Acute otitis media and otitis media with effusion are common childhood disorders, a source of significant morbidity, and a leading cause of antibiotic prescription in primary health care. Although effective treatments are available, some shortcomings remain, and thus better treatments would be welcome. Recent discoveries within the field of otitis media research relating to its etiology and pathogenesis have led to further investigation aimed at developing novel treatments. This article provides a review of the latest evidence relating to the understanding of acute otitis media and otitis media with effusion, current treatment strategies, their limitations, new areas of research, and novel strategies for treatment.

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Update on otitis media – prevention and treatment

The prevalence of ear disorders has spurred efforts to develop drug delivery systems to treat these conditions. Here, recent advances in drug delivery systems that access the ear through the tympanic membrane (TM) are reviewed. Such methods are either non-invasive (placed on the surface of the TM), or invasive (placed in the middle ear, ideally on the round window [RW]). The major hurdles to otic drug delivery are identified and highlighted the representative examples of drug delivery systems used for drug delivery across the TM to the middle and (crossing the RW also) inner ear.

Drug Delivery across Barriers to the Middle and Inner Ear

Vaginal epithelial drug delivery.

Engineering PLGA nano-based systems through understanding the influence of nanoparticle properties and cell-penetrating peptides for cochlear drug delivery

Background Idiopathic sudden sensorineural hearing loss (ISSNHL) is common, and defined as a sudden decrease in sensorineural hearing sensitivity of unknown aetiology. Systemic corticosteroids are widely used, however their value remains unclear. Intratympanic injections of corticosteroids have become increasingly common in the treatment of ISSNHL. Objectives To assess the effects of intratympanic corticosteroids in people with ISSNHL. Search methods The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; CENTRAL (2021, Issue 9); PubMed; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials (search date 23 September 2021). Selection criteria We included randomised controlled trials (RCTs) involving people with ISSNHL and follow‐up of over a week. Intratympanic corticosteroids were given as primary or secondary treatment (after failure of systemic therapy). Data collection and analysis We used standard Cochrane methods, including GRADE to assess the certainty of the evidence. Our primary outcome was change in hearing threshold with pure tone audiometry. Secondary outcomes included the proportion of people whose hearing improved, final hearing threshold, speech audiometry, frequency‐specific hearing changes and adverse effects. Main results We included 30 studies, comprising 2133 analysed participants. Some studies had more than two treatment arms and were therefore relevant to several comparisons. Studies investigated intratympanic corticosteroids as either primary (initial) therapy or secondary (rescue) therapy after failure of initial treatment. 1. Intratympanic corticosteroids versus systemic corticosteroids as primary therapy We identified 16 studies (1108 participants). Intratympanic therapy may result in little to no improvement in the change in hearing threshold (mean difference (MD) ‐5.93 dB better, 95% confidence interval (CI) ‐7.61 to ‐4.26; 10 studies; 701 participants; low‐certainty). We found little to no difference in the proportion of participants whose hearing was improved (risk ratio (RR) 1.04, 95% CI 0.97 to 1.12; 14 studies; 972 participants; moderate‐certainty). Intratympanic therapy may result in little to no difference in the final hearing threshold (MD ‐3.31 dB, 95% CI ‐6.16 to ‐0.47; 7 studies; 516 participants; low‐certainty). Intratympanic therapy may increase the number of people who experience vertigo or dizziness (RR 2.53, 95% CI 1.41 to 4.54; 1 study; 250 participants; low‐certainty) and probably increases the number of people with ear pain (RR 15.68, 95% CI 6.22 to 39.49; 2 studies; 289 participants; moderate‐certainty). It also resulted in persistent tympanic membrane perforation (range 0% to 3.9%; 3 studies; 359 participants; very low‐certainty), vertigo/dizziness at the time of injection (1% to 21%, 3 studies; 197 participants; very low‐certainty) and ear pain at the time of injection (10.5% to 27.1%; 2 studies; 289 participants; low‐certainty). 2. Intratympanic plus systemic corticosteroids (combined therapy) versus systemic corticosteroids alone as primary therapy We identified 10 studies (788 participants). Combined therapy may have a small effect on the change in hearing threshold (MD ‐8.55 dB better, 95% CI ‐12.48 to ‐4.61; 6 studies; 435 participants; low‐certainty). The evidence is very uncertain as to whether combined therapy changes the proportion of participants whose hearing is improved (RR 1.27, 95% CI 1.15 to 1.41; 10 studies; 788 participants; very low‐certainty). Combined therapy may result in slightly lower (more favourable) final hearing thresholds but the evidence is very uncertain, and it is not clear whether the change would be important to patients (MD ‐9.11 dB, 95% CI ‐16.56 to ‐1.67; 3 studies; 194 participants; very low‐certainty). Some adverse effects only occurred in those who received combined therapy. These included persistent tympanic membrane perforation (range 0% to 5.5%; 5 studies; 474 participants; very low‐certainty), vertigo or dizziness at the time of injection (range 0% to 8.1%; 4 studies; 341 participants; very low‐certainty) and ear pain at the time of injection (13.5%; 1 study; 73 participants; very low‐certainty). 3. Intratympanic corticosteroids versus no treatment or placebo as secondary therapy We identified seven studies (279 participants). Intratympanic therapy may have a small effect on the change in hearing threshold (MD ‐9.07 dB better, 95% CI ‐11.47 to ‐6.66; 7 studies; 280 participants; low‐certainty). Intratympanic therapy may result in a much higher proportion of participants whose hearing is improved (RR 5.55, 95% CI 2.89 to 10.68; 6 studies; 232 participants; low‐certainty). Intratympanic therapy may result in lower (more favourable) final hearing thresholds (MD ‐11.09 dB, 95% CI ‐17.46 to ‐4.72; 5 studies; 203 participants; low‐certainty). Some adverse effects only occurred in those who received intratympanic injection. These included persistent tympanic membrane perforation (range 0% to 4.2%; 5 studies; 185 participants; very low‐certainty), vertigo or dizziness at the time of injection (range 6.7% to 33%; 3 studies; 128 participants; very low‐certainty) and ear pain at the time of injection (0%; 1 study; 44 participants; very low‐certainty). 4. Intratympanic plus systemic corticosteroids (combined therapy) versus systemic corticosteroids alone as secondary therapy We identified one study with 76 participants. Change in hearing threshold was not reported. Combined therapy may result in a higher proportion with hearing improvement, but the evidence is very uncertain (RR 2.24, 95% CI 1.10 to 4.55; very low‐certainty). Adverse effects were poorly reported with only data for persistent tympanic membrane perforation (rate 8.1%, very low‐certainty). Authors' conclusions Most of the evidence in this review is low‐ or very low‐certainty, therefore it is likely that further studies may change our conclusions. For primary therapy, intratympanic corticosteroids may have little or no effect compared with systemic corticosteroids. There may be a slight benefit from combined treatment when compared with systemic treatment alone, but the evidence is uncertain. For secondary therapy, there is low‐certainty evidence that intratympanic corticosteroids, when compared to no treatment or placebo, may result in a much higher proportion of participants whose hearing is improved, but may only have a small effect on the change in hearing threshold. It is very uncertain whether there is additional benefit from combined treatment over systemic steroids alone. Although adverse effects were poorly reported, the different risk profiles of intratympanic treatment (including tympanic membrane perforation, pain and dizziness/vertigo) and systemic treatment (for example, blood glucose problems) should be considered when selecting appropriate treatment. 

Intratympanic corticosteroids for sudden sensorineural hearing loss

Drug delivery to the ear is used to treat conditions of the middle and inner ear such as acute and chronic otitis media, Meniere’s disease, sensorineural hearing loss and tinnitus. Drugs used include antibiotics, antifungals, steroids, local anesthetics and neuroprotective agents. A literature review was conducted searching Medline (1966–2012), Embase (1988–2012), the Cochrane Library and Ovid (1966–2012), using search terms ‘drug delivery’, ‘middle ear’, ‘inner ear’ and ‘transtympanic’. There are numerous methods of drug delivery to the middle ear, which can be categorized as topical, systemic (intravenous), transtympanic and via the Eustachian tube. Localized treatments to the ear have the advantages of targeted drug delivery allowing higher therapeutic doses and minimizing systemic side effects. The ideal scenario would be a carrier system that could cross the intact tympanic membrane loaded with drugs or biochemical agents for the treatment of middle and inner ear conditions.

Drug delivery to the ear

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Drug delivery to the ear