Introduction

Meniere’s disease (MD) is an inner ear disorder characterized by recurrent episodes of spontaneous vertigo, tinnitus, sensorineural hearing loss, and ear fullness [1]. It is one of the most common otogenic diseases around the world, with an incidence of 17–513 patients per 100,000 persons [2]. The pathogenic mechanisms of MD may include genetic, viral, immune, and anatomical factors, while endolymphatic exudative disorders are considered to be the main causative factor, but no consensus has been reached due to the complexity of the mechanisms involved in the development of MD [3]. Therefore, current treatment of MD mainly includes alleviation of acute vertigo and prevention of recurrence.

The choice of diagnosis and treatment usually depends on the different etiology and the severity of vertigo. The initial treatment is a symptomatic and comprehensive treatment based on drug therapy, which mainly reduces vertigo symptoms by regulating autonomic nerve function and improving inner ear microcirculation. About 85% of MD patients can be prevented from vertigo if they receive proper treatment and change lifestyles, but still 15% cannot control vertigo well [4]. For patients with refractory or recurrent vertigo who are ineffective to drug treatment, the corresponding surgical treatment should be selected according to the patient’s condition [5]. Tympanic injection of gentamicin or hormones and surgical procedures such as endolymphatic sac surgery (ESS), labyrinthectomy, and vestibular resection are optional for refractory MD. The indications are frequent, severe vertigo, and poor response to conservative treatment for more than 6 months.

Based on different aims, the surgical methods of vertigo can be divided into three categories: the surgical methods aiming at the possible causes and pathogenesis of vertigo, the surgical methods aiming at the obstruction of the vestibular conduction pathway, and the surgical methods for the reconstruction of vestibular and cochlear functions [6]. Semicircular canal plugging (SCP) is performed by opening a window in the semi-gauge bone canal and filling it with bone powder, fascia, biological glue, and other materials, or by laser blocking or blocking the flow of internal lymphatic fluid and the stimulation of otoconia on the ampulla crest receptor to control the vertigo. Hand techniques belonging to the second class [7].

SCP is initially used to treat benign paroxysmal positional vertigo [8] and later extends to other otogenic vertigo diseases. Yin et al. [9]. First advocated triple semicircular canal plugging (TSCP) as a surgical treatment for MD. Since then, multiple reports showed that TSCP in the treatment of MD could be well controlled [7, 10–12]. Compared with traditional vestibular surgery for Meniere’s disease, TSCP has the following advantages: It has a higher vertigo control rate and hearing retention rate, better protection of otolith function, shorter postoperative imbalance time, and faster establishment of mid-axis compensation, so it is widely used. The preservation of cochlear function is critical for SCP [13]. However, no study has characterized the effect of TSCP on the hearing of MD patients. Therefore, this meta-analysis depicted the postoperative hearing loss rate of MD patients after TSCP treatment, aiming to provide a better understanding of the effect of TSCP on hearing during MD treatment.

This systematic review and meta-analysis aim to evaluate the effects of TSCP on hearing outcomes in individuals diagnosed with MD. The primary objective is to determine the rate of hearing loss following TSCP treatment, utilizing the American Academy of Otolaryngology-Head and Neck Surgery (AO-HNS) guidelines for assessing changes in pure tone audiometry (PTA) thresholds. Hearing loss will be categorized based on the magnitude of the threshold increase: "hearing loss" is defined as an increase of 10 dB or more compared to preoperative levels, and "severe hearing loss" is defined as an increase of 20 dB or more. Additionally, the secondary objective is to assess vertigo control rates post-TSCP treatment, applying AO-HNS guidelines to categorize control outcomes into "complete vertigo control" (indicating no vertigo attacks) and "substantial vertigo control" (denoting a significant reduction in vertigo attacks). Through a comprehensive synthesis of available literature, this study aims to elucidate the impact of TSCP on hearing function in MD patients, contributing valuable insights into the efficacy of TSCP as a therapeutic intervention for managing MD-related symptoms, particularly its influence on hearing outcomes.

Materials and methods

Results

Studies selection

Our system retrieved articles published as of December 31, 2022. A total of 295 studies were initially identified by the literature search and 5 additional articles were obtained in the references (S2 File), of which 210 duplicates were deleted and the remaining 90 articles were subsequently assessed for eligibility. After a review of article title and abstract, 25 of 65 articles were selected to read the full text. Among them, 15 articles were excluded because the number of patients with reported postoperative hearing loss did not meet the inclusion criteria. Then, the full text of 10 articles was reviewed and 3 papers were excluded because their definitions of hearing loss after TSCP surgery were not consistent with our inclusion criteria. Finally, the remaining 7 articles were included in this systematic review and meta-analysis (Fig 1).

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Fig 1. Research selection procedure based on the PRISMA flowchart.

https://doi.org/10.1371/journal.pone.0314348.g001

Characteristics of included articles

The characteristics of the included study are shown in Table 1 [7, 12, 20–24]. A total of 7 articles and 367 participants were enrolled. All participants were Chinese with 45% of male and 55% of female. They were all MD patients who previously received medication for more than 6 months and failed to control vertigo well. The duration time of MD ranged from 6 months to 120 months, and the mean postoperative follow-up time ranged from 10 months to 60 months. Hearing tests were conducted according to AO-HNS guidelines in all studies. The change in mean PTA threshold was calculated and classified as "hearing loss" or "severe hearing loss". Mean PTA thresholds for preoperative and postoperative hearing were reported in 2 studies. The baseline characteristics of all studies, including author and year of publication, total population, age, sex, number of people with hearing loss, duration of disease, and duration of follow-up were shown in Table 1. In addition, the assessment of bias risk showed that 7 studies had a low risk of biases (NOS score ≥ 5). The details of each NOS score are shown in the S2 Table.

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Table 1. The characteristics of studies included in the systematic review and meta-analysis.

https://doi.org/10.1371/journal.pone.0314348.t001

Hearing loss rate and vertigo control rate

Seven studies with 367 MD patients were included to analyze the rate of hearing loss after TSCP treatment, of whom 86 had hearing loss after TSCP. In a meta-analysis of the included studies, the rate of hearing loss was 22.0% (95% CI: 0.16–0.28, z = 5.77, p < 0.01) (Fig 2A). These studies had no significant heterogeneity (I² = 39.11%; p = 0.13). As for vertigo control, a total of 360 patients with stage A/B vertigo were well controlled after TSCP. The vertigo control rate of these studies was 99.0% (95% CI: 0.97–1.00, z = 124.22, p = 0.00) and no significant heterogeneity was detected among these studies (I² = 0.00%; p = 0.97) (Fig 2B).

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Fig 2. Rates of hearing loss and vertigo control.

(A) presents the rate of hearing loss after Triple Semicircular Canal Plugging (TSCP) treatment among patients with Meniere’s disease (MD), derived from a meta-analysis of included studies. (B) It depicts the vertigo control rate after TSCP treatment among MD patients, also based on a meta-analysis.

https://doi.org/10.1371/journal.pone.0314348.g002

Subgroup analysis

Further, we conducted a subgroup analysis to explore the effect of duration of disease and follow-up time on hearing loss and vertigo control rates in MD patients after TSCP.

Subgroup analysis of hearing loss.

Follow-up time. The length of follow-up time may cause hearing fluctuation in MD patients. Of the included studies, the mean follow-up time of 3 studies was less than 24 months and that of 4 studies was more than 24 months. Subgroup analysis showed that studies with follow-up time less than or more than 24 months had hearing loss rates of 20% (95% CI: 0.07, 0.38) and 23% (95% CI: 0.18, 0.29), respectively. The inter-group heterogeneity test showed no significant heterogeneity between subgroups (p = 0.756) (Fig 3A).

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Fig 3. Subgroup analysis.

(A) displays the subgroup analysis of hearing loss rates based on follow-up time after TSCP treatment. (B) presents the subgroup analysis of hearing loss rates according to the duration of disease in MD patients. (C) illustrates the subgroup analysis of vertigo control rates based on follow-up time after TSCP treatment. (D) depicts the subgroup analysis of vertigo control rates according to the duration of disease in MD patients.

https://doi.org/10.1371/journal.pone.0314348.g003

Duration of disease. The duration of the disease may be associated with impaired vestibular and cochlear function of the seven studies, two studies had a mean duration of disease of less than 12 months and that of five studies was greater than 12 months. Subgroup analysis showed that the rate of hearing loss in those with duration time less than or more than 12 months was 14% (95% CI: 0.05, 0.26) and 24% (95% CI: 0.19, 0.29), respectively. No significant inter-group heterogeneity was detected between subgroups (p = 0.121) (Fig 3B).

Subgroup analysis of vertigo control.

Follow-up time. To explore whether extended follow-up time would lead to a decrease in vertigo control rate, we conducted a subgroup analysis based on the follow-up time of MD patients. Of the 7 studies included, 3 had a mean follow-up time of less than 24 months, and 4 had a mean follow-up time of more than 24 months. Subgroup analysis showed a vertigo control rate of 99% (95% CI: 0.95, 1.00) in studies with follow-up less than 24 months and that of 99% (95% CI: 0.97, 1.00) in studies with follow-up longer than 24 months. The inter-group heterogeneity test showed no significant heterogeneity among all groups (p = 0.951) (Fig 3C).

Duration of disease. MD affected vestibular function if the duration of the disease was long, so the duration of the disease was analyzed by subgroup analysis. Of the seven studies, 2 had a mean duration of disease of less than 12 months and 5 had that of more than 12 months. Subgroup analysis showed that the vertigo control rate in those with a duration time less than or more than 12 months was 100% (95% CI: 0.96, 1.00) and 99% (95% CI: 0.97, 1.00), respectively. The inter-group heterogeneity test showed that there was no significant heterogeneity among the groups (p = 0.408) (Fig 3D).

Discussion

Meniere’s disease (MD) is one of the most common vertigo disorders, characterized by its prevalence in adults aged 40–60 years [25]. The distinctive feature of this disease is the fluctuation of symptoms, with periods of ups and downs. Vertigo episodes can last from minutes to hours, and positional vertigo may occur between or during episodes [26]. In addition, many patients also experience a feeling of pressure or fullness in the ear, accompanied by different forms of tinnitus [27]. Although the basic pathology of MD was identified as endolymphatic hydrops by autopsy in the 1930s [28], the etiology and mechanism of endolymphatic hydrops remain unclear, leading to confusion and uncertainty in the treatment of the disease. Due to the lack of targeted and systematic treatment, a considerable number of patients inevitably develop from early stage to late stage.

Because the pathogenesis of the disease is not clear, the treatment is mainly aimed at controlling the onset of vertigo and delaying hearing loss. Therefore, the treatment of MD is lack of targeted and systematic, resulting in a considerable number of patients inevitably developing from the early stage to the late stage and requiring surgical treatment. The main purpose of surgical treatment is to control vertigo. Traditional vertigo surgery includes endolymphatic sac surgery, vestibular neurectomy, and labyrinthyectomy [16]. With the exception of endolymphatic sac surgery, the latter two procedures completely destroy vestibular function. Endolymphatic sac surgery is the most popular surgical treatment for MD, recommended by the International Federation of Otolaryngology Societies (IFOS) as a third-line treatment but there is a lack of definitive evidence. Labyrinthectomy can better control vertigo but has a cost of complete hearing loss. Vestibular surgical operation has a higher vertigo control rate, but it may lead to facial dysfunction and intracranial infection.

In recent years, due to the concern about the quality of life of patients after vertigo control, the treatment concept of vertigo surgery has also changed significantly. In addition to the focus on the control of vertigo, there is an increasing emphasis on the preservation of residual vestibular and cochlear function and even the reconstruction of function. For example, recent studies have reported that MD can be treated by TSCP, endolymphatic aqueduct occlusion, vestibular implantation, and labyrinth surgical cochlear implantation [29]. In most patients with advanced MD, although vestibular and auditory functions are severely damaged, they are not completely lost. Residual function is still very important, especially for some patients who develop from unilateral to bilateral disease. Therefore, it is very important to preserve vestibular function as much as possible to maintain the balance of the body. In addition, preservation of vestibular and cochlear end organs provides the basis and opportunity for better treatments that may occur in the future [30].

In recent years, TSCP has been reported as a new treatment for MD [9, 31]. In terms of vertigo control, several studies have shown that TSCP can effectively control vertigo at a rate of 97%-100% in MD, which is consistent with the results of our meta-analysis [11, 12, 20, 32]. In addition, as a new inner ear operation, TSCP also has the advantage of reducing chronic postoperative imbalance or vertigo caused by exercise compared with traditional operations such as vestibular resection or labyrinthectomy. Studies have shown that although vertigo symptoms are relieved in most MD patients receiving labyrinthetic surgery, only 50% of them can return to normal work and life [32]. Moreover, vestibular resection is shown to cause longer delays before returning to work [33]. In addition, patients receiving TSCP have a better chance of preserving residual hearing compared with traditional surgery such as disruptive labyrinthectomy. Therefore, the optimal option for vertigo management and hearing rehabilitation is to use TSCP and cochlear implantation simultaneously in patients who had considerable or complete hearing loss prior to surgery [34]. Moreover, for patients whose hearing is available via using hearing aids, their hearing is worth preserving.

TSCP is a novel treatment for MD that can affect hearing although it doesn’t directly affect the cochlea or the cochlear nerve. It remains unclear how TSCP causes hearing loss, which may caused by exolymphatic leakage, inner ear bleeding, ruptured membranous labyrinth, serous labyrinthitis, infection, etc. An investigation on guinea pigs revealed inflammation and fibrosis close to the TSCP surgery site [35]. Another study on guinea pigs suggested that intraoperative membranous labyrinthia injury could lead to severe hearing loss whereas intraoperative peripheral lymphatic leakage would not affect hearing26. Moreover, the duration of the surgery may be correlated with the severity of the hearing loss. The viability of cochlea may be influenced by a shift in membranous labyrinthian pressure during TSCP [12].

TSCP has the advantage of preserving hearing, vestibular, and cochlear function [13]. The membrane-limiting muscle and the external ventricular lymphatic valve are the separating mechanisms between the upper (vestibular) and lower (auditory) labyrinthae [36], which may account for hearing preservation in some patients after TSCP treatment. However, several studies revealed that although the hearing and vestibular function of MD patients were improved during the follow-up, the inner ear function of some patients remained impaired [11, 37, 38].

Currently, no systematic review or study has been done to reveal the frequency of hearing loss after TSCP surgery. Herein, we included seven studies exploring hearing alteration and vertigo control after TSCP in Chinese MD patients. In these studies, the hearing loss rate ranged from 7% to 36%, and a meta-analysis estimated that patients who underwent TSCP surgery had a hearing loss rate of 22.0% (95% CI: 0.16–0.28). The majority of MD patients have a hearing loss of 10–20 dB. Results of subgroup analysis revealed that the duration of disease and follow-up time had limited effects on postoperative hearing loss. We acknowledge that this meta-analysis has some limitations. The studies included in this meta-analysis are cross-sectional, case-control, and cohort studies but not randomized, which has inherent heterogeneity of the findings. Second, data on hearing loss in Chinese MD patients following TSCP surgery are not sufficient to expand the results to all MD patients. Moreover, the number of studies and samples in this meta-analysis is limited. Hence, a prospective large-scale study is needed to verify our findings.

The study has several limitations that should be acknowledged. Firstly, the included studies primarily focused on Chinese populations with Meniere’s disease, which may limit the generalizability of the findings to other ethnic groups or geographic regions. Variations in genetic factors, disease characteristics, and treatment responses across different populations could impact the applicability of the results beyond the studied population. The study design of the included articles was mainly observational (cross-sectional, case-control, cohort), lacking randomized controlled trials. This variation in study design could introduce biases and limit the ability to establish causality between TSCP and hearing outcomes in MD patients. Furthermore, the number of studies included in the meta-analysis was relatively small, potentially limiting the statistical power and generalizability of the findings. A larger sample size and more studies from diverse populations would enhance the robustness and reliability of the conclusions. Additionally, the duration of follow-up varied across the included studies, ranging from 10 to 60 months. This variation in follow-up duration could impact the assessment of long-term outcomes following TSCP treatment and might contribute to heterogeneity in the reported results. Moreover, the study did not extensively explore potential confounding factors or patient characteristics (such as comorbidities, severity of MD symptoms, and surgical techniques) that could influence hearing outcomes following TSCP surgery. The lack of detailed information on these factors may limit the ability to draw definitive conclusions about the effects of TSCP on hearing preservation. The meta-analysis focused primarily on hearing outcomes and vertigo control rates after TSCP treatment. Other important outcomes, such as quality of life measures, patient-reported outcomes, or adverse events related to TSCP, were not comprehensively assessed in this study. The study provides valuable insights into the effects of TSCP on hearing outcomes in MD patients, these findings should be interpreted with caution due to the identified limitations. Future research should aim to address these limitations by conducting well-designed RCTs with larger, more diverse populations and longer follow-up durations to better understand the efficacy and safety of TSCP as a treatment for MD.

Conclusions

Our meta-analysis of seven studies explored the hearing loss and vertigo control rates after TSCP treatment in MD patients, which indicated that TSCP was efficient in controlling vertigo but with a 22% risk of hearing loss and a pure tone threshold drop of approximately 10–20 dB. In MD patients who have failed to control the symptoms by conventional treatment or non-destructive surgery such as an endolymphatic capsule, TSCP can not only effectively relieve vertigo, but also preserve residual hearing in most patients. If there exists hearing loss, it can be treated by using hearing aids or cochlear implantation. Meanwhile, TSCP may lead to partial hearing loss in stage I and II MD patients, therefore, it should be comprehensively considered when scheduling TSCP. As for the safety of TSCP, no complication has been reported in the included studies. However, the results of this analysis have some limitations, so caution should be exercised in interpreting our conclusions, and more randomized trials are needed to validate our findings.

Supporting information