To ensure transparency and completeness in our reporting of this review, we employed the PRISMA guidelines.^[16] We duly registered the review protocol in PROSPERO (CRD42024556800). Our PECO protocol defined the characteristics and scope of our inquiry and led the systematic review and meta-analysis. Our PECO protocol was as follows in particular: Patients having orthodontic treatment comprised the population; patients receiving COT or CAT made up the exposure; the comparison was between COT and CAT (although this group was not considered to be strictly mandatory taking into account the exploratory focus of the study); the primary outcome of interest was the perception of pain assessed using the Visual Analog Scale (VAS) or sEMG activity in the masticatory muscles. Table 1 provides an explanation of the various inclusion and exclusion criteria that were used.

We searched multiple electronic databases, including PubMed, Scopus, Web of Science, Cochrane Library, Google Scholar, Embase, and CINAHL for relevant literature. To guarantee a comprehensive and focused search, the search protocol used a combination of Boolean operators and MeSH (Medical Subject Headings) keywords (“clear aligner therapy” OR “invisible orthodontics” OR “CAT”) AND (“conventional orthodontic treatment” OR “fixed orthodontic appliance” OR “COT”) AND (“pain perception” OR “pain intensity” OR “pain threshold”) AND (“surface electromyography” OR “sEMG” OR “electromyographic activity”) AND (“masticatory muscles” OR “temporalis muscle” OR “masseter muscle” OR “medial pterygoid muscle”). There were no limitations on the publication date or study design; the search was restricted to studies that were published in English.

The pertinent data from the qualifying studies were extracted using a standardized data extraction procedure. A pre-made data extraction form that had been pilot-tested and improved before the actual data extraction procedure was used by two reviewers to independently extract the data. The study characteristics, participant characteristics, intervention features, outcome measures, and outcomes were all included in the data extraction form.

The study design, publication year, country of origin, sample size, age, sex, and orthodontic treatment characteristics were among the data items that were chosen for extraction. Other features of the intervention included the type of CAT or COT, duration of treatment, and frequency of appointments. The outcome measures included pain perception outcomes (measured by VAS) and sEMG activity outcomes (such as muscle activity and electromyographic signals). The results included mean and standard deviation values for pain perception and sEMG activity outcomes, as well as any other pertinent findings. Any disagreements among the reviewers were settled by third-party arbitration or consensus.

Using the ROBINS-I tool^[17] and the Cochrane’s RoB 2.0 tool,^[18] two reviewers independently assessed the bias risk in each study. These tools analyze the risk of bias across numerous domains, with the overall risk of bias for each study then being established by evaluating the ratings across the domains.

The meta-analysis determined the mean difference (MD) for pain perception outcomes by comparing the VAS scores and sEMG activity scores of the CAT and COT groups and odds ratio (OR) comparison between patients requiring analgesics across both the groups. Anticipated heterogeneity between studies was believed to be accounted for by a random-effects model. Forest plots, a visual depiction of the effectiveness of CAT versus COT in terms of pain perception and sEMG activity, were used to display the meta-analysis results.

The identification step proceeded with a thorough search of electronic databases and registries, obtaining a total of 255 records [Figure 1]. Subsequently, a careful screening process was done to identify duplicate records, resulting in the removal of 49 duplicate entries. Automation technologies were deployed to assist in the screening process, but no records were identified as ineligible by this means. No records were eliminated for other reasons, so a total of 206 records were found eligible for further evaluation.

Upon screening, no records were eliminated at this level, and all 206 reports were sought for retrieval. However, 39 records were not retrieved, leaving 167 reports to be examined for eligibility. A thorough evaluation procedure ensued, wherein reports were rejected based on preset criteria. Specifically, 51 animal studies, 36 literature reviews, and 48 case reports were omitted, as they did not match the inclusion criteria. In addition, 23 reports were ruled off-topic, resulting in a total of 167 reports being eliminated. At the end, a total of 9 studies^[19-27] met the qualifying criteria and were included in the review.

As per the ROBINS-I tool [Figure 2], Alajmi et al.^[19] and Miller et al.^[24] revealed moderate bias, whereas Dellavia et al.^[21] and Nota et al.^[25] showed minimal bias. Lou et al.^[23] and Tran et al.^[26] revealed substantial bias in certain categories but low bias in others. In contrast, the RoB 2.0 tool [Figure 3] found that Casteluci et al.^[20] and White et al.^[27] had some worries in many domains, whereas Gao et al.^[22] had some problems in only one domain.

The studies included in the review, as presented in Table 2, comprised a total of 9 trials published between 2007^[24] and 2022.^[21] The sample sizes ranged from 16^[21] to 110^[22] participants, with a median sample size of 39. In terms of study design, the assessments revealed a mix of observational and interventional studies. Three randomized controlled trials were identified,^[20,22,27] which provided high-level evidence for the interventions examined. In addition, four prospective studies^{[21,23,25,26]} and one prospective, longitudinal cohort study^[24] were included, which offered valuable insights into the research questions. Only one observational, retrospective study^[19] was included in the review.

Alajmi et al.^[19] compared CAT (30) and Conventional Fixed Appliances (30) treatment groups, revealing a significant difference in pain perception measured by the VAS between the two groups (P < 0.01). Casteluci et al.^[20] examined orthodontic aligners (OAs) (20) and fixed appliances (FAs) (19) treatment groups but did not assess pain perception. Dellavia et al.^[21] compared OAs (OA) (9) and Fixed Orthodontic Appliances (FOA) (7) treatment groups, finding no significant difference in pain perception (P = 0.65). Gao et al.^[22] compared CAT (55) and FAs (55) treatment groups, revealing no significant difference in pain perception (P = 0.56).

Lou et al.^[23] examined CAT treatment groups but did not assess pain perception. Miller et al.^[24] compared OAs and FAs treatment groups, finding a significant difference in pain perception (P < 0.001). Nota et al.^[25] examined CAT treatment groups but did not assess pain perception. Tran et al.^[26] compared OAs and Temporary FOAs treatment groups, finding no significant difference in muscular pain. White et al.^[27] examined OAs and FA treatment groups, revealing a significant difference in pain perception (P < 0.05).

The forest plot presented in Figure 4 illustrates the comparison of VAS scores and sEMG activity scores between CAT and COT groups. The results indicate that the overall MD in VAS scores between CAT and COT groups was −2.77 (95% confidence interval [CI]: −7.25, 1.71), suggesting a nonsignificant difference (P = 0.23). However, individual studies varied, with White et al.^[27] reporting a significant difference in VAS scores (MD = −7.84, P < 0.00001) and Casteluci et al.^[20] reporting a nonsignificant difference (MD = −2.20, P = 0.0001). The heterogeneity test revealed significant heterogeneity among studies (I² = 100%). In contrast, the sEMG activity scores showed a nonsignificant difference between CAT and COT groups (MD = −0.80, P = 0.60). Overall, the results suggest that the difference in VAS scores and sEMG activity scores between CAT and COT groups was not statistically significant.

The forest plot presented in Figure 5 illustrates the comparison of OR for patients requiring analgesics between CAT and COT groups, assuming a RE model and 95% CI. The results indicate that the overall OR for patients requiring analgesics was 0.23 (95% CI: 0.08, 0.65), suggesting a significant difference between CAT and COT groups (P = 0.005). The individual studies demonstrated consistent results, with Alajmi et al.,^[19] Casteluci et al.,^[20] Miller et al.,^[24] and White et al.^[27] reporting ORs of 0.26, 0.28, 0.25, and 0.10, respectively. Notably, the heterogeneity test revealed no significant heterogeneity among studies (τ² = 0.00, χ² = 0.36, df = 3, P = 0.95, I² = 0%). Overall, the results suggest that patients in the CAT group were less likely to require analgesics compared to those in the COT group.

The findings of this study should be interpreted in the context of several limitations. The significant heterogeneity observed among studies (I² = 100%) may have arisen from differences in study designs, populations, and outcome measures, which could have impacted the precision of the estimates. In addition, the small number of studies included in the meta-analysis may have limited the generalizability of the results. Furthermore, the lack of standardization in pain assessment tools and sEMG measurements may have introduced variability in the outcomes.

Nil.

The authors of this manuscript declare that they have no conflicts of interest, real or perceived, financial or non-financial in this article.