Intratympanic Research Articles

Intratympanic injections made from eutectic liquid (camphor and menthol)-based oil-less emulsions containing morin hydrate-lipoid E80 complex: An approach to augment drug permeation into inner ear region in a healthy rabbit model

Morin hydrate (MH, flavonols of plants, family-Moraceae) promotes inner ear stem cell survival and differentiation process to preserve the healthy hearing function. However, round window membrane (RWM) of inner ear provides a barrier for MH to reach an adequate amount at inner ear region. Since MH possesses a low aqueous solubility (28.72 ± 0.97 μg/ml), intratympanic (IT) injections of camphor-menthol eutectic liquid-based oil-less emulsions containing MH-Lipoid E80 complex was developed to promote MH ferrying action across RWM. At 360 min post-dissolution time point, the MH solution displayed 92.88 ± 6.26 % drug release, but the drug-Lipoid E80 complex-loaded oil-less emulsions showed 58.05 ± 11.62 % only. The MTT assay results indicate the possible non-toxicity of oil-less emulsions to L-929 cells up to 100 μg/ml concentration. Significant differences were seen between the Cmax and AUC0-t values observed at 90 min in the perilymph after the IT injections of MH solution (14.13 ± 0.33 × 103 ng/ml & 429.55 ± 9.20 × 103 ng min/ml) and MH-Lipoid E80 complex-loaded oil-less emulsions (117.93 ± 4.24 × 103 ng/ml & 5529.46 ± 37.65 × 103 ng min/ml) into the healthy albino rabbits. Hence the IT injections of eutectic liquid-based oil-less emulsions could facilitate the drugs crossing over of RWM in the inner ear regions.

Results of a New Treatment Protocol for Sudden Sensorineural Hearing Loss Using Betamethasone for Intratympanic Therapy.

Introduction Sudden sensorineural hearing loss (SSNHL) is defined as a rapid sensation of hearing impairment in one or both ears. Based on its personal impact on patients, the present study advances the analysis of new treatments for the prompt recognition and management of SSNHL, with higher chances of improvements in terms of hearing recovery and quality of life of the patients. Objective To describe the intratympanic (IT) corticoid infiltration technique, to demonstrate the efficacy of betamethasone injection as a sequential treatment in patients whose initial systemic steroid treatment failed, as well as to compare its use in different treatment periods. Methods The present clinical trial was conducted with 37 patients referred to our office with the diagnosis of SSNHL, from September 2019 to May 2022, who provided informed consent to participate. Results Even dividing the analysis of increasing the pure tone average (PTA) or speech recognition threshold (SRT) between the difference into initiation of the salvage therapy in up to 15 days of the sudden deafness event, and between 15 days and 3 months of the event, we did not find any difference in hearing improvement. Conclusion Intratympanic corticosteroid therapy is prescribed when conventional therapy fails or when there is a limitation to the use of corticosteroids due to the presence of systemic disorders. As such, new drugs, such as bethametasone, are studied and show promising results.

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.

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 &lt; 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 &lt; 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.

A phase 1 clinical trial of DB-020 intratympanic injections administered prior to high-dose cisplatin chemotherapy to reduce ototoxicity.

6100 Background: Hearing loss (HL) as a result of cisplatin (CP) chemotherapy is common. DB-020 is a formulation of sodium thiosulfate for intratympanic (IT) injection being developed to reduce CP ototoxicity. This phase 1 study was designed to evaluate safety and tolerability of repeated IT injections of DB-020 and compare CP-induced hearing changes with DB-020 vs placebo. Methods: Patients scheduled for at least three cycles of CP and cumulative exposure of ≥280 mg/m2 were randomized to blinded, bilateral, IT injection with DB-020 (12% or 25%) in one ear and placebo in the other ear, once every 3 or 4 weeks, ≤3 hours before receiving CP. Patients naïve to CP with moderate or severe HL at baseline were excluded. Ototoxicity was defined by American Speech-Language-Hearing criteria: ≥20 dB threshold increase at any one test frequency, or ≥10 dB threshold increase in any two adjacent frequencies, or loss of response at three consecutive frequencies where responses were previously obtained. Severe ototoxicity was defined as ≥20 dB threshold increase in any two adjacent frequencies. Pre-specified analyses evaluated safety, ototoxicity (with McNemar’s test using the last observation carried forward), and average threshold shifts (from air conduction audiometry, analyzed with a mixed model with repeated measures). This is the final analysis of the data set following the interim analysis presented in 2023. Results: Twenty-two patients were randomized with a mean age of 55 years (86% male; 100% white). Pre-DB-020 treatment, mean cumulative CP dose was 255 mg/m2, and 95% had head and neck cancers; 5% had lung cancer. Twenty patients had both baseline and follow-up audiometry, and 18/20 had baseline audiograms within 5 dB of the median threshold for age-matched controls. Free CP systemic levels (overall mean cumulative CP dose was 254.7 mg/m2) were similar to reference values. Acute or temporary ear pain (18/22 patients, 82%), and tinnitus (11/22 patients, 50%) were common. Ear pain was more common in DB-020 treated ears, and tinnitus in placebo treated ears. No persistent tympanic perforations, no serious adverse events in the ear and labyrinth disorders category, and no deaths were reported. Ototoxicity was significantly more common and severe in placebo treated ears. Conclusions: In this initial clinical trial experience, there was no significant safety signal, and DB-020 IT injections showed a meaningful reduction in CP-induced ototoxicity. Clinical trial information: NCT04262336 . [Table: see text]

Sound Exposure Promotes Intratympanic Drug Delivery to the Inner Ear.

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. Animal model blinded study. Animal facility of a tertiary medical center. Bilateral IT dexamethasone or gentamicin was applied to 15 tested rats. Following injections, each rat was exposed for 3minutes to free field 30 dB sound pressure level (SPL), 512 vHz noise, with 1external 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. 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. 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.

A silk-based hydrogel containing dexamethasone and lipoic acid microcrystals for local delivery to the inner ear

Local drug delivery has been exploited recently to treat hearing loss, as this method can both bypass the blood-labyrinth barrier and provide sustained drug release. Combined drug microcrystals (MCs) offer additional advantages for sensorineural hearing loss treatment via intratympanic (IT) injection due to their shape effect and combination strategy. In this study, to endow viscous effects of hydrogels, nonspherical dexamethasone (DEX) and lipoic acid (LA) MCs were incorporated into silk fibroin (SF) hydrogels, which were subsequently administered to the tympanic cavity to investigate their pharmaceutical properties. First, we prepared DEX and LA MCs by a traditional precipitation technique followed by SF hydrogel incorporation (SF+DEX+LA). After characterization of the physicochemical features, including morphology, rheology, and dissolution, both a suspension of combined DEX and LA MCs (DEX+LA) and SF+DEX+LA were administered to guinea pigs by IT injection, after which the pharmacokinetics, biodegradation and biocompatibility were evaluated. To our surprise, compared to the DEX+LA group, the pharmacokinetics of the SF+DEX+LA hydrogel group did not improve significantly, which may be ascribed to their nonspherical shape and deposition effects of the drugs MCs. The cochlear tissue in each group displayed good morphology, with no obvious inflammatory reactions. This combined MC suspension has the clear advantages of no vehicle, easy scale-up preparation, and good biocompatibility and outcomes, which paves the way for practical treatment of hearing loss via local drug delivery.

Biosafety and potency of high-molecular-weight hyaluronic acid with intratympanic dexamethasone delivery for acute hearing loss.

Objective: This study evaluated the potential of high-molecular-weight hyaluronic acid (HHA) as an intratympanic (IT) drug delivery vehicle for dexamethasone (D) in treating acute hearing loss. We compared the efficacy, safety, and residence time of HHA to the standard-of-care IT drug delivery method. Methods: Endoscopic examinations were used to track tympanic membrane (TM) healing post-IT injection. Micro-computed tomography (CT) was used to gauge drug/vehicle persistence in the bulla air space. Histological analyses covered the middle ear, TM, and hair cell counts. Auditory brainstem responses (ABR) were used to measure hearing thresholds, while high-performance liquid chromatography (HPLC) was employed to quantify cochlear perilymph dexamethasone concentrations. Results: The HHA + D group had a notably prolonged drug/vehicle residence time in the bulla (41 ± 27days) compared to the saline + D group (1.1 ± 0.3days). Complete TM healing occurred without adverse effects. Histology revealed no significant intergroup differences or adverse outcomes. Hearing recovery trends favored the HHA + D group, with 85.0% of ears showing clinically meaningful improvement. D concentrations in cochlear perilymph were roughly double in the HHA group. Conclusion: HHA is a promising vehicle for IT drug delivery in treating acute hearing loss. It ensures extended residence time, augmented drug concentrations in targeted tissues, and safety. These results highlight the potential for HHA + D to excel beyond existing standard-of-care treatments for acute hearing loss.

Efficacy and preservation of hearing with low-dose gentamicin in unilateral meniere's disease: A clinical symptomatology-based study

PurposeMeniere's disease (MD), a disorder of the inner ear, presents numerous therapeutic challenges, and intratympanic (IT) gentamicin has been proposed for intractable cases. However, controversy regarding dosage and method persists. The purpose of this study was to assess the efficacy and safety of low-dose IT gentamicin on vertigo attacks in MD using a clinical symptomatology-based method, wherein administration was repeated only if vertigo attacks recurred, with a 2-week interval between injections. Materials and methodsThis study included 88 patients with unilateral intractable MD. All patients received one to five IT injections with 0.5 ml of 10 mg of gentamicin (80 mg/2 ml) with an interval of 2 weeks between injections. Vertigo attacks were evaluated before and after therapy and categorized into classes A–F according to the 2015 Equilibrium Committee criteria. Audiovestibular assessments, including Pure Tone Audiometry and Vestibulo-Ocular Reflex evaluations, were performed. ResultsBefore treatment, patients had an average of 4.4 vertigo attacks/month; after treatment, this average decreased to 0.52. The majority of patients (57 %) reached Class A or B vertigo control with five or fewer gentamicin injections. VOR gain was slightly affected on the healthy side and significantly reduced on the affected side. No hearing deterioration was found in any of the treated patients. ConclusionsLow-dose IT gentamicin administration based on clinical symptomatology can produce a satisfactory control of vertigo attacks after treatment. This protocol primarily affected the vestibular function, as demonstrated by the significant reduction in VOR gain on the affected side, while avoiding cochlear damage. The lack of adverse events and preservation of hearing underscore the safety and efficacy of this method. These findings have significant clinical implications, suggesting that a low-dose, clinical symptomatology-based gentamicin treatment regimen could be an effective and safe strategy for managing unilateral Meniere's disease in a larger population.

Primary versus salvage intratympanic steroid treatment for idiopathic sudden sensorineural hearing loss.

The objective of this research is to compare primary and salvage intratympanic (IT) steroid treatments in terms of hearing outcomes in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). The patients were randomized into two (primary and salvage) groups. Both groups received systemic steroid treatment for 2 weeks. The primary group also received IT dexamethasone injection three times during the treatment period, whereas the salvage group received IT dexamethasone injection only if no or slight recovery was noted at the 2-week follow-up. If needed, salvage steroid injection was administered three times during the following 2 weeks. Hearing recovery was analyzed according to the modified American Academy of Otolaryngology-Head and Neck Surgery criteria. The degrees of hearing improvement at the 3-month follow-up were similar in the two groups. Compared with baseline, the pure-tone average values and speech discrimination scores improved by 38.45 ± 21.95 dB HL and 34.32% ± 30.55%, respectively, in the primary group and 36.80 ± 22.33 dB HL and 31.87% ± 27.88%, respectively, in the salvage group (p = .762 and .659, respectively). In addition, the complete or partial hearing recovery rates were also similar in the primary and salvage groups (67.7% vs. 73.3%, respectively; p = .780). In the salvage group, 18 patients required no IT steroid injection because they recovered after systemic steroid treatment. Primary and salvage IT steroid treatments for ISSNHL led to similar outcomes. In summary, salvage IT steroid injection is recommended for patients with ISSNHL patients to prevent unnecessary IT injection. 2.

#3625 TREATMENT OUTCOMES FOR IDIOPATHIC SUDDEN SENSORINEURAL HEARING LOSS IN DIALYSIS PATIENTS

Abstract Background and Aims Idiopathic sudden sensorineural hearing loss (ISSNHL) is one of the most challenging complications nephrologists encounter when treating dialysis patients (pts). Since no previous study has compared the treatment response of dialysis pts to that of non-dialysis pts, physicians have difficulty managing these pts. This study aimed to investigate the treatment outcome of dialysis pts with ISSNHL. Method In this single-center, retrospective, observational study, 700 pts diagnosed with ISSNHL between January 2005 and December 2021 at Asan Medical Center, Korea were enrolled. Among them, 47 were dialysis pts and 653 were non-dialysis pts. Non-dialysis pts were compared using a 5:1 propensity score matching (PSM) analysis to balance pre-existing clinical characteristics. High-dose systemic steroid therapy or intra-tympanic (IT) steroid injections were administered according to the standard protocol. The pure tone average (PTA) of the two groups was compared before initiating the treatment, and after 2 weeks and 2 months of treatment. The degree of improvement in the hearing was evaluated using Siegel's criteria. Results Without PSM, the age, prevalence of diabetes or hypertension, initial hearing threshold by each frequency level (0.5, 1, 2, and 4 kHz), and treatment strategies were statistically different between the two groups. In the PS-matched cohort, none of the measured confounding variables were statistically different between the two groups (Table 1). Two months after steroid treatment, the average improvement in pure tone audiometry (p = 0.025) and the percentage of complete response according to Siegel's criteria were significantly higher in the non-dialysis pts group than the dialysis pts group (27.2% vs. 6.4%) (Table 2). Conclusion This study suggests that dialysis pts have significantly worse treatment outcomes for ISSNHL compared to non-dialysis pts.

A phase 1 clinical trial of DB-020 intratympanic injections administered prior to high dose cisplatin chemotherapy to reduce ototoxicity.

6043 Background: Hearing loss with cisplatin (CP) chemotherapy is common. DB-020 is a formulation of thiosulfate for intratympanic (IT) injection being developed to reduce CP ototoxicity. The primary objective of this Phase 1 study was to evaluate the safety and tolerability of repeated IT injections of DB-020. A secondary objective was to compare hearing changes with DB-020 vs. placebo. Methods: Subjects scheduled for at least 3 cycles of CP and cumulative exposure of ≥280 mg/m2 were randomized to blinded, bilateral, IT injection with DB-020 (12% or 25%) in one ear and placebo in the other, once every 3 or 4 weeks, up to 3 hours before receiving CP. Subjects with moderate or severe hearing loss at baseline were excluded. Ototoxicity was defined by American Speech-Language-Hearing criteria: ≥20 dB threshold increase at any one test frequency, or ≥10 dB threshold increase in any two adjacent frequencies, or loss of response at three consecutive frequencies where responses were previously obtained. Severe ototoxicity was ≥20 dB threshold increase in any two adjacent frequencies. A pre-specified interim analysis evaluated safety, ototoxicity (with Mcnemar’s test using the last observation carried forward), and average threshold shifts (from air conduction audiometry, analyzed with a mixed model with repeated measures). Results: Nineteen subjects were randomized, with mean age of 57 years (84% male and 100% white) and mean cumulative CP dose 248 mg/m2. Most (95%) had head and neck cancers (5% had lung cancer). Seventeen subjects had both baseline and follow-up audiometry, and 16/17 had baseline audiograms within 5 dB of the median threshold for age-matched controls. Free CP systemic levels were similar to reference values. Ear pain (15/19 subjects, 78.9%) and tinnitus (8/19 subjects, 42.1%) were common. Ear pain was more common in DB-020 treated ears, and tinnitus was more common in placebo treated ears. There were no tympanic perforations, no serious adverse events in the category of ear and labyrinth disorders, and no deaths. Ototoxicity was significantly more common and more severe in placebo treated ears (Table). As the overall study objectives were met at this interim analysis, no further enrollment was pursued. Conclusions: In this initial clinical trial experience there was no significant safety signal, and DB-020 IT injections showed a meaningful reduction in cisplatin ototoxicity. These results warrant further clinical development. Clinical trial information: NCT04262336 . [Table: see text]

Efficacy of Oral versus Intratympanic Steroids in the Treatment of Idiopathic Sudden Sensorineural Hearing Loss: A 1-year Randomized Control Trial

Background: Sudden sensorineural hearing loss (SSNHL) is a common otologic emergency, with hearing loss of 30 dB or greater at three contiguous frequencies, and an abrupt onset within 3 days or fewer, with no recognizable cause. Aims and Objectives: In this study, the efficacy of intratympanic (IT) injections of dexamethasone are compared with oral prednisolone and the behaviour of the different audiometric curves in response to both the steroid therapies in studied. Materials and Methods: Patients presenting with SSNHL to the Department of ENT, Head and Neck Surgery at Government Multi Speciality Hospital, Chandigarh, were subjected to routine tests. Informed written consent was taken from each patient, and cases meeting the selection criteria were included in the study. Pure-tone audiometry was done before starting treatment. Patients were randomly assigned into two groups based on their enrollment number. Those in Group 1 were treated with three doses of 0.3–0.6 mL IT injections of dexamethasone (4 mg/mL) on alternate days and those in Group 2 received OP 1 mg/kg/day with tapering doses. Pure-tone audiogram (PTA) will be repeated after 2 weeks, 4 weeks, and 8 weeks from the first dose. Results: In the IT dexamethasone group, the pretreatment PTA was 61.05 dB while the posttreatment PTA was 37.45 dB. The hearing gain was 23.6 dB. In the oral steroid group, pretreatment PTA was 66.79 while posttreatment PTA was 47.36 dB. The hearing gain was 19.43 dB. The hearing gain in both the groups was statistically significant; however, there was no statistical difference between the two in terms of superiority of efficacy (P &gt; 0.05). Conclusion: The treatment of SSNHL still remains a challenge among the otologists. The present study establishes that the efficacy of IT steroids was as good as the oral steroid therapy for the management of SSNHL as both the modalities showed significant hearing improvement. Hence, IT steroid can be used as a first-line therapy in patients with. Our study also uncovered the fact that patients who come with shorter duration of onset recover quickly compared to those patients who delay their treatment. Hence, IT steroid can be used as a primary modality of treatment instead of a salvage therapy in the selected group of patients.

Injectable Poloxamer Hydrogel Formulations for Intratympanic Delivery of Dexamethasone.

In this study, we prepared and evaluated an injectable poloxamer (P407) hydrogel formulation for intratympanic (IT) delivery of dexamethasone (DEX). DEX-loaded P407 hydrogels were characterized in terms of thermogelation, drug loading capacities, particle size, and drug release. The in vivo toxicity and drug absorption of the DEX-loaded P407 formulation after IT injection were evaluated using an animal model by performing histopathological analysis and drug concentration measurements. The P407 hydrogel effectively solubilized hydrophobic DEX and demonstrated a sustained release compared to the hydrophilic DEX formulation. The in vivo study showed that the hydrogel formulation delivered considerable drug concentrations to the inner ear and displayed a favorable safety profile without apparent cytotoxicity or inflammation. P407 hydrogel can be useful as an injectable inner ear delivery formulation for hydrophobic drugs due to their biocompatibility, drug-solubilizing capacity, thermogelation, and controlled release.

Evaluation of prednisolone and prednisolone sodium succinate concentrations in human plasma and inner ear perilymph during cochlear implantation 24 h after intratympanic injection

Background The use of intratympanic (IT) steroids has drastically increased over the past 10–15 years to manage many otological pathologies. Objectives This study aimed to compare the concentrations of prednisolone and prednisolone sodium succinate (SS) in the plasma and inner ear perilymph of participants who underwent cochlear implantation 24 h after IT injection. Materials and methods It was a prospective comparative randomized study. Twenty participants received an IT injection of prednisolone SS ∼24 h before the cochlear implantation. The other five participants received an IT saline injection and represented the control group. Perilymph and blood were sampled during the cochlear implantation surgery. Results Both prednisolone and prednisolone SS were still present in perilymph ∼24 h after the IT administration. Only prednisolone was present in the blood plasma of seven participants (35%). Conclusion IT injection of prednisolone SS resulted in high perilymph concentrations of prednisolone and prednisolone SS, which could stay in the perilymph for at least 24 h. Using a mini-endoscope during the IT injection may effectively detect barriers infront of the round window membrane, increasing the drug concentration in the inner ear. Significance IT injection is an effective method for delivering prednisolone to the inner ear.

Comparative Study Between Low Level Laser Therapy and Intra Tympanic Steroids Injection in Treatment of Tinnitus

Persistent tinnitus can result in serious problems and morbidity, especially at the psychological and socio-professional levels. Although many treatments exist for the resolution of tinnitus symptomatology, total eradication of symptom rarely occurs.

Intratympanic steroid treatment can reduce ROS and immune response in human perilymph investigated by in-depth proteome analysis.

Intratympanic (IT) steroid treatment is one of the most widely used and effective treatments for inner ear disorders such as sudden sensorineural hearing loss (SNHL). However, a clear mechanism of IT steroids in inner ear recovery has not yet been revealed. Therefore, we investigated proteome changes in extracted human perilymph after steroid treatment. In this study, we applied a tandem mass spectrometry (MS/MS)-based proteomics approach to discover global proteome changes by comparing human perilymph after steroid treatment with non-treated perilymph group. Using liquid chromatography-MS/MS analysis, we selected 156 differentially expressed proteins (DEPs) that were statistically significant according to Student's t-test. Functional annotation analysis showed that upregulated proteins after steroid treatment are related to apoptosis signaling, as well as reactive oxygen species (ROS) and immune responses. The protein-protein interaction (PPI) clusters the proteins associated with these processes and attempts to observe signaling circuitry, which mediates cellular response after IT steroid treatments. Moreover, we also considered the interactome analysis of DEPs and observed that those with high interaction scores were categorized as having equivalent molecular functions (MFs). Collectively, we suggest that DEPs and interacting proteins in human perilymph after steroid treatment would inhibit the apoptotic and adaptive immune processes that may lead to anti-inflammatory effects.

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

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. Retrospective chart review. Tertiary otology practice. Patients with ISSNHL treated with IT steroid between April 2003 and December 2020. IT steroid injection and audiometric evaluation. 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. 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. 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.

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.