INTRODUCTION
Adult patients with single-sided deafness (SSD) often experience poor sound source localization, reduced speech understanding in noise, reduced quality of life (QoL), and debilitating tinnitus (Van de Heyning et al., 2008 ; Vermeire & Van de Heyning, 2009 Arndt et al., 2011 ; Jacob et al., 2011 Faber et al., 2013 Linstrom et al., 2009 ; Yuen et al., 2009 ; Martin et al., 2010
Cochlear implantation has been shown to significantly improve localization, speech understanding in noise, and QoL, and significantly reduce tinnitus severity in adult SSD patients (e.g., Van de Heyning et al., 2008 Arts et al., 2012 ; Firszt et al., 2012 ; Cadieux et al., 2013 ; Nawaz et al., 2014 ; Tokita et al., 2014 ; Vlastarakos et al., 2014 ; Härkönen et al., 2015 ; Mertens et al., 2015 , 2016a Távora-Vieira et al., 2013 Zeitler et al., 2015 ; Cabral Junior et al., 2016 ; Friedmann et al., 2016 Hoth et al., 2016 ; Kitoh et al., 2016 ; Rahne & Plontke, 2016 ; Arndt et al., 2017 ; Dillon et al., 2017 Finke et al., 2017 ; Sladen et al., 2017ab Arndt et al., 2015 ; Sharma et al., 2016 ; Greaver et al., 2017 ; Polonenko et al., 2017 ; Sladen et al., 2017c ; Thomas et al., 2017 Arndt et al., 2011 ; Tokita et al., 2014 ; Vlastarakos et al., 2014 ; van Zon et al., 2015
Most of the above SSD CI studies were conducted in Europe. Early studies primarily targeted reduction of tinnitus severity via cochlear implantation. Later studies showed significant improvements in localization, speech understanding in noise, and QoL. While there are a number of SSD CI users in the United States, most have been implanted “off label” and CIs are currently not approved for SSD patients. Recently, there have been several Food and Drug Administration (FDA)–approved and investigator-initiated clinical trials for cochlear implantation in SSD patients in the United States. Clinical trials are necessary to demonstrate the risks and benefits of cochlear implantation for SSD patients. FDA approval would allow SSD patients in the United States to experience the benefits of cochlear implantation demonstrated in previous European studies.
In this study, we report the outcomes of an FDA-approved clinical trial “Cochlear Implants for Adults with Single-sided Deafness” (NCT02259192). This prospective, investigational device exemption study was a collaborative effort among the University of Southern California, the University of California, Los Angeles, and the House Clinic. The MED-EL Corporation provided the CI devices, covered all clinical expenses during the study, and provided research support. The primary objective of the study was device safety in terms of cochlear implantation and its effect on hearing function in the contralateral normal-hearing (NH) ear. Device safety was assessed in terms of the number of unexpected serious adverse events associated with the surgical procedure and everyday use of the CI. The effect of cochlear implantation on NH function was assessed by comparing baseline (before surgery) pure-tone average (PTA) thresholds across 0.5, 1.0, and 2.0 kHz in the NH ear to PTA thresholds 1, 3, and 6 mo after activating the CI speech processor; an increase in unaided PTA threshold >10 dB in the nonimplanted ear would indicate a hearing loss AE. The capacity of the CI to interfere with the NH ear was also assessed in terms of speech understanding in noise when speech and noise were presented directly in front of the subject. Speech understanding in noise was quantified as the speech reception threshold (SRT), defined as the signal-to-noise ratio (SNR) needed to produce 50% correct recognition of words in sentences in noise (Plomp & Mimpen, 1979 Nilsson et al. (1994
The study also included a number of secondary objectives. The efficacy of cochlear implantation for SSD patients was assessed in terms of clinical audiological measures (PTA thresholds, word and sentence recognition in quiet), localization, speech understanding in noise with and without spatial cues, tinnitus severity, and QoL. These longitudinal measures provided some estimate of the time course of adaptation to the CI. While previous studies with bilaterally deaf CI users have shown that most adaptation to electric hearing occurs during the first 3 to 6 months of CI use (Waltzman et al., 1986 ; Spivak & Waltzman, 1990 ; Holden et al., 2013 ; Sladen et al., 2017a Mertens et al., 2017
As noted above, many previous studies have shown benefits of cochlear implantation for SSD patients. In some studies, CI benefits were assessed relative to performance before implantation (e.g., Arndt et al., 2011 ; Punte et al., 2011 ; Kitoh et al., 2016 ; Dillon et al., 2017 Firszt et al., 2012 ; Mertens et al., 2015 Távora-Vieira et al., 2015 Döge et al., 2017 Arndt et al., 2017 ; Mertens et al., 2015
METHODS
Subjects
Subjects were recruited from the House Clinic in Los Angeles CA, and in response to the study announcement on clinicaltrials.gov. Table 1 shows the inclusion and exclusion criteria for the study. Eleven SSD patients enrolled in the study. One patient withdrew before cochlear implantation because the patient decided to pursue a different CI device (rather than the MED-EL device, which was the only one available for this study). This left 10 subjects (5 male, 5 female) who completed the study. The mean age at implantation was 57.6 ± 10.3 years, and the mean duration of deafness was 3.2 ± 2.1 years. No subject had previous experience with CROS or BCD devices. Demographic information for the 10 subjects who completed the study is shown in Table 2 . All subjects provided written informed consent, in accordance with the local institutional review board of record (St. Vincent’s institutional review board no. 14–019).
TABLE 1.: Inclusion and Exclusion Criteria for the Clinical Trial
TABLE 2.: Subject Demographic Information
Project Timeline
Figure 1 shows the project timeline for each subject. After screening patients for potential candidacy during standard clinical appointments, potential candidates were informed of the study and, if interested, were contacted to discuss the study further. If the subject wished to enroll in the study, informed consent was obtained in writing. An initial evaluation followed that included obtaining medical history, neuro-otological testing, videonystagmography (VNG) testing, administration of vaccines, computed tomography scan of the internal auditory canal, and a physical examination. Baseline audiological measures were also collected for each ear, including pure-tone thresholds and word and sentence recognition in quiet. If the subject met the candidacy requirements, the subject was scheduled for CI surgery within 6 mo of the audiological evaluation. During this time, baseline localization, speech understanding in noise, and tinnitus severity were measured; subjects also completed questionnaires relating to tinnitus, dizziness, and QoL. Approximately 1 mo after surgery, the CI processor was activated and audiological measures were re-collected. Audiology, localization, speech understanding in noise, and tinnitus severity were re-measured at 1, 3, and 6 mo postactivation of the CI; questionnaires were also re-administered at 6 mo postactivation. A neuro-otological examination and caloric VNG testing were performed at 6 mo postactivation.
Figure 1.: Timeline for the experimental protocol.
Audiological Measures
To determine candidacy (and to serve as baseline measures after enrollment in the study), air conduction and bone conduction pure-tone thresholds were measured for each ear at 0.125, 0.25, 0.5, 1.0, 2.0, 4.0, and 8.0 kHz. Inclusion criteria were PTA thresholds across 0.5, 1.0, and 2.0 kHz ≥70 dB HL in the ear to be implanted, and PTA thresholds ≤25 dB HL in the NH ear with no audiometric frequency ≥35 dB HL. Speech audibility thresholds (SATs) in quiet were also measured. Recognition of Hearing in Noise Test (HINT; Nilsson et al., 1994 Peterson and Lehiste, 1962 Spahr et al., 2012
For baseline measures, audiometric thresholds and SATs were measured using ER3A insert earphones; to measure performance in the ear to be implanted, 40 dB contralateral masking noise was delivered to the NH ear. Baseline word and sentence recognition were measured in sound field; to measure performance in the ear to be implanted, 55–60 dB of masking noise was delivered to the NH ear via insert earphone. After activating the speech processor, audiological measures were re-collected separately for the NH ear and CI ear (aided). Note that unaided thresholds with the CI ear were not collected after implantation.
Sound Source Localization
Localization was measured in sound field using a 12-speaker array and stimuli and methods similar to Chan et al. (2008
Loudspeakers were at ear level and spaced 15 degrees apart behind the subject, and spaced 1 m from the center of the subject’s head. The stimulus was a broadband impulse sound (gunshot) presented at 65 dBA; the presentation level from trial to trial was roved by 6 dB to reduce the availability of loudness cues for localization. Before formal testing in each condition, subjects were given a preview playing the stimulus from each of 12 sound source locations in order. During testing, a sound source (loudspeaker) was randomly selected (without replacement), and the stimulus was delivered from that source. The subject responded by clicking on one of the loudspeakers shown on a computer screen that mirrored the speaker locations, after which a new stimulus was presented. Subjects were instructed not to move their head during testing. Stimuli were presented twice from each sound source (24 trials in each test block). Localization accuracy was quantified in terms of root mean square error (RMSE). A minimum of two test runs were conducted for each listening condition; if the difference in RMSE between the two test runs was greater than 10 degrees, a third test run was conducted. The mean RMSE was calculated across test runs.
Speech Understanding in Noise
Speech understanding in noise was measured in sound field, with and without spatial cues. Speech performance was measured before CI surgery and again at 1, 3, and 6 mo postactivation. Performance was measured with NH ear alone (CI off, CI ear plugged and muffed) and with both ears (binaural). Speech (S) was always presented directly in front of the listener. Noise (N) was presented to the CI ear (S0NCI ), in front of the listener (S0N0), or to the NH ear (S0NNH ). Note that in the binaural baseline condition, the ear to be implanted was not plugged or muffed.
Speech understanding in noise was quantified in terms of the SRT. Speech materials consisted of HINT sentences produced by a single male talker (Nilsson et al., 1994 Chan et al. (2008 CI condition and 6 dB for the S0N0 and S0NNH condition. If the subject repeated 50% or more of the words correctly, the noise level was increased by 2 dB; if the subject repeated less than 50% of the words correctly, the noise level was reduced by 2 dB. The final six reversals in SNR were averaged as the SRT. A minimum of two runs were completed for each listening and spatial condition. If the difference in SRTs between the first two runs was more than 2 dB, a third SRT was measured. SRTs were averaged across test runs.
Tinnitus Severity
Tinnitus severity was measured using a visual analog scale (VAS) with the CI on and off, as in previous SSD CI studies (Van de Heyning et al., 2008
Questionnaires
To estimate the impact of cochlear implantation on SSD patients’ everyday life, a number of questionnaires were administered before implantation and 6 mo postactivation, including:
Tinnitus Functional Index (TFI). The TFI (Meikle et al., 2012
Dizziness Handicap Inventory (DHI). The DHI (Jacobsen and Newman, 1990) is a validated, self-reported rating of the impact of dizziness on a respondent’s everyday life. The DHI contains 25 questions that the respondent must answer according to “Never” (0 points), “Sometimes” (2 points), and “Always” (4 points). A score of 100 indicates maximum dizziness severity and impact and a score of 0 indicates no dizziness.
Speech, Spatial, and Qualities of Hearing scale (SSQ). The SSQ was originally developed as an assessment tool for hearing aid fitting and associating hearing impairment with the subjective level of disability (Gatehouse and Noble, 2004
Glasgow Hearing Aid Benefit Profile (GHABP). The GHABP (Gatehouse, 1999
RESULTS
Safety
All subjects were implanted without major surgical complications. Full insertion of the electrode array was reported in all subjects. Adverse events were reported in 5 of the 10 subjects. S1 experienced facial nerve stimulation on several electrodes at loud but comfortable levels. This was resolved during mapping by increasing the pulse duration. Subject S3 experienced periorbital edema that resolved spontaneously a few days postoperatively. Subject S5 experienced mild postoperative balance disturbance that persisted for several weeks but resolved spontaneously. Subject S8 reported postauricular pain as a result of wearing the Sonnet processor. Moleskin was added to the area of the processor that was producing the discomfort; however, the subject continued to report pain after prolonged use. Four months postactivation and approximately 2 mo before protocol requirements, she was fit with the Rondo in an effort to allow the subject to comfortably and consistently use her CI; this resolved the issue. Subject S10 reported taste disturbance that had not yet been resolved at his most recent medical follow-up at 6 mo postactivation.
Audiology
Figure 2 shows boxplots of PTA thresholds, SATs, CNC word recognition scores in quiet, and HINT sentence recognition scores in quiet with the NH ear and the CI ear, as a function of test interval. Table 3 shows baseline audiometric thresholds for the ear to be implanted. Baseline preoperative PTAs and HINT scores for the CI ear were all within the inclusion criteria. The mean improvement for CNC word recognition relative to baseline was 66.8, 76.0, and 84.0 percentage points at 1, 3, and 6 mo postactivation, respectively. The mean improvement for HINT sentence recognition in quiet relative to baseline was 36.4, 40.7, and 51.1 percentage points at 1, 3, and 6 mo postactivation, respectively. A two-way repeated-measures analyses of variance (RM ANOVA) was performed for each audiological outcome measure, with ear (NH, CI) and test interval (baseline, 1, 3, and 6 mo postactivation) as factors; complete results are shown in Table 4 . For all outcome measures at all intervals, NH performance was significantly better than CI performance (p < 0.05 in all cases). For all outcome measures, there was no significant difference in NH performance across test intervals (p > 0.05 in all cases). For all outcome measures, CI performance at 1, 3, and 6 mo postactivation was significantly better than baseline (p < 0.05 in all cases), with no significant difference among postactivation test intervals (p > 0.05 in all cases).
TABLE 3.: Baseline Audiometric Thresholds (dB HL) in the Ear to be Implanted
TABLE 4.: Results of Two-Way RM ANOVAs for Audiology Measures
Figure 2.: Boxplots of audiology measures as a function of test interval. The top panels show data with the NH ear only and the bottom panels show data with the CI ear only. From left to right, data are shown for PTA thresholds (across 0.5, 1.0, and 2.0 kHz), SATs, CNC word recognition in quiet, and HINT sentence recognition in quiet. The shaded areas in the top row indicated inclusion criteria for the NH ear; the shaded areas in the bottom row indicated inclusion criteria for the CI ear. The boxes show the 25th and 75th percentiles, the error bars show the 5th and 95th percentiles, the circles show outliers, the solid lines show the median, and the dashed lines show the mean.
Localization
The top two panels in Figure 3 show RMSE in localization with the NH ear alone (left) and with binaural listening (right), as a function of test interval. The bottom two panels show the change in RMSE with binaural listening relative to performance with the NH ear alone at each interval postactivation (left), or relative to baseline binaural performance (right); values <0 indicate better performance after cochlear implantation. Relative to the NH ear alone, mean RMSE was reduced by 15.1, 14.0, and 18.2 degrees at 1, 3, and 6 mo postactivation, respectively. Relative to binaural baseline, mean RMSE was reduced by 6.7, 7.6, and 11.5 degrees at 1, 3, and 6 mo postactivation, respectively. A two-way RM ANOVA was performed on the localization data, with listening condition (NH, binaural) and test interval (baseline, 1, 3, 6 mo postactivation) as factors; complete results are shown in Table 5 . There was no significant difference in localization with the NH ear alone across test intervals (p > 0.05 in all cases). Binaural performance was significantly better than with the NH ear alone at 1, 3, and 6 mo postactivation (p < 0.05 in all cases). Binaural performance was significantly better than binaural baseline only at 6 mo postactivation (p < 0.05).
TABLE 5.: Results of a Two-Way RM ANOVA for Localization
Figure 3.: Boxplots of localization RMSE scores as a function of test interval. The top left panel shows RMSE with the NH ear only; the top right panel shows RMSE with binaural listening. The bottom left panel shows the change in binaural RMSE scores postactivation relative to NH scores at each interval (binaural – NH at each interval). The bottom right panel shows the change in binaural RMSE scores postactivation relative to baseline binaural scores (binaural at each interval – binaural baseline). For the bottom panels, scores <0 indicate a benefit to wearing the CI. The boxes show the 25th and 75th percentiles, the error bars show the 5th and 95th percentiles, the circles show outliers, the solid lines show the median, and the dashed lines show the mean.
Speech Understanding in Noise
The top panels in Figure 4 show SRTs with the NH ear alone and the bottom panels show SRTs with binaural listening for each spatial condition, as a function of test interval. The top panels in Figure 5 show the change in SRTs with binaural listening relative to the NH ear alone at 1, 3, and 6 mo postactivation; the bottom panels in Figure 5 show the change in SRTs with binaural listening relative to binaural baseline. Values <0 indicate better performance after cochlear implantation.
Figure 4.: Boxplots of SRTs in noise for the different spatial conditions, as a function of test interval. The top panels show SRTs with the NH ear only, and the bottom panels show SRTs with binaural listening. The boxes show the 25th and 75th percentiles, the error bars show the 5th and 95th percentiles, the circles show outliers, the solid lines show the median, and the dashed lines show the mean.
Figure 5.: Boxplots of changes in SRTs for the different spatial conditions, as a function of test interval. The top panels show changes in binaural SRTs postactivation relative to NH SRTs at each interval (binaural – NH at each interval). The bottom panels show changes in binaural SRTs postactivation relative to baseline binaural scores (binaural at each interval – binaural baseline). Scores <0 indicate a benefit to wearing the CI. The boxes show the 25th and 75th percentiles, the error bars show the 5th and 95th percentiles, the circles show outliers, the solid lines show the median, and the dashed lines show the mean.
Two-way RM ANOVAs were performed on the SRT data for each spatial condition, with listening condition and test interval as factors; complete results are shown in Table 6 . Relative to binaural baseline, there was no significant improvement in binaural SRTs for S0NCI across test sessions; binaural SRTs were significantly better at 1, 3, and 6 mo postactivation for S0N0 (p < 0.05 in all cases), and significantly better at 3 and 6 mo postactivation for S0NNH (p < 0.05 in both cases). Relative to the NH-only performance after cochlear implantation, there was no significant improvement in SRTs for any test interval or spatial condition (p > 0.05 in all cases). Note that NH-only SRTs significantly improved at 6 mo postactivation, relative to baseline, which may have contributed to the improved binaural performance.
TABLE 6.: Results of Two-Way RM ANOVAs Performed on SRTs for Each Spatial Condition
The top panels of Figure 5 also show binaural squelch (re: CI ear), summation, and head shadow (re: CI ear) for 1, 3, and 6 mo postactivation. One-way RM ANOVAs were performed on binaural squelch (re: CI ear), summation, and head shadow (re: CI ear), spatial release from masking (SRM) relative to the NH ear and to the CI ear, with test interval (baseline, 1, 3, and 6 mo postactivation) as the factor; complete results are shown in Table 7 . There was no significant effect of test interval for head shadow, squelch, summation, or SRM (p > 0.05 in all cases).
TABLE 7.: Results of One-Way RM ANOVAs for Head Shadow, Squelch, Summation, and SRM; Test Interval Was the Factor
Tinnitus Severity VAS
The top panels in Figure 6 show tinnitus severity VAS scores with the CI off (left) and the CI on (right), as a function of test interval. The bottom panels in Figure 6 show the change in VAS scores with the CI on, relative to the CI off at each test interval postactivation (left), or relative to the baseline score with the CI off (right); values <0 indicate reduced tinnitus with the CI on. A two-way RM ANOVA was performed on the VAS data, with listening condition (CI off, CI on) and test interval as factors; complete results are shown in Table 8 . The VAS scores were significantly lower with the CI on than with the CI off at 1, 3, and 6 mo postactivation (p < 0.05 in all cases). The VAS scores were also significantly lower with the CI on 1, 3, and 6 mo postactivation than with the CI off at baseline (p < 0.05 in all cases).
TABLE 8.: Results of Two-Way RM ANOVAs Performed on Tinnitus VAS Scores
Figure 6.: Boxplots of tinnitus VAS scores as a function of test interval. The top left panel shows VAS scores with the CI off; the top right panel shows VAS scores with the CI on. The bottom left panel shows the change in VAS scores postactivation with the CI on, relative to the CI off (CI on – CI off at each interval). The bottom right panel shows the change in VAS scores postactivation with the CI on relative to baseline VAS scores before implantation (CI on at each interval – baseline). For the bottom panels, scores <0 indicate a benefit to wearing the CI. The boxes show the 25th and 75th percentiles, the error bars show the 5th and 95th percentiles, the circles show outliers, the solid lines show the median, and the dashed lines show the mean.
Tinnitus Functional Index (TFI)
The top left panel of Figure 7 shows boxplots of TFI scores before implantation and 6 mo postactivation. The mean TFI scores was reduced by 22.9 points. A one-way RM ANOVA was performed on the TFI data, with test interval (baseline, 6 mo postactivation) as the factor; complete results are shown in Table 9 . The TFI scores were significantly lower 6 mo postactivation (p = 0.010).
TABLE 9.: Results of One-Way RM ANOVAs Performed on Questionnaire Data Collected at Baseline and at 6 Mo Postactivation
Figure 7.: Boxplots of TFI (top left), DHI scores (top right), and SSQ scores for the Speech (bottom left), Spatial (bottom middle) and Quality (bottom right) at baseline and at 6 mo postactivation. The boxes show the 25th and 75th percentiles, the error bars show the 5th and 95th percentiles, the circles show outliers, the solid lines show the median, and the dashed lines show the mean.
Dizziness Handicap Inventory (DHI)
The top right panel of Figure 7 shows boxplots of DHI scores before implantation and 6 mo postactivation. The mean DHI scores was reduced by 4.6 points. A one-way RM ANOVA was performed on the DHI data, with test interval as the factor; complete results are shown in Table 9 . There was no significant difference in DHI scores between baseline and 6 mo postactivation (p = 0.661).
SSQ
The bottom panels of Figure 7 shows boxplots of SSQ scores before implantation and 6 mo postactivation for the Speech, Spatial, and Quality subtests of the SSQ. Mean scores improved by 2.3, 3.0, and 1.0 points for Speech, Spatial, and Quality, respectively. One-way RM ANOVAs were performed on the SSQ data, with test interval as the factor; complete results are shown in Table 9 . Significant improvements were observed for the Speech (p = 0.003), Spatial (p < 0.001), and Quality subtests (p = 0.034).
Glasgow Hearing Aid Benefit Profile (GHAPB)
Figure 8 shows boxplots of GHABP scores 6 mo postactivation for each of the six listening scenarios: listening to the television with the volume adjusted for others in the room, conversation in a quiet room, conversation on the street, conversation in a group, Personal issue 1 (P1), and Personal issue 2 (P2). The top six panels show scores for listeners’ worry, difficulty with the CI off, and difficulty with the CI on for the various listening scenarios; for these panels, lower scores are better. Across all listening scenarios, mean scores were 3.3, 3.2, and 2.8 for worry, difficulty with the CI off, and difficulty with the CI on, respectively. A one-way RM ANOVA was performed on the difficulty data averaged across listening scenarios, with listening condition (CI off, CI on) as the factor; complete results are shown in Table 9 . Difficulty was significantly reduced with the CI on (p = 0.015).
Figure 8.: Boxplots of GHABP scores for different listening conditions collected at 6 mo postactivation. The top six panels show scores regarding how much worry the listening condition poses, how much difficulty with the CI off, and how much difficulty with the CI on; lower scores are better. The bottom six panels show how often the patient wears the CI, how helpful the CI is, and how satisfied they are with the CI; higher scores are better. The boxes show the 25th and 75th percentiles, the error bars show the 5th and 95th percentiles, the circles show outliers, the solid lines show the median, and the dashed lines show the mean.
The bottom six panels of Figure 8 show scores for how much subjects used the CI for different listening scenarios, how helpful they felt they CI was for different listening scenarios, and how satisfied they were with the CI for different listening scenarios; for these panels, higher scores are better. Across all listening scenarios, mean scores were 4.4, 3.5, and 3.8 for CI use, helpfulness of the CI, and satisfaction with the CI, respectively.
Correlational Analyses
Demographic factors age at CI and duration of deafness were compared with localization RMSE and to binaural SRTs in noise for the S0N0 and S0NNH conditions at baseline, 6 mo postactivation, and for the change in performance (6 mo – baseline). Pearson correlation analyses showed no significant relationship between either demographic factor and localization or binaural SRTs (p > 0.05 in all cases).
Behavioral performance was compared with subjective reports from questionnaire data at baseline, 6 mo postactivation, and for the change in performance. Tinnitus VAS scores were significantly correlated with TFI scores at 6 mo postactivation (r = 0.63; p = 0.033), but not at baseline (r = 0.24; p = 0.514). No significant correlations were observed between VAS or TFI scores and SRTs for the various spatial conditions, between HINT sentence recognition in quiet or SRTs in noise for the various spatial conditions, between localization or speech SRTs in noise and SSQ scores or GHABP scores (p > 0.05 in all cases)
DISCUSSION
Safety
While AEs were reported in five subjects, most were resolved within 4 weeks. One of the safety concerns for this study was the capacity of the CI ear to interfere with NH function. The PTA thresholds with the NH ear alone were not significantly affected after cochlear implantation, and PTA thresholds did not increase by more than 10 dB after implantation for any subject 6 mo postactivation. There was no significant change in SATs, CNC word recognition in quiet, and HINT sentence recognition in quiet with the NH ear alone before or after implantation (Table 4 ). The SRTs in noise for S0NCI and S0NNH with the NH ear alone were not significantly affected after cochlear implantation (Table 6 ). Surprisingly, there was a small but significant improvement for NH-only SRTs for the S0N0 condition at 6 mo postactivation (Table 6 ), possibly due to procedural learning or some unclear benefit of the CI on NH-only performance. The SRTs with the NH ear alone did not increase by more than 4 dB for any subject at 6 mo postactivation; the maximum decrement in SRT among all subjects was 0.17 dB after implantation. Thus, long-term experience with electric hearing did not significantly interfere with contralateral acoustic hearing function.
Audiology
Not surprisingly, aided PTA thresholds, SATs, word recognition in quiet, and sentence recognition in quiet in the CI ear alone greatly improved 1 mo postactivation, beyond which there were no significant changes (Table 4 ). Mean recognition of CNC words in quiet with the CI ear alone was 51.1% correct at 6 mo postactivation, comparable with mean CI-only CNC scores in some SSD-CI studies (e.g., 47.3% correct in Firszt et al., 2012 Friedmann et al., 2016 Dillon et al., 2018 Holder et al., 2017 Sladen et al., 2017b Zeitler et al., 2015 Sladen et al., 2017b Friedmann et al., 2016
Tinnitus Severity
The reduction in tinnitus severity was the strongest benefit of cochlear implantation. Note that severe tinnitus was not part of the inclusion or exclusion criteria for this study. Cochlear implantation significantly reduced tinnitus VAS scores (Table 8 ), consistent with previous studies that also used a VAS (Punte et al., 2011 ; Mertens et al., 2013 Van de Heyning et al., 2008 ; Buechner et al., 2010 ; Punte et al., 2011 ; Mertens et al., 2016a Van de Heyning et al., 2008 Punte et al., 2011 Punte et al., 2011 Mertens et al., 2013
Cochlear implantation also significantly reduced TFI scores (Table 9 ), consistent with previous studies that used other tinnitus questionnaires (Van de Heyning et al., 2008 ; Mertens et al., 2016a ; Dillon et al., 2018 Newman et al., 1996 Henry et al., 2014 p = 0.033), but no correlation at baseline (p > 0.05) or between the changes in VAS and TFI scores (p > 0.05). This suggests that at 6 mo postactivation, the acutely measured VAS scores were indicative of tinnitus severity subjects experienced during the previous week.
Localization
The mean RMSE with binaural listening at 6 mo postactivation was 34.1 degrees, slightly higher than in other SSD CI studies (e.g., 28.0 degrees in Dorman et al., 2015 Kitoh et al., 2016 Zeitler et al., 2015 Dillon et al., 2017 Litovsky et al., 2018 Table 5 ). There was great variability in terms of improvement in binaural localization; relative to baseline binaural, reductions in RMSE ranged from 1.5 to 27.6 degrees. Note that some subjects had some low-frequency hearing in the ear to be implanted that might have aided in baseline binaural localization. It is unclear whether this residual acoustic hearing was preserved after cochlear implantation. Unfortunately, binaural localization with the CI off (with no plugging or muffing of the CI ear), which would have been directly comparable with baseline binaural, was not measured.
Relative to NH-only performance, the mean CI benefit for localization at 6 mo postactivation was 18.2 degrees, less than in some SSD CI studies (e.g., 26.1 degrees in in Távora-Vieira et al., 2015 Grossmann et al., 2016 Litovsky et al., 2018
Speech Understanding in Noise
At 6 mo postactivation, the SRT for HINT sentences in noise with binaural listening for S0N0 was −4.2 dB, comparable with SRTs for Oldenburg Sentence Test sentences in Rahne and Plontke (2016 Grossmann et al., 2016 Friedmann et al., 2016 NH ), binaural SRTs significantly improved at 3 and 6 mo postactivation, relative to binaural baseline. The mean SRT was −2.6 dB, comparable with previous studies (e.g., −2.0 dB for BKB sentences in Távora-Vieira et al., 2013 Friedmann et al., 2016 Grossmann et al., 2016
Relative to NH-only, there was no significant CI benefit for any of the spatial conditions and no significant CI benefits were observed for head shadow, squelch, summation, or SRM. This finding is in agreement with some previous studies (e.g., Vermiere & Van de Heyning, 2009; Arndt et al., 2011 ; Mertens et al., 2015 ; Döge et al., 2017 Mertens et al. (2017
Quality of Life
The mean scores for the Speech, Spatial, and Quality subtests of the SSQ at 6 mo postactivation were 5.7, 5.5, and 6.8, respectively; the total SSQ score was 5.0. The total SSQ score was somewhat less than observed in some previous SSD CI studies (e.g., 6.1 in Vermiere & Van de Heyning, 2009; 7.0 in Dillon et al., 2018 Louza et al., 2017 Mertens et al., 2015
Significant improvements were observed for Speech, Spatial, and Quality subtests of the SSQ (Table 9 ), similar to previous studies with SSD CI patients (Vermiere and Van de Heyning, 2009; Arndt et al., 2011 ; Távora-Vieira et al., 2015 ; Dillon et al., 2018 NH ), and the Speech subtest from the SSQ all significantly improved, there were no significant correlations between behavioral and subjective measures. This result is different from Dillon et al. (2018)
When data were averaged across all listening scenarios, mean GHABP scores at 6 mo postactivation were 3.2 for “worry,” 3.3 for “difficulty with the CI off,” 2.4 for “difficulty with the CI on,” 4.3 for “how much the CI was used,” 3.4 for “how helpful the CI seemed,” and 3.7 for “how satisfied with the CI.” These scores were substantially higher than those reported by Louza et al. (2017 Table 9 ), consistent with Dillon et al. (2018) Dillon et al. (2018) Dillon et al. (2018)
The mean total DHI score at 6 mo postactivation was 18.6. Relatively few SSD CI studies have included dizziness severity as part of outcome measures. Doobe et al. (2015 Hansen et al. (2013 Fig. 7 ), there was no significant change in dizziness severity between baseline and 6 mo postactivation. At baseline, six out of the 10 subjects exhibited no handicap (0–15 score), two exhibited a mild handicap (16–34 score), one exhibited a moderate handicap (36–53 score), and one exhibited a severe handicap (>54 score). At 6 mo postactivation, five out of the 10 subjects exhibited no handicap, four exhibited a mild handicap, and one exhibited a moderate handicap (36–53 score). Five of the subjects reported slightly increased dizziness severity at 6 mo postactivation; while elevated, scores generally remained within the same category of dizziness severity. Note that the subject who initially reported a severe handicap (88 score) at baseline reported no handicap (2 score) at 6 mo postactivation.
Benefit of Cochlear Implantation: Binaural Performance Over Time Versus Binaural Benefit
The degree and time course of CI appeared to depend on the outcome measure and the point of comparison. Here, two points of comparison were considered: (1) binaural performance before versus after implantation (as in Arndt et al., 2011 ; Punte et al., 2011 ; Kitoh et al., 2016 ; Mertens et al., 2016b Dillon et al., 2017 Firszt et al., 2012 ; Mertens et al., 2015 Távora-Vieira et al., 2015 Döge et al., 2017
In this study, NH-only performance was measured by plugging and muffing the CI ear, which attenuated any residual low-frequency hearing. For example, mean baseline RMSE for localization was 6.9 degrees better with binaural than with NH-only listening. For subjects S2, S4, and S7, who had low-frequency thresholds of 70 dB HL, baseline RMSE was more than 36.4, 10.8, and 20.0 degrees better with binaural than with NH-only listening, suggesting the plug and muff greatly attenuated the acoustic hearing in the ear to be implanted. For these subjects, binaural performance was better than NH-only performance at 1, 3, and 6 mo postactivation, but it is difficult to know if this advantage was due to the CI or to residual acoustic hearing that might have been preserved after surgery. Unfortunately, unaided thresholds in the CI ear were not re-measured after implantation. Data from these subjects suggest that the CI benefit for localization may differ when compared with baseline binaural or to NH-only performance and may depend on the availability of acoustic hearing in the implanted ear.
Immediate (i.e., 1 mo postactivation) and significant CI benefits were observed for tinnitus VAS scores, relative to baseline measures or to postimplantation measures with the CI off (Table 8 ). Immediate and significant CI benefits were also observed for localization relative to NH-only performance after implantation; relative to baseline binaural performance, localization did not significantly improve until 6 mo postactivation (Table 4 ). As noted above, residual acoustic hearing in the ear to be implanted may have contributed to better baseline binaural localization.
The point of comparison strongly affected the degree of CI benefit for speech understanding in noise. Relative to binaural baseline, significant reductions in binaural SRTs were observed as soon as 1 mo postactivation for the S0N0 condition and 3 mo postactivation for the S0NNH condition (Table 6 ). However, relative to NH-only performance after implantation, there were no significant CI benefits for any of the spatial conditions. As noted above, NH-only performance was significantly better at 6 mo postactivation for the S0N0 condition; though not significant, improvements in mean NH-only SRTs were observed for other spatial conditions and test intervals (top panels in Fig. 4 ). The source of this variability in NH-only performance is unclear. It is possible that some procedural learning may have occurred. Alternatively, cochlear implantation may have reduced overall stress or tinnitus, even when the implant was off. Mertens et al. (2013 Mertens et al. (2015
Methodological Issues and Limitations to This Study
In this study, word and sentence recognition in quiet with the CI only (bottom right panels of Fig. 2 ) were measured in sound field using contralateral masking noise presented to the NH ear via insert earphone. Performance was 0% correct at baseline for both measures, suggesting that the 55 to 60 dB of contralateral masking noise was sufficient. Performance with the CI only was significantly and substantially better at 1, 3, and 6 mo postactivation. While the masking noise may have been sufficient to block the NH contribution to performance in sound field, it is unclear whether it may have affected CI-only performance. Continuous noise at a sufficient level in the NH ear may increase tinnitus or may have a central masking effect, either of which might affect CI-only performance.
When measuring localization and SRTs in noise with the NH ear only, the CI ear was plugged and muffed, which nominally provided 55 dB of attenuation. This was especially important for evaluating localization. As noted above, some subjects had small amounts of low-frequency hearing in the ear to be implanted (Table 3 ) that may have contributed to baseline localization, even with the plug and muff. It is unclear whether this acoustic hearing was preserved after cochlear implantation. Adequate attenuation of low-frequency hearing in the CI ear is needed to measure performance with the NH ear alone, which is important to fully characterize the CI benefit for localization.
We also attempted to measure SRTs in noise with the CI ear alone for the different spatial conditions. Unfortunately, plugging and muffing the NH ear was not sufficient to consistently reduce the contribution of the NH ear to CI-only performance, as performance with the CI ear alone was often comparable with that with the NH ear alone. Ideally, CI-only performance for SSD patients (and for bimodal CI patients) should be measured with direct connection to the CI processor (e.g., via direct audio input, or DAI). In such a scenario, it is important to calibrate the DAI to microphone input, and to disable mixing settings that blend some amount of the microphone input with the DAI signal. Such a calibrated DAI approach would be helpful to measure audiometric thresholds, everyday listening settings, and speech performance with the CI, which may be difficult to measure in sound field when there is substantial acoustic hearing.
The number of patients in this prospective FDA clinical trial (n = 10) somewhat limits the extent to which the findings can be generalized to the larger population. The inclusion criteria of normal hearing in the nonimplanted ear further limits generalizations; if patients with mild-to-moderate hearing loss were included, CI benefits would likely be larger, especially for speech perception in noise. Nonetheless, the present data show that the CI is safe for SSD patients, largely restores audibility and speech understanding in quiet to the deaf ear, greatly reduces tinnitus severity, greatly improves QoL, and significantly improves localization, with some improvements in speech understanding in noise under certain test conditions. These findings are line with many previous studies. As a clinical trial, these data should also encourage larger scale studies aimed at expanding indications for cochlear implantation to include SSD patients.
CONCLUSIONS
This prospective, longitudinal study provides a comprehensive view of CI benefits for SSD patients during the first 6 mo of implant use. Major findings include:
All SSD patients benefitted from cochlear implantation in terms of localization, speech understanding, tinnitus severity, and QoL. The largest CI benefits were for tinnitus reduction and the smallest benefits were for speech understanding in noise.
No surgical complications or serious adverse events were noted. Most AEs were resolved soon after surgery. No significant decrements in NH-only performance were noted after implantation, suggesting that the CI did not interfere with NH ear function.
The degree and time course of CI benefit depended on the outcome measure and the reference point. Relative to baseline binaural measures, immediate benefits were observed for tinnitus severity and speech performance; localization did not significantly improve until 6 mo postactivation. Relative to NH-only performance after implantation, immediate benefits were observed for tinnitus severity and localization; however, no benefits were observed for speech performance in noise, due to the variability in NH-only performance. To more fully understand the benefits of cochlear implantation for SSD patients, both reference points should be considered.
There were few correlations between behavioral and subjective outcome measures, suggesting that both are important to characterize the benefit of cochlear implantation for SSD CI patients.
ACKNOWLEDGEMENTS
The authors thank all the SSD patients who participated in this study. The authors thank Justin Aronoff and David Landsberger for their help with the initial design of this study, and Suzanne Gutierrez for coordination support during the study. The authors also thank three anonymous reviewers for helpful comments. MED-EL provided the cochlear implants and speech processors for the study, as well as support for research and publication costs.
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