A Randomised Controlled Trial Comparing Intratympanic Gentamicin with Methylprednisolone in Meniere's Disease with Good Hearing.

A randomized prospective parallel group trial was done to compare the efficacy of intratympanic low dose gentamicin with methylprednisolone in treating intractable unilateral Meniere's disease with serviceable hearing. STUDY DESIGN: Randomised prospective parallel group trial. SETTING: Tertiary care centre in South India. SUBJECTS AND METHODS: Forty patients with unilateral Meniere's disease and serviceable hearing with vertigo following 6 months of conservative therapy were enrolled between November 2018 and March 2020. Twenty patients were administered with one dose of intratympanic Gentamicin (40 mg/ml) and the other half were given intratympanic Methylprednisolone (40 mg/ml, 4 injections given on alternate days). Pure tone audiogram, speech discrimination score, number of vertigo episodes, dizziness handicap inventory, tinnitus handicap inventory and functional scores were compared before treatment, 3 months later and up to 24 months. There was no significant difference between the two treatments with regard to short term as well as long term DHI scores, THI scores, Functional level score and average pure tone audiogram of patients. In patients with unilateral Meniere's disease who have good hearing, one dose of Gentamicin had equivalent effect to that of four doses of Methylprednisolone in vertigo and tinnitus control, hearing preservation and quality of life.

Comparative efficacy of intratympanic gentamicin and intratympanic corticosteroid in the treatment of Meniere's disease: a systematic review and meta-analysis.

Purpose: We aimed to evaluate the efficacy of gentamicin compared to corticosteroids for the treatment of Meniere's disease. Methods: An extensive search was conducted in PubMed, Embase, and Web of Science until May 2024. For continuous outcomes, pooled effect estimates were determined by calculating the weighted mean difference (WMD), while for binary outcomes, the risk ratio (RR) was used, each accompanied by their respective 95% confidence intervals (CIs). Heterogeneity among the studies was assessed using Cochran's I 2 and Q statistics. Results: A total of 12 studies were selected, involving 694 patients. Our analysis found that the gentamicin group demonstrates superior vertigo control rates compared to the corticosteroid group (RR: 1.36, 95% CI: 1.13 to 1.65, p < 0.001). In subgroup analysis, the gentamicin group showed a higher vertigo control rates at 6 months compared to the corticosteroid group (RR: 1.69, 95% CI: 1.28 to 2.24, p < 0.001); however, there was no statistically significant difference between the two groups at 12 months (RR: 1.48, 95% CI: 0.88 to 2.49, p = 0.14). Regarding changes in pure tone average, the corticosteroid group was superior to the gentamicin group (WMD: 4.41, 95% CI: 3.31 to 5.52, p < 0.001). Conclusion: Our study suggests that the intratympanic gentamicin group achieves higher vertigo control rates, whereas the corticosteroid group demonstrates better improvement in pure tone averages. However, the high heterogeneity in vertigo control rates warrants caution. Larger sample-sized randomized controlled trials are needed to further validate these findings.

Dexamethasone nanocrystals-embedded hydroxypropyl methylcellulose hydrogel increases cochlear delivery and attenuates hearing loss following intratympanic injection.

Herein, dexamethasone (DEX) nanocrystalline suspension (NS)-embedded hydrogel (NS-G) was constructed using a hydroxypropyl methylcellulose (HPMC) polymer to enhance cochlear delivery and attenuate hearing loss following intratympanic (IT) injection. Hydrophobic steroidal nanocrystals were prepared using a bead milling technique and incorporated into a polysaccharide hydrogel. The NS-G system with HPMC (average molecular weight, 86,000 g/mol; 15 mg/mL) was characterized as follows: rod-shaped drug crystalline; particle size <300 nm; and constant complex viscosity ≤1.17 Pa·s. Pulverization of the drug particles into submicron diameters enhanced drug dissolution, while the HPMC matrix increased the residence time in the middle ear cavity, exhibiting a controlled release profile. The IT NS-G system elicited markedly enhanced and prolonged drug delivery (> 9 h) to the cochlear tissue compared with that of DEX sodium phosphate (DEX-SP), a water-soluble prodrug. In mice with kanamycin- and furosemide-induced ototoxicity, NS-G markedly enhanced hearing preservation across all frequencies (8-32 kHz), as revealed by an auditory brainstem response test, compared with both saline and DEX-SP. Moreover, treatment with NS-G showed enhanced anti-inflammatory effects, as evidenced by decreased levels of inflammation-related cytokines. Therefore, the IT administration of DEX NS-loaded HPMC hydrogels is a promising strategy for treating hearing loss.

Association of contrast-enhanced MRI of inner ear and caloric response in patients with clinically diagnosed ipsilateral delayed endolymphatic hydrops.

BACKGROUND: Patients with delayed endolymphatic hydrops (DEH) often show caloric hypofunction and endolymphatic hydrops (ELH) on gadolinium (Gd) enhanced magnetic resonance imaging (MRI) of the inner ear. OBJECTIVES: We aimed to investigate the relationship between the ELH in vivo and caloric results in ipsilateral DEH. MATERIAL AND METHODS: Twelve patients with ipsilateral DEH were included, who underwent delayed MRI following intratympanic Gd application, pure-tone audiometry, caloric test, and video head impulse test (vHIT). RESULTS: For the affected ears, the overall prevalence of inner ear hydrops was 91.7%, including 75% in the cochlear and 50% in vestibular compartment. For the non-affected ears, the overall prevalence of inner ear hydrops was 25%, including 25% in cochlear and 16.7% in vestibular region. Caloric hypofunction was demonstrated in 75% of the affected ears. No pathologic vHIT were found. Caloric results were in agreement with the radiological evidence of inner ear hydrops on affected and non-affected ears in 9 cases. There was fair concordance between inner ear hydrops and canal paresis abnormality on the affected side. CONCLUSIONS AND SIGNIFICANCE: MRI provides auxiliary evidence of ELH in vivo in the ipsilateral DEH-affected ears. The association between morphological alterations and caloric hypofunction warrants further investigation.

The Optimal Head Position Following Intratympanic Injection: A Research Based on HRCT Reconstruction.

Objective: This study aimed to investigate the optimal head position (OHP) following intratympanic injection, a critical intervention in treating inner ear disorders. Identifying OHP is essential to maximize drug retention in the middle ear, thereby significantly enhancing the therapeutic efficacy by mitigating the significant issue of injectate leakage through the eustachian tube (ET). Exploratory various positions of ET orifice and round window (RW) were investigated and associated with head movements. Methods: Twenty-two (10 males and 12 females) anonymized high-resolution computed tomography (HRCT) datasets of patients without structural ear disease were selected from January 2022 to December 2022 in the study. The subjects were categorized into two groups: children (≤18 years) and adult group (>18 years). The reconstruction of the ET orifice and RW from HRCT were analyzed using Mimics software and the distances from the center point of ET orifice or the center point of RW to the reference plane were defined as distance of ET orifice (DET) and distance of RW (DRW). Results: In the supine position, the OHP for intratympanic injection was 23°of pronation and 24° of posterior extension, and the maximum distance between the ET orifice and RW (DET-RW) was 9.29 ± 2.13 mm. As the head position extended posteriorly beyond 43°, DET was relatively high compared with DRW, resulting in the OHP a fully posteriorly extended 90° of the head being the optimal position with DET-RW of 2.13 ± 1.60 mm in the supine position, however, it is not realized in human beings. Moreover, the OHP had no obvious relevance corresponding to age following intratympanic injections. Conclusion: Our study suggested that OHP after intratympanic injections treatment consists of supine position, along with a slight pronation and posterior extension.

The comparison between intratympanic gentamicin prehabilitation and postoperative virtual reality exposure to standard vestibular training in patients with vestibular schwannoma.

OBJECTIVE: Resection of the vestibular schwannoma causes acute peripheral vestibular loss. The process of central compensation starts immediately afterward. The rehabilitation goal is to support this process and restore the quality of life. MATERIALS AND METHODS: In this prospective single-center study, 67 consecutive patients underwent vestibular schwannoma resection (40 females, mean age 52 ± 12 years). The patients were divided into three groups: the prehabilitation with intratympanic gentamicin group, the virtual reality group (optokinetic stimulation via virtual reality goggles in the first ten days after the surgery), and the control group. All patients were examined with objective methods and completed questionnaires before the prehabilitation, before the surgery, at the hospital discharge, and after three months. RESULTS: Intratympanic gentamicin prehabilitation leads ipsilaterally to a significant aVOR reduction in all semicircular canals (p < 0.050), the increase of the unilateral weakness in air calorics (p = 0.026), and loss of cVEMPs responses (p = 0.017). Prehabilitation and postoperative exposure to virtual reality scenes improved the patient's perception of vertigo problems according to Dizziness Handicap Inventory (p = 0.039 and p = 0.076, respectively). These findings conform with the optokinetic testing results, which showed higher slow phase velocities at higher speeds (40 deg/s) in both targeted groups compared to the control group. CONCLUSION: Preoperative intratympanic gentamicin positively affects peripheral vestibular function, influencing balance perception after VS resection. In long-term follow-up, prehabilitation and postoperative exposure to virtual reality improve patients' quality of life in the field of vertigo problems.

Therapeutic efficacy of methylprednisolone sodium succinate via diverse administration routes for mid- to high-frequency sudden sensorineural hearing loss.

BACKGROUND: Sudden sensorineural hearing loss (SSNHL), characterized by a rapid and unexplained loss of hearing, particularly at moderate to high frequencies, presents a significant clinical challenge. The therapeutic use of methylprednisolone sodium succinate (MPSS) via different administration routes, in combination with conventional medications, remains a topic of interest. AIM: To compare the therapeutic efficacy of MPSS administered via different routes in combination with conventional drugs for the treatment of mid- to high-frequency SSNHL. METHODS: The medical records of 109 patients with mid- to high-frequency SSNHL were analyzed. The patients were divided into three groups based on the route of administration: Group A [intratympanic (IT) injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection], Group B (intravenous injection of MPSS combined with mecobalamin and Ginkgo biloba leaf extract injection), and Group C (single IT injection of MPSS). The intervention effects were compared and analyzed. RESULTS: The posttreatment auditory thresholds in Group A (21.23 ± 3 .34) were significantly lower than those in Groups B (28.52 ± 3.36) and C (30.23 ± 4.21; P < 0.05). Group A also exhibited a significantly greater speech recognition rate (92.23 ± 5.34) than Groups B and C. The disappearance time of tinnitus, time to hearing recovery, and disappearance time of vertigo in Group A were significantly shorter than those in Groups B and C (P < 0.05). The total effective rate in Group A (97.56%) was significantly greater than that in Groups B and C (77.14% and 78.79%, χ 2 = 7.898, P = 0.019). Moreover, the incidence of adverse reactions in Groups A and C was significantly lower than that in Group B (4.88%, 3.03% vs 2.57%, χ 2 = 11.443, P = 0.003), and the recurrence rate in Group A was significantly lower than that in Groups B and C (2.44% vs 20.00% vs 21.21%, χ 2 = 7.120, P = 0.028). CONCLUSION: IT injection of MPSS combined with conventional treatment demonstrates superior efficacy and safety compared to systemic administration via intravenous infusion and a single IT injection of MPSS. This approach effectively improves patients' hearing and reduces the risk of disease recurrence.

Assessing the Efficacy of Tragal Pumping in a Novel Tympanostomy Tube-Rat Model.

Objective: Tragal pumping (TP) is a practice of pushing on the tragus to raise pressure within the external auditory canal and is a commonly recommended adjunctive maneuver believed to facilitate the introduction of ototopical medications into the middle ear cavity via a tympanostomy tube. To investigate the efficacy of TP in the penetration of eardrops into the middle ear cavity via tympanostomy tube, we established the novel tympanostomy tube-rat model. We investigated the histology of the middle ear to determine the efficacy in moving fluid into the middle ear. Study Design: Prospective controlled animal study. Setting: Animal laboratory in a university hospital. Methods: Ten rats were recruited, and a tympanostomy tube insertion and green dye eardrops into outer ears were performed on bilateral ears. TP was performed only on 1 ear and was not applied on the other ear in each rat. Green dye in a middle ear cavity in hematoxylin and eosin-stained temporal bone sections was evaluated by blinded experts in microscopic anatomy (staining grade) and by using Image J software (staining level). The results of these 2 methods were statistically validated. Results: The staining grade (P < .001) and the staining level (P < .001) were significantly higher in the ears which we applied TP than in the control ears. The results of 2 methods were significantly and positively correlated (r = .898, P < .001). Conclusion: Our results showed that the TP accelerate the penetration of eardrops into the middle ear cavity in the tympanostomy tube-rat model.

Trends in Procedural Management of Meniere's Disease: Analysis of a National Insurance Claims Database.

Objective: This study used a national insurance claims database to analyze trends in procedural management of Meniere's disease. Study Design: Retrospective cohort analysis. Setting: Database study using United States inpatient and outpatient insurance claims submitted from January 2003 to December 2021. Subjects and Methods: The Merative MarketScan Commercial and Medicare Claims Databases were queried for adults (≥18 years) with a diagnosis of Meniere's Disease according to International Classification of Diseases codes. Patients receiving procedures per Current Procedural Terminology codes for endolymphatic sac surgery, vestibular nerve section, labyrinthectomy, and intratympanic dexamethasone or gentamicin were identified. Temporal trends were analyzed by calculating annual percent change (APC) in the proportion of patients receiving procedures using Joinpoint regression. Results: A total of 16,523 unique patients with MD receiving procedural management were identified. From 2003 to 2021, the proportion of patients managed with intratympanic dexamethasone increased (APC 1.76 [95% CI 1.53-1.98], P < .001). The proportion of patients receiving intratympanic gentamicin increased from 2003 to 2015 (APC 4.43 [95% CI 1.29-7.66], P = .008) but decreased from 2015 to 2021 (APC -10.87 [95% CI -18.31 to -2.76], P = .013). The proportion of patients receiving endolymphatic sac surgery (APC: -10.20 [95% CI -11.19 to -9.20], P < .001) and labyrinthectomy (APC: -6.29 [95% CI -8.12 to -4.42], P < .001) decreased from 2003 to 2021. Conclusion: From 2003 to 2021, there has been an increase in the use of intratympanic dexamethasone and a decrease in the use of intratympanic gentamicin, endolymphatic sac surgery, and labyrinthectomy for procedural management of Meniere's Disease.

Endolymphatic duct blockage surgery vs. intratympanic steroids for treatment of refractory Ménière's disease.

PURPOSE: To compare the effectiveness of the Endolymphatic duct blockage (EDB) and intratympanic methylprednisolone(ITMP) injection to control refractory Ménière's disease(MD) symptoms and evaluate their impact on hearing level. STUDY DESIGN: Retrospective study in a tertiary care center. METHODS: 36 received ITMP injection and 52 EDB. Mean outcome measures at 24 months included vertigo control, tinnitus, aural fullness and hearing level: pure-tone average (PTA), bone conduction average(BCA) and speech discrimination score(SDS). RESULTS: At 24 months postoperatively, 90.4% of the EDB group had complete control of vertigo and 43.4% of the ITMP group (p = 0.001). There was no significant difference in tinnitus or aural fullness control (p = 0.34 and p 0.21 respectively). In each group, the drop in tinnitus and aural fullness frequency at 24 months were significant for EDB (p = 0.03; p < 0.001 respectively) and for ITMP group in tinnitus (p = 0.03) but not aural fullness (p = 0.063). At 24 months, PTA, BCA and SDS were significantly worst in the ITMP group when compared to preoperative levels (p = 0.038, p = 0.027, p = 0.016). PTA in the EDB group was stable with no difference compared to ITMP group (p = 0.48). BCA and SDS in the EDB group were stable and better than the ITMP group (p = 0.032; p = 0.036). In each group, vestibular paresis was not significantly different before (p = 0.06) and after treatment (p = 0.68). CONCLUSION: EDB is more effective than the ITMP for controlling the vertigo symptoms of Ménière's disease and in preserving hearing function. It is a novel surgical technique with promising results for a complete treatment of Ménière's disease. ITMP decreases the frequency and the severity of the symptoms but only control vertigo in 27.8% of cases.

Management of Idiopathic Sudden Sensorineural Hearing Loss (ISSNHL) Intratympanic Platelet-Rich Plasma (PRP) Versus Intratympanic Steroid Injections: A Cross-Sectional Study.

<b><br>Introduction:</b> Idiopathic sensorineural hearing loss of 30 decibels (dB) or more over at least three contiguous audiometric frequencies with an onset of less than 3 days is referred to as sudden sensorineural hearing loss (ISSNHL) and is known as an ENT (ear, nose, and throat) emergency. When a patient's hearing suddenly deteriorates, they become confused, anxious, and worried. One of the primary therapies for sudden sensorineural hearing loss is intratympanic steroids. Intratympanic injections of platelet-rich plasma (PRP) improve inner ear hair cells, which enhances hearing.</br> <b><br>Aim:</b> To show the safety and efficacy of intratympanic PRP injection in the management of ISSNHL in comparison with intratympanic steroid injection.</br> <b><br>Methods:</b> The study group was comprised of 100 patients who had experienced ISSNHL within 30 days with no retrocochlear pathology, as demonstrated by a negative MRI scan. 50 patients received 6 intratympanic steroid injections, while the remaining 50 patients received 2 intratympanic injections of PRP at a 1-week interval.</br> <b><br>Results:</b> A total of 39 patients with PRP injection noted an improvement in their hearing of 25 db after 2 weeks and of 30 db after 2 months, with improved speech discrimination of 26% after 2 weeks and of 28% after 2 months. 31 patients with intratympanic steroid injection noted an improvement in their hearing of 18 db after 2 weeks and of 22 db after 2 months, with improved speech discrimination of 21% after 2 weeks and of 24% after 2 months.</br> <b><br>Conclusions:</b> PRP appears safe and efficient for the treatment of ISSNHL, with a low cost and no systemic side effects, as with oral steroids. Therefore, such research should be continued.</br>.

Sound Exposure Promotes Intratympanic Drug Delivery to the Inner Ear.

OBJECTIVE: To investigate the impact of sound exposure, with the resultant windows vibration on perilymphatic concentrations following intratympanic (IT) dexamethasone and gentamicin in an animal model. STUDY DESIGN: Animal model blinded study. SETTING: Animal facility of a tertiary medical center. METHODS: Bilateral IT dexamethasone or gentamicin was applied to 15 tested rats. Following injections, each rat was exposed for 3 minutes to free field 30 dB sound pressure level (SPL), 512 vHz noise, with 1 external auditory canal plugged (contralateral control). Following noise exposure, perilymph was obtained from both ears. Drug concentrations were measured using ultrahigh-performance liquid chromatography-mass spectrometer. RESULTS: For dexamethasone, the average (±SD) perilymphatic steroidal concentration was 0.417 µg/mL (±0.549) in the control ears versus 0.487 µg/mL (±0.636) in the sound-exposed ears (P = .008). The average (±SD) gentamicin perilymphatic concentration was 8.628 µg/mL (±2.549) in the sound-exposed ears, compared to 4.930 µg/mL (±0.668) in the contralateral control (nonsound exposed) ears. Sound exposure promoted steroidal and gentamicin diffusion to the inner ear by an averaged (±SD) factor of 1.431 and 1.730 (±0.291 and 0.339), respectively. CONCLUSION: Low-intensity noise (30 dB SPL) was found to enhance dexamethasone phosphate and gentamicin diffusion to the inner ear (by an averaged factor of ∼1.4 and 1.7, respectively) in a murine model.

Uso de anestésicos tópicos para procedimientos timpánicos: revisión de la literatura / Use of topical anesthetics for tympanic procedures: a literature review

Los procedimientos intratimpánicos se realizan frecuentemente de manera ambulatoria en los policlínicos de otorrinolaringología. Dada la inervación de la membrana timpánica, estos procedimientos generan disconfort y dolor, por lo que la aplicación previa de anestésicos tópicos sobre la membrana timpánica y el conducto auditivo externo es habitual. Pese a su uso, no hay evidencia clara sobre la efectividad de estos y el correcto modo de aplicación. Se realizó una revisión de la literatura sobre la aplicación y uso de anestésicos tópicos previo a procedimientos intratimpánicos, donde pudimos concluir que actualmente no hay un estándar de oro para prevenir el dolor en los pacientes sometidos a procedimientos intratimpánicos, ya que en la mayoría de los estudios no se logró diferencia significativa entre el uso de anestésicos tópicos v/s placebo, al comparar dolor a los 5 y 45 minutos post procedimiento.

A literature review was performed to assess the use and efficacy of topical anesthetics in intratympanic procedures. The analysis led to the conclusion that a gold standard for pain prevention procedures is still lacking, as the majority of studies revised did not show statically significant differences between the use of topic anesthetics and placebo when compared pain at 5 and 45 minutes after procedures.

Trends in Management of Ménière Disease: A TriNetX Network Database Analysis.

This study investigated management practices for Meniere's disease (MD) and their temporal trends from 2008 to 2022 within the TriNetX network database. Study cohort included adult patients (≥18 years) with the diagnosis of MD from TriNetX's multi-institutional medical records (n = 77,493). MD diagnosis and management were queried based on the international classification of diseases, tenth revision, current procedural terminology, and RXNorm codes. Temporal trends were analyzed using joinpoint regression. There was significant increase in rates of relevant medications prescribed within 12 months of MD diagnosis from 2008 to 2022 (annual percent change [APC]: 1.2 [95% confidence interval, CI: 0.4-1.9]). There were no significant changes in rate of intratympanic injection within 12 months of MD diagnosis (1.7 [95% CI: -1.1 to 4.5]). Rate of endolymphatic sac surgery and labyrinthectomy any time after MD diagnosis gradually decreased from 2008 to 2022 at APC of -8.1 (95% CI: -11.8 to -4.2) and -11.0 (95% CI: -14.0 to -7.7), respectively. Use of relevant medications has significantly increased during the early management of MD and the overall use of surgical treatments has decreased.

Erratum: Surgical procedure of intratympanic injection and inner ear pharmacokinetics simulation in domestic pigs.

[This corrects the article DOI: 10.3389/fphar.2024.1348172.].

Easing the Burden of Tinnitus: A Narrative Review for Exploring Effective Pharmacological Strategies.

Many individuals seek medical attention for tinnitus, desiring relief from the distress caused by the condition; however, the treatment process is far from straightforward. The most effective treatments for chronic subjective tinnitus, such as tinnitus retraining therapy (TRT) and cognitive behavioral therapy (CBT), require considerable time and efforts. As a result, many of them express a desire for alleviation through medication. While it is true that medication is not generally recommended in treatment guidelines for chronic subjective tinnitus, in specific situations such as when accompanied by symptoms of depression or anxiety-drugs like antidepressants or anxiolytics may have a meaningful impact on symptom reduction. Additionally, medication can prove effective in certain specialized forms of tinnitus, such as typewriter tinnitus, as opposed to chronic subjective tinnitus. Although intratympanic dexamethasone injections for tinnitus have been reported to lack efficacy compared to a placebo, if patients perceive subjective satisfaction due to a placebo effect, it holds significance. From the perspective of patients suffering from tinnitus, even if the therapeutic mechanism is set aside, experiencing some degree of relief through certain medications can enhance compliance with evidence-based treatments like TRT and CBT.

Comparison of side effects of different steroids used in intratympanic injections.

OBJECTIVES: This study aimed to compare the side effects of different steroids used in the intratympanic injections (IT). METHODS: One hundred and sixty patients diagnosed with sudden sensorineural hearing loss and undergoing IT were assigned to four groups based on the type or concentration of steroids administered (Group DM5: 5 mg/ml Dexamethasone sodium phosphate; Group DM10: 10 mg/ml Dexamethasone sodium phosphate; Group MP: 40 mg/ml Methylprednisolone sodium succinate; Group BM: 4 mg/ml Betamethasone sodium phosphate). Each group comprised 40 patients, and all participants received IT six times. The study assessed and compared the degrees and duration of pain, dizziness, and tympanic membrane damage following IT. Patients were asked to report the pain they felt using the numeric rating scale (NRS). RESULTS: NRS scores for pain after IT showed significant differences among the four groups (p < 0.001). The average NRS scores for pain in each group were as follows: Group DM5: 1.53 ± 1.04; Group DM10: 1.45 ± 1.30; Group MP: 4.33 ± 2.22; Group BM: 6.03 ± 1.46. The durations of pain after IT also exhibited significant differences among the four groups (p < 0.001), with the longest duration observed in Group MP at 31.93 ± 15.20 min. CONCLUSION: Different types of steroids could lead to varying degrees of pain when used in IT. Betamethasone could cause the most severe pain, and methylprednisolone could result in the longest duration of pain.

Surgical procedure of intratympanic injection and inner ear pharmacokinetics simulation in domestic pigs.

Introduction: One major obstacle in validating drugs for the treatment or prevention of hearing loss is the limited data available on the distribution and concentration of drugs in the human inner ear. Although small animal models offer some insights into inner ear pharmacokinetics, their smaller organ size and different barrier (round window membrane) permeabilities compared to humans can complicate study interpretation. Therefore, developing a reliable large animal model for inner ear drug delivery is crucial. The inner and middle ear anatomy of domestic pigs closely resembles that of humans, making them promising candidates for studying inner ear pharmacokinetics. However, unlike humans, the anatomical orientation and tortuosity of the porcine external ear canal frustrates local drug delivery to the inner ear. Methods: In this study, we developed a surgical technique to access the tympanic membrane of pigs. To assess hearing pre- and post-surgery, auditory brainstem responses to click and pure tones were measured. Additionally, we performed 3D segmentation of the porcine inner ear images and used this data to simulate the diffusion of dexamethasone within the inner ear through fluid simulation software (FluidSim). Results: We have successfully delivered dexamethasone and dexamethasone sodium phosphate to the porcine inner ear via the intratympanic injection. The recorded auditory brainstem measurements revealed no adverse effects on hearing thresholds attributable to the surgery. We have also simulated the diffusion rates for dexamethasone and dexamethasone sodium phosphate into the porcine inner ear and confirmed the accuracy of the simulations using in-vivo data. Discussion: We have developed and characterized a method for conducting pharmacokinetic studies of the inner ear using pigs. This animal model closely mirrors the size of the human cochlea and the thickness of its barriers. The diffusion time and drug concentrations we reported align closely with the limited data available from human studies. Therefore, we have demonstrated the potential of using pigs as a large animal model for studying inner ear pharmacokinetics.

[Role of intratympanic glucocorticoid treatment in sudden hearing loss]. / Stellenwert der intratympanalen Glukokortikoidtherapie in der Behandlung des Hörsturzes.

Idiopathic sudden sensorineural hearing loss (ISSNHL) is one of the most common diseases in otolaryngology. Its etiology remains unknown. Furthermore, there is only a low 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 a benefit 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 a small benefit over systemic treatment alone (low effect size, low evidence).

Modified intratympanic steroid therapy for sudden sensorineural hearing loss via tympanic tube and gelfoam as a salvage treatment.

Background: Sudden sensorineural hearing loss (SSNHL) is a prevalent emergency in ear, nose, and throat practice. Previous studies have demonstrated that intratympanic steroid therapy (IST) can serve as a salvage treatment for SSNHL after the failure of systemic steroid therapy (SST). Objective: This study aimed to analyze the efficacy of modified IST involving the insertion of a tympanic tube and gelfoam as a salvage treatment for patients with SSNHL, and to explore its associated factors. Methods: Totally, 74 patients who were aged 22-81 years with SSNHL were enrolled and allocated to either the control group (n = 25) or the treatment group (n = 49) based on their treatment modalities. All patients received SST lasting for at least 7 days. Subsequently, patients in the treatment group, after SST failure, underwent IST twice a week for 2-6 weeks, while the control group did not. Efficacy was assessed by the improvement in pure tone average at the affected frequency at the beginning and end of IST. Results: Hearing improvement in all patients after IST in the treatment group was 9.71 ± 14.84 dB, with significant improvement at affected frequencies (250-8000 Hz) compared with the control group (P < 0.05). The findings indicated the duration from the onset of SSNHL to the beginning of IST as an independent factor for pure tone average improvement after treatment (P = 0.002), whereas age, duration of SST, and time of IST were not (P > 0.05). Conclusion: The modified IST was demonstrated to be a safe and effective method as a salvage treatment for SSNHL. This study explored the efficacy of a modified IST approach, incorporating the utilization of tympanic tubes and gelfoam as key components. The findings underscore the advantages of gelfoam as a strategic drug carrier placed in the round window niche. By minimizing drug loss, extending action time, and increasing perilymph concentration, gelfoam enhances the therapeutic impact of IST, contributing to improved hearing outcomes in patients with SSNHL.