Steroid Efficacy on Audiologic Recovery in Patients With Sudden Sensorineural Hearing Loss and Vestibular Schwannoma: A Retrospective Review.

OBJECTIVES: The objectives of this study are to (i) estimate the incidence of vestibular schwannoma (VS) among patients in an integrated healthcare system who present for evaluation of sudden sensorineural hearing loss (SSNHL) and (ii) evaluate the efficacy of empiric steroid therapy on audiologic recovery among SSNHL patients ultimately diagnosed with VS. METHODS: A retrospective chart review was performed on patients presenting with SSNHL in 2021 at a multicenter integrated healthcare system serving over 4 million members. Patient demographics, audiometric data, VS diagnosis, therapeutic steroid intervention, and data regarding treatment response were recorded. A clinically significant audiometric improvement was defined as (i) an increase of 15% in word recognition score, (ii) a decrease of 15 dB in four-frequency pure-tone average (PTA) using frequencies of 500, 1000, 2000, and 4000 Hz, or (iii) a PTA of <20 dB on follow-up audiogram. RESULTS: Six hundred fifty-eight patients were reviewed, of which 309 (56.0% male; mean, 57.5 years) met the inclusion criteria with audiometric data and magnetic resonance imaging data. Ten patients (70.0% male; mean, 51.3 years) were found to have VS. Of these, five patients received oral steroid therapy alone, and five had combination therapy (oral + intratympanic steroid injections). No patients received intratympanic steroid therapy alone. Median PTA improvement with steroid therapy was 3.1-dB hearing loss, and median word recognition score improvement was 16.5%. Six of 10 patients demonstrated clinically significant audiometric improvement with steroid therapy. CONCLUSION: This study represents the largest US-based study showcasing the prevalence of VS in patients originally presenting with SSNHL. It also reinforces previous findings that VS does not preclude trials of steroid therapy.

The impact of labyrinthine magnetic resonance signal alterations on the treatment of sudden sensory-neural hearing loss.

BACKGROUND: Sudden sensory-neural hearing loss (SSNHL), with positive findings on magnetic resonance imaging (MRI), possibly related to labyrinthine hemorrhage, is a rare condition and difficult to be diagnosed. OBJECTIVES: We evaluated the role of MRI in detecting labyrinthine signal changes and the impact of these changes on the prognosis of SSNHL after the intratympanic corticosteroid injection. METHODS: A prospective study was held between January and June 2022. We included patients who complained of SSNHL, either idiopathic (30 patients) or labyrinthine signal alterations (14 patients), as diagnosed by MRI performed 15 days after the SSNHL onset. In addition, all patients underwent a course of intratympanic prednisolone injections. RESULTS: 83.3% of the idiopathic group showed a complete or marked improvement after the intratympanic injection. Conversely, most cases of positive MR signal alterations (92.8%) had slight or poor improvement after the therapeutic course. CONCLUSIONS: Our study revealed that MRI imaging is essential for assessing any SSNHL case. It can diagnose labyrinthine hemorrhage, whose course and prognosis differ significantly from idiopathic SSNHL. SIGNIFICANCE: Intratympanic prednisolone injection was effective in managing idiopathic SSNHL. On the other hand, this therapeutic modality was ineffective in improving SSNHL associated with labyrinthine hemorrhage.

Discriminant Analysis of the Prognostic Factors for Hearing Outcomes in Patients with Idiopathic Sudden Sensorineural Hearing Loss.

BACKGROUND: This study aims to determine and assess prognostic variables that might affect the hearing result in patients with idiopathic sudden sensorineural hearing loss following intratympanic steroid injection. METHODS: In total, 190 patients with idiopathic sudden sensorineural hearing loss received intratympanic steroid injection. Two hearing indices (recovery and nonrecovery) will be analyzed as dependent variables; patient's age, time period between the onset of hearing loss and treatment, initial level of hearing (hearing loss pre), type of audiogram curve (upsloping, downsloping, and flat), presence of vertigo, presence of tinnitus, and diabetes) will be analyzed as prognostic factor variables. RESULTS: Recovery was seen in 72% of the patients. Different preinjection audiogram curves and hearing grades had a significant effect on recovery, absence of vestibular symptoms and no diabetic history were noted to have a good prognosis. Delay in treatment by more than 30 days from the onset of hearing loss was associated with a worse prognosis. CONCLUSION: Idiopathic sudden sensorineural hearing loss associated with late treatment plan more than 1 month, presence of vertigo, diabetes, and profound prehearing loss were negative prognostic factors. Whereas age, gender, and presence of tinnitus did not affect prognosis. More stable response was obtained when intratympanic steroids were added within 1 month after diagnosis, and the patient presented with mild or moderate hearing loss grade, flat or downsloping pure tone audiometery curve, and absence of vertigo and nondiabetic with significantly good results.

Efficacy of Intratympanic OTO-104 for the Treatment of Ménière's Disease: The Outcome of Three Randomized, Double-Blind, Placebo-Controlled Studies.

OBJECTIVE: To determine the efficacy of intratympanic OTO-104 for the treatment of Ménière's disease. STUDY DESIGNS: Three randomized, double-blind, placebo-controlled, multicenter studies of OTO-104 in patients with Ménière's disease. SETTING: The United States and throughout Europe. PATIENTS: Individuals with Ménière's disease aged 18 to 85 years. INTERVENTIONS: All three studies were conducted according to a similar protocol, whereby after a 1-month lead-in period, eligible patients received a single intratympanic injection of either 12 mg OTO-104 (otic formulation of dexamethasone in thermosensitive poloxamer) or placebo (1:1) and were observed for 3 months. MAIN OUTCOME MEASURES: The primary efficacy endpoint was measured by the number of definitive vertigo days (DVDs) at month 3. Secondary objective was OTO-104 safety and tolerability including adverse events, audiometry, tympanometry, and otoscopic examinations. RESULTS: Although OTO-104 demonstrated numerically greater reductions in DVD compared with placebo across all three studies, statistical significance versus placebo (primary efficacy endpoint) was only achieved in one study, the AVERTS-2 study (n = 174, p = 0.029). Secondary vertigo efficacy endpoints were statistically significant at month 3 in that study including vertigo severity, the effect of vertigo on daily activity (days at home sick or bedridden), and vertigo frequency. In the AVERTS-1 study, which did not meet the primary endpoint, a subgroup analysis of the 115 patients (69.7% of study population) who did not previously receive intratympanic steroid injections demonstrated that OTO-104 patients had significantly lower mean DVD at month 3 than patients receiving placebo (1.9 for OTO-104 versus 3.0 for placebo; p = 0.045). Importantly, a significant placebo response was observed across studies in Ménière's disease patients. OTO-104 and the intratympanic injection procedure were well tolerated. CONCLUSIONS: In all three high-quality, randomized, double-blind, placebo-controlled, multicenter studies, a single intratympanic injection of 12 mg OTO-104 demonstrated numerically greater reductions in vertigo versus placebo in patients with Ménière's disease, but statistical separation from placebo was demonstrated in only one of the studies. OTO-104 was safe and well tolerated.(Otonomy, Inc. funded; NCT02717442, NCT02612337, NCT03664674).

Hearing loss and COVID-19: an umbrella review.

INTRODUCTION: COVID-19 can result in an extensive range of extrapulmonary, and neurological signs and symptoms such as olfactory and/or taste dysfunction, and otologic symptoms. The aim of this study was to investigate the hearing loss manifestation from COVID-19. METHODS: The goal of this umbrella review was to examine hearing loss associated with COVID-19 disease. English literature published until October 15, 2022 in online databases including PubMed, Scopus, Web of Science, and Embase was considered for this purpose. Eligibility of the articles for subsequent data extraction was evaluated in a two-step selection process with consideration to an inclusion/exclusion criterion. This review followed the PRISMA protocol and the Amstar-2 checklist for quality assessment. RESULTS: A total of four treatment strategies were used by different studies which included oral corticosteroids, intratympanic corticosteroids, combined oral and intratympanic corticosteroids, and hyperbaric oxygen therapy. Five studies investigated corticosteroid use in the forms of oral or intratympanic injection; four studies reported (complete or partial) hearing improvements after steroid treatment, while one study stated no significant improvement in hearing function. One study reported that oral corticosteroid monotherapy alone was not effective, while vestibular symptoms were ameliorated by a combination of oral prednisone, intratympanic dexamethasone injection, and hydroxychloroquine. CONCLUSION: The findings suggest that despite being one of the rare complications of COVID-19, hearing loss can impact a patient's quality of life. The most common type reported was sensorineural hearing loss, which can be diagnosed with variable techniques.

The effectiveness of intratympanic steroid injection in addition to systemic corticosteroids in the treatment of idiopathic sudden sensorineural hearing loss.

There is a lot of controversy about the efficacy of intratympanic steroid (ITS) therapy in idiopathic sudden sensorineural hearing loss (ISSHL). ITS are reported to have effect on ISSNHL and ITS with additional systemic therapy are also effective. In the primary treatment of ISSHL, achieving the correct diagnosis rapidly is paramount, as early initial treatment greatly increases the chance of hearing recovery. A retrospective study took place from 2010 to 2017 in the 1st ENT Clinic of Athens. Participants were inward patients that were first examined and diagnosed with ISSNHL in the Emergency Department and afterwards admitted in the clinic. In 2014 our Clinic changed the Treating Protocol of ΙSSNHL. We compared the audiological results of the patients treated with the previous protocol (intravenous steroids) with those treated with the new protocol (concurrent intravenous and intratympanic steroids). The main outcome measure was the hearing threshold before treatment and after completion of therapy. We retrieved from the hospital medical records the following demographic and clinical data: sex, age, date of admission, comorbidities, hearing threshold per frequency on admission and on discharge day and time period between onset of symptoms and initial treatment. We concluded that both intratympanic steroids and systemic steroids alone appear equally effective, however the use of both intratympanic and systemic steroids together is likely superior to either used alone. Intratympanic steroids likely offer additional benefit as a secondary/salvage therapy in patients who fail initial systemic steroid therapy.

Skull-vibration-induced nystagmus test in patients who are candidates for intratympanic gentamicin injection.

Objective: This study aims to evaluate the utility of the skull-vibration-induced nystagmus test (SVINT) in the selection of patients with Ménière's disease (MD) for intratympanic injection of gentamicin. To date the indications for this treatment have been based only on subjective elements. Methods: A retrospective study was performed in 20 patients diagnosed with unilateral MD. SVINT were performed monthly and the evoked responses were evaluated. After 6 months, the results from patients who were candidates for gentamicin treatment (G group) were compared with those who did not need it (nG group). Correlation with Dizziness Handicap Inventory (DHI) score was evaluated. Results: 120 tests were performed. Positive SVINTs were identified in 52 cases (43.3%) and included excitatory nystagmus in 18 (34.7%), inhibitory nystagmus in 28 (53.8%), and atypical pattern in 6 cases (11.5%). A significant increase excitatory nystagmus was recorded in group G (p = 0.00001). Moreover, there was a significant increase in the DHI score in group G compared with the nG group (p < 0.0001) and in patients with evoked excitatory nystagmus. Conclusions: The finding of excitatory nystagmus during SVINTs performed on several occasions in the follow-up prior to intratympanic injection of gentamicin strengthens this therapeutic choice.

Retrospective study of risk factors for tympanic membrane perforation in the early period after intratympanic steroid injection.

OBJECTIVE: Intratympanic steroid injection (ITSI) can be an effective treatment for sudden sensorineural hearing loss or Meniere's disease. Tympanic membrane (TM) perforation after ITSI is a major complication which needs additional treatment. The purpose of this study is to assess the factors associated with TM perforation after ITSI. METHODS: We obtained the clinical data of patients who underwent ITSI treatment at the Department of Otolaryngology JR Tokyo General Hospital from April 2013 to March 2021. The data included age, sex, treated side, number of injections, average interval between injections, TM anesthesia with Zentöl solution, which contains phenol, any history of diabetes and any concurrent use of oral or intravenous steroids. We evaluated the association between these variables and TM perforation after ITSI using the Student's t-test, the chi-squared test, univariate logistic regression analysis and multivariate logistic regression analysis. TM perforation was defined as a case in which perforation was observed at least once during outpatient visits. RESULTS: Records of 205 ears in 190 patients were analyzed. The overall proportion of TM perforation in the early period after ITSI was 12.7% (26 out of 205 ears), which decreased to 9.3% (19 out of 205 ears) and 5.9% (12 out of 205 ears) at the 1- and 3-month follow-ups, respectively. The proportion of TM perforation in the early period after ITSI without TM anesthesia was 3.5% (5 ears out of 145 ears), which decreased to 1.4% (2 ears) or 0% at the 1- or 3- month follow-ups, respectively. The use of tympanic anesthetics which contain phenol was significantly associated with TM perforation in univariate logistic regression analysis (odds ratio: 15.08, 95% confidence interval: 5.34-42.56, p < 0.001) and in multivariate analysis (odds ratio: 20.76, 95% confidence interval: 6.31-68.3, p < 0.001). All TM perforation cases without TM anesthesia healed spontaneously or with paper tympanic closure treatment. TM perforation in 6 ears out of 21 ears with TM anesthesia did not heal during the follow-up. CONCLUSION: The overall proportion of TM perforations from the early period after ITSI was 12.7%, 9.3% at the 1-month post-ITSI outpatient follow-up, 5.9% at the 3-month post-ITSI outpatient follow-up. Tympanic anesthesia was significantly associated with TM perforation after ITSI, which indicated that TM anesthesia with solutions containing phenol is not recommended for ITSI.

Intratympanic Substance Distribution After Injection of Liquid and Thermosensitive Drug Carriers: An Endoscopic Study.

OBJECTIVE: In the treatment of inner ear conditions, intratympanic injection emerges as an important drug delivery method. Novel compounds designed for intratympanic injection are routinely loaded in viscous drug carriers. To date, it is unclear if they can freely distribute in the middle ear. The aims of this study were to investigate the middle ear distribution of different drug carriers during intratympanic injection and to determine an optimal injection method for thermosensitive hydrogels. METHODS: Twenty-one human temporal bones were intratympanically injected with fluid drug carriers or poloxamer-407 hydrogels at different tympanic membrane injection sites (inferior, anterior-superior) using different needle types (Whitacre, Quincke). Fluid distribution was evaluated via an endoscopic view. Injection volume, duration, backflow, and overall safety were analyzed. RESULTS: Liquid drug carriers distribute effortlessly in the middle ear, whereas an additional ventilation hole is advantageous when applying thermosensitive hydrogels. The round window is coated with required volumes between 150 and 200 µl, irrespective of the injection position. Required volumes to also coat the stapedial footplate ranged from 310 to 440 µl. Use of the Whitacre-type needle reduced backflow to the ear canal and enabled longer tympanic membrane visibility when no additional ventilation hole was placed. CONCLUSION: Intratympanic injection is a safe and reliable method for the application of thermosensitive hydrogels. The round window niche is readily filled regardless of the injected formulation and injection position. Although fluid drug carriers distribute effortlessly in the middle ear, the placement of an additional ventilation hole might facilitate the application of viscous hydrogels.

[Perilymphatic fistula in inner ear treated with blood patch].

Perilymphatic fistula (PLF) is a rare condition with a pathological communication between the inner ear and usually the middle ear, causing both cochlear and vestibular symptoms. PLF is typically treated with either a conservative approach or surgically with grafting. But a new treatment has been proposed: intratympanic injection of autologous blood, blood patch. This is a case report of a 21-year-old woman who presented herself with PLF and was successfully treated with blood patch.

Standardization of Outcome Measures for Intratympanic Steroid Treatment for Idiopathic Sudden Sensorineural Hearing Loss.

OBJECTIVE: To identify variability in reported hearing outcomes for intratympanic (IT) steroid treatment of idiopathic sudden sensorineural hearing loss (ISSNHL) by comparing outcomes using the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) guideline with other published criteria. STUDY DESIGN: Retrospective chart review. SETTING: Tertiary otology practice. PATIENTS: Patients with ISSNHL treated with IT steroid between April 2003 and December 2020. INTERVENTIONS: IT steroid injection and audiometric evaluation. MAIN OUTCOME MEASURES: 1) Rates of full, partial, or no recovery using the AAO-HNS guideline versus other reported criteria, and 2) correlation analyses of demographic and clinical variables with response to IT steroid. RESULTS: Using AAO-HNS reporting criteria, full recovery of the pure-tone average was noted in 25.68% of patients. Applying eight other published outcomes criteria to this patient cohort classified full recovery in 14.87 to 40.54% of patients. Similarly, AAO-HNS criteria classified "no recovery" in 51.35% of our patients, whereas applying the other reported criteria showed an average rate of 62.16% no recovery and as high as 82.43% of patients without recovery. Younger age ( p = 0.003; effect size, 0.924) and IT injection within a week of onset ( p < 0.001; effect size, 1.099) positively correlated with full recovery. There was no impact of prior or concurrent oral steroids, or number of steroid injections on outcome. CONCLUSION: Great variability exists in the literature for assessment of IT steroid outcomes in ISSNHL. Standard reporting of outcomes as per the AAO-HNS SSNHL guideline is recommended to consistently characterize IT steroid efficacy and allow comparison across studies.

Safety and efficacy of intratympanic histamine injection as an adjuvant to dexamethasone in a noise-induced murine model.

The safety and efficacy of intratympanic (IT) histamine (HIS) injection as an adjuvant to increase the inner ear penetration of dexamethasone (DEX) was investigated in this study. IT injections of DEX-only, 1% HIS+DEX and 4% HIS+DEX were performed in mice with noise-induced hearing loss. An inflammatory reaction in the middle ear was observed only in the 4% HIS+DEX group although no serious cytotoxic effects on the organ of Corti (OC) were observed at that concentration. Compared with the DEX-only group, the perilymphatic concentration of DEX was approximately two times higher in the 1% HIS+DEX group and approximately five times higher in the 4% HIS+DEX group. The expression of the DEX receptor in the cochlea was significantly increased in the 4%-HIS+DEX group. HIS appeared to induce transient damage the microstructure of the RWM with recovery observed within 3 weeks. The 1 and 4% HIS + DEX groups showed a significant recovery of the OC compared with the control group and they also achieved significantly better hearing restoration at 8 kHz in the DPOAE hearing test (P < .05) when compared to the DEX-only group. IT HIS temporarily disrupts the structure of the RWM and middle ear mucosa and significantly enhances the inner ear penetration of DEX. Therefore, IT HIS injection could be a simple and effective adjuvant therapy to increase perilymph concentration of DEX and achieve OC recovery after cochlear damage.

[Tolerance and acceptance of intratympanic injections]. / Toleranz und Akzeptanz der intratympanalen Injektion.

BACKGROUND: Intratympanic steroids are a therapeutic component in sudden hearing loss related to cochlear affection. Little has been published on patients' acceptance and tolerance to date. MATERIALS AND METHODS: A total of 84 patients were asked about health conditions and circumstances surrounding their intratympanic therapy. RESULTS: The patients comprised 38 women and 46 men, aged 57.2 years on average, who had mostly been referred by their ENT physician for second-line treatment. Reported were injection pain by 3.6%, discomfort by 22.6%, tolerability by 67.9%, and painlessness by 41.7% (more than one answer possible). Whereas 77.4% recommended intratympanic treatment, reasons for no recommendation were lack of efficacy and an unpleasant sensation. CONCLUSION: The majority of patients rated intratympanic therapy as bearable and recommendable. Close patient guidance seems to be an important part of the treatment.

Prognostic factors in elderly patients after an intra-tympanic steroid injection for idiopathic sudden sensorineural hearing loss.

BACKGROUND: Idiopathic sudden sensorineural hearing loss (ISSNHL) presents with emergent hearing impairment and is mainly treated with steroids. However, limited data exist regarding the prognostic factors among elderly patients (>65 years old) who receive an intra-tympanic steroid injection (ITSI). Therefore, we investigated the prognostic factors in these patients. METHODS: Between July 2016 and March 2022, we retrospectively enrolled 105 elderly patients (>65 years old) with unilateral ISSNHL who were treated with an ITSI, and recorded their clinical and audiological variables. RESULTS: The patients had a mean age of 72.03 ± 6.33 years and mean hearing level gain of 22.86 ± 21.84 dB, speech reception threshold (SRT) gain of 15.77 ± 35.27 dB, and speech discrimination score (SDS) gain of 19.54 ± 27.81 %. According to Siegel's criteria, 5 (4.76 %), 44 (41.91 %), 46 (43.81 %), and 10 (9.52 %) patients had complete recovery, partial recovery, slight improvement, and no improvement, respectively. In the univariate analysis, vertigo (odds ratio [OR] = 0.290, 95 % confidence interval [CI]: 0.130-0.651, p = 0.002) and profound hearing loss on pure tone audiometry (PTA; OR = 0.233, 95 % CI: 0.101-0.536, p = 0.004) were negative prognostic factors among elderly ISSNHL patients. In the multivariate analysis, vertigo (OR = 0.300, 95 % CI: 0.128-0.705, p = 0.005) and profound pure tone audiometry (OR = 0.240, 95 % CI: 0.101-0.570, p = 0.001) were independent adverse prognostic factors among elderly ISSNHL patients. CONCLUSIONS: We demonstrated the treatment outcomes of 105 elderly ISSNHL patients after an ITSI. Vertigo and profound PTA are independent adverse risk factors among elderly ISSNHL patients, and patients with these risk factors require active treatment.

Intratympanic corticosteroid injection as a first-line treatment of the patients with idiopathic sudden sensorineural hearing loss compared to systemic steroid: A systematic review and meta-analysis.

OBJECTIVES: The current study aimed to investigate if there is a difference in the use of intratympanic steroid therapy (IST), compared to systemic steroid treatment (SST), as an initial treatment for patients with sudden sensorineural hearing loss (SSNHL) by a meta-analysis design performed on the mean pure-tone average (PTA) improvement and the complete recovery rate. METHODS: A systematic literature review was performed on randomized controlled trials published from 1990 to August 2020 in some databases including PubMed/MEDLINE, Scopus, Embase, Web of Science, Cochrane library/CENTRAL, Ovid, ProQuest, Google Scholar, and clinical trials.gov. The primary outcomes of interest were pure-tone average improvement and complete recovery rates. RESULTS: Six eligible studies with 496 patients (250 patients in the IST group and 246 subjects in the SST group) were included in this study. The pooled standardized mean difference of the PTAs was estimated as 0.07 (95% CI = -0.10 to 0.25; I2 = 0.0%, P = 0.668), and the pooled odds ratio of complete recovery rate was obtained as 1.00 (95% CI = 0.66 to 0.151; I2 = 31.6, P = 0.199). Moreover, the pooled standardized mean difference of pure-tone average for the intratympanic steroid treatment group compared to the patients with oral steroid treatment was 0.07 (95% CI = -0.12 to 0.26; I2 = 0.0%, P = 0.526). CONCLUSIONS: The current study demonstrated that the effect of intratympanic injection of corticosteroid, as a first-line treatment, is not statistically different from the systemic route in improving the hearing outcomes among patients with SSNHL.

Probability of clinically significant hearing recovery following salvage intratympanic steroids for sudden sensorineural hearing loss in the 'real world'.

OBJECTIVE: This study aimed to determine the probability of hearing recovery in patients with idiopathic sudden sensorineural hearing loss following salvage intratympanic steroids. METHOD: A retrospective review of all patients receiving salvage intratympanic steroid injections for idiopathic sudden sensorineural hearing loss was performed (January 2014 to December 2019). Twenty-two patients were identified, of whom 15 met inclusion criteria. Pre- and post-treatment audiograms were compared with the unaffected ear. Hearing recovery was categorised based on American Academy of Otolaryngology Head and Neck Surgery criteria. RESULTS: Only 1 patient out of 15 (6.7 per cent) made a partial recovery, and the remainder were non-responders. The median duration of time between symptom onset and first salvage intratympanic steroid treatment was 52 days (range, 14-81 days). No adverse reactions were observed. CONCLUSION: 'Real world' patients with idiopathic sudden sensorineural hearing loss present differently to those in the literature. Sudden sensorineural hearing loss should be diagnosed with care and intratympanic steroid injections initiated early if considered appropriate. Patients should make an informed decision on treatment based on prognostic factors and local success rates.

Consensus on intratympanic drug delivery for Menière's disease.

PURPOSE: Intratympanic (IT) drug delivery receives attention due to its effectivity in treatment for Menière's disease (MD). Due to the release of the consensuses and new evidence on IT drug delivery for MD have been published, the review with a view to supplementing the details of IT treatment of MD is indispensable. METHODS: The literatures on IT injection for MD treatment over the last two decades are retrieved, International consensus (ICON) on treatment of Menière's disease (2018), Clinical Practice Guideline (2020) and European Position statement on Diagnosis and Treatment of Meniere's Disease (2018) are taken into account for reference, and follow advice from experts from Europe, USA and China. RESULTS: Experts agree on the following: (1) The effectiveness of IT methylprednisolone (ITM) on vertigo control seems to be somewhat better than that of IT dexamethasone (ITD), and ITM can restore hearing in some cases. (2) Due to the ototoxicity of aminoglycosides, the application of intratympanic gentamicin (ITG) in MD patients with good hearing is conservative. However, some studies suggest that ITG with low doses has no significant effect on hearing, which needs to be further proved by clinical studies with high levels of evidence. (3) Currently, generally accepted treatment endpoint of ITG is no vertigo attack in a 12-month period or a vestibular loss in objective tests in the affected ear. CONCLUSION: More studies with high level of evidence are needed to evaluate the drug type, efficacy, and therapeutic endpoint of IT therapy for MD.

Optimal N-acetylcysteine concentration for intratympanic injection to prevent cisplatin-induced ototoxicity in guinea pigs.

BACKGROUND: Cisplatin is a chemotherapy drug that can induce sensorineural hearing loss. At present, no otoprotective agent is approved for use. OBJECTIVES: This study investigated the optimal concentration of intratympanic N-acetylcysteine (NAC) to prevent cisplatin-induced ototoxicity in a guinea pig model. MATERIALS AND METHODS: Guinea pigs (n = 64) were treated with a single intratympanic injection containing different NAC concentrations or saline (control) 3 days prior to intraperitoneal injection with cisplatin. The threshold change in the auditory brainstem response was assessed. RESULTS: Four weeks after intraperitoneal cisplatin injection, only the group that received 2% NAC exhibited significant otoprotection (p < .05) compared with the control. Otoprotection was observed at all the frequencies tested (1k, 2k, 4k, and 8k Hz). The 2% NAC group also exhibited significant otoprotection (p < .05) compared with the other NAC groups (at 1k, 2k, 4k, and 8k Hz). The 4% NAC group exhibited significantly reduced hearing capacity (p < .05) in the fourth week compared with controls. CONCLUSIONS AND SIGNIFICANCE: Intratympanic NAC administration is an efficient and safe means of preventing cisplatin-induced ototoxicity. In our animal model, the optimal intratympanic NAC concentration was 2%; concentrations of 4% loss of otoprotection.