Intratympanic Steroid Injection

Anatomy and Physiology

Tympanic Membrane

The tympanic membrane (TM), approximately 1cm in diameter, is a thin ovoid semitransparent pearly-grey membrane separating the external ear canal from the tympanic cavity of the middle ear. The membrane consists of the pars tensa, which is much larger, and the thinner pars flaccida. The pars tensa is thicker and more fibrous because it has three layers. It consists of the outer layer, continuous with the skin on the external canal; the inner layer, continuous with the mucous membrane lining the middle ear; and then between the two, a layer of radial and circular fibers that give the membrane its tension and stiffness. These radial and circular fibers are present antero-inferiorly. The thinner pars flaccida is a small portion superior posteriorly and is devoid of a fibrous layer. The tympanic membrane transmits sound in the form of air vibrations to the auditory ossicles in the middle ear.

The handle of the malleus (one of the auditory ossicles) is embedded in the TM and is normally visualized near the umbo. In a healthy ear, the anterior cone of light, observed when light from an otoscope illuminates the membrane, is visible antero-inferiorly from the umbo.

Middle Ear

The middle ear is an air-filled chamber contained within the petrous part of the temporal bone. It is divided into the space directly medial to the TM, known as the tympanic cavity, and the area superior to the TM, known as the epitympanic recess. The Eustachian tube connects the tympanic cavity to the nasopharynx. The auditory ossicles within the middle ear transmit sound vibrations from the tympanic membrane to the oval window, which is an opening to the cochlea of the internal ear.

Internal Ear

The internal (or inner) ear contains the vestibulocochlear organ. This is the sensory system for balance and hearing and is composed of the cochlear duct, semicircular canals, utricle, and saccule. The membranous labyrinth, containing endolymph, is located within the perilymph-filled bony labyrinth. The bony labyrinth has a series of cavities - the cochlea, vestibule, and semicircular canals. The cochlea contains the cochlear duct, which is involved in hearing. There are two permeable openings from the middle ear into the internal ear - the round window and the oval window. The round window is located in the round window niche inferoposterior to the oval window. The stapes bone transmits vibration to the oval window, which causes the round window to move in the opposite phase, which in turn allows the fluid in the cochlea to move, enabling hearing.

The blood-labyrinth barrier, or blood-perilymph barrier, is the barrier between the capillary vasculature and fluids of the internal ear, and it restricts entry of most blood-borne compounds into internal ear tissues, thereby regulating the composition of the fluid.[8]

Physiology

The cochlea is one of the most difficult organs to access for drug delivery. Systemic administration can be limited by the blood-labyrinth barrier, which reduces the exchange of fluid between plasma and the inner ear.[9][10] As a result, local intratympanic administration appears more preferable in many cases.

Intratympanic administration is minimally invasive but does rely on diffusion through middle ear barriers, primarily the round window membrane and oval window for drug entry into the cochlea.[10][8] Many clinical studies suggest that ITS over systemic administration delivers higher concentrations of steroid to the inner ear.[11][12] Compared to intravenous steroid injection, one study demonstrated the perilymph levels to be 260x higher following ITS along with much lower plasma concentrations.[13][14]

Steroids are delivered through the tympanic membrane via a needle into the middle ear space and then absorbed and diffused primarily through the semi-permeable round window membrane but also the oval window annular ligament and small lacunar mesh into the inner ear perilymph.[13][15][16] The round window membrane is a semi-permeable that provides a little impediment to the movement of most drugs or other molecules into the inner ear. The communication pathway between scala tympani and the organ of Corti and spiral ganglion ensures that drugs delivered through the round window will be delivered rapidly to hair cells and nerve cells.[13]

The mechanism behind SSNHL can be multifactorial and is not completely understood. However, there is an increasing suggestion that it involves immunomodulatory cells and proinflammatory cytokines in the inner ear along with tumor necrosis factor, causing a reduction in cochlear blood flow. Glucocorticoid treatment centers around their antioxidant and anti-inflammatory effects.[17] Intratympanic corticosteroids appear to affect both ion homeostasis and immune suppression, providing a protective mechanism against certain inflammatory mediators that have harmful effects on the cochlea.[13][18] Efficacy may be affected by round window niche adhesions or plugs.[8] 

Meniere's Disease diagnosis is based on episodic unilateral clinical symptoms of vertigo combined with fluctuating low-frequency sensorineural hearing loss, tinnitus, and aural fullness. Since it has been suggested that the condition is a disorder of an immune-mediated endolymphatic sac, glucocorticoids are used as treatment. Meniere's disease results from a failure of inner ear homeostatic mechanisms regulating endolymph and perilymph, nerve and intercellular signaling, metabolism, and blood flow.[15][19] Clinically the sensorineural hearing loss seems to be progressive and fairly resistant to treatment, whereas episodic vertigo can be responsive to treatment. Conservative and medical interventions can control or eliminate 90% of vertigo attacks; however, the remaining group does not respond that is usually treated with intratympanic drug administration. This can be in the form of either a gentamicin or steroid injection. Both forms have been shown to be equally effective at reducing vertigo attacks. However, steroid injection has the advantage of being non-ablative, reducing the risk of hearing or fixed vestibular loss.[19][15]

Indications

Idiopathic Sudden Sensorineural Hearing Loss

Primary Treatment

• Immediately following diagnosis
• Most studies suggest that early treatment is associated with a better outcome.[18][13]
• A clinical study in 2011 monitoring 250 patients found no difference between intratympanic and oral steroids as first-line treatment.[20]

Salvage (rescue) Treatment

• Offered when patients have incomplete recovery after initial therapy for SSNHL.[21]
• Some studies suggest better hearing outcomes when it is used after failed systemic therapy.[11]
• Recommended within 2 to 6 weeks after the onset of symptoms.[6]
• The most commonly used option in ISSNHL.[22] 
• Haynes, et al. found with intratympanic dexamethasone for SSNHL, after failed systemic therapy, 40% of patients showed improvement in hearing compared to 9.1% in the control group.[1]

Combined Treatment

• This involves ITS in combination with oral corticosteroids.
• Some studies have shown benefits, especially for patients with moderate to severe hearing loss, while others found none.[22] Some studies have shown that combination steroid therapy (intratympanic and systemic administration) shows no benefit compared to simultaneous or systemic therapy alone in hearing recovery for patients with SSNHL.[23][24]

Meniere Disease

In 2018 The International Consensus (ICON) on the treatment of Meniere's Disease recommended ITS as second-line therapy when medical treatment has failed.[7]

There is good evidence suggesting that ITSI can be used as an effective treatment for refractory Meniere disease, particularly for vertigo control, reducing the number of attacks.[25] A double-blind, randomized controlled trial in 2016 showed that corticosteroid injections could provide reliable, complete vertigo control at 2 years in approximately 50% of cases after just a single course.[25] However, the effectiveness of ITSI is most pronounced when conservative medical management has failed, and ITS treatment is provided as-needed therapy.[15]

Refractory Tinnitus

In a study by Yener et al., high concentrations of steroid in the inner ear from an ITS injection could reduce tinnitus by increasing blood flow to the inner ear. The majority of papers suggest that ITSI is most effective in acute tinnitus rather than chronic.[26]

Autoimmune Inner Ear Diseases

In autoimmune inner ear diseases (AIED), a corticosteroid is a first-line treatment.[26]

Contraindications

Following are the contraindications:

• Uncooperative patient: absolute patient cooperation is required to ensure safe and successful administration.
• A patient with an intact tympanostomy tube (corticosteroid can be instilled via the tube).
• Acute otitis externa
• An intratympanic tumor or vascular abnormality
• Suboptimal view of the important landmarks of the tympanic membrane

Equipment

The following equipment is required:

• Appropriately sized ear speculum
• Binocular otology microscope
• A syringe with a 25-gauge spinal needle
• Cottonwool soaked with Emla cream 5% or phenol, or xylocaine 10% spray applied to tympanic membrane for 30 minutes. Some physicians use local anesthesia with a subcutaneous injection of 1% lidocaine with 1:100,000 adrenaline. No one mode of local anesthetic has been found to be more efficacious over other methods.[27][28]
• Steroid - methylprednisolone (30 to 62.5mg/mL) - at body temperature to prevent caloric reaction and a fresh preparation as preservatives can cause pain or irritation to the middle ear.[29]

Preparation

• It is essential to provide patient education and consent before performing the procedure.
• It is important to warn the patient that they may feel dizzy following the procedure, so it is advised that they have someone to take them home.
• Position the patient in a comfortable position supine in a chair with their head rotated to the contralateral ear.
• Use a binocular otology microscope and speculum to visualize the anteroinferior quadrant of the tympanic membrane.
• Wax and debris in the external auditory canal may need to be removed to ensure good visualization of the entire tympanic membrane.
• Topical anesthetic (Xylocaine 10 mg/dose spray, or lidocaine/prilocaine cream 5%) placed on the anteroinferior quadrant of the tympanic membrane.

Technique or Treatment

Here is the technique:

• 0.4 to 0.8 mL methylprednisolone is injected using a 25-gauge spinal needle through the anteroinferior anesthetized region into the middle ear space until full.
• Consider a secondary perforation, known as a borehole, made on the tympanic membrane to relieve pressure. At the same time, the medication is being injected, avoiding barotrauma to the round window. Alternatively, a pressure-equalization tube (grommet) can be placed for patients requiring regular intratympanic medication.
• Following administration, the patient remains supine with injected ear up and avoids swallowing, yawning, or speaking for 20 to 30 minutes to facilitate steroid passage across the round window membrane and prevent leakage into the eustachian tube.

Complications

Intratympanic steroids have minimal morbidity; however, there are some potential complications or side effects that must be considered and thoroughly discussed with the patient before undergoing the procedure.

The most common side effects are transient dizziness, injection site pain, and a burning sensation.[30]

Other possible complications or side effects include:

• Pain 
• Ear fullness
• Vertigo (generally temporary)
• Headache
• Dizziness
• Persistent tympanic membrane perforation
• Tinnitus
• Infection
• Syncopal episode
• Hearing loss
• Tongue numbness[30]

Clinical Significance

Clinical Advantages of Intratympanic Injection

• No systemic side effects due to no systemic absorption therefore advantageous in patients in which systemic steroids are contraindicated
• More targeted delivery with ITS, therefore higher local concentration of the drug compared to systemic steroids.
• Low morbidity
• Avoids 'first-pass' metabolism
• Reduced volume of drug required compared to systemic steroids
• The procedure is generally well-tolerated
• Relatively easy to perform as an outpatient procedure requiring only topical local anesthesia
• Low cost

Enhancing Healthcare Team Outcomes

ISSNHL has high rates of spontaneous recovery; reported rates range from 32 to 65%. ITS treatment modality needs to be used cautiously due to a lack of confirmed understanding of the underlying etiology of some inner ear diseases.[31]

An interprofessional team, particularly between the otolaryngologist, audiovestibular doctor, and audiologist, should provide a holistic and integrated approach to care that can help achieve the best possible outcomes. 

It is important that the ISSNHL is recognized early and referred appropriately to give these patients the opportunity access to ITS, should it be appropriate. Studies have shown that earlier time to initiating injections produce higher rates of hearing improvement.[32] ITS is a procedure that is easily performed, relatively safe, and very effective with a low complication rate and few contraindications.

A study by Sugihara et al. (2018) suggested the frequency of intratympanic steroid injections does not significantly affect hearing outcomes.[32]

Following treatment, there should be an audiological follow-up with a repeat audiometric assessment. One study found that the recovery rate on the 7th day of treatment to be useful for predicting final hearing recovery.[33] If there is no improvement in repeat audiometry, then a further ITS may be considered.

Nursing, Allied Health, and Interprofessional Team Monitoring

• Regular audiometric testing may be required to monitor the hearing levels.
• If a course of ITS is unsuccessful in providing adequate improvement in the hearing, then the patient may be considered for hearing aid device assessment, if appropriate.