Effect of intratympanic steroid administration on sensorineural hearing loss associated with acute otitis media

Heywood, Rebecca; Ifeacho, Sonna; Narula, A.

doi:10.1017/s0022215116001110

Cited by 6 publications

(3 citation statements)

References 9 publications

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“…Systemic administration of steroid drugs is the preferred route in everyday clinical practice, but high doses are needed to reach therapeutic concentrations across the BLB, which can lead to systemic side effects (30). Injection through the tympanic membrane into the middle ear is an alternative modality that bypasses the BLB and minimizes systemic effects (32). However, steroid solutions clear quickly from the middle ear and, therefore, require frequent administration.…”

Section: Introductionmentioning

confidence: 99%

Protection of lipopolysaccharide-induced otic injury by a single dose administration of a novel dexamethasone formulation

Murillo-Cuesta,

Lara,

Bermúdez-Muñoz

et al. 2023

Preprint

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Background. The blood-labyrinth barrier (BLB) separates the inner ear from the circulation and is critical for maintaining ionic homeostasis and limiting the entry of deleterious agents. BLB integrity is disrupted by bacterial lipopolysaccharide (LPS), among other deleterious agents, which elicits a strong inflammatory response in the inner ear leading to irreversible otic damage. Prolonged administration of systemic corticosteroids is the available treatment, which shows both limited efficacy and major adverse effects. SPT-2101 is a novel in situ-forming gel formulation of dexamethasone allowing slow and sustained drug release after single intratympanic administration. Methods. We used a rat model of LPS-induced injury to define the functional, cellular and molecular mechanisms associated to BLB dysfunction and the protection by SPT-2101. Hearing was assessed by auditory brainstem response (ABR) recording, BLB permeability by gadolinium dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and Evans blue extravasation. Gross cochlear histology and cellular alterations were studied by hematoxylin-eosin staining and immunofluorescence. RT-qPCR, PCR array and western blotting were used to assess transcriptional and protein changes. Results. LPS-challenged rats showed BLB breakdown and altered permeability as shown by the progressive increase in cochlear gadolinium uptake and Evans blue incorporation. LPS administration increased the cochlear expression of the LPS toll-like receptors Tlr2 and co-receptor Cd14, pro-inflammatory cytokines and receptors such as Il1b and ll1lr, and also the oxidative stress and inflammasome mediators NRF2 and NLRP3. LPS also increased IBA1-positive macrophage infiltration in the lateral wall and spiral ganglion. A single intratympanic injection of SPT-2101 protected BLB integrity and prevented otic injury. Comparable effects were obtained by repeated administration of systemic dexamethasone, but not by a single dose. SPT-2101 administration normalized molecular inflammatory mediators and suppressed macrophage infiltration. Conclusions. Our data indicate that single local administration of dexamethasone formulated as SPT-2101 protects BLB functional integrity during endotoxemia, providing a novel therapeutic opportunity to treat diseases related to BLB dysfunction.

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Section: Introductionmentioning

confidence: 99%

Protection of lipopolysaccharide-induced otic injury by a single dose administration of a novel dexamethasone formulation

Murillo-Cuesta,

Lara,

Bermúdez-Muñoz

et al. 2023

Preprint

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“…Most of these cases received corticosteroids as initial therapy[ 11 ]. Furthermore, intratympanic steroid administration is suggested as salvage therapy when initial therapy fails[ 11 , 12 ]. However, AOM-associated sudden sensorineural hearing loss is a rare otological condition and the mechanism and treatment methods have not been defined.…”

Section: Introductionmentioning

confidence: 99%

“…Most studies concerning AOM-associated sudden sensorineural hearing loss are case reports and retrospective in nature[ 12 - 14 ], hence, the etiology of AOM-associated sudden hearing loss has not been fully established. One of the hypotheses is that effusion in the middle ear causes vibration limitation and hypoxia of two windows, which leads to bone conduction hearing loss[ 15 ].…”

Section: Introductionmentioning

confidence: 99%

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

Cao¹,

Yi²

2021

WJCC

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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.

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Preclinical and clinical otoprotective applications of cell-penetrating peptide D-JNKI-1 (AM-111)

Eshraghi

Aranke

Salvi³

et al. 2018

Hearing Research

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Effect of intratympanic steroid administration on sensorineural hearing loss associated with acute otitis media

Abstract: The results of our study suggest that intratympanic steroids provide a valuable contribution to the treatment of acute infective sensorineural hearing loss and may provide additional benefit by virtue of a concentrated local steroid effect in patients who do not respond to antibiotics.

Cited by 6 publications

References 9 publications

Protection of lipopolysaccharide-induced otic injury by a single dose administration of a novel dexamethasone formulation

Protection of lipopolysaccharide-induced otic injury by a single dose administration of a novel dexamethasone formulation

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

Preclinical and clinical otoprotective applications of cell-penetrating peptide D-JNKI-1 (AM-111)

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