Intratympanic Dexamethasone in Sudden Sensorineural Hearing Loss

Abstract

Sudden sensorineural hearing loss can be a frightening experience for the sufferer and needs immediate treatment. Systemic steroid therapy has been the mainstay of treatment of this condition but concerns about their side effects has led to their use by intratympanic injection. We studied the results of intratympanic dexamethasone (IT-Dexa) both as a primary therapy and as salvage treatment after failure of oral steroids. A total of 39 patients of SSNHL were studied prospectively. Of these 23 were given oral steroids. Ten of these showed no response and were treated with IT-Dexa 4 mg/ml twice a week for two weeks. In addition, 16 patients who reported later than two weeks or had concomitant medical disorders like diabetes and/or hypertension were treated with IT-Dexa. While oral steroids showed hearing improvement (≥ 10 dB) in 56.5% patients, the recovery rate was 62.5% and 80% in those treated primarily with IT-Dexa and as salvage therapy respectively. There was a negative correlation of delay in institution of treatment with hearing recovery. Conclusion: intratympanic dexamethasone is a safe and effective treatment and should be offered to patients as a primary treatment modality and also as salvage therapy after failure of oral steroids. For best results the treatment should be started at the earliest.

Introduction

Sudden sensorineural hearing loss (SSNHL), a condition first described by de Kelyn [1], is commonly defined as abrupt onset of hearing loss of at least 30 dB in three consecutive frequencies on a standard audiogram occurring over a period of three days or less. It can be a frightening experience for the sufferer impacting quality of life and needs immediate treatment. Since prior audiometry is not available, the hearing loss is usually defined in relation to the opposite ear’s thresholds [2]. Mostly it is unilateral although bilateral involvement in up to 4% cases has been reported and it is often but not always accompanied by tinnitus and/or vertigo. Its incidence has been reported to be 5–27 per 100,000 per year in the USA [3]. The incidence increases with age, ranging from 11 per 100,000 for patients younger than 18 years to 77 per 100,000 for those above 65 years with an overall slight male preponderance [4]. This probably is an underestimate since many who recover spontaneously never seek medical treatment [5]. The recovery rates in treated patients have been reported to be from 49 to 89% and spontaneous recovery of untreated patients with sudden SNHL ranges from 30 to 65% [4]. This means that to be really effective, the treatment must show improvement over this rate. These figures make the distinction between spontaneous recovery and efficiency of early treatment rather nebulous.

The etiology of this condition is not yet fully understood. A large number of causes are attributed to SSNHL but only in about 10%, the actual etiology can be identified. When the cause remains obscure despite thorough investigation, it is classified as idiopathic. The various theories of its causation include viral infections, inflammatory or immune mediated reactions, vascular insufficiency, intralabyrinthine membrane rupture, drug toxicity etc. Certain conditions which can cause SSNHL include otologic surgery, noise trauma, barotrauma, Meniere’s disease, acoustic neuroma, syphilis, toxoplasmosis, diabetes mellitus, multiple sclerosis, sarcoidosis, Lyme’s disease, mumps, HIV, polyarteritis nodosa, Cogan’s syndrome, malingering and migraines [6]. Many vascular and hematological pathologies have been associated with SSNHL. These include emboli, transient ischemic attacks, sickle cell anemia, macroglobulinemia and subdural hematoma among many others [7]. It has been reported that patients with iron-deficiency anemia [8], osteoporosis [9] and chronic otitis media [10] are significantly at greater risk of developing SSNHL. Up to 4.7% of patients who initially present with SSNHL will be diagnosed with some other otologic disorder over a period of time as their disease progresses [11]. This coupled with the fact that SSNHL caused by vestibular schwannomas can potentially recover spontaneously or after treatment with systemic steroids [11] calls for a thorough work up of patients with SSNHL.

Many treatments have been tested and found to be ineffective. These include free radical scavenging vitamins, gingko biloba, magnesium; agents that decrease blood viscosity (dextran, pentoxiphyline, procaine, heparin) and vasodilator agents (histamine, papaverine, verapamil, carbogen, antiviral drugs etc. [12]. In the 2012 clinical practice guidelines of American Academy of Otolaryngology and Head Neck Surgery [2] hyperbaric oxygen has been kept as an option but only when combined with steroid therapy.

There is no gold standard for the management of SSNHL. A significant number (30–65%) of patients will recover spontaneously within two weeks [3]. Poor prognosis is seen in over 60-year-old, diabetics and those with associated vertigo, profound hearing loss and delay in treatment beyond two weeks. Treatment with high dose steroids, either oral or intravenous is considered by most to be the standard of care since the landmark trial by Wilson et al. [13]. There have been conflicting reports about the efficacy of oral steroids in SSNHL. While Wilson et al. reported hearing improvement in 78% of patients having moderate hearing loss with steroid therapy vs 38% in the placebo group, others have questioned their efficacy [14–16]. Nevertheless, the Clinical Practice Guidelines for Sudden Hearing Loss [2] recommended a 10-to-14-day course of oral prednisolone (60 mg/day for 7 days with 7-day taper) as initial treatment of SSNHL. However, many clinicians are apprehensive about their use because of their potential side effects like insomnia, dizziness, weight gain, sweating, flushing, mood swings, gastritis, decompensation of diabetes mellitus and hypertension, reactivation of tuberculosis, osteoporosis and rarely osteonecrosis, pancreatitis, cataracts, myopathy and opportunistic infections. A short course of oral prednisolone has been reported to lead to partial inhibition of the hypothalamus–pituitary–adrenal axis in up to 40% of patients and this increases the risk of Addisonian crisis during physiologic stress like acute illness or surgery [17]. On the other hand, Alexander and Harris [18] demonstrated that even in long term steroid treatment (up to 22 weeks), for autoimmune ear disease, the most frequent adverse effect was hyperglycemia and weight gain; severe events like osteonecrosis and fractures being more commonly seen in those with pre-existing bone and joint problems.

In order to offset the potential side effects of systemic steroids, Silverstein et al. [19] reported the use of intratympanic steroids which allows for the delivery of small amounts of the drug to the inner ear. Because of the blood-labyrinthine barrier, systemic steroids have a limited ability to reach the inner ear and the intratympanic administration provides a direct route for absorption via the round window membrane [4]. The improvement in hearing with steroids can occur in three ways viz. anti-inflammatory effect; by altering the inner ear’s fluid and electrolyte balance, thus affecting the endocochlear potentials; and by increasing cochlear blood flow [20].

We undertook this study to evaluate the efficacy of intratympanic dexamethasone for management of sudden sensorineural hearing loss as a primary treatment and as salvage therapy in cases which failed to show improvement with systemic steroids.

Study Design

This was a prospective study conducted in the Department of E.N.T., Head and Neck Surgery Government Medical College and S.M.G.S. Hospital, Jammu for a period of 15 months starting November 2018. Informed consent was taken from all the patients and prior approval of the institutional ethics committee was obtained. The study was done on patients attending E.N.T.OPD and diagnosed as sudden SSNHL.

Inclusion criteria: sudden unilateral SNHL of 30 dB over at least three frequencies developing within 72 h, normal or near normal hearing in the contralateral ear and age > 18 years.

Exclusion criteria: otologic surgery in the past, hearing loss after radiotherapy, acoustic trauma, barotrauma, head injury; fluctuating hearing loss; evidence of acute otitis media, chronic otitis media, cholesteatoma, otosclerosis or retro cochlear lesion.

A thorough clinical work up of all the patients was done including a detailed history and a complete ENT examination. Investigations included complete blood counts, fasting blood sugar, renal function tests, liver function tests, thyroid function tests, VDRL, ESR and RA factor. Audiologic assessment included pure tone audiometry with speech discrimination score, tympanometry, SRT, SISI, BERA and tone decay tests. Radiologic assessment including MRI and HRCT temporal bone was done wherever clinically indicated.

Methodology

The patients who presented to us within two weeks of onset of hearing loss (N = 23) were prescribed oral steroids (Prednisolone) 60 mg daily for 1 week and this was tapered during the next 7 days. This formed Group A. Sixteen patients who were diabetic, were having any other contraindication for oral steroids or presented to us after 2 weeks of onset of hearing loss were given primary intratympanic dexamethasone treatment (Group B). The patients (N-10) who did not show improvement in pure tone average after completion of oral therapy were given intratympanic steroids as salvage therapy (Group C). No patient in any group discontinued treatment due to intolerance or side-effects. No associated treatment in the form of vitamins or antiviral drugs was given. The patients who presented with vertigo were treated symptomatically and were given IT-Dexa after vertigo subsided in an average of 3.4 days.

Method of Intratympanic Injection

The patient was placed supine with head tilted to opposite side. Under microscopic guidance, the tympanic membrane was anaesthetized by applying a minute amount of carbolic acid and dexamethasone (4 mg/ml) was injected with 27 gauze spinal needle slowly in the postero-inferior quadrant with the needle facing towards the round window. The subjects were asked to maintain this position and avoid swallowing for at least 30 min. Four such injections were given biweekly for 2 weeks. The amount of dexamethasone injected ranged from 0.4 to 0.8 ml.

Review audiograms were done at the end of 2nd week and at 1 month after completion of therapy. Patients who did not show any response underwent a follow up audiogram at 3 months. The response to treatment was considered if a change was recorded in pure tone average by calculating the difference in PTA before intratympanic injections and the PTA at 1 month. The pure tone average was calculated by taking 6 frequencies, viz. 0.25, 0.5, 1, 2, 4 and 8 kHz. The response was further graded following criteria by Furuhashi et al. [21] who classified outcomes as complete recovery, marked improvement, partial improvement or non-recovery (Table 1). The p-value of pre and post treatment pure tone audiogram was calculated using IBM SPSS version 21 software.

Table 1.

Improvement related to treatment delay

Treatment delay	Oral steroid (N = 23)		Primary IT-Dexa (N = 16)		Salvage (N = 10)
	Total Pts.	Improved	Total Pts.	Improved	Total Pts.	Improved
< 7 Days	13	13 (100%)	7	6 (85.7)	0	0
8–14 Days	5	0	0	0	5	5 (100%)
15–21 Days	4	0	0	0	5	3 (75%)
> 21 Days	1	0	9	4 (44.4%)	0	0
Total	23	13 (56.5%)	16	10 (62.5%)	10	8 (80%)

Observations

Patient Profile

During the study period, a total of 44 patients were diagnosed with SSNHL. Out of these, 5 patients did not turn up after the initial diagnosis and were excluded from the study. Of the 39 patients studied, the mean age was 46.97 ± 13.34 years. The youngest patient was just over 18 and the oldest 68 years. One third of the patients were in the seventh decade of life while 60% patients were in the 41–60 age group. There was an almost equal distribution of males and females (20:19). The average age of men was 48.86 ± 11.47 years and women 44.53 ± 15.44 years. The mean age was 39.15 ± 13.79 years in group A, 50.75 ± 12.58 years in group B and 51.1 ± 10.04 years in group C. Almost half the patients (51.3%) presented within 7 days, 3 (7.7%) during the second week, 5 (12.8%) during the third week and the rest 11(28.2%) after the third week of onset of hearing loss. One patient reported after 50 and another after 60 days. Associated symptoms included vertigo in 5 (12.8%), tinnitus in 14 (35.9%) and both vertigo and tinnitus in 4 (10.3%). Co-morbidities were observed in 11 patients (28.2%) viz. diabetes mellitus in 5, hypertension in 2, both diabetes mellitus and hypertension in 2, hypothyroidism and rheumatoid arthritis in one each. Pure tone audiometry showed the average hearing loss to be 73.87 ± 19.96 dB. The amount of hearing loss was profound in 10 (25.6%), severe in 9 (23.1%), moderately severe in 10 (25.6%), moderate in 9 (23.1%) and mild in one patient (2.5%).

Comparison of Recovery Rate Among Groups

The recovery rates among the three groups were evaluated in two ways. Using Furuhashi criterion, successful recovery was seen in 47.8% in group A, 30% in group B and 31.5% in group C. However, using the ≥ 10 dB criterion the results were 56.5%, 62.5% and 80% respectively; the average recovery rate in all groups being 79.4%. Little change in PTA was noticed in those who underwent the test again at three months.

Overall Hearing Improvement (This is shown in Fig. 1)

Fig. 1.

Showing pre- and post-treatment hearing levels and improvement in the three groups

The average hearing loss in all 39 patients was 73.87 ± 19.95 dB at presentation and 45.46 ± 23.97 dB after treatment, with improvement in hearing of 28.41 ± 22.5 dB; a hearing gain 0f ≥ 10 dB being seen in 31(79.4%) patients. In group A, the average hearing sensitivity before and after treatment was 72.30 ± 19.45 and 36.82 ± 19.72 dB respectively with a hearing gain of 35.47 ± 24.92 dB. However, of the 13 patients who responded to oral steroid therapy, the average PTA before and after treatment was 70.38 ± 24.91 and 22.92 ± 9.72 with a hearing gain of as much as 47.69 ± 25.24 dB. In group B, PTA was 76.12 ± 19.45 dB before and 57.87 ± 24.63 dB after IT-Dexa with hearing gain of 18.25 ± 13.63 dB. In group C, the pre- and post-treatment PTA was 74.80 ± 9.23 and 54.90 ± 13.51 dB with an average gain of 19.80 ± 16.03 dB. The patients in all three groups had significantly improved hearing thresholds compared to their pre-treatment status (f = 8.98, p-0.01). Hearing improvement was seen in 56.5% in group A, 62.5% in group B and 80% in group C. The difference in these groups was not statistically significant (p = 0.477).

Hearing Improvement Related to Age

We compared our results in two age groups. Of the 32 patients below 60 years, the ≥ 10 dB improvement was seen in 81.25% patients and in the 7 patients above 60 years, it was 85.71%. This was not statistically significant. (p value = 0.63).

Improvement Related to Treatment Delay

This is shown in Table 2.

Table 2.

Furuhashi criterion for hearing improvement

Complete recoverya	PTA ≤ 25 dB or identical to the Contralateral, non-affected ear
Marked improvementb	PTA improvement > 30 dB
Slight improvement	PTA improvement between 10 and 30 dB
No recovery	PTA improvement < 10 dB

^aComplete recovery or marked improvement = successful treatment. PTA  six frequency pure tone average (250, 500, 1 K, 2 K, 4 K, 8 K)

The overall average delay in instituting treatment was 14.58 ± 14.23 days, being 9.04 ± 6.20, 22.56 ± 18.49 and 14.80 ± 4.89 days in group A, B and C respectively. In group A, all 13 (100%) patients in whom treatment was started within one week (Avg. delay 4.6 days) of onset of symptoms and none of the 10 who presented later than one week (Avg. delay 14.8 days) showed ≥ 10 dB improvement. In the salvage group C, none of the patients started treatment during the first week or after the third week. In this group, all the 5 (100%) who reported during the second week and 3 out of 5 (75%) who reported during the third week had hearing gain of ≥ 10 dB. In group B, the 10 patients who showed ≥ 10 dB improvement started treatment with an average delay of 21.9 days. This included 5 out of 7 (71.4%) who started treatment during the first week (Avg. delay 4.86 days) and 5 out of 9 (55.5%) who did so after 3 weeks (Avg. delay 32.3 days). Successful recovery as defined by the Furuhashi criterion was seen in 11 of 23(47.8%) [Avg. delay 4.3 days] in group A; 3 out of 10 (30%) in group C [Avg. delay 13.7 days] and 6 out of 16 (37.5%) with an average delay of 7.6 days in group B. We also compared the rate of improvement in those in whom treatment was started before 14 days and those who got the treatment after 14 days of onset of hearing loss. We found a significant difference in group A, ≥ 10 dB improvement being seen in 72.2% cases (N = 18) in whom the delay was less than 14 days as compared to no improvement in those who reported after 14 days (N-5) [p value = 0.003]. Similarly, in group B, this figure was 85.7% (6/7) vs 33.3% (4/9) [p = 0.06]. However, in group C, the difference in improvement in those presenting before and after 14 days failed to achieve statistical significance (p = 0.111).

Hearing Improvement and Severity of Hearing Loss

For severity of hearing loss, we compared those having > 90 dB (profound) with those having less than 90 dB hearing loss. Out of the 10 patients who had profound hearing loss (Avg. 102.10 ± 9.37 dB), 8 (80%) showed improvement with an average hearing gain of 57.50 ± 31.81 dB. Of the 23 patients given oral steroids, 4 out of 5 (80%) with profound hearing loss showed complete recovery. They all started treatment within one week of onset. The fifth patient (group C) showed marked recovery after IT-Dexa. In group B, 3 out of 5 (60%) showed recovery including 2 with marked and one with slight improvement. This is in contrast to those whose hearing loss was less than 90 dB at presentation with an average PTA of 64.13 ± 11.38 dB and an improvement of only 22.82 ± 14.37 dB. Irrespective of the severity of hearing loss, significant improvement was seen in both groups (p = 0.002 and 0.000).

Hearing Improvement in Diabetics

There were 7 diabetics who underwent intratympanic injections as primary therapy, of these, 5 were treated within one week of onset of hearing loss with a mean delay of 5.2 days. Four out of the 5 (80%) showed successful recovery by Furuhashi criterion and one showed slight improvement making the result 100% by ≥ 10 dB criterion. Of this, 2 had profound hearing loss. No recovery was seen in 2 of 7 who had a mean delay of 17.5 days. The lone patient who was given IT-Dexa after a delay of 50 days showed slight improvement. The diabetics had a pre-treatment PTA of 81.14 ± 21.50 and improvement of 21.42 ± 15.66 dB. This was statistically significant (t = 3.62; p value = 0.01).

Complications

Out of 26 patients who received IT-Dexa, 8 patients experienced pain during the procedure, 9 experienced transient vertigo and 2 developed tympanic membrane perforation which healed on follow up at 1 month. Bleeding from ear was seen in 1 patient due to external auditory canal trauma which was controlled by keeping an antiseptic ear wick overnight.

Discussion

For several years after the study by Wilson et al. [13], systemic steroid therapy had been the mainstay of treatment of SSNHL. The concern about their side-effects led to their use by intratympanic injection. Intratympanic steroids are used in three ways viz. as salvage therapy after failure of initial systemic steroids, in combination with systemic steroids or as initial treatment when systemic steroids or their side effects are not tolerated or contraindicated as in brittle diabetes, tuberculosis, glaucoma, cataract, myasthenia gravis, chronic renal failure etc. Although intratympanic steroids are an option in the primary setting, there is no consensus regarding their dosage schedule and supremacy over the traditional treatment [22]. In their meta-analysis, Garavello et al. [23] did not find any difference between systemic and intratympanic steroid administration and their study supports the use of intratympanic steroids for use as salvage treatment. The 2019 AAO H&N clinical practice guidelines [3] recommend that intratympanic corticosteroids be offered to patients with incomplete recovery from SSNHL 2–6 weeks after onset of symptoms. Dispenza et al. [24] concluded that intratympanic dexamethasone should be suggested to all patients who fail the initial systemic treatment since the later seems to exert a protective role for the inner ear and also may help to re-establish blood flow through the spiral ganglion to the organ of Corti. Battaglia et al. [16] noted that methylprednisolone and dexamethasone showed similar pharmacokinetics but hypothesized that a lower binding affinity for methylprednisolone could result in reduced treatment efficacy when compared with dexamethasone. However, a recent study [25] found no superiority of the two drugs over each other in the primary treatment of SSNHL. Parnes et al. [26] evaluated intratympanic dexamethasone, hydrocortisone and methylprednisolone in guinea pigs. Of these, methylprednisone achieved the highest concentration for the longest duration in both endolymph and perilymph but on clinical application, some patients did not tolerate the burning discomfort in ear or throat caused by methylprednisolone. Chandershekhar [4] demonstrated significantly higher perilymph concentrations of dexamethasone following intratympanic versus systemic administration in a guinea pig model. Bird et al. [27] performed the first human study evaluating steroid concentrations following intratympanic and intravenous administration and found significantly higher perilymph concentrations with the former. A multi-center, double-blinded, placebo-controlled study [16] found that patients treated with intratympanic dexamethasone + high dose prednisolone taper have a higher likelihood of hearing recovery than those treated with high dose prednisolone taper only. According to the authors, the most likely explanation for the success of combination therapy as compared with oral steroids or intratympanic dexamethasone alone is that a maximal dose of corticosteroids is delivered to the damaged inner ear which not only receives systemic prednisolone via labyrinthine blood vessels that remain patent but also receives dexamethasone via diffusion through the round window thus preventing or delaying the initiation of hair cell apoptosis. Anyah et al. [28] reported that there is a statistically and clinically significant response to treatment (oral steroids + It dexa) in late presenters; hearing improvement was observed even in patients whose treatment was started up to three months from symptom onset.

The method of intratympanic perfusion has varied. Some inject it directly using a single puncture of the tympanic membrane, whereas others use two punctures to ‘vent out’ the middle ear space. Some fill in the middle ear space every 10 min while others do not. Unfortunately, there is no general consensus but it is reasonable that the physician should ensure that there is enough medicine in the middle ear for 30 min after the injection [29] since this seems to be an optimal time for diffusion through the round window membrane as shown by Plontke and Salt [30]. Intratympanic steroids have also been used in a sustained manner using microcatheters and micro wicks or via a tympanostomy tube [31, 32]. Since these practices can increase the chances of tympanic membrane perforation, we used direct intratympanic injection and observed that once the fine needle is withdrawn, the injection site collapses keeping the fluid in the middle ear. Similar observation was made by Labatut et al. [33].

The definition of success for hearing improvement varies in different studies and various criteria have been used by different authors. The commonest criterion is the improvement of ≥ 10 dB in PTA after treatment. Such a liberal criterion can mislead us into overestimating the effectiveness of steroids and has little clinical value [34]. We used the stricter Furuhashi criteria [21] which is a more practical one and grades hearing improvement as complete recovery, marked recovery, slight recovery and no recovery (Table 2). Nevertheless, the ≥ 10 dB gain criterion was also used by us to compare the results of the present study with a large number of studies that had used it. Wilson et al. [13] defined recovery as complete if the improvement in hearing was within 10 dB, partial if it was within 50% and no recovery if it was less than 50% of the pre-treatment level. Others have used Hayne’s [34] criterion (20 dB gain in PTA); Siegel’s criterion (Hearing < 45 dB and gain > 15 dB) [35] or AAO-H&N criterion of serviceable hearing.

In our study, patients diagnosed with sudden SNHL and more than 18 years of age were included. Patients with Meniere’s disease, retro cochlear disease, fluctuating hearing loss and that induced by autoimmune disease, trauma, radiation, noise, or any other identifiable cause for sudden hearing loss were excluded from the study. Pre- treatment and post- treatment audiometric evaluations were analyzed. Patient variables as they related to recovery were studied and included patient age, time to onset of therapy, presence of diabetes and severity of hearing loss.

We preferred dexamethasone over methylprednisolone because dexamethasone has a greater anti-inflammatory effect than methylprednisolone [36], has lesser local side effects and it achieves greater inner ear concentration. There is no universally accepted protocol for the use of intratympanic steroids [37]. The strength of solution has varied from 2–4 to 25 mg/ml and the number of injections from single to weekly or biweekly. In the present study, the ubiquitously available dexamethasone (4 mg/ml) was used as intratympanic injection biweekly for 2 weeks.

It is generally accepted that early intervention in SSNHL improves the recovery rate and thus, it is essential to diagnose SSNHL early and treat it as an emergency. A problem in the management of SSNHL is its timely diagnosis. The delay in diagnosis may be due to patient factor or the physician factor. The patient with SSNHL usually feels a fullness or blockage of the ear, a common symptom associated with upper respiratory catarrh, or cerumen impaction; is not worried about it and does self-treatment with anti-cold medications, ear drops etc. before seeking medical advice. On the other hand, an ignorant physician may treat it as Eustachian catarrh unless an attempt is made to perform a simple tuning fork test to find the type of hearing loss and follow it up with a pure tone audiogram. If performed without proper masking, the audiogram may show conductive or mixed deafness but a high index of suspicion should lead the astute physician to the right diagnosis. Wherever audiometric facilities are not available, treatment can be started on the basis of a properly performed tuning fork test.

Our patient data did not show any significant difference between the three groups in respect of age, sex, side of ear, and initial PTA thresholds. The patients who received IT-Dexa as primary therapy had recovery rate of 62.5%. This is less than reported in some other studies (Table 3A) [38–42] ranging from 64.9 to 86%, using the ≥ 10 dB criterion. However, the treatment delay in those studies was only 2–7 days compared to 22 days in our study. By using Furuhashi criterion, successful recovery was seen in only 37.5%. We found an average gain in hearing of 18.25 ± 13.63 dB compared to 31 dB reported by Battaglia et al. [43] whose patients had a treatment delay of 11 ± 14 days compared to ours of 22.56 ± 18.49 days.

Table 3.

Results of some studies on IT-Dexa in SSNHL

Author	Number of patients	Recovery (%)	Dose of IT-Dexa	No. of injections	Treatment delay (days)
(A) AS PRIMARY THERAPY
Han et al. [39]	27	79	5 mg/ml	2 inj./wk. × 2 wks	3
Kara et al. [40]	29	86	4 mg/ml	Daily for 5 days	3
Dispenza et al. [24]	25	80	4 mg/ml	one inj./wk. × 4 wks	7
Tsai et al. [41]	128	68	5 mg/ml	2 inj./wk. × 2 wks	< 7
Bae et al. [38]	94	64.9	5 mg/ml	2 inj./wk. × 2 wks	7.3
Lim et al. [42]	45	80	5 mg/ml	2 inj./wk/ × 2 wks	NA
Present study (2019)	16	62.5	4 mg/ml	2 inj./wk. × 2 wks	22
(B) AS SALVAGE THERAPY
Silverstein et al. [19]	8	25	Various doses	up to 3/wk. × 3/4 wks	NA
Gouveris et al. [44]	21	72.4	8 mg/ml	2.7 Avg	5.47
Ho et al. [45]	15	53	4 mg/ml	3 inj. In 3 wks	19.7
Choung et al. [47]	33	38.2	5 mg/ml	2 inj./wk. × 2 wks	28
Present study (2019)	10	80	4 mg/ml	2 inj./wk. × 2 wks	14.8

In the salvage group, the recovery rates have ranged from 25 to 72.4% in different studies (Table 3B) [19, 44, 45, 47] using the ≥ 10 dB criterion but there is a wide variation in the treatment delay ranging from 5.4 to 28 days. By the same criterion, we found improvement in 80% of those who received IT-Dexa as salvage therapy. However, this figure was as low as 30% when considering successful outcome by Furuhashi criterion. This was similar to that reported by Gouveris et al. [44] who found complete recovery (hearing within 10 dB of normal ear) in 33.3% and partial (≥ 10 dB improvement) in 39.1%. The effectiveness of intratympanic steroids as salvage therapy in patients showing poor response to oral steroids has been highlighted by others [45–47]. The improved results with the sequential therapy of oral steroids and IT-Dexa in our salvage group are similar to those seen with combination therapy as reported by Battaglia et al. (vide supra). A significant finding in our study was the relationship of delay in treatment to the hearing outcomes. Excellent results were seen in all patients treated within one week of onset of symptoms (100% in group A and 85.7% in group B) Since group C patients were given IT-Dexa after failure of oral steroids, none in that group received the treatment within one week. In those who received IT-Dexa as salvage therapy after failure of initial oral treatment, 100% improvement(≥ 10 dB) was seen in those who received treatment during the second week and 75% in those who had it during the third week. Banerjee and Parnes [48] found improvement in 69% in those who received treatment within 10 days compared with 31% in those treated after 10 days. We observed slight improvement in 2 of the 6 patients who received IT-Dexa after 30 days and one patient who received after 50 days. Haynes et al. [34] found that no patient who received IT-Dexa after 36 days recovered. Chandershekhar [4] did find improvement in a patient who got IT-Dexa after 60 days. Anyah et al. [28] concluded that there is a benefit in treating patients with SSNHL if the time since onset is less than 60 days. However, Bae et al. [38] found no adverse prognostic factors among the non-responders. A systematic review of literature [49] reported that patients of SSNHL receiving intratympanic steroids had PTA improvement of 15 dB or more in 37.5–54.5% and suggested to offer this line of treatment as salvage to patients after as little as 10 days after an unsuccessful first line systemic therapy. A recent study [5] attempted to correlate the treatment success (by Furuhashi criterion) with delay between onset of disease and beginning of intratympanic steroid therapy, concluded that each day of delay decreases the probability of success by 3%. Battaglia et al. [43] also found that the PTA improvement is significantly better if the patients are treated within 7 days. This further emphasizes the need for early start of treatment. It is pointless to wait for results of other tests since that could miss this time window and deny the patient a better therapeutic result. None the less, those presenting late should not be deprived of this safe treatment modality.

We did not find any correlation of hearing improvement with age of patients unlike Banerjee and Parnes [48] who concluded that patients younger than 60 years have a trend towards better recovery. Contrary to many studies [13, 36, 48, 50, 51], we found an excellent recovery rate of 80% in ten patients who presented with profound deafness. All of them received treatment within the first week of onset, thus highlighting the importance of early institution of treatment. The severity of hearing loss at presentation did not affect the outcome.

It is generally thought that diabetic patients with SSNHL have poor recovery rates. While Haynes et al. [34] found no difference in results of IT-Dexa in diabetics and non-diabetics, Chandershekhar [4] reported 100% recovery in the three diabetics who underwent IT-Dexa treatment. Our diabetic patients also did quite well showing recovery in 5/7(71%). The lone patient given IT-Dexa after 50 days of onset of symptoms did show slight improvement.

The limiting factor of the study was the small number of patients in each group, and also it was not a double-blind placebo controlled one. Nevertheless, there was a definite benefit to the patients with all the three treatment modalities. Successful recovery by Furuhashi criterion was observed in 47.8% of those who took oral steroids, 37.5% in those treated with primary IT-Dexa and 30% in those who got IT-Dexa as salvage therapy. Using the ≥ 10 dB criterion which has been used by most researchers, our results were 56.5%, 62.5% and 80% respectively. We got good results in diabetics treated with IT-Dexa. There was a negative correlation of delay in institution of treatment with successful outcomes. Maximum hearing gain was seen in those treated with oral steroids within one week of onset. However, a randomised controlled study is needed to confirm the results.

There is no doubt that the comfort, cost and convenience of oral therapy are better than intratympanic treatment since the later involves repeated physician visits and a 30 min period of lying supine after each of the many visits, yet the minimally invasive technique of intratympanic steroid injection gives reasonably good results both as a primary and salvage therapy, has the advantage of few systemic side-effects, is easy to perform, has a low complication rate, is well tolerated by patients, makes it possible to treat only the affected ear and can be safely given to patients in whom systemic steroids are contraindicated, not tolerated or refused. It is imperative that the treatment is instituted as early as possible by sensitizing the clinicians to early recognition of this condition and proper patient counselling. However, late presenters should also be given a trial of treatment.

Conclusions

Oral steroids have been the mainstay of treatment of SSNHL but their use is limited by their side effects and contraindications. The intratympanic steroid therapy obviates these problems and can give equivalent results. It is recommended that this modality of treatment should be offered to willing patients after proper counselling as a primary therapy and also to those who fail the oral steroids. To get optimal results the treatment should be instituted as soon as possible and the clinicians should be sensitized to be cognizant of this clinical entity.

Declarations

Conflict of interest

The authors declare that they have no conflict of interest.