Intratympanic Glucocorticoid Research Articles

Role of intratympanic glucocorticoid treatment in sudden hearing loss

Idiopathic sudden sensorineural hearing loss (ISSNHL) is one of the most common diseases in otolaryngology. Its etiology remains unknown. Furthermore, there is only alow level of evidence for the efficacy of established treatment modalities. In addition to systemic glucocorticoids, intratympanic corticosteroid treatment (ICT) has become increasingly important for treatment of ISSNHL. Different application strategies and treatment regimens have been described; however, uniform standards do not yet exist. ICT may be used for primary treatment as well as salvage therapy. Current data from meta-analyses show no benefit of intratympanic versus systemic primary therapy for sudden hearing loss (moderate evidence) but suggest abenefit of intratympanic secondary treatment over no treatment or placebo (high effect size, low evidence). Regarding combination of systemic and local glucocorticoid therapy in primary treatment of hearing loss, there may be asmall benefit over systemic treatment alone (low effect size, low evidence).

Hyperbaric oxygen therapy as an adjunct to corticosteroid treatment in sudden sensorineural hearing loss: a retrospective study.

A retrospective clinical study was conducted to test the impact of including hyperbaric oxygen therapy in the treatment of patients with sudden sensorineural hearing loss (SSNHL). A total of 63 adult patients with sudden sensorineural hearing loss diagnosed between 2015 and 2023 were divided into two groups: 36 patients treated with intratympanic glucocorticoid and orally administered glucocorticoid who also underwent hyperbaric oxygen therapy and 27 patients treated with intratympanic glucocorticoid and prolonged orally administered glucocorticoid (without hyperbaric oxygen therapy). An audiological evaluation was performed using pure-tone audiometry. Average hearing gain as measured by pure tone average was 12.5 dB HL (+/- 19.9 dB HL) in the patients treated with steroids combined with HBOT, and was 14.1 dB HL (+/- 17.9 dB) in the patients treated with steroids alone. Successful treatment (complete recovery or marked improvement) was observed in 27.8% of the patients in the first group and in 25.5% in the second group. There was no statistically significant difference between the groups. Both groups of patients-those treated with glucocorticoids and those treated with glucocorticoids and HBOT-had similar hearing outcomes. A prospective, controlled, and randomized study would provide more reliable knowledge about the efficacy of HBOT in treating SSNHL.

Safety and audiological outcome in a case series of tertiary therapy of sudden hearing loss with a biodegradable drug delivery implant for controlled release of dexamethasone to the inner ear.

BackgroundIntratympanic injections of glucocorticoids have become increasingly common in the treatment of idiopathic sudden sensorineural hearing loss (ISSHL). However, due to their fast elimination, sustained applications have been suggested for local drug delivery to the inner ear.Materials and methodsThe study is based on a retrospective chart review of patients treated for ISSHL at a single tertiary (university) referral center. We included patients who were treated with a solid, biodegradable, poly(D,L-lactic-co-glycolic acid) (PLGA)-based drug delivery system providing sustained delivery of dexamethasone extracochlear into the round window niche (n = 15) or intracochlear into scala tympani (n = 2) for tertiary therapy of ISSHL in patients without serviceable hearing after primary systemic and secondary intratympanic glucocorticoid therapy. We evaluated the feasibility and safety through clinical evaluation, histological examination, and functional tests [pure-tone threshold (PTA), word recognition scores (WRS)].ResultsWith adequate surgical preparation of the round window niche, implantation was feasible in all patients. Histologic examination of the material in the round window niche showed signs of resorption without relevant inflammation or foreign body reaction to the implant. In patients where the basal part of scala tympani was assessable during later cochlear implantation, no pathological findings were found. In the patients with extracochlear application, average preoperative PTA was 84.7 dB HL (SD: 20.0) and 76.7 dB HL (SD: 16.7) at follow-up (p = 0.08). The preoperative average maximum WRS was 14.6% (SD: 17.9) and 39.3% (SD: 30.7) at follow-up (p = 0.11). Six patients (40%), however, reached serviceable hearing. The two patients with intracochlear application did not improve.ConclusionThe extracochlear application of the controlled release system in the round window niche and – based on limited observations - intracochlear implantation into scala tympani appears feasible and safe. Due to the uncontrolled study design, conclusions about the efficacy of the treatment are limited. These observations, however, may encourage the initiation of prospective controlled studies using biodegradable controlled release implants as drug delivery systems for the treatment of inner ear diseases.

Effectiveness of Various Treatments for Sudden Sensorineural Hearing Loss—A Retrospective Study

(1) Background: A retrospective clinical study was conducted to compare the effectiveness of different pharmacological and non-pharmacological regimens for treating sudden sensorineural hearing loss (SSNHL). (2) Methods: Adult patients (n = 130) diagnosed with sudden sensorineural hearing loss (SSNHL) and hospitalized between 2015 and 2020 were enrolled in this study. Depending on the treatment regimen applied, patients were divided into five groups. Inclusion criteria were as follows: (i) hearing loss of sudden onset; (ii) hearing loss of at least 30 dB at three consecutive frequencies; (iii) unilateral hearing loss; (iv) age above 18 years. Exclusion criteria were as follows: (i) no follow-up audiogram; (ii) bilateral hearing loss; (iii) recognized alternative diagnosis such as tumor, disorder of inner ear fluids, infection or inflammation, autoimmune disease, malformation, hematological disease, dialysis-dependent renal failure, postdural puncture syndrome, gene-related syndrome, mitochondrial disease; and (iv) age below 18 years. (3) Results: Complete recovery was found in 14% of patients (18/130) and marked improvement was found in 6% (8/130), giving an overall success rate of 20%. The best results were obtained in the second group (i.e., patients given intratympanic glucocorticoid + prolonged orally administered glucocorticoid) where the success rate was 28%. In general, the older the patient, the smaller the improvement in hearing, a correlation that was statistically significant. (4) Conclusions: In treating SSNHL, the highest rate of hearing recovery—28%—was in the group of patients given intratympanic corticoid plus prolonged treatment with orally administered glucocorticoid.

Efficacy of Intratympanic Glucocorticoid Steroid Administration Therapy as an Initial Treatment for Idiopathic Sudden Sensorineural Hearing Loss During the COVID-19 Pandemic.

Systemic administration of glucocorticoid steroids is the most common initial treatment for idiopathic sudden sensorineural hearing loss (ISSNHL); however, due to the prevalence of coronavirus disease, the indications for this treatment must be carefully determined. The aim of this study was to investigate the efficacy of intratympanic steroid therapy as an initial treatment for idiopathic SSNHL. Sixty-eight patients with idiopathic ISSNHL who were treated with intravenous or intratympanic steroids were included in this study. Patients were retrospectively evaluated regarding preoperative grade, type of additional treatment, outcome of treatment, and side effects of each treatment. In 46 cases, patients received intravenous steroid therapy as the initial treatment, while 22 patients received intratympanic steroid therapy; 10 patients underwent salvage treatment due to inadequate improvement of symptoms. Regarding additional treatment, intravenous steroid monotherapy was used in 37 patients. The outcomes were similar after both treatments; 16 (43%) and 11 (52%) patients treated exclusively with intravenous and intratympanic steroids, respectively, were completely cured. There were no significant differences in the effects between the 2 treatments, indicating that they were almost equally effective. The side effects observed in patients treated with intravenous steroid therapy were increased blood pressure, acute gastric mucosal disorder, and insomnia. None of these side effects were observed in any of the patients treated with intratympanic steroids; however, 1 case of perforation of the tympanic membrane occurred due to the procedure. There were no significant differences in posttreatment outcomes between patients treated with either intratympanic or intravenous steroids. The therapeutic effects were comparable, and no severe side effects were observed; therefore, intratympanic steroid therapy may be considered useful as an initial treatment for ISSNHL in the context of widespread coronavirus disease.

Effects of intratympanic gentamicin and intratympanic glucocorticoids in Ménière's disease: a network meta-analysis.

Intratympanic therapies, usually including glucocorticoid and gentamicin, are becoming worldwide used in clinical practice of Ménière's disease today. However, clinical efficacy and safety of these two therapies are still in controversial. Electronic searches in PubMed, CENTRAL, Web of Science, EMBASE, CINAHL, ClinicalTrials.gov and the European Union Clinical Trials Register were conducted from inception until September 2020. The pre-specified protocol of this systematic review and meta-analysis has been registered and published in November 2018 (PROSPERO Identifier: CRD42018114389). All randomized controlled trials of intratympanic gentamicin or glucocorticoids for Ménière's disease, compared with each other or placebo, were considered for this review. Ten studies with 455 patients met the inclusion criteria. Pooled results indicated significant advantage of intratympanic gentamicin and glucocorticoids over placebo treatments in vertigo control (gentamicin vs placebo: risk rate, RR, 2.56; 95% CI 1.18-5.54; glucocorticoids vs placebo: RR, 3.02; 95% CI 1.36-6.73). There was no significant difference between gentamicin and glucocorticoids in vertigo control (gentamicin vs placebo: RR, 1.18; 95% CI 0.97-1.45). Intratympanic glucocorticoids showed better hearing protective results than gentamicin (change of pure tone audiometric, PTA, mean difference, MD, - 6.48dB; 95% CI - 11.84 to - 1.13dB; change of speech discrimination scale, SDS, MD 7.69%; 95% CI 0.83-14.55%). Intratympanic gentamicin and glucocorticoids are two effective approaches to control vertigo symptoms for Ménière's disease. Glucocorticoids showed a potentially better hearing protective role over gentamicin.

Vestibular prognosis in idiopathic sudden sensorineural hearing loss with vestibular dysfunction treated with oral or intratympanic glucocorticoids: a protocol for randomized controlled trial

BackgroundIdiopathic sudden sensorineural hearing loss (ISSNHL) is a rapid-onset sensorineural hearing impairment with unclear etiology and unsatisfying treatment effects. Vestibular dysfunction has been considered as a poor indicator in the clinical manifestations and prognosis of ISSNHL, which occurred in approximately 28–57% cases. Glucocorticoids, administered through oral or intratympanic way, are currently regularly and standardly applied for ISSNHL to improve the hearing outcome. However, the vestibular prognosis of ISSNHL after routine treatments remains seldom explored. This study aims to compare the effectiveness of oral and intratympanic glucocorticoids in ISSNHL with vestibular dysfunction in terms of the pattern and trajectory of possible process of vestibular function recovery.Methods/designA randomized, outcome-assessor- and analyst-blinded, controlled, clinical trial (RCT) will be carried out. Seventy-two patients with ISSNHL complaining of vestibular dysfunction appearing as vertigo or imbalance will be recruited and randomized into either oral or intratympanic glucocorticoid therapy group with a 1:1 allocation ratio. The primary outcomes will be vestibular function outcomes assessed by sensory organization test, caloric test, video head impulse test, cervical vestibular evoked myogenic potential, and ocular vestibular evoked myogenic potential; the secondary outcomes include self-reported vestibular dysfunction symptoms; dizziness-related handicap, visual analogue scale for vertigo and tinnitus; and pure tone audiometry. Assessments of primary outcomes will be performed at baseline and at 4 and 8 weeks post-randomization, while assessments of secondary outcomes will be performed at baseline and 1, 2, 4, and 8 weeks post-randomization.DiscussionPrevious intervention studies of ISSNHL included only hearing outcomes, with little attention paid on the prognosis of vestibular dysfunction. This trial will be the first RCT study focusing on the progress and prognosis of vestibular dysfunction in ISSNHL. The efficacy of two commonly used therapies of glucocorticoids will be compared in both auditory and vestibular function fields, rather than in the hearing outcome alone.Trial registrationClinicalTrials.gov NCT03974867. Registered on 23 July 2019

Effects of Intratympanic Gentamicin and Intratympanic Glucocorticoids in Ménière’s Disease: A Network Meta-Analysis of Randomized, Controlled Trials

Backgroud: Controversies exist in choosing Intratympanic gentamicin or intratympanic glucocorticoids for Meniere’s disease. Methods: To assess the treatment effects and safety among intratympanic gentamicin, glucocorticoids and placebo therapy in Meniere disease. Electronic searches in PubMed, the Cochrane Central Register of Controlled Trials (CENTRAL), Web of Science, MEDLINE, BIOSIS Previews, Embase, CINAHL, ClinicalTrials.gov and the European Union Clinical Trials Register were conducted from inception until March 2019. All randomized controlled trials of intratympanic gentamicin or glucocorticoids for Meniere’s disease, compared with each other or placebo therapy, were considered for this review. Two independent reviewers extracted study data and performed quality assessment using the Cochrane Risk of Bias Tool. Network meta-analysis on vertigo control, function level scales (FLS), hearing outcomes and tinnitus handicap inventory (THI) were calculated with a Bayesian approach using the R package netmeta (version:3.5.2). The quality of primary outcomes was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach. Findings: 10 studies of RCTs (455 patients) met inclusion criteria as described. Pooled results indicated significant advantage of intratympanic gentamicin and glucocorticoids over placebo treatments in vertigo control (gentamicin vs placebo: risk rate, RR, 2.56; 95%CI, 1.18 to 5.54; glucocorticoids vs placebo: RR, 3.02; 95%CI, 1.36 to 6.73). The comparison between gentamicin and glucocorticoids did not show a statistically significant result (RR 0.85; 95%CI, 0.69 to 1.03). FLS also showed improvements in intratympanic therapies over placebo. For PTA and SDS, intratympanic glucocorticoids showed better hearing protective results than gentamicin (change of PTA, MD, -6.48 dB; 95%CI, -11.84 dB to -1.13 dB; change of SDS, MD 7.69%; 95%CI, 0.83% to 14.55%),but no statistical significance in comparisons with placebo. No difference was found in THI among three approaches. Interpretation: Intratympanic gentamicin and glucocorticoids are two effective approaches to control vertigo symptoms for Meniere’s disease. Compared with gentamicin, glucocorticoids showed a potentially better hearing protective role, and intratympanic gentamicin therapy was not associated with high risk of hearing loss than placebo. Funding Statement: The authors have no funding to disclose. Declaration of Interests: The authors have no financial relationships, or conflicts of interest to disclose. Ethics Approval Statement: This research was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement for reporting systematic reviews and meta-analyses of studies that evaluate healthcare interventions, and the PRISMA extension statement for reporting of systematic reviews incorporating NMA of health care interventions. The pre-specified protocol of this systematic review has been registered in November 2018 (PROSPERO Identifier: CRD42018114389).

A prospective controlled study on the proper time of intratympanic steroid for profound sudden sensorineural hearing loss of total frequency type

Objective: To investigate the proper time of intratympanic steroid as combination therapy in treatment of patients with profound sudden sensorineural hearing loss(SSNHL) of total frequency type. Methods: This prospective study included 50 patients with SSNHL in the First Affiliated Hospital of Chongqing Medical University from June 2017 to February 2018.All these patients had profound hearing loss averaged more than 81 dB at all frequencies (250-8 000 Hz). They were divided into two groups.The patients in group A were treated with simultaneous oral prednisone (1 mg/kg, qd) and intratympanic methylprednisolone (40 mg, qd) for 5 days.The patients in group B were treated with oral prednisone for 5 days as in group A, and then those who had no significant improvement were subsequently treated with intratympanic methylprednisolone (40 mg, qd)for further 5 days.All patients were treated with additional intravenous batroxobin and ginkgo biloba leaves extract.Following examination of pure tone audiogram, hearing gains and effective rates were statistically analyzed in both groups with SPSS software package(version 20.0). Results: Hearings in both groups were improved significantly after treatment.In group A(20 cases), hearing gain was (29.2±22.7) dB and total effective rate was 65.0%, while in group B(22 cases), they were (27.3±22) dB and 68.2% respectively.There were no significant differences in hearing gain and recovery rate between two groups (hearing gain, P=0.793; total effective rate, P=0.827). Conclusions: For patients with profound SSNHL of total frequency type, the efficacies of intratympanic steroid as simultaneous and subsequent therapy are equivalent. Therefore, subsequent intratympanic glucocorticoid is recommended for SSNHL patient of total frequency type to reduce complications and medical expenses.

Controlled release dexamethasone implants in the round window niche for salvage treatment of idiopathic sudden sensorineural hearing loss.

To evaluate the feasibility and hearing outcome of a biocompatible degradable dexamethasone releasing implant for continuous drug delivery to the round window membrane in patients with idiopathic sudden sensorineural hearing loss (ISSHL) and insufficient recovery after systemic high dose glucocorticoid therapy. Five patients with profound or moderate-to-severe hearing loss after systemic high-dose prednisolone for ISSHL received local salvage therapy with a controlled release dexamethasone implant in the middle ear. Pieces of a sterile rod shaped poly(D,L-lactide-co-glycolide) PLGA polymer matrix containing a total of 0.7 mg dexamethasone, which is approved for intravitreal use were implanted into the round window niche. Intraoperative handling and feasibility and hearing recovery as measured by change in pure tone threshold, final word recognition score, and categories of improvement were evaluated. The implants were surgically placed without major difficulties. The mean hearing threshold significantly improved at follow up by 31 ± 31 dB HL (from 94 ± 27 to 63 ± 36 dB HL; p < 0.05). Two of five patients recovered completely. One patient showed partial hearing recovery with serviceable hearing. Although no drugs are currently approved for local therapy of inner ear disorders, there is increasing evidence that intratympanic glucocorticoids are effective as salvage therapy in ISSHL. The present study has shown encouraging results with a biodegradable polymer delivery system, demonstrating the translation of preclinical studies with controlled drug delivery into clinical practice.

Preclinical evaluation of thermoreversible triamcinolone acetonide hydrogels for drug delivery to the inner ear.

Intratympanic glucocorticoid therapy aims to reduce the side effects associated with systemic long-time therapy of inner ear diseases or traumata after cochlear implantation. For that purpose, thermoreversible hydrogels being fluid at room temperature but solid at body temperature are known to be appropriate drug delivery systems. In this work, the two key parameters sol-gel transition time and temperature of Poloxamer 407 (POX 407) based hydrogels containing oto-compatible micronized triamcinolone acetonide (TAAc) were evaluated by rheological experiments varying the concentrations of the different compounds. A 20% POX 407 hydrogel in PBS containing 30% TAAc emerged as the most appropriate formulation. Oscillation-rotation-oscillation studies at two temperature levels were found to be an useful in-vitro test system for the hydrogel which revealed sufficient storage stability at 4 °C, injectability of the sol, solidification within 20s at body temperature and persistent stiffness indicating prolonged adhesion at the round window membrane. According to the in-vitro release studies using the Transwell™ system, absorption of the poor water soluble TAAc is partly due to the low amount of dissolved drug but predominantly due to micellar transport resulting in a cumulative release of 262.6±13.4 μg TAAc within one week followed by a sustained release of 193.1±8.3 μg TAAc within the next three weeks. Thus, the formation of POX 407 micelles is the basis not only for gel formation but also absorptivity of TAAc. All in all, fine tuned rheological experiments and absorption studies emerged as useful tools for preclinical evaluation of intratympanally administered hydrogels.

The role of preoperative, intratympanic glucocorticoids for hearing preservation in cochlear implantation: A prospective clinical study

Hearing Preservation is becoming increasingly important in cochlear implantation as there is growing evidence that preserving the residual hearing, especially in the low frequencies in combination with the electric stimulation can significantly improve hearing and speech outcomes in noise. Besides the ongoing development of atraumatic implant electrodes and insertion techniques, the implementation of pharmacologic hair cell protection is thought to increase hearing preservation. This study investigates the effects of preoperative intratympanic glucocorticoid application on hearing preservation rates in cochlear implantation. Prospective interventional study. Tertiary neurotology referral center. Patients undergoing cochlear implantation with measurable preoperative hearing thresholds using either a Flex soft electrode or a Flex EAS electrode depending on the degree of residual low frequency hearing. Preoperative intratympanic steroid application during cochlear implantation via round window insertion. Level of hearing preservation after cochlear implantation; electrode- and frequency-specific hearing preservation rates. Preoperative hearing thresholds were comparable in the control group and the interventional Flex soft group (70.5 db±12.5 dB vs. 73.5 dB±10.5 dB, P=.27). As per selection criteria the low-frequency hearing thresholds were significantly lower in interventional Flex EAS groups when compared to the control group. Hearing preservation was significantly better in the interventional group with no case of complete hearing loss in this group (11 dB±2.5 dB vs. 19.5 dB 3.5 dB, P<.05). The interventional group displayed a higher stability of hearing preservation after implantation (r=.8, P=.03). Level of hearing preservation was higher when a specific hearing preservation electrode was used (r=.85, P<.05). Hearing preservation in the low frequencies was significantly higher than in the high frequencies. Our study suggests that the additional preoperative use of intratympanic glucocorticoids improves and stabilizes hearing preservations rates in round window cochlear implantation for adults and children with residual hearing.

糖皮质激素鼓室给药治疗突发性聋的系统评价

目的：系统评价糖皮质激素鼓室注射治疗突发性聋的有效性及安全性，为临床决策提供切实有效的依据。 方法：检索 Cochrane Library, PubMed, EMBASE, CBM, CNKI, VIP及万方等数据库的中英文文献。纳入糖皮质激素鼓室注射(ITD)vs 对照组（全身糖皮质激素/安慰剂治疗）的随机对照试验(RCT)。根据 Cochrane Handbook 5.0.1 标准对纳入研究进行质量评价，用 RevMan 5.0.2 软件进行Meta 分析。结果：纳入5 个 RCTs，共 285 例患者。Meta 分析示，两组听力恢复率差异有统计学意义OR(95% CI)为3.94(1.03,15.12)，糖皮质激素鼓室注射组(ITD)在250 HZ处较对照组表现出显著地听力恢复(p Objective To assess the efficacy and safety of intratympanic glucocorticoids for sudden sensorineural hearing loss. Methods We searched the Cochrane Library, PubMed, EMBASE, CBM,CNKI, and VIP databases and International Clinical Trials Registry website of World Health Organization using the key words “glucocorticoids”, “hearing loss” for the literatures of English and Chinese. Randomized controlled trials (RCTs) of intratympanic glucocorticoids versus placebo or intratympanic glucocorticoids versus controlled group（oral glucocorticoid/placebo）for sudden sensorineural hearing loss were included. According to the Cochrane Handbook for Systematic Reviews of Interventions Version 5.0.1, we assessed the quality of the included RCTs. A meta-analysis was carried out with the Cochrane Collaboration’s software RevMan 5.0.2. Results Five RCTs which contained 285 patients were included. Meta-analysis illustrated that there was sta-tistically significant on hearing recovery rate between the two groups (OR:3.94, 95% CI: 1.03-15.12). Hearing of pure tone average also improved significantly with intratympanic glucocorticoids therapy at 250HZ (p < 0.05). We found no statistically significant on the speech reception threshold (p = 0.20). Conclusion Com-pared with the control group, intratympanic glucocorticoids can significantly increase the hearing recovery rate of patients. Given the limitation of sample size of included studies into consideration, the results of this systematic review are still uncertain. Multi-center, large-scale, double-blinded randomized control trials are needed to confirm the available evidence.

Intratympanic glucocorticoids for sudden sensorineural hearing loss

This is a protocol for a Cochrane Review (Intervention). The objectives are as follows: To assess the efficacy, the effectiveness and the risks of adverse events of intratympanically applied glucocorticoids versus placebo therapy, versus no therapy or versus systemic application of glucocorticoids for treating unilateral sudden idiopathic sensorineural hearing loss, when given as a primary therapy or as a secondary (i.e. rescue or salvage) therapy after failure of systemic treatment.

Outcomes research analysis of continuous intratympanic glucocorticoid delivery in patients with acute severe to profound hearing loss: Basis for planning randomized controlled trials

Conclusions. The data presented herein form the basis for conducting randomized placebo-controlled clinical trials evaluating the safety and efficacy of salvage treatment in patients with idiopathic sudden severe sensorineural hearing loss (but not anacusis) refractory to initial systemic therapy. Comparison of different application protocols and drug delivery systems will allow assessment of the value of continuous versus intermittent intratympanic glucocorticoid drug delivery. Objectives. To describe and critically evaluate the results of continuous intratympanic glucocorticoid delivery in patients with acute unilateral severe and profound sensorineural hearing loss refractory to initial systemic therapy and to compare the outcome with a historical control group. Material and methods. In a retrospective chart review, treatment results were analyzed in 23 patients with acute severe and profound hearing loss and failure of systemic standard therapy who received a continuous intratympanic delivery of glucocorticoids as a salvage treatment. Audiological results were compared within the local therapy group and with the results of an historical control group who did not receive salvage treatment. The study and control groups were matched with respect to hearing loss after initial systemic treatment failure. Results. The average pure-tone threshold after intratympanic salvage treatment showed a statistically significant improvement of 15 dB (95% CI 7–24 dB; p<0.001). After exclusion of patients with complete anacusis, i.e. a non-measurable hearing threshold, the local therapy group showed a significantly better improvement (mean 19 dB; 95% CI 6–32 dB) than the historical control group (mean 5 dB; 95% CI − 2–11 dB; p<0.05).