## 2 Inner Ear Injury and Glucocorticoid Therapy
### Cochlear Implantation and Glucocorticoid Therapy  
The now commonly practiced cochlear implantation procedure aims to restore the hearing capacity and improve the quality of life. This surgical procedure is fairly routine and is typically performed under general anesthesia. A small retro-auricular incision is made, the implant is then placed under the skin and the electrode is inserted into the cochlea through the round window (Figure 1). Nevertheless, during the procedure, the delicate structures of the cochlea are exposed to a direct trauma [25; 26]. Rapid inflammation ensues as the cascading molecular agents of the tissue injury rage onward, including an avalanche of ROS molecules; these events lead to hair cell death and a subsequent loss of the residual biological hearing capacity [27; 28; 29; 30; 31]. Later on, fibrosis forms around the implanted electrode, a physiological phenomenon that occurs around practically any foreign object, and jeopardizes the conductive functionality of the device [32]. The procedure of a cochlear implantation is, therefore, still evolving. Factors that benefit hearing preservation during a cochlear implantation have thus far included modified surgical practices (the angle and speed of the electrode insertion), flexible electrode arrays and the use of steroids [33]. The standard of care most widely includes dexamethasone. Due to its potent anti-inflammatory and anti-proliferative properties, dexamethasone decreases post-operative inflammation and diminishes the fibrotic processes. There is, however, no consensus regarding the optimal timing, dosage and route of the steroidal administration as all methods to date have led to relatively satisfactory hearing preservation [33; 34]. A glucocorticoid treatment in the context of a cochlear implantation can also be systemically administered. Several studies suggest that systemic glucocorticoids prior to a cochlear implantation improve hearing preservation. According to a prospective non-randomized study, patients treated with prolonged glucocorticoid regions of combined oral and i.v. routes beginning 3 days before surgery had significantly superior hearing preservation outcomes 6 months post-surgery compared with the untreated control group. Positive hearing preservation differences were detected not only when compared with the control group, but also when compared with the standard treatment group, which began an i.v. treatment 30 min prior to surgery [35]. When testing short-term single-dose regimens, a double-blind placebo-controlled trial found that patients undergoing a cochlear implantation and treated immediately before surgery with a single high dose of i.v. methylprednisolone had no difference in hearing preservation or electrode impedance compared with the placebo group [36]. To avoid a systemic glucocorticoid exposure, the treatment may be introduced using an intratympan delivery. Prospective clinical studies have shown that an intratympanic glucocorticoid therapy prior to an electrode insertion whilst repeatedly delivering glucocorticoids throughout the surgical procedure results in better post-operative hearing preservation [37]. This was tested using intratympan methylprednisone immediately after an intubation [38] and intratympanic dexamethasone 15 min before an electrode insertion [39]. Yet, there are several limitations to these studies; dexamethasone was applied together with hyaluronic acid, which minimizes the surgical trauma and seals the cochlea, thereby increasing the exposure to the drug. Accordingly, a double-blind placebo-controlled randomized trial showed that applying a polymeric sponge soaked with methylprednisolone onto the round window membrane during cochlear implantation surgery resulted in lower post-operative inner ear symptoms [40]. Moreover, the glucocorticoid treatment group also exhibited a lower electrode impedance from the middle portion of the electrode array, possibly pointing towards a minimal accumulation of fibrosis around the electrode array.