1 BACKGROUND

The most frequent reason for patients to undergo a cosmetic dentistry treatment (AACD, 2013), which includes periodontal plastic surgeries, was ‘to improve physical attractiveness and self-esteem’. Taking the costs and morbidity associated with periodontal plastic surgeries into account, it is important that treatments provide a stable and aesthetical long-term outcome. Various techniques [e.g., coronally advanced flap (CAF), tunnel technique (TUN), laterally positioned flap (LPF), etc.)], flap designs (e.g., CAF with/without vertical releasing incisions, TUN with/without split-flap, etc.), adjuncts [e.g., free gingival graft (FGG), connective tissue graft (CTG), enamel matrix derivatives (EMD), soft tissue substitutes (STS), membranes for guided tissue regeneration (GTR), etc.], and endless combinations thereof have been introduced for the treatment of gingival recessions (GR), that is, to achieve root coverage. Numerous systematic reviews and consensus reports (AlSarhan et al., 2019; Cairo et al., 2014; Chambrone, Ortega, et al., 2019; Chambrone & Tatakis, 2015; Cheng et al., 2015; Graziani et al., 2014; Moraschini & Barboza, 2016; Tatakis et al., 2015; Tavelli et al., 2018; Tavelli, Barootchi, Cairo, et al., 2019; Tonetti et al., 2014) have been conducted during recent years, reflecting the increased interest in plastic periodontal surgical procedure in both the profession and the patients (Madianos et al., 2016). Most systematic reviews conclude that CAF + CTG should be considered as the ‘gold standard’ for single Miller class I and II GR, also coined as recession type (RT) 1 (Cairo, 2017; Cairo et al., 2014; Chambrone, de Castro Pinto, & Chambrone, 2019; Chambrone, Ortega, et al., 2019; Chambrone & Tatakis, 2015; Tatakis et al., 2015; Tonetti et al., 2014); significantly less evidence is available for multiple GR and GR with interdental attachment loss (i.e., Miller class III and IV, respectively RT 2 and 3; Cairo, 2017; Chambrone, de Castro Pinto, & Chambrone, 2019; Chambrone, Ortega, et al., 2019; Chambrone & Tatakis, 2015; Graziani et al., 2014; Tatakis et al., 2015; Tonetti et al., 2014). The outcome of treatment is determined by the surgical technique and precision (e.g., flap design/tension/thickness/positioning, micro-surgical approach, etc.; Baldi et al., 1999; Cairo, 2017; Cairo, Cortellini, et al., 2016; Chambrone & Tatakis, 2015; Dodge et al., 2018; Pini Prato et al., 2000; Pini Prato et al., 2005; Skurska et al., 2015; Tatakis et al., 2015; Zucchelli et al., 2019), but also by site-specific [e.g., initial depth and width of the GR, tooth location, gingival thickness, papilla height, keratinised tissue width (KTW), frenula, etc.] (Cairo, 2017; Chambrone, de Castro Pinto, & Chambrone, 2019; Cortellini & Bissada, 2018; Huang et al., 2005; Pini Prato, Franceschi, et al., 2018; Pini Prato, Magnani, & Chambrone, 2018; Pini-Prato et al., 2012; Rasperini et al., 2020; Saletta et al., 2001; Tatakis et al., 2015; Zucchelli et al., 2018; Zucchelli et al., 2019), and patient-related (e.g., smoking status, compliance, oral hygiene habits, etc.; Cairo, 2017; Chambrone, Ortega, et al., 2019; Chambrone & Tatakis, 2015; Tatakis et al., 2015) parameters.

Recently, two systematic reviews (Dai et al., 2019; Tavelli, Barootchi, Cairo, et al., 2019) addressed the question of time on the stability of root coverage procedures. One of them (Dai et al., 2019) summarised the available literature with at least 24 months follow up until July 2018. Based on primarily pairwise meta-analyses (i.e., short- vs. long-term and comparisons of different techniques) the results indicated that mean root coverage (RC) worsened over time for CAF, but not for CAF + CTG; further, the complete root coverage (CRC) rate and KTW was significantly higher at the long-term outcome for CAF + CTG compared to CAF only. CAF + EMD displayed no significant changes in terms of CRC rate comparing short- versus long-term results. In the other review (Tavelli, Barootchi, Cairo, et al., 2019) the effect of time (but not specifically the long-term effect) was assessed by means of network meta-analyses (NMA), including all studies presenting data for at least two different time points (e.g., after 3 and 12 months). The authors concluded that primarily CTG-based procedures appeared sufficient to achieve stable results over time, while flap only or flap with the addition of EMD or STS showed a tendency for relapse. Unfortunately, all studies presenting data with a follow-up >80 months (i.e., four studies in total) were excluded from this specific analysis. In this context, the 10th European Workshop on Periodontology (Tonetti et al., 2014) and the recently updated Cochrane systematic review (Chambrone, Ortega, et al., 2019), have advocated that ‘long-term’ should be considered as having at least 5 years follow-up. Hence, no comprehensive summary of long-term outcomes of root coverage procedures (i.e., ≥5 years), specifically, is existing so far, but it seems relevant, considering the relatively high number of recently published individual long-term studies (Barootchi et al., 2019; de Santana et al., 2019; Kroiss et al., 2019; Petsos et al., 2020; Tavelli, Barootchi, Di Gianfilippo, et al., 2019).

Thus, the present systematic review aimed to address the following focused question according to the Population, Intervention, Comparison, Outcomes, Study Design (PICOS) criteria (Miller & Forrest, 2001): ‘In patients with single or multiple GR, what is comparatively the long-term outcome (≥ 5 years) of root coverage procedures with a flap alone or flap with adjuncts (soft tissue grafts or substitutes, bone grafts or substitutes, membranes, or biologic agents) and/or different flap designs in terms of clinical outcome parameters?’. Further, the aim was to provide a hierarchy of interventions by means of NMA, wherever possible.

2 MATERIALS AND METHODS

2.6 Statistical analysis

For statistical analysis only RCT fitting to one of the following four groups were considered eligible: (a) single Miller class I and/or II (RT 1) GR, (b) single Miller class III and/or IV (RT 2 and 3) GR, (c) multiple Miller class I and/or II (RT 1) GR, (d) multiple Miller class III and/or IV (RT 2 and 3) GR. Hence, CT and studies including patients with single and multiple GR and/or Miller class I/II and III/IV, were not considered as comparable. All outcomes were measured using the mean difference, except for CRC, which was measured using the odds ratio in the logarithmic scale (log OR). NMA was intended for each outcome; for details see Appendix 2 (including Figure 1 and Appendix 3).

3 RESULTS

3.4 Synthesis of results

Eight RCT (de Santana et al., 2019; Kuis et al., 2013; Leknes et al., 2005; McGuire et al., 2012; McGuire et al., 2014; McGuire & Scheyer, 2016; Pini Prato et al., 2011; Rasperini et al., 2018) reported on the treatment outcomes of single Miller class I/II GR. Only two RCT (Tavelli, Barootchi, Di Gianfilippo, et al., 2019; Zucchelli et al., 2014) reported on the treatment outcomes of multiple Miller class I/II GR, including four different types of intervention and could not be compared/pooled. The remaining studies were either not randomised or included a mixture of single and multiple GR. Hence, any attempt for a (N)MA was only possible for single Miller class I/II GR; one (Pini Prato et al., 2011) of the eight studies had to be excluded as it was comparing CAF versus CAF with different methods of root surface modifications. However, due to lack of similarity in clinical and methodological characteristics across the trials and observed comparisons, any synthesis of the trials was not performed. Therefore, the present overview is primarily of descriptive nature. Figure 1 and Appendix 3 illustrate the networks for the primary and secondary outcomes of the study; for details see also Appendix 2. Further, an overview of the results of the seven studies on single Miller class I/II GR is provided by forest plots (Figure 2 for the primary outcome parameters; Appendix 8 for the secondary outcome parameters) and bubble plots (Figure 3 for the primary outcome parameters; Appendix 9 for the secondary outcome parameters).

4 DISCUSSION

The primary aim of GR treatment is CRC, with natural appearance of the tissues, and stability of the outcome on the long-term. The present systematic review aimed to provide an overview of the available literature on the long-term outcome of root coverage procedures and to provide – if possible – recommendations on which techniques have the highest probability for a successful outcome on the long-term. The results of one of the most recent systematic reviews (Chambrone, Ortega, et al., 2019), including studies with short-term follow-up provided the following ranking in terms of clinical outcomes and cost-to-benefit ratio for single Miller class I/II GR: (a) CAF + CTG, (b) CAF + ADMA, (c) CAF + EMD, (d) CAF + CM, and (e) CAF. Significantly less evidence was available for multiple Miller class I/II GR, but the authors suggested that a similar hierarchical order, with that in single GR, might apply.

Most available controlled clinical, long-term studies regarded single Miller class I/II GR; that is, one CT and eight RCT with a follow-up of 5–14 years. Unfortunately, the lack of clinical and methodological homogeneity in the included trials alongside the limited number of trials (Figure 1) to allow for a moderator analysis (that would have adjusted the results for the observed clinical and methodological heterogeneity), rendered the application of NMA and pairwise meta-analysis not feasible. Therefore, the overview presented herein is primarily of descriptive nature. When excluding the CAF group of a single study (Leknes et al., 2005) with significantly inferior outcomes than what is usually reported (i.e., mean residual RD of about 2.5 mm), the mean residual RD ranged for the CAF and CAF + CTG groups from 0.46 to 1.15 mm and from 0.19 to 0.5 mm, respectively; CRC ranged from 33 to 60% and from 66.7 to 88.2%, respectively. Thus, it seems there is a tendency for more favourable treatment outcomes with CAF + CTG. This is supported by the fact that 2 CAF + CTG groups (Francetti et al., 2018; Rasperini et al., 2018) showed ‘creeping attachment’ over time resulting in a lower mean residual RD at FE compared to IM. In general, except for the above-mentioned CAF group presenting especially bad outcomes (Leknes et al., 2005), all interventions for treating single GR showed acceptable stability of the outcome, with an increase in RD of ≤0.55 mm, on average, after the IM. Based on the results of the few individual studies, CAF + CTG appeared also superior in the direct comparisons to CAF + EMD (McGuire et al., 2012), to CAF + CM (McGuire & Scheyer, 2016), and to CAF + grafting (McGuire et al., 2014). Only a single RCT (de Santana et al., 2019) assessed another flap design (i.e., LPF) after 5 years showing also low mean residual RD (i.e., 0.3 mm) with high increase in KTW (i.e., 3.4 mm) and a high stability over time.

Regarding the treatment of multiple Miller class I/II (and III) GR, the few available studies showed better outcomes for CAF + CTG compared to only CAF (Pini-Prato et al., 2010; Zucchelli et al., 2014) or to ADMA (Kroiss et al., 2019). In particular, CAF groups slightly lost over the years from what was originally achieved (i.e., 0.2 mm increase in RD), while the addition of a CTG resulted in a minor improvement from IM to FE (i.e., ‘creeping attachment’ occurred); the mean residual RD for the CAF + CTG group was only 33–50% of the CAF group (Pini-Prato et al., 2010, Zucchelli et al., 2014). Use of ADMA as an alternative to CTG with CAF (Kroiss et al., 2019; Tavelli, Barootchi, Di Gianfilippo, et al., 2019), yield similar or higher mean residual RD compared to what was reported in other studies for CAF alone and 2- to 9-times higher values compared to CAF + CTG. Additionally, in both studies (Kroiss et al., 2019, Tavelli, Barootchi, Di Gianfilippo, et al., 2019) assessing CAF + ADMA, the CAF + AMDA groups lost about two-times more in RD over the years compared to what was reported in other studies for CAF only, and no ‘creeping attachment’ was observed. In contrast, one RCT (Moslemi et al., 2011) reported superior results for CAF + ADMA compared to CAF + CTG. However, in this specific study the mean RD at baseline (i.e., prior to intervention) was 0.46 mm higher in the CAF + CTG group and the mean residual RD after intervention was unexpectedly high in the CAF + CTG group (i.e., 1.83 mm; this is about three- to five-times higher than what is reported in most of the other studies included herein); additionally, the CAF + ADMA group showed again no long-term stability, by losing almost 1 mm in RD from IM to FE. Similarly, in another controlled but non-randomised study (Dominiak et al., 2006) showing inferior results for CAF + CTG compared to CAF + GTR, again the CAF + CTG group presented with a mean RD at baseline being 0.75 mm higher compared to the CAF + GTR group.

In perspective, the lack of long-term data of controlled clinical trials with at least 5 years follow-up for several interventions and combination approaches (i.e., TUN + CTG, CAF + EMD, CAF + CM, CAF + CTG + EMD, etc.) has to be kept in mind. However, taking also non-prospective and/or shorter follow-ups into account, a 6-year retrospective analysis (Bhatavadekar et al., 2019) indicated comparable results for the comparison CAF + CTG versus TUN + CTG with the results being within the range of the RCTs (Pini-Prato et al., 2010, Zucchelli et al., 2014) included herein. In terms of combination treatments, 3-year results of CAF + CTG versus CAF + CTG + EMD have been recently published (Mercado et al., 2020a) indicating some advantages by the addition of EMD. The principle of EMD being advantageous – especially on the long-term – would be its potential to actually achieve at least partly periodontal regeneration instead of ‘only’ a long junctional epithelium (McGuire et al., 2016). However, due to the extra financial burden for the patient and the overall limited and unclear data on the histological outcome of healing after adjunct use of EMD, future long-term trials assessing EMD as only or as additional adjunct are warranted.

There was no evidence from controlled clinical trials about the long-term outcome of treatment of GR with interdental attachment loss (i.e., Miller class III/IV or RT 2/3) – neither for single nor for multiple defects. Nevertheless, there are medium-term data (i.e., 3 years follow-up; Cairo et al., 2015; Mercado et al., 2020b) as well as 20-year case series (Pini Prato, Franceschi, et al., 2018; Pini Prato, Magnani, & Chambrone, 2018) available with the latter probably providing the best long-term evidence available at the moment with a direct comparison of the outcome of GR without (Miller class I) or with interdental attachment loss (Miller class III) treated either by CAF (Pini Prato, Magnani, & Chambrone, 2018) or CAF + CTG (Pini Prato, Franceschi, et al., 2018). For both interventions the presence of interdental attachment loss significantly reduced the chance to achieve CRC after 1 year. However, while in sites treated with CAF recurrence of GR was significantly associated with the presence of interdental attachment loss, this was not the case for sites treated with CAF + CTG; that is, similar to what was described above for single and multiple GR without interdental attachment loss, the addition of CTG appears to provide better long-term stability.

In this context, except from the type of surgical intervention, other factors should also be considered as relevant for a successful long-term outcome. In particular, specific surgical details (e.g., releasing incisions, details on CTG harvesting, root conditioning, etc.), site-related (e.g., phenotype, GR width, cervical lesions, etc.) and patient-related factors (e.g., smoking), and performance of supportive periodontal treatment (i.e., frequency, surveillance of oral hygiene habits, etc.) are debated as potentially relevant in achieving and maintaining a successful treatment result and thereby reducing the probability of GR recurrence. Herein it was attempted to give an overview of such frequently discussed parameters and their reporting frequency (Appendix 6 and 7). Regular supportive periodontal treatment, including specifically the close surveillance of oral hygiene habits, is considered as a major determinant of long-term success (Cairo et al., 2014; Dai et al., 2019; Leknes et al., 2005; McGuire et al., 2014; Moslemi et al., 2011; Pini Prato, Franceschi, et al., 2018; Rasperini et al., 2018; Zucchelli et al., 2014; Zucchelli & De Sanctis, 2005); for example, a horizontal toothbrushing technique increased the risk for a relapse 11-times (Moslemi et al., 2011). Further, the tooth region appears to affect the probability of achieving CRC (Zucchelli et al., 2018; Zucchelli et al., 2019). Naturally, this cannot be altered by the surgeon, but one should consider assessing different techniques separately in the upper and lower anterior sextant, which have been described as having the best and worst probability for a good outcome, respectively (Zucchelli et al., 2019). Additionally, a low baseline KTW as well as KTW <2 mm after the intervention were reported as negative predictors (Barootchi et al., 2019; Pini Prato et al., 2011; Pini Prato, Franceschi, et al., 2018; Pini Prato, Magnani, & Chambrone, 2018; Pini-Prato et al., 2012; Tavelli, Barootchi, Cairo, et al., 2019; Tavelli, Barootchi, Di Gianfilippo, et al., 2019), while the gain of KTW might be affected by the chosen technique [e.g., by leaving the CTG exposed or not exposed (Dodge et al., 2018)].

In this context, although CAF + CTG is described as the ‘gold standard’, CTG as an adjunct might not be necessary in every single case; that is, recent studies indicated that a thick tissue at baseline might not need the addition of a CTG (Cairo, Cortellini, et al., 2016; Rasperini et al., 2019, 2020). Hence, one can speculate whether the gingival thickness at the end of the procedure is the main determining factor for long-term stability and not necessarily the addition of a CTG; for example, in one of the RCT (Tavelli, Barootchi, Di Gianfilippo, et al., 2019) a gingival thickness ≥1.2 mm after 6 months was a significant predictor for stability of the gingival margin later on. However, the gingival phenotype/thickness was not reported in >70% of the studies included herein. Details on the CTG harvesting procedure itself might be another relevant factor (Tavelli, Ravidà, Lin, et al., 2019). Different harvesting techniques (split-flap procedure or de-epithelialised CTG) result in different tissue compositions of the graft (Bertl et al., 2015), which might affect the resulting tissue thickness but potentially also the risk for keloid formation. Nevertheless, a large variation in terms of reporting frequency (5.5–95%) of these and other potentially relevant factors was observed (Appendix 6).

Root coverage procedures are primarily cosmetic dentistry and aim to improve patient aesthetics (Cairo, 2017; Cairo, Pagliaro, et al., 2016). Hence, also aesthetic outcomes (based on both, professional evaluation as well as on patient perception) and PROMs should be evaluated. Ten out of 18 studies herein reported on various PROMS, ranging from dentin hypersensitivity to colour/texture/contour match, aesthetic scores, and patients' satisfaction. Although the analysis is again limited to an overview (Table 4), some tendencies can be deducted. Procedures including a CTG harbour the risk to be less favourable in terms of colour, texture, and contour match compared to the adjacent tissues, in terms of keloid formation, and in terms of patients' preference of the procedure. However, at least among the studies included herein, the overall patient satisfaction with the final outcome was not negatively affected by the adjunct of a CTG. These findings are well in agreement with short-term results on aesthetic- and patient-related outcomes following root coverage procedures recently summarised (Cairo et al., 2020).

Based on a primarily descriptive summary presented herein, a few recommendations for future studies and for the clinical praxis can be provided:

5 CONCLUSIONS

CONFLICT OF INTEREST

The authors declare there is no conflict of interest.