Controlled release of dexamethasone from fibrin sealant for intratympanic administration in inner ear therapy

The aim of the present work was to show the sustainability of fibrin sealant in releasing dexamethasone and adjust the protocol for clinical application of the novel method in the treatment of Meniere’s disease (MD) and sudden sensorineural hearing loss (SSHL).Gelation occurred shortly after mixing dexamethasone-containing fibrinogen with thrombin.Dexamethasone was constantly released for at least 16 d at a stable level after 7d in protocol 1 (low-dose),while it was robustly released within 4 d and slowed afterward until 10 d in protocol 2(high-dose).There were significant differences among the time points in Protocol 2 (p<0.01,ANOVA),and the exponential model with the formula y=15.299*e~(-0.483*t) fits the association.The estimated concentration of dexamethasone released on 7 d in protocol 2 was slightly lower than that observed in protocol 1.The fibrin sealant is capable of constantly releasing dexamethasone with adjustable dynamics.Targeted and minimally invasive administration of the material can be achieved in the clinic by sequential injections of the fluids using a soft-tipped catheter.

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.

Intratympanic injection of hydrogel nanodrug for the prevention and treatment of sensorineural hearing loss

Safe and efficient drug delivery to the inner ear has always been the focus of prevention and treatment of sensorineural deafness.The rapid development of nanodrug delivery systems based on hydrogel has provided a new opportunity.Among them,thermo-sensitive hydrogels promote the development of new dosage form for intratympanic injection.This smart biomaterial could transform to semisolid phase when the temperature increased.Thermo-sensitive hydrogel nanodrug delivery system is expected to achieve safe,efficient,and sustained inner ear drug administration.This article introduces the key techniques and the latest progress in this field.

Intratympanic dexamethasone injection for sudden sensorineural hearing loss in pregnancy

BACKGROUND As sudden sensorineural hearing loss(SSNHL)rarely occurs in pregnant women,there is a lack of knowledge and relevant research on its management.AIM To investigate the effect of intratympanic dexamethasone injection in the treatment of pregnant patients with SSNHL.METHODS A retrospective chart review was made for the period between June 2017 and August 2019 at our Department of Otorhinolaryngology-Head and Neck Surgery.Pregnant women who met the criteria for SSNHL were included and grouped based on the therapeutic modalities.The treatment group received intratympanic dexamethasone(2.5 mg)q.o.d.for a total of four times,while the control group received no medication other than bed rest and medical observations.All the patients were under close care of obstetricians.Pure-tone audiograms were performed before and after treatment.RESULTS Eleven patients who met the inclusion criteria were assigned to the treatment group(n=7)and the control group(n=4).The mean age of patients was 31.2±3.8 years;the right ear was affected in seven(63.64%)cases.Two patients(18.2%)suffered from vertigo,10(90.9%)suffered from tinnitus and 6(54.5%)suffered from aural fullness.The time from onset to clinic visit was relatively short,with a mean time of 1.3±0.9 d.All the women were within the second or third trimester;the average gestation period was 26.0±6.2 wk.The pure-tone averages at onset between the two groups were similar.After one wk of therapy,the treatment group had a curative rate of 57.1%and a significantly better hearing threshold and greater improvement compared to the control group(all P<0.05).Some patients experienced transient discomfort from intratympanic injections that disappeared after getting rest,while none had permanent complications.All patients delivered healthy full-term neonates with an average Apgar score of 9.7±0.5.CONCLUSION Intratympanic dexamethasone injections can be used as a first-line therapy in pregnant women with SSNHL.

Idiopathic sudden sensorineural hearing loss:Effectiveness of salvage treatment with low-dose intratympanic dexamethasone

Objectives:To evaluate hearing outcome of salvage treatment with intratympanic steroids(ITS)in idiopathic sudden sensorineural hearing loss(ISSNHL)refractory to initial systemic steroid(SS)therapy.Material and methods:A retrospective medical chart review was conducted on 54 consecutive patients with ISSNHL refractory to SS.Salvage treatment with a low dose intratympanic dexamethasone(4 mg/ml)was offered after one week of primary treatment.Patients were divided into two groups:25 patients accepted ITS(treatment group)and 29 patients did not undergo additional treatment(control group).A pure tone average(PTA)gain of at least 10 dB was considered hearing improvement.Results:Hearing improvement rate was higher in ITS group compared to control group(40%vs.13.8%,p=0.035).A mean PTA improvement of 8.6±9.8 dB was observed in the ITS group and,whereas the control group had an average hearing gain of 0.7±2 dB(p<0.001).Audiometric analysis revealed a significant hearing gain in ITS group at all tested frequencies compared to control group(p<0.05).Analysis of the selected variables,identified intratympanic steroid treatment as the only independent prognostic factor for hearing improvement(OR=4.2,95%CI:1.1e15.7;p=0.04).Conclusion:Intratympanic low dose dexamethasone is effective in patients with incomplete hearing recovery after primary systemic steroid treatment.

Intratympanic corticosteroids in Ménière's disease:A mini-review

This article reviews the effectiveness of intratympanic corticosteroids for vertigo control in Meniere's disease at 2-years follow-up according to the guidelines expressed by the American Academy of Otolaryngology-Head & Neck Surgery. Despite the increased use of intratympanic corticosteroids for vertigo control in Meniere's disease there is debate as to their effectiveness, particularly compared to gentamicin. Even so,after just a single course of injections, corticosteroids can reliably provide complete vertigo control(Class A) at 2-years in about 50% of cases as indicated in a recent double-blind randomized controlled clinical trial(Patel et al., 2016). But the effectiveness of intratympanic corticosteroids truly increases when treatment is provided 'as-needed', whereby complete vertigo control is established in up to 91% of cases. On the basis of available literature, there is good evidence to recommend the use of intratympanic steroid treatment for vertigo control in Meniere's disease, but patients must be monitored for non-response. The rationale for treating patients as-needed and the possible reasons for corticosteroid nonresponse are discussed.

A comparison of effects of systemic and intratympanic steroid therapies for sudden sensorineural hearing loss:A meta-analysis

Objective:To evaluate the efficacy and safety of intratympanic and systemic steroid therapies in the initial treatment of Sudden Sensorineural Hearing Loss(SSNHL) patients.Methods:A comprehensive search of PubMed,Wanfang database and CNKI(China National Knowledge Infrastructure) was performed covering the period from January 1990 to July 2014.A meta-analysis was conducted after filtering by the criteria of Cochrane Collaboration.Three hundred fifty six subjects in nine studies allocated to the group of intratympanic steroid therapies and 343 controls receiving systemic steroid therapies met the criteria for meta-analysis.The data were extracted and analyzed using the Rev Man 5.3 meta-analysis software.Results:The total effectiveness rate in SSNHL patients receiving intratympanic steroid therapies did not differ statistically from patients receiving systemic therapies(RR = 1.08,95%CI = 0.99-1.99,P = 0.10),although the rate of full hearing recovery in this group differed significantly from patients receiving systemic therapies(RR = 1.29,95%CI = 1.00-1.66,P = 0.05).Conclusion:Local steroid therapy appears to generate higher rate of complete hearing recovery than systemic steroid treatment as an initial treatment for SSNHL,which may be especially useful for patients in whom systemic steroids are contraindicated.

Intratympanic vs systemic use of steroids as first-line treatment for sudden hearing loss:A meta-analysis of randomized,controlled trials

Background Sudden sensorineural hearing loss(SSNHL)is a common disease in otology,and steroids play an important role in its treatment.Steroids can be administered systemically or locally,and the efficacies of different administration routes remain controversial.Methods We searched the Cochrane,EMBASE,PubMed,Web of Science,CNKI,Wanfang and Weipu databases for randomized controlled trials(RCTs)on glucocorticoid treatments for SSNHL to compare the efficacy of topical and systemic steroid administration.The Review Manager 5.4 software was used for synthesis of data:the rate of reported hearing improvement and change in pure-tone audiometry(PTA).Results In all the included studies,when intratympanic administration was compared to systemic therapies,the risk difference(RD)using reported hearing improvement as an outcome measure was 0.08(95%CI:0.01–0.14,I2=45%).Using PTA changes as an outcome measure in 4 studies,the mean difference(MD)was 10.43 dB(95%CI:3.68–17.18,I2=81%).Hearing improvement RD was also compared among different types of steroid,recovery criteria,follow-up times and diagnostic criteria,and showed no significant differences exception for recovery criteria(>10 dB)(RD-0.06,95%CI:0.14-0.2,I2=0%).Conclusion As the initial treatment for SSNHL,topical steroids seem to be superior to systemic steroid administration,especially in patients with contraindications to systemic steroids usage.However,further verification based on high-quality research is needed.

Role of Intratympanic Steroids in the Management of Idiopathic Sudden Sensori Neural Hearing Loss— Our Experience of 67 Cases

Objective: To assess the outcomes of intratympanic steroids in the management of idiopathic sudden sensorineural hearing loss. Study Design: Retrospective study. Setting: Academic tertiary care medical centre. Materials and Methods: A total of 67 patients with idiopathic sudden sensorineural hearing loss were included in our study. Pre- and post-injection audiograms were taken to assess the outcomes in improvement in hearing. Hearing outcomes were assessed with respect to duration of onset of treatment and age of the patient. Improvement in the speech discrimination score was also assessed. Results: A total of 67 patients were included in our study of which unilateral cases were 59 and bilateral cases were 8. Subjectively 35 patients reported improvement in hearing after the therapy while objectively we found 44 ears [41 patients] had improvement. The mean PTA pre ITS was 62.7 and after ITS it was 56.3. Maximum improvement was noted at 2000 Hz and 1000 Hz. Conclusion: Intratympanic steroids can be offered as a first line therapy for idiopathic sudden sensorineural hearing loss as it is minimally invasive, and can be performed as an office based procedure with no systemic side effects. No major complications have been reported in our study and results have been satisfactory.

Role of Intratympanic Steroids in the Management of Meniere’s Disease—A Review of 151 Cases

Objective: To assess the outcomes of hearing and vertigo in patients with Meniere’s disease who were treated with intratympanic methylprednisolone. Study Design: Retrospective study. Setting: Tertiary referral hospital. Methods: In our study with 151 patients [191 ears] were diagnosed as Menieres as per 1995 AAO-HNS guidelines. As an office based procedure these patients were treated with intratympanic methyl prednisolone. Results: There was a 98.6% improvement in the vertigo control rate, a 73.82% improvement in hearing and 29.31% had a definitive improvement in tinnitus. Conclusion: We conclude from our study that intratympanic steroid injection significantly controls vertigo, tinnitus and improves hearing in Meniere’s disease with minimal complications. Hence, it can be tried as a first line treatment for patients with Meniere’s disease.

Sudden sensorineural hearing loss treated with intratympanic dexamethasone injection

Objective To evaluate the effect of different protocols of intratympanic dexamethasone injection in patients with unilateral sudden sensorineural hearing loss (SSNHL) who have failed to respond to typical medical treatment (including systemic steroid treatment). Methods From January 2005 to January 2008, 71 patients who were diagnosed with unilateral SSNHL and failed typical medical treatment received intratympanic dexamethasone injection. Four injection protocols were employed: injection of 0.3 ml dexamethasone(5 mg / ml) three times a week for 3 weeks for a total dose of 13.5 mg (Group I, n=16); injection of 0.6 ml (5 mg / ml) dexamethasone three times a week for 3 weeks for a total dose of 27 mg (Group II, n=18); injection at 0.3 ml(5 mg/ml) week for 6 weeks for a total dose of 9 mg (Group III, n=18); injection at 0.3 ml (5 mg / ml) / 2 days for a total dose of 4.5 mg (Group IV n=19). Hearing recovery was assessed by pure tone audiogram. Results The total effective rate was 37.5%, 38.89%, 33.33% and 36.84% for each treatment protocol, respectively, with no statistical difference between them (P > 0.05). The results suggest that a total dose of 4.5 mg (injected once a week for 3 weeks) is the most adequate protocol, and increasing dose or injection frequency yields no additional benefits. Conclusion Intratympanic dexamethasone significantly improves the prognosis of SSNHL. Small dose at low injection frequency is sufficient. Further multicenter studies are needed to determine the standard treatment protocol.

Intratympanic Injections: An Unsolved Mystery

Aims: The aim of this study was to test the effectiveness of intratympanic dexamethasone injections as a treatment for severe disabling tinnitus and also observe its effect on hearing loss if any. Materials and Methods: Thirty patients with severe disabling tinnitus in the age group 20 to 60 years were selected and randomly assigned to receive intratympanic injections of a dexamethasone solution 4 mg/ml (0.5 ml) or isotonic saline (0.5 ml) solution under topical anaesthesia, once per week for 4 weeks using a zero degree endoscope. Improvement in tinnitus was assessed using a visual analog scale, considering 2-point improvement as significant and alteration in hearing if any was noted by pure tone audiometery before and after the therapy. Results: The improvement in tinnitus was not significant, with no alteration in audiometery reports. Conclusions: Intratympanic therapy is an attractive mode of treatment because of its highly targeted delivery, low concentration of the drugs required and a very good patient tolerance. Although there has been no breakthrough in intratympanic therapy for tinnitus or other otological conditions, accessibility to the inner ear through the semipermeable round window membrane holds many promises in the near future.

Evaluation of intratympanic dexamethasone for treatment of refractory sudden sensorineural hearing loss

Objective: To observe and compare the efficacy of intratympanic application of dexamethasone (DXM) for the treatment of refractory sudden sensorineural hearing loss (SSNHL), the DXM was given in three different ways: by tympanic membrane injection, by drip through a ventilation tube, and by perfusion through a round window catheter. Methods: We conducted a nonrandomized retrospective clinical trial involving 55 patients with refractory SSNHL. For 21 patients (the perfusion group), DXM (2.5 mg/0.5 ml) was perfused transtympanically through a round window catheter using an infusion pump for 1 h twice a day for 7 d giving a total amount of 35.0 mg. For 23 patients (the injection group), DXM (2.5 mg/time) was injected by tympanic membrane puncture at intervals of 2 d on a total of four occasions giving a total amount of 10.0 mg. For 11 patients (the drip group), DXM (2.5 mg/0.5 ml) was dripped via a ventilation tube placed by myringotomy, once on the first day and twice a day for the remaining 6 d giving a total amount of 32.5 mg. Thirty-two patients with refractory SSNHL who refused to undertake further treatments were defined as the control group. Hearing recovery and complications were compared among the groups. Hearing results were evaluated based on a four-frequency (0.5, 1.0, 2.0, 4.0 kHz) pure tone average (PTA). Results: Post-treatment audiograms were obtained one month after treatments were completed. The improvements in average PTA for the perfusion, injection, and drip groups were 9.0, 8.6, and 1.7 dB, respectively. Hearing improvement was significantly greater in the perfusion and injection groups than in the control group (1.4 dB) (P<0.05). In the perfusion group, 8 out of 21 patients (38.1%) had a PTA improvement of 15?56 dB (mean 29.8 dB); in the injection group, 8 out of 23 patients (34.8%) had a PTA improvement of 16?54 dB (mean 24.9 dB); in the drip group, 1 of 11 patients (9.1%) had a PTA improvement of 26.0 dB; in the control group, 3 out of 32 patients (9.4%) had a PTA improvement of 15?36 dB (mean 14.9 dB). Conclusions: Topical intratympanic application of DXM is a safe and effective method for the treatment of SSNHL cases that are refractory to conventional therapies.

耳后注射神经节苷酯联合鼓室内注射甲泼尼龙治疗难治性突发性聋的临床研究

目的评价鼓室内注射甲泼尼龙联合耳后注射神经节苷酯治疗难治性突发性聋的临床疗效,为难治性突发性聋的治疗提供理论依据。方法以2019年9月~2022年1月于宜兴市人民医院和淮安市第二人民医院就诊的难治性突发性聋患者98例作为研究观察对象,随机分为观察组49例和对照组49例,观察组给予鼓室内注射甲泼尼龙联合耳后注射神经节苷脂治疗,对照组单纯行鼓室内注射甲泼尼龙治疗,通过随访调查,对两种不同治疗方法的临床效果进行对比分析。结果随访发现观察组患者治愈率明显高于对照组,差异具有显著性(P<0.05);两组患者不良反应发生率无明显差异,差异无统计学意义(P>0.05),对照组复发率明显高于观察组,差异显著(P<0.05)。结论鼓室内注射甲泼尼龙联合耳后注射神经节苷酯较单纯鼓室内注射甲泼尼龙治疗难治性突发性聋效果显著、复发率低,有一定的临床推广价值。

鼓室注射地塞米松磷酸钠注射液与注射用甲泼尼龙琥珀酸钠治疗突发性聋疗效观察及不良反应分析

目的探讨地塞米松磷酸钠注射液与注射用甲泼尼龙琥珀酸钠鼓室内注射治疗突发性聋的临床疗效并分析两种注射治疗后的不良反应。方法 2018年9月~2019年12月收治的单侧突发性聋患者94例,按数字表法随机分为A组(注射用甲泼尼龙琥珀酸钠组)和B组(地塞米松磷酸钠注射液组)各47例,分别行鼓室内注射注射用甲泼尼龙琥珀酸钠和鼓室内注射地塞米松磷酸钠注射液治疗,分析两组患者治疗前后纯音听阈值变化情况,并观察两组不良反应和空腹血糖变化情况。结果两组患者治疗后纯音听阈较治疗前均有明显改善(A组:t=9.86,P=0.001;B组:t=2.91,P=0.005),A组总有效率82.9%,B组总有效率为63.8%,两组总有效率比较,差异有统计学意义(χ2=4.41,P=0.036);两组总体不良反应率比较,差异无统计学意义(P>0.05);两组治疗前后空腹血糖变化比较,差异无统计学意义(P>0.05)。结论两种治疗方法均能改善突发性聋患者的纯音听阈,但注射用甲泼尼龙琥珀酸钠效果较地塞米松磷酸钠注射液更佳,两者的不良反应情况基本相仿。

鼓室注射甲泼尼龙治疗重度以上突发性聋的疗效观察

近年来，国内外已经越来越多地将鼓室注射类固醇激素应用于治疗突发性聋（sudden deafness，SD）。我科对46例重度以上突发性聋患者分别给予全身地塞米松及鼓室内注射甲泼尼龙治疗，现报道如下。

鼓室注射曲安奈德治疗突发性聋疗效分析

突发性聋（sudden deafness,SD）是一种病因复杂且不完全清楚的感音神经性聋,在数小时或几天内听力下降至最低点,发病率很高,是耳科急症之一。SD的治疗方法较多,类固醇激素的治疗作用已经得到认可,基本上成为一种常规用药。我科对45耳患者应用鼓室注射曲安奈德治疗突发性聋,取得良好效果。

两种激素鼓室灌注治疗重度以上突发性聋的疗效观察

近年来,越来越多的研究聚焦于鼓室内灌注激素治疗突发性聋（sudden deafness,SD）。2010年1月~2013年3月我科对99例重度以上SD患者分别给予全身或鼓室内注射激素治疗,现将治疗结果报道如下。

Audiological characteristics and exploratory treatment of a rare condition of acute-otitis-media-associated sudden sensorineural hearing loss

BACKGROUND Acute otitis media(AOM)is a common disease that is more prevalent in children.Most studies concerning AOM-associated sudden sensorineural hearing loss are case reports and retrospective in nature,hence the etiology of AOM-associated sudden hearing loss has not been fully established.AIM To analyze audiological characteristics of AOM-associated sudden hearing loss and evaluate efficacy of combined tympanostomy tube placement(TTP)and intratympanic methylprednisolone.METHODS Eight adult patients who were diagnosed with AOM-associated sudden hearing loss and ineffectively treated by conventional medical therapy were enrolled in this study.Basic data were collected,and pure tone audiometry was performed to assess the audiological characteristics.Combination therapy with TTP and intratympanic methylprednisolone injection was given to the patients.RESULTS Mixed or sensorineural hearing loss was observed at high frequencies(2–4 kHz).All the cases in this study were cured after TTP and intratympanic methylprednisolone.After treatment,the average hearing threshold at affected frequencies was significantly lower than those in the pretreatment group(P<0.05)and was similar to that in the healthy ears(P>0.05).CONCLUSION AOM rarely induces sudden sensorineural hearing loss.Combination therapy with TTP and intratympanic methylprednisolone injection may be effective after failure of conventional medical treatment.

Postaurical injection is a systemic delivery supported by symmetric distribution of Gd-DOTA in both the ipsilateral and contralateral ears

Postaurical injection of therapeutics was recently applied in clinical practice to treat inner ear diseases based on supposed existence of a direct channel from the postaurical area to the inner ear. Doubting on the associated reports and aiming to provide evidence on the inner ear uptake mechanism, the present study tracked the dynamic distribution of gadolinium-tetra-azacyclo-dodecane-tetra-acetic acid(Gd-DOTA) in rat inner ears after postaurical injection using MRI. A targeted tympanic medial wall delivery was utilized as control. The results showed that, at the early time points after postaurical injection, Gd-DOTA distributed mainly in tissues surrounding the bulla, temporal bone and skull and neck space. In the inner ear, there was gradual uptake of Gd-DOTA on both the ipsilateral and contralateral sides with equal signal intensities. There was no sign of direct channel carrying the agent from the postaurical area to the inner ear. Targeted tympanic medial wall delivery induced significantly greater uptake of Gd-DOTA in the inner ear than did postaurical injection. At 30 min post-administration, targeted tympanic medial wall delivery yielded 4.6-folds higher signal intensity than did postaurical injection. The total dose of Gd-DOTA delivered by the targeted tympanic medial wall approach was only 0.1% of that delivered by postaurical injection. In conclusion, postaurical injection is a systemic administration, which is similar to hypodermic injection, rather than a focal delivery method. By contraries, targeted tympanic medial wall delivery induces fast and abundant uptake of Gd-DOTA in the ipsilateral inner ear without significant distribution in unwanted areas.