analysis and publication bias

Due to the high risk of bias in some included articles, we used sensitivity analysis to evaluate the robustness of the meta-analysis results. We attempted to remove each study to test the stability of our findings and the sensitivity analysis result showed no significant change in the combined results of heterogeneity, indicating that our results were statistically reliable (Fig. 3).

Fig. 3.

Sensitivity analysis to evaluate the robustness of the meta-analysis results. CI: confidence interval

Use Egger test to analyze potential publication bias. There was no significant publication bias observed in the WMD of VSS between the experimental group and the control group(p = 0.933) (Fig. 4).

Fig. 4.

Egger’s funnel plot analysis to detect publication bias for the effect of laser therapy on postoperative scar of cleft lip. WMD, weighted mean difference

Discussion

General interpretation of main results

In this meta-analysis and systematic review of the efficacy of CO₂ laser treatment for postoperative cleft lip scars, we included 5 articles with 255 participants meeting the inclusion criteria. The results show that laser therapy has a good effect and benefit on the postoperative scar of cleft lip (WMD = 4.39, 95%CI = 0.54–8.23; Five studies with 255 participants; Low evidentiary certainty, I² = 99.4%).

Strengths and limitations of the review

There are several strengths in Our meta-analysis. First, we searched all relevant databases as thoroughly as possible to include more studies which met the criteria. Second, we performed GRADE evidence quality grading to reflect the accuracy of the effect estimates. Therefore, our analysis could well reflect the experiment effect and illustrate the clinical guiding significance of the indicator.

There are also limitations in our study. First, despite conducting the risk of bias assessment, the study reports unclear information regarding sequence generation and allocation concealment in the included studies. This lack of clarity may impact the overall quality of the evidence. Second, the results had relatively high statistical heterogeneity (I² = 99.4%) across the studies and the GRADE evidence quality is relatively low (Low evidentiary certainty). In addition, due to the small number of studies included and the small sample size, we were not able to draw conclusive results or conduct subgroup analyses to determine the sources of heterogeneity and further evaluate these studies. Also, the study has shown insufficient data on other outcome variables except VSS, restricting the comprehensive evaluation of laser treatment efficacy. The included studies predominantly originate from China and Egypt, limiting the generalizability of the findings to diverse populations. Due to the large differences in laser types, dosages and treatment timing, as well as the large differences in the age of the subjects, we cannot further evaluate and draw more specific conclusions. In addition, all the patients in the study were only followed for 6–12 months, which may not capture the long-term efficacy or recurrence data. The maturation of scars takes several years, and gradual improvement of scars can be observed for a long time after wound healing [36]. A more extended follow-up could provide a comprehensive understanding of laser therapy efficacy. More RCTs with high quality are needed in the future.

In conclusion, the current conclusions may change with the increase of studies. Our results should be interpreted with caution considering the existence of multiple conditions.

Implications for practice, policy, and future research

Scar formation is an inevitable result of cleft lip repair surgery. To make matters worse, the inevitable movement of the upper lip can lead to a tendency to disperse the wound edge during wound healing, and the risk of scar hypertrophy is further increased. All of this bring great psychological burden and social pressure to patients and their families [37].

It is necessary to plan strategically in order to minimize intervention and maximize the effect of facial repair [38]. There have been many scar repair methods applied to postoperative scars of cleft lip surgery, and have shown relatively good therapeutic effects. However, their limitations have also been exposed at the same time. Secondary surgical repair is common, which poses a great challenge to surgeons due to the multiple scars on the cleft lip and the lack of repaired cleft lip tissue [39]. In addition, surgery brings more pain to patients than other treatment methods. Pressure garments and scar massage are the most convenient, economical and least painful repair methods, yet there are significant individual differences and high compliance is necessary [15]. Silicone therapy is also common and inexpensive in clinical practice, but it poses a safety hazard for young children to ingest or inhale foreign objects [19]. Injecting botulinum toxin type A can temporarily inhibit the movement of surrounding muscles and has been proven to have good scar repair effects. However, the occurrence of complications troubles doctors and patients, and there is still controversy over the injection site and scope [40]. In summary, there is a need for better clinical methods for treating postoperative scars in cleft lip surgery.

Laser is a revolutionary method of treatment with a remarkable effect on the skin after trauma and surgical scars [41]. Compared to these methods, laser therapy brings less pain to patients and does not require patients to master professional rehabilitation knowledge, resulting in excellent efficacy and a lower probability of long-term complications [42]. Studies have shown that laser therapy can stimulate the full thickness remodeling and reconstruction of target skin areas (including epidermis and dermis) to prevent collagen proliferation [43], which has shown very good effects in improving lesion height, erythema, and pliability [44]. Aida et al. first reported the application of CO₂ fractional laser in postoperative scar of cleft lip in 2018, proving the safe and effective use of CO₂ fractional laser, with high satisfaction of patients [45]. Therefore, it is considered to have good prospects in the repair of scars after clinical cleft lip surgery [27]. Jahanbin et al. [10] concluded that CO2 laser treatment can reduce the electromyography activity of the upper lip at rest While Yasseai et al. believe that CO2 laser can help increased the vestibular depth [46] and increase upper lip length [47] in patients after surgery.

In terms of treatment timing, some scholars advocate early laser intervention for scar, such as 1–4 weeks after surgery [48, 49] because it can promote the reduction of scar hyperplasia index, and the duration of scar hyperplasia is also significantly shortened, with no obvious postoperative adverse reactions [50]. However, it is also believed that scar at maturity (3 months to 1 year after scar formation) is more convenient to treat, so scar boundaries are clearer and its properties are more stable, and it is difficult to transform into other tissues [51].

Since 2018, clinical studies on the efficacy of CO₂ laser treatment for postoperative scar after cleft lip have gradually emerged. Although there are few articles, they have all reached positive conclusions. Although our meta-analysis based on these articles produced great heterogeneity, we could not get a conclusive answer, it is still of great reference value. We believe that the prospect of CO₂ laser therapy is very considerable. If there are more studies on the mechanism, efficacy and prognosis of CO₂ laser therapy for postoperative scar of cleft lip, then with the maturity of CO₂ laser therapy, patients are highly likely to be free from the interference of facial scar to a large extent, so as to be more psychologically and physically healthy.

Conclusions

In conclusion, our meta-analysis supports a significant therapeutic effect of CO₂ laser therapy on postoperative cleft lip scar, especially in the early stages.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Abbreviations

PRISMA

Preferred reporting items for systematic reviews and meta-analyses

The GRADE guidelines

The grading of recommendations assessment, development, and evaluation guidelines

WMD

Weighted mean difference

VSS

Vancouver scar scale

RCT

Randomized controlled trial

CI

Confidence interval

VAS

Visual analog scale

Author contributions

XP and HC proposed ideas, constructed article writing ideas, searched literature, extracted information, analyzed data and wrote manuscripts. ZZ and ZY participated in the literature search section and prepared the figures and tables while the manuscript was reviewed a second time. MC reviewed manuscripts, made constructive comments, and participated in the design and coordination. All authors contributed to this article and approved the version submitted.

Funding

This work was supported by Cross-disciplinary Research Fund of Shanghai Ninth People’s Hospital, Shanghai Jiao Tong university School of Medicine (JYJC202226).

Data availability

All relevant data are within the manuscript and its supplementary information files. Further inquiries can be directed to the corresponding author.

Declarations

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.