BACKGROUND: Intratympanic corticosteroids are commonly used in the treatment of Menière\'s disease (MD). However, few and small randomised controlled trials (RCT) on the effectiveness of intratympanic corticosteroids have been performed. A recent Cochrane review suggested that a well-conducted placebo-controlled RCT with a large study population is required to evaluate the effectiveness of the use of intratympanic corticosteroids in MD. The following protocol describes a phase-3 multicentre, double-blinded, randomised, placebo-controlled trial to compare the effectiveness of methylprednisolone (62.5 mg/mL) to a placebo (sodium chloride 0.9%).
METHODS: We aim to recruit 148 patients with unilateral MD from six hospitals in the Netherlands. Patients will be randomly assigned to either the methylprednisolone or the placebo group. Two injections will be given, one at baseline and one after 2 weeks. Follow-up assessments will be done at 3, 6, 9 and 12 months. The primary outcome will be the frequency of vertigo attacks. Attacks will be evaluated daily with the DizzyQuest app. Secondary outcomes include hearing loss, tinnitus, health-related quality of life, use of co-interventions and escape medication, (serious) adverse events and cost-effectiveness. These will be evaluated with audiometry and multiple commonly used, validated questionnaires. For the primary and secondary outcomes mixed model analysis, generalised estimating equation analysis and logistic regression analysis will be used.
BACKGROUND: This study was submitted via the Clinical Trials Information System, reviewed and approved by the Medical Research Ethics Committee Leiden The Hague Delft and the local institutional review board of each participating centre. All data will be presented ensuring the integrity and anonymity of patients. Results will be published in scientific journals and presented on (inter)national conferences.
BACKGROUND: This study is registered at ClinicalTrials.gov Protocol Registration and Results System, with the registration ID: NCT05851508.

Endolymphatic hydrops has been documented as a possible complication of cochlear implantation; however, few studies have addressed its treatment. We describe the first case ever reported of delayed endolymphatic hydrops after a cochlear implant successfully treated with intratympanic gentamicin injection. A detailed discussion of this case with a focus on its management and outcomes will be provided in comparison with literature data. The intratympanic gentamicin injection has been demonstrated to be an effective treatment for symptomatic endolymphatic hydrops after cochlear implantation. We advocate further studies to validate this strategy as a promising alternative to surgical labyrinthectomy.

OBJECTIVE: Intratympanic injection of corticosteroids (ITC) and gentamicin therapy (ITG) are widely used treatments for vertigo in Meniere\'s disease (MD). Even though studies show good results after cochlea implantation (CI) in MD patients when compared to non-MD groups, there is no indication on the effect of ITC and ITG prior to CI on hearing after CI. This study compares the post-operative hearing of CI patients with and without MD and patients who have received ITG or ITC prior to CI.
METHODS: In a retrospective case control study, adult patients with MD who received CI from 2002 till 2021 were compared to a matched control group of CI patients without MD. Patients with prior ITC/ITG were extracted from MD group. Pre-operative audiological results were measured and trends across post-operative monosyllabic word recognition score at 65 decibels (WRS65CI) at switch-on, 3-6 months, 1 year and last yearly value were analyzed across all groups.
RESULTS: 28 MD ears were compared with 33 control ears. From MD ears 9 had received ITG and 6 ITC prior to CI. WRS65CI increased significantly with time within MD and control groups, but no difference in WRS65CI was found between these 2 groups. ITG ears showed fluctuating WRS65CI after CI with no change across time, while ITC ears showed significant increase in trend of WRS65CI values across time.
CONCLUSIONS: MD and non-MD patients showed comparable hearing results after CI. Prior ITC might positively influence hearing preservation after CI in MD patients whereas ITG group showed fluctuating hearing.

OBJECTIVE: This was a randomized, double-blind, placebo-controlled Phase 2 study to evaluate the efficacy and safety of intratympanic OTO-313 in patients with subjective unilateral tinnitus.
METHODS: Patients with moderate to severe unilateral tinnitus of 2-12 months duration were enrolled. A single intratympanic injection of OTO-313 or placebo was administered to the affected ear and patients were evaluated during a 16-weeks follow-up period. Efficacy was assessed using the Tinnitus Functional Index (TFI), daily ratings of tinnitus loudness and annoyance, and Patient Global Impression of Change (PGIC).
RESULTS: Intratympanic administration of OTO-313 and placebo produced reductions in tinnitus with a similar percentage of TFI responders at Weeks 4, 8, 12, and 16. Reductions in daily ratings of tinnitus loudness and annoyance, and PGIC scores were also similar between OTO-313 and placebo groups. No significant differences in mean TFI scores between OTO-313 and placebo were observed for pre-specified strata regarding tinnitus duration (≥ 2 to ≤ 6 months and > 6 to ≤ 12 months) and TFI baseline scores (≥ 32 to ≤ 53 points and ≥ 54 to 100 points), although the results numerically favored OTO-313 in patients in the ≥ 2 to ≤ 6 months strata. These results also demonstrated an unexpectedly high placebo response particularly amongst patients with chronic tinnitus, despite training implemented to mitigate placebo response. OTO-313 was well-tolerated with a similar incidence of adverse events compared to placebo.
CONCLUSIONS: OTO-313 did not demonstrate a significant treatment benefit relative to placebo due in part to a high placebo response. OTO-313 was safe and well-tolerated.

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.
CONCLUSIONS: 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.

To determine the efficacy of intratympanic OTO-104 for the treatment of Ménière\'s disease.
Three randomized, double-blind, placebo-controlled, multicenter studies of OTO-104 in patients with Ménière\'s disease.
The United States and throughout Europe.
Individuals with Ménière\'s disease aged 18 to 85 years.
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.
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.
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.
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).

UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
UNASSIGNED: 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.
Skull-vibration-induced nystagmus test in pazienti candidati a gentamicina intratimpanica.
UNASSIGNED: Questo studio si prefigge di valutare l’utilità dello skull-vibration-induced nystagmus test (SVINT) nel selezionare, tra i pazienti affetti da malattia di Ménière (MD), quelli candidabili a iniezione intratimpanica di gentamicina. A oggi l’indicazione a questo trattamento si basa su criteri soggettivi.
UNASSIGNED: È stato eseguito uno studio retrospettivo in 20 pazienti con una prima diagnosi di MD unilaterale valutando le risposte oculomotorie evocate allo SVINT eseguito durante i controlli mensili. Dopo 6 mesi sono state confrontate le risposte ottenute nei pazienti che sono stati candidati a trattamento con gentamicina (G group) rispetto a quelle ottenute nei pazienti non candidati (nG group) indagando inoltre la correlazione con il Dizziness Handicap Inventory (DHI).
UNASSIGNED: Il test è risultato positivo in 52 casi su 120 (43,3%) con nistagmo evocato di tipo eccitatorio in 18 (34,7%), inibitorio in 28 (53,8%) e atipico in 6 casi. La frequenza del pattern eccitatorio è risultata maggiore nel G group rispetto al nG group (p = 0,00001), inoltre questo pattern correlava con un punteggio DHI maggiore.
UNASSIGNED: La presenza, in più occasioni, di un nistagmo eccitatorio allo SVINT può essere un criterio oggettivo a sostegno della scelta di trattare il paziente mediante iniezioni intratimpaniche di gentamicina.

BACKGROUND: 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.
CONCLUSIONS: 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.

OBJECTIVE: This study investigated the impact of eustachian tube (ET) function (ETF) on therapeutic success on candidates for intra-tympanic administration of steroids (ITAoS), due to idiopathic sudden sensorineural hearing loss (ISSNHL).
METHODS: Medical chart review in two university-affiliated medical centers was performed. Included were consecutive adult patients diagnosed with unilateral ISSNHL between 2012 and 2019 who were treated with ITAoS due to incomplete or no recovery following systemic steroidal therapy. ETF was assessed by means tympanometry, before the initiation of ITAoS. The cohort was divided into an ET dysfunction group (ETD(+)) and a functioning ET group (control: ETD(-)). The audiologic response to treatment was recorded at the last follow-up.
RESULTS: A total of 64 suitable patients [median (interquartile, IQR) age 49 (38-63) years] were enrolled. The ETD(+) group included 20 patients and the remaining 44 patients served as controls. Demographic and clinical parameters were not significantly different between the two groups at presentation. Hearing thresholds were improved significantly better, at frequencies 250, 500, 1, 2, 4, and 8 kHz (p = 0.001-0.040) in the ETD(+) group.
CONCLUSIONS: ETD(+) is associated with better efficacy of ITAoS.
METHODS:

OBJECTIVE: 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.
CONCLUSIONS: More studies with high level of evidence are needed to evaluate the drug type, efficacy, and therapeutic endpoint of IT therapy for MD.