Intratympanic Injection Research Articles

Safety and Efficacy of Intratympanic Alpha-Lipoic Acid Injection in a Mouse Model of Noise-Induced Hearing Loss.

Alpha-lipoic acid (ALA) is an antioxidant with oto-protective effects. In the present study, the safety and effectiveness of ALA therapy after noise-induced hearing loss was confirmed based on the administration method. The safety of intratympanic ALA (IT-ALA) was evaluated with oto-endoscopy and middle ear mucosa morphologic study. Perilymph ALA concentrations according to the administration routes were compared, and the efficacy of ALA was investigated through hearing tests and cochlear histological studies. The middle ear mucosa was swollen 1 week after IT-ALA but completely recovered within 3 weeks. ALA concentration in the perilymph was significantly higher in the IT-ALA group. Recovery of organ of Corti morphology and hearing levels were predominant in the IT-ALA group compared with the intraperitoneal injection group (IP-ALA) and showed similar rescue effects in the IT-dexamethasone group (IT-DEX). Interleukin-1 beta and nuclear factor-kappa B expression was significantly downregulated in the IT-ALA group. IT-ALA showed better cochlear recovery from acoustic trauma with higher inner ear penetration rate than IP-ALA. The rescue effect of IT-ALA after noise-induced hearing loss was similar to IT-DEX; however, the ALA and DEX mechanisms are different. IT-ALA appears to be another safe and effective treatment modality after acoustic trauma and comparable to IT-DEX.

Consensus on intratympanic drug delivery for Menière's disease

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 Menière'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: ①The 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. ②Due 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. ③Currently, 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.

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

BackgroundIdiopathic 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. MethodsBetween 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. ResultsThe 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. ConclusionsWe 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.

Possible Neoplastic or Proliferative Effects of Intra-Tympanic Platelet-Rich Plasma on the MiddleEarMucosa: A Myth or a Fact to Consider?

Platelet-rich plasma is a frequently used plasma-derived material; however, a possible neoplastic or proliferative effect is one of the limiting issues in its use. The aim of our experimental study was to investigate the long-term histological effects of platelet-rich plasma on the middle ear mucosa. The rats were divided into 2 groups randomly (groups 1 and 2). Group 1 represented the control group and 8 rats were included in this group. To the left ear, 0.3 mL of normal saline solution was administered intra-tympanically. No injections were done to the right ears. Group 2 represented the platelet-rich plasma group and 11 rats were included. To the left ears, 0.3 mL of platelet-rich plasma and to the right ears 0.3 mL of normal saline solution was administered intra-tympanically. The intra-tympanic platelet-rich plasma injections were done twice with an interval of 1 week. All animals were sacrificed in the third month. The degree of mucosal thickness, the presence of metaplasia, atypical cells, myofibroblastic infiltration, angiogenesis, and acute or chronic inflammation were evaluated histopathologically. Histopathological findings in the right and left ears in each group were compared in itself. The degree of inflammation and mucosal thickness were significantly higher in the perforated and saline administered side, in group 1 (P < .001). In group 2, the degree of angiogenesis was significantly higher in the platelet-rich plasma administered side (P < .001). The degree of mucosal thickness was significantly higher in the saline administered side (P < .001). Considering the anti-inflammatory and regenerative features and its safety, intra-tympanic-PRP may, in the future, be an alterna- tive to current intra-tympanic treatment modalities.

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

This study aimed to determine the probability of hearing recovery in patients with idiopathic sudden sensorineural hearing loss following salvage intratympanic steroids. 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. 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. '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.

Quality of life after intratympanic steroid injection for Ménière's disease.

ObjectiveThis study explores how treatment with intratympanic steroid injection affects quality of life, as well as several subjective complaints in patients with Ménière's disease.MethodsPatients filled in the Ménière's Disease Outcome Questionnaire (MDOQ) and answered questions about subjective complaints. Scores before and after treatment were compared using paired t tests.ResultsForty‐nine patients treated with intratympanic steroid injection were included. Quality of life was improved in 36 (73%) patients, the same in 9 (18%) patients, and lower in 4 (8%) patients. Overall, the mean change in MDOQ was +20.6 points (95% confidence interval +14.5 to +26.7 points, p < 0.001). The improvement was seen in the emotional, physical, and mental domain. Most patients experienced less vertigo and instability but did not notice change in subjective hearing, tinnitus, or aural fullness after treatment.ConclusionTreatment with intratympanic steroid injection leads to an improvement in quality of life in most patients. Moreover, the procedure is only minimally invasive. Based on the findings in this study, treatment with ITS should be discussed with every patient suffering from vertigo attacks due to active Ménière's disease.Level of evidenceLevel 4

AB211. SOH22ABS077. Intratympanic dexamethasone injection for tinnitus

Background: Tinnitus affects over 60% of people at some stage of their lives and are often short-lived. A small cohort of patients experience intractable debilitating tinnitus, unrelated to hearing loss or vertigo syndromes. Management strategies include tinnitus masking techniques, cognitive behavioural therapy, and more recently, neuromodulation. Intratympanic dexamethasone injection for intractable tinnitus has been described although the evidence for such intervention is not strong.

Duration of symptom control following intratympanic dexamethasone injections in Meniere’s disease

PurposeIntratympanic (IT) injections of corticosteroids have emerged as a non-ablative alternative to gentamicin in the management of refractory Meniere’s disease. However, currently, the duration of the symptom control achieved via intratympanic corticosteroids is under reported.MethodsWe retrospectively reviewed the notes of all patients who underwent IT injections of dexamethasone for the treatment of definite Meniere’s disease at a single tertiary referral university centre over a 6-year period. We included demographic information, the number of procedures patients required, duration of symptom-control achieved (time interval between repeat IT injections), and the presence of co-morbidities, with a focus on the presence of autoimmune disease.ResultsWe identified 27 patients who underwent a total of 42 procedures; 23/27 (85.2%) patients demonstrated clinical response with a median period of symptom control of 14.5 months (range 1–64, IQR 10.25). The median longest asymptomatic period per patient was 19 months (range 11–64, IQR: 18). Interestingly, all patients with autoimmune disease (7/27) demonstrated a clinical response; autoimmune disease was found to be a statistically significant predictor of response to treatment (p = 0.002). In patients who received repeated treatment following disease relapse, there was no difference in duration of symptom-control achieved.ConclusionsIT steroids can provide an effective alternative to gentamicin ablation. Symptom control is achieved for a median of 14.5 months, and treatment can be repeated with no loss of efficacy. Those patients who have an underlying autoimmune co-morbidity are more likely to demonstrate a clinical response to therapy, which may provide insight into the underlying pathophysiology of Meniere’s disease.

Betahistine alleviates benign paroxysmal positional vertigo (BPPV) through inducing production of multiple CTRP family members and activating the ERK1/2-AKT/PPARy pathway

BackgroundBetahistine is a clinical medication for the treatment of benign paroxysmal positional vertigo (BPPV). Otolin, a secreted glycoprotein with a C-terminal globular domain homologous to the immune complement C1q, has been identified as a biomarker for BPPV. However, the role of complement C1q/TNF-related proteins (CTRPs) with a C-terminal globular domain in BPPV is unclear, so we explored the change of CTRPs in betahistine treated BPPV.MethodsWe treated BPPV patients with Betahistine (12 mg/time, 3 times/day) for 4 weeks and observed the clinical efficacy and the expression of CTRP family members in BPPV patients. Then, we constructed a vertigo mice model of vestibular dysfunction with gentamicin (150 mg/Kg) and a BPPV model of Slc26a4loop/loop mutant mice. Adenoviral vectors for CTRP expression vector and small interfering RNA were injected via the intratympanic injection into mice and detected the expression of CTRP family members, phosphorylation levels of ERK and AKT and the expression of PPARγ. In addition, we treated mice of vestibular dysfunction with Betahistine (10 mg/Kg) and/or ERK inhibitor of SCH772984 (12 mg/Kg) and/or and PPARγ antagonist GW9662 (1 mg/Kg) for 15 days, and evaluated the accuracy of air righting reflex, the time of contact righting reflex and the scores of head tilt and swimming behavior.ResultsAfter treatment with Betahistine, the residual dizziness duration and the score of the evaluation were reduced, and the expression of CTRP1, 3, 6, 9 and 12 were significantly increased in BPPV patients. We also found that Betahistine improved the accuracy of air righting reflex, reduced the time of contact righting reflex and the scores of head tilt and swimming behavior in gentamicin-treated mice and Slc26a4loop/loop mutant mice. The expression levels of CTRP1, 3, 6, 9 and 12, phosphorylation levels of ERK and AKT, and PPARγ expression were significantly increased, and the scores of head tilt and swimming behavior were decreased in vestibular dysfunction mice with overexpression of CTRPs. Silencing CTRPs has the opposite effect. SCH772984 reversed the effect of Betahistine in mice with vestibular dysfunction.ConclusionBetahistine alleviates BPPV through inducing production of multiple CTRP family members and activating the ERK1/2-AKT/PPARy pathway.

Otitis media-induced cochlear immune response and opportunistic ototoxicity

Lipopolysaccharide (LPS), an essential component of the bacterial endotoxin, activates tissue macrophages and triggers the release of inflammatory cytokines. In animal models, intratympanic (i.t.) injection of LPS is known to simulate acute otitis media (AOM) and modifies the structure and function of the inner ear. However, whether LPS-induced AOM modulates the uptake of ototoxic aminoglycosides in vivo is unclear. Here, we established an AOM mouse model to investigate the gentamicin uptake in the inner ear and the change of cochlear inflammation for pertaining ototoxicity mechanisms. We found that LPS-induced AOM switched on the cochlear inflammatory response, including macrophage infiltration and upregulation of pro-inflammation cytokines, and significantly enhanced the cochlear uptake of gentamicin. Potential mechanisms of enhanced drug uptake may include increased strial permeability due to acute middle-ear inflammation, resulting in higher drug concentration in the stria vascularis and the endolymph, and subsequently higher drug uptake by hair cells. Other possible mechanisms, such as the activation of specific candidate channels and endocytosis followed by inflammation, need to be further interrogated. In sum, this study improves our understanding of drug trafficking in the pathological cochlea and provides a reference for drug treatment of AOM while protecting the inner ear function.

Symptoms: Sudden Hearing Loss and Vertigo

Symptoms: Sudden Hearing Loss and Vertigo

Clinicoaudiological evaluation of hearing improvement in patients with sensorineural hearing loss using intratympanic platelet rich plasma versus steroid injection

&lt;p&gt;&lt;strong&gt;Background: &lt;/strong&gt;SNHL is a heterogenous disorder, which can arise due to damage to pathway for sound impulses from the hair cells of inner ear to auditory nerve. This study is&lt;strong&gt; &lt;/strong&gt;to evaluate and compare the effect of intratympanic instillation of PRP in patients having sensorineural hearing loss with steroid therapy.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Methods: &lt;/strong&gt;A&lt;strong&gt; &lt;/strong&gt;prospective observational study carried out in the department of ENT, NSCB medical college Jabalpur. The cases were selected who presented with sensorineural hearing loss and mixed hearing loss with intact TM. Total of 54 cases were enrolled in the study from 1March, 2020 to 31 August 2021.Preoperative PTA was recorded. 0.5 ml of intratympanic platelet rich plasma and 0.5 ml of steroid dexamethasone administered. Postoperative PTA was done after 15 days of intratympanic injection and results recorded.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Results&lt;/strong&gt;: In our study the mean age of the participants was 40.4 years. Bilateral and gradual hearing loss were common in the present study. The improvement from baseline to follow up period was higher in PRP group compared to DEXA group. It is statistically significant (p=0.001). The improvement in hearing loss is decreasing with the increase in age. The study revealed that hearing improvement with PRP is better than steroid.&lt;/p&gt;&lt;p&gt;&lt;strong&gt;Conclusions: &lt;/strong&gt;The study concluded that the hearing improvement was more with single injection of PRP than dexamethasone.&lt;/p&gt;

Low-Dose Intratympanic Gentamicin for Unilateral Ménière's Disease: Accuracy of Early Vestibulo-Ocular Reflex Gain Reduction in Predicting Long-Term Clinical Outcome.

BackgroundThe number of intratympanic gentamicin (ITG) injections needed to achieve vertigo control in patients with intractable Ménière's disease (MD) may vary from a single dose to several instillations. Changes in different vestibular test results have been used to define an endpoint of treatment, including the decrease of the vestibulo-ocular reflex (VOR) gain elicited by the head-impulse test.ObjectiveTo assess the accuracy of the VOR gain reduction after horizontal canal stimulation, as measured with the video head-impulse test (vHIT) 1 month after the first intratympanic injection, in predicting the need for one or more instillations to control vertigo spells in the long term.MethodsThe VOR gain reduction was calculated in 47 patients submitted to (ITG) therapy 1 month after the first instillation.ResultsSingle intratympanic treatment with gentamicin has a 59.6% efficacy in vertigo control in the long term. Hearing change in the immediate period after treatment (1 month) is not significant to pre-treatment result and is similar for patients who needed multiple doses due to recurrence. Chronic disequilibrium and the need for vestibular rehabilitation were less frequent in patients with a good control of vertigo with just one single injection of gentamicin. A fair accuracy was obtained for the VOR gain reduction of the horizontal canal (area under the curve = 0.729 in the Receiver Operating Characteristic analysis) in predicting the need for one or more ITG.ConclusionsSingle intratympanic treatment with gentamicin is an effective treatment for patients with MD. That modality of treatment has very limited damaging effect in hearing. The degree of vestibular deficit induced by the treatment is significant as measured by the reduction in the gain of the VOR but not useful for prognostic purposes.

Clinical application of MIIRMR as a salvage method in gadolinium-enhanced MRI after intra-tympanic injection

Background Three-dimensional fluid-attenuated inversion-recovery (3 D-FLAIR) and real inversion-recovery (3 D-real IR) sequences are used to detect endolymphatic hydrops (EH), but medium inversion-time inversion-recovery imaging with magnitude reconstruction (MIIRMR) may be more sensitive. Aims We investigated the inner-ear visualisation success rate and EH detection rates of 3 D-FLAIR and 3 D-real IR, and whether salvage MIIRMR could improve EH detection. Materials and Methods Fifty-one patients (102 ears) with episodic or chronic vestibular syndrome were injected intra-tympanically with 8-fold diluted gadolinium, and 3 D-FLAIR and 3 D-real IR images obtained 24-h post-injection. If 3 D-FLAIR inner-ear visualisation failed, additional MIIRMR was performed. The success and EH detection rate increase by MIIRMR was calculated. The diagnostic performance of combined MIIRMR + 3D-FLAIR + 3D-real IR for Meniere’s disease (MD) was evaluated. Results The success rates of 3 D-FLAIR and 3 D-real IR were 88.90% and 72.55%, respectively. MIIRMR increased the success and EH detection rates by 11.10% and 6.86%, respectively. In MD, MIIRMR increased these rates by 10.53% and 10.53%, respectively. 3 D-FLAIR + 3D-real IR + MIIRMR had 92.11% sensitivity, 79.68% specificity, 72.92% positive-predictive value, and 94.44% negative-predictive value for MD diagnosis. Conclusion and significance MIIRMR can improve success and EH detection rates when 3 D-FLAIR fails. Combined MIIRMR + 3D-FLAIR + 3D-real IR is more valuable for diagnosing MD than conventional sequences.

Dexamethasone does not affect endolymphatic hydrops (EH) in patients with Meniere's disease within 24 h, and intratympanic administration of gadolinium plus dexamethasone simplifies high-quality imaging of EH using a novel protocol of 7 min

BackgroundIntratympanic administration of gadolinium chelate allows for a better visualization of endolymphatic hydrops (EH) using MRI than intravenous injection and was recently further improved to facilitate high-quality imaging of EH in 7 min. The aim of the present study was to simplify the intratympanic administration protocol by mixing gadolinium chelate with therapeutic dexamethasone and to evaluate the effects of this mixture on the visualization of EH in MRI. Materials and methodsIn an in vitro study, the potential impact of gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) on the stability of dexamethasone was evaluated by analyzing dynamic changes in dexamethasone with high-performance liquid chromatography (HPLC) after mixing with Gd-DTPA. Ten patients with definite Meniere's disease (MD) were recruited to study the potential interference of dexamethasone on MRI visualization of EH, and 49 patients with MD were recruited to evaluate the effect of intratympanic injection of Gd-DTPA mixed with dexamethasone on MRI of EH using a 3T MR machine and a novel heavily T2-weighted 3-dimensional fluid-attenuated inversion recovery reconstructed using a magnitude plus zero-filled interpolation (hT2FLAIR-MZFI) sequence. ResultsThe retention times and peak area of dexamethasone in HPLC were not modified by the addition of Gd-DTPA. EH grading in the cochlea and vestibule was not influenced in any ear by intratympanic injection of dexamethasone. Excellent inner ear images were obtained from all patients, and EHs with various grades were displayed. There were significant correlations between diagnosis and cochlear EH (p < 0.01, Spearman's Rho), between diagnosis and vestibular EH (p < 0.01, Spearman's Rho), and between cochlear and vestibular EH (p < 0.01, Spearman's Rho). The distribution of Gd-DTPA plus dexamethasone negatively correlated with the grade of vestibular EH. Injury of the endolymph-perilymph barrier was detected in one cochlea and three vestibules of 59 inner ears with MD. ConclusionsIntratympanic administration of Gd-DTPA plus dexamethasone yielded high-quality MRI images of EH in patients with MD using a novel 7-min protocol and simplified the clinical application. Intratympanic administration of Gd-DTPA plus dexamethasone might be used to test its therapeutic effect in future work. Level of evidence3.

Effectiveness of Intratympanic Dexamethasone Injection for Tinnitus Treatment: A Systematic Review and Meta-Analysis.

ObjectivesIntratympanic dexamethasone injection (ITDI) has been introduced as a treatment option for subjective tinnitus. However, the effects of ITDI on patients with tinnitus remain unclear. In the present systematic review and meta-analysis, we evaluated the effectiveness of ITDI for tinnitus treatment.MethodsWe searched Medline, the Cochrane Central Register of Controlled Trials, and Embase. Four double-blind randomized controlled trials that tested the efficacy of ITDI compared with a placebo were deemed eligible for a quantitative meta-analysis, while four prospective studies and seven retrospective studies reporting the effectiveness of ITDI on tinnitus treatment were included in a qualitative synthesis.ResultsIn the four studies included in the quantitative meta-analysis, ITDI did not show evidence of tinnitus improvement compared with placebo (odds ratio [OR], 1.38; 95% confidence interval, 0.53–3.61). In the 11 studies included in the qualitative synthesis, seven retrospective studies without controls reported rates of tinnitus improvement after ITDI ranging from 35.9% to 91.3%. In the four prospective studies with controls, ITDI seemed to be effective when combined with other drugs for tinnitus treatment.ConclusionITDI alone did not show a significant effect for treating tinnitus compared with placebo. However, the potential of combination treatment of ITDI with other drugs for tinnitus therapy should be further studied in more systematic research.

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.

Intratympanic corticosteroid as salvage therapy in treatment of idiopathic sudden sensorineural hearing loss: A systematic review and meta-analysis

BackgroundThe standard treatment of idiopathic sudden sensorineural hearing loss (ISSNHL) constitutes of systemic oral corticosteroid. Although oral corticosteroid might revert the acute deafness, some patients with ISSNHL display a more treatment refractory course. For these patients, corticosteroid installed directly into the middle ear has become a more frequent treatment, due to the potential benefits of a high, local concentration compared to a systemic administration. As such, for patients being refractory to standard treatment, intratympanic injection of a high dosage of corticosteroid as salvage therapy may be beneficial. ObjectivesTo evaluate the efficacy of intratympanic corticosteroid (ITC) as a salvage treatment of ISSNHL. MethodsA systematic literature search was performed in relevant databases. Both randomized trials and observational studies were considered for inclusion. The risk of bias was evaluated using the Cochrane risk of bias tool (randomized trials) or ROBINS-I tool (observational studies). Meta-analysis was performed to investigate the improvement of PTA (dB) and number of patients displaying recovery following salvage ITC injections. Occurrence of serious side effects was investigated. Finally, the certainty of the evidence was evaluated using the GRADE approach. ResultsEleven relevant studies were identified (4 randomized trials and 7 observational studies). Both observational and randomized trials showed that salvage ITC significantly increased the number of patients displaying recovery. No serious adverse events were identified in any of the included studies. The certainty of evidence ranged from moderate to very low, due to risk of bias, imprecision, and heterogeneity. ConclusionCollectively, our findings indicate that salvage ITC treatment may be a beneficial and safe treatment for patients with sudden hearing loss, who otherwise are refractory to standard treatment approaches. However, the evidence level indicates need for a cautious interpretation of especially the magnitude of effect and thus the extrapolation on how much the individual may improve from this treatment. Furthermore, it remains to be investigated whether treatment outcomes may vary across different patient groups presenting with ISSNHL. This potential variation in treatment response should be kept in mind, when counselling the patient. Trial registration numberThe protocol is registered in PROSPERO. Registration number: CRD42019130586.

Salvage intratympanic steroid therapy for sudden sensorineural hearing loss: our real-life experience in 32 patients

To examine the role of salvage intratympanic steroid injections in patients presenting with idiopathic sudden sensorineural hearing loss following a poor response to initial oral steroid treatment. A retrospective analysis of patient records over the course of four years was conducted, and pure tone thresholds were reviewed before treatment, after oral steroid therapy and six weeks after intratympanic steroid injection therapy. After oral steroid therapy alone, there was a mean average threshold change of 6.2 dB HL (range, -13.8-33.8 dB). This change was statistically significant for severely affected patients (those with an average presenting threshold of over 71 dB). The mean average threshold improvement following intratympanic steroid injection therapy was 2.9 dB (range, -22.5-61.3 dB); this was not statistically significant. Some patients experienced moderate improvement following intratympanic steroid injection therapy; however, no specific subgroup was identified to benefit more from intratympanic steroid injection therapy.

Frequency-specific prediction model of hearing outcomes in patients with idiopathic sudden sensorineural hearing loss.

The hearing outcome of idiopathic sudden sensorineural hearing loss (ISSNHL) is hard to predict. We herein constructed a multiple regression model for hearing outcomes in each frequency separately in an attempt to achieve practical prediction in ISSNHL. We enrolled 235 consecutive in-patients with ISSNHL who were treated in our department from 2015 to 2020 (average hearing level at 250-4000Hz ≥ 40dB; time from onset to treatment ≤ 14days; 126 males/109 females; age range 17-87years (average 61.0years)). All patients received systemic prednisolone administration combined with intratympanic dexamethasone injection. The pure-tone hearing threshold of 125-8000Hz was measured at every octave before (HLpre) and after (HLpost) treatment. A multiple regression model was constructed for HLpost (dependent variable) using five explanatory variables (age, days from onset to treatment, presence of vertigo, HLpre, and hearing level of the contralateral ear). The multiple correlation coefficient increased as the frequency increased. Strong correlations were seen in high frequencies, with multiple correlation coefficients of 0.784/0.830 for 4000/8000Hz. The width of the 70% prediction interval was narrower for 4000/8000Hz (± 18.2/16.3dB) than for low to mid-frequencies. Among the five explanatory variables, HLpre showed the largest partial correlation coefficient for any frequency. The partial correlation coefficient for HLpre increased as the frequency increased, which may partially explain the high multiple correlation coefficients for high frequencies. The present model would be of practical use for predicting hearing outcomes in high frequencies in patients with ISSNHL.