Can self-fitting over-the-counter (OTC) hearing aids provide similar outcomes compared with hearing aids fitted according to audiologist best practices?In this randomized clinical trial of 64 adults with hearing loss, self-reported and speech-in-noise benefit was equivalent between the self-fitting OTC and audiologist-fitted hearing aid conditions at the end of 6 weeks.These findings suggest that a self-fitting OTC hearing aid may be an effective intervention option for individuals with mild to moderate hearing loss and produce self-perceived and clinical outcomes similar to those of an audiologist-fitted hearing aid. This randomized clinical trial compares the effectiveness of a self-fitting over-the-counter hearing aid with remote support with an audiologist-fitted hearing aid using best practice in adults with hearing loss. Hearing loss is a highly prevalent condition, with numerous debilitating consequences when left untreated. However, less than 20% of US adults with hearing loss use hearing aids. Over-the-counter (OTC) hearing aids became available in October 2022 to improve access and affordability. However, clinical effectiveness studies of available OTC hearing aids using the existing devices in the market are limited.To compare the clinical effectiveness of a self-fitting OTC hearing aid with remote support and a hearing aid fitted using audiologist-fitted best practices.This randomized clinical effectiveness trial was conducted between April 14 and August 29, 2022. Sixty-eight adults with self-perceived mild to moderate hearing loss were recruited and randomly assigned to either the self-fitting or the audiologist-fitted group. Following bilateral hearing aid fitting, participants first completed a 2-week, take-home field trial without any support. Access to fine-tuning for both groups was only available after the 2-week trial. Support and adjustment were provided remotely for the self-fitting group per request and by the audiologist for the audiologist-fitted group. Participants were then reassessed after an additional 4-week take-home trial.A commercially available self-fitting OTC hearing aid was provided to participants in the self-fitting group who were expected to set up the hearing aids using the commercially supplied instructional material and accompanying smartphone application. In the audiologist-fitted group, audiologists fitted the same hearing aid according to the National Acoustics Laboratories nonlinear version 2 algorithm for prescriptive gain target using real-ear verification with hearing aid use instruction.The primary outcome measure was self-reported hearing aid benefit, measured using the Abbreviated Profile of Hearing Aid Benefit (APHAB). Secondary measures included the International Outcome Inventory for Hearing Aids (IOI-HA) and speech recognition in noise measured using an abbreviated speech-in-noise test and a digits-in-noise test. All measures were completed at baseline and at 2 intervals following hearing aid fitting (2 and 6 weeks).r = −0.2 ) or 4-frequency pure-tone average . After the 2-week field trial, the self-fitting group had an initial advantage compared with the audiologist-fitted group on the self-reported APHAB  and IOI-HA  but not speech recognition in noise. At the end of the 6-week trial, no meaningful differences were evident between the groups on any outcome measures.Sixty-four participants were included in the analytic sample , with equal numbers of participants (n = 32) randomized into each group. The groups did not differ significantly in age (effect size In this randomized clinical effectiveness trial, self-fitting OTC hearing aids with remote support yielded outcomes at 6 weeks post fitting comparable to those of hearing aids fitted using audiologist best practices. These findings suggest that self-fitting OTC hearing aids may provide an effective intervention for mild to moderate hearing loss.NCT05337748ClinicalTrials.gov Identifier:  Until recently, people with hearing loss could only obtain hearing aids after consultation with a credentialed dispenser.A person with hearing loss can benefit from a range of interventions to curtail detriment to quality of life. Most adults experience hearing loss that is sensorineural and permanent, leaving hearing aids as the most common intervention option.7 The President’s Council of Advisors on Science and Technology and the National Academies of Sciences, Engineering and Medicine, both organizations that inform the American federal government, also highlighted the role that over-the-counter (OTC) hearing aids could play in addressing the accessibility gap.8 Consequently, the US Food and Drug Administration (FDA) passed the Reauthorization Act of 2017, directing the creation of an OTC hearing aid category.9 The final regulations were recently published and went into effect on October 17, 2022.10 This new category of preset OTC and self-fitting OTC hearing aids has quickly become available at a substantially reduced cost when compared with prescription hearing aids.11A working group for accessible and affordable hearing care was established by the National Institute on Deafness and Other Communication Disorders. They identified priority research areas for progressing hearing care access, including the development of self-testing, self-fitting hearing aids.12 In summary, a self-fitting hearing aid has the following key properties: (1) an automated fitting or in situ test approach, (2) the ability to operate without clinician assistance, and (3) user options to alter settings using accompanying controls or software.13 Earlier research validated specific elements of the self-fitting process, including the accuracy of measuring pure-tone thresholds16 and aspects of usability.18 Additionally, alternative procedures for gain prescription were validated, including using different preset fitting parameters20 and user self-selected settings.21The concept of self-fitting hearing aids was introduced more than a decade ago.21 but none consider factors beyond the hearing aid such as postfitting support, troubleshooting, or remote adjustments.20 This study compared the effectiveness of a self-fitting OTC hearing aid with remote support and an audiologist-fitted hearing aid using best practices. The hypothesis was that self-reported outcomes and speech recognition in noise benefit of the self-fitting group would be noninferior to those of the audiologist-fitted group.Preliminary data provided to the FDA from various device manufacturers suggest that OTC hearing aids may be an acceptable intervention for mild to moderate hearing loss. However, there are limited well-controlled clinical studies reporting on OTC efficacy and effectiveness, especially using devices on the market. The few published trials available support relatively equivalent performance outcomes,CONSORT) reporting guideline. This parallel-designed study consisted of 2 arms, self-fitting and audiologist-fitted groups, with equal participant allocation to both. Due to the nature of the trial, blinding was not possible. The trial protocol and statistical analysis plan are found in This randomized clinical effectiveness trial was conducted at the University of Pretoria, Pretoria, South Africa, between April 14 and August 29, 2022. The Humanities Research Ethics Committee at the University of Pretoria reviewed and approved the study protocol, and all participants provided written informed consent before participation. We followed the Consolidated Standards of Reporting Trials  conducted through the hearing aids. Participants in the audiologist-fitted group were fitted with the same hearing aids by the research audiologists using hearing thresholds measured using a calibrated audiometer in a soundproof booth. Real ear verification ensured that the hearing aid output matched a criterion standard fitting algorithm  at 0.5, 1.0, 2.0, and 4.0 kHz within a 5-dB tolerance limit, considered best-practice clinical verification , each registered with the Health Professions Council of South Africa, were involved in performing the procedures. All participants were fitted with hearing aids bilaterally. Participants in the self-fitting group were provided self-fitting OTC hearing aids in their standard commercial packaging (Lexie Lumen [Lexie Hearing]) through the study audiologists.After the baseline evaluation to determine eligibility for participation, randomization was performed by the researcher using a random number generator. Hearing aid fitting was completed in a second session, and participants completed a 2-week field trial. During these 2 weeks, no assistance or fine-tuning via the Lexie remote support service was allowed for the self-fitting group nor was adjustment by the audiologist for the audiologist-fitted group. This design procedure isolated the benefit of fitting from the influence of online support on the self-fitting group participants. At the first follow-up, the audiologist conducted fine-tuning for the audiologist-fitted group on request. Participants in the self-fitting group were informed that they could contact remote support for troubleshooting or adjustment. After another 4-week field trial, the final assessments were conducted.26 and was the primary outcome of the study. Ranges for APHAB are 1% to 99% (unaided and aided), where a lower score indicates less communication difficulty and a higher score indicates greater communication difficulty. When calculating benefit (unaided − aided), a higher score indicates a higher degree of benefit. Four subscales are evaluated, namely (1) ease of communication, (2) reverberation, (3) background noise, and (4) aversiveness. The global score is the mean score for all subscales, excluding aversiveness. The International Outcome Inventory for Hearing Aids (IOI-HA)27 was also included as a secondary outcome measure for self-reported benefit and determined the effectiveness of a hearing aid intervention in 7 domains. Benefit was rated using an ordinal response scale of 1 to 5, with a lower score indicating worse outcomes and a higher score indicating better outcomes. The IOI-HA was completed after hearing aid fitting at the first follow-up (T1) and final assessment (T2).The outcome measures were administered at 3 time points, including the baseline unaided condition (T0) and aided conditions at 2 weeks (T1) and 6 weeks (T2) post fitting. The Abbreviated Profile of Hearing Aid Benefit (APHAB) is a 24-item self-assessment inventory to rate communication difficulties in different listening situations28 and a digits-in-noise (DIN) test.30 The tests were conducted at baseline (unaided) and aided at the 2 follow-up sessions. The QuickSIN test measures a signal-to-noise ratio (SNR) loss of hearing using sentences presented in 4-talker babble noise, consisting of 18 lists of 6 sentences each with 1 sentence per SNR level (+25 to 0 dB SNR). After conducting a practice list, participants were presented with 3 lists to obtain the QuickSIN score. Mean scores of 3 lists are accurate to about 1.6 dB at the 95% CI.28 Stimuli were presented at a comfortable listening intensity in the sound field at 0° azimuth with the listener seated 1 m away from a loudspeaker. The DIN test was performed in the same audiometric setup. The test measures the decibel SNR where a listener could accurately recognize 50% of 23 randomly presented digit triplets  presented adaptively (one-up one-down procedure) in speech-weighted background masking noise.29 Real-ear verification using live-speech mapping at 65-dB International Speech Test Signal was used to determine and compare real-ear–aided responses between the 2 groups 21 in their 2020 study. Participants 18 years and older who self-reported mild to moderate hearing loss in response to an advertisement and had no history of outer or middle ear disease 90 days before study inquiry were invited to attend a baseline session to establish candidacy based on comprehensive air- and bone-conduction audiometry. Participants with normal hearing thresholds (<20-dB hearing level [HL]) at all frequencies , who had possible outer or middle ear pathology, or who had severe hearing loss with thresholds at 0.5, 1.0, 2.0, and 4.0 kHz more than 80-dB HL at 2 or more frequencies were excluded. All participants had bilateral hearing loss. Furthermore, participants with air-bone gaps more than 20-dB HL at 3 or more frequencies between 0.5, 1.0, 2.0, and 4.0 kHz were excluded. As detailed in t test were used to test whether differences between 2 independent (unrelated and unpaired) groups were statistically significant. Two-tailed tests were used, as the interest was in whether there was a significant difference between 2 groups, regardless of which group had the higher median (Mann-Whitney test) or mean (t test). Continuous variables  were compared using Mann-Whitney tests for nonnormal distributed variables and independent samples t tests for normal variables. The IOI-HA scores were compared using the Mann-Whitney test, as the results are ordinal response categories. Clinically meaningful differences were reported considering effect size and 95% CI. Cohen d was used for t test findings, and effect size r was calculated as z/√N for Mann-Whitney tests. Cohen d effect size was interpreted as small (d ≤ 0.2), small to medium (d > 0.2 to d < 0.5), medium (d = 0.5), medium to large (d > 0.5 to d < 0.8), and large (d ≥ 0.8)31; effect size for Mann-Whitney tests, as small (r ≤ 0.1), small to medium (r > 0.1 to r < 0.30), medium (r = 0.3), medium to large (r > 0.3 to r < 0.5), and large (r ≥ 0.5).31 Effect sizes were considered clinically meaningful when they were medium or larger.We performed all statistical analyses using SPSS statistics, version 28.0 (IBM Corporation). The Mann-Whitney test and the independent samples r = −0.2 ) or pure tone average   , the audiologist-fitted (n = 32) and self-fitting (n = 32) groups did not differ significantly in age (effect size to 0.4]) . Furtherd, 0.6 ) and on the APHAB global benefit scores  (32 compared with the audiologist-fitted group participants (21 [66.6%]), although the overall effect size was small.Unaided baseline scores across all subscales and the global score of the APHAB were not significantly different between the groups . Two wee0 to 0]) . After t0 to 0]) . Howeverr = 0.3 )  at T1. After the 6-week trial (T2), none of the IOI-HA items or total score were significantly different between the groups.Based on the IOI-HA conducted at T1, participants in the self-fitting group reported meaningfully longer hearing aid use per day (effect size .0-0.5]) . None ofd = 0.3 ) or DIN  test. Benefit scores were determined by subtracting aided from unaided scores  or 6 weeks . Consistent with the DIN results, QuickSIN benefit was also not meaningfully different between the groups at 2 weeks  or 6 weeks . However, at 6 weeks (T2), the proportion of participants performing better than the 90% critical difference for the QuickSIN (1.8 dB)28 was 20 (62.5%) and 14 (43.8%) for the audiologist-fitted and self-fitting groups, respectively.At baseline (T0), there were no significant differences between the groups for either the QuickSIN (Cohen d scores C and D. Frequency of requested hearing aid adjustment and support for the groups between 2 and 6 weeks post fitting is worth noting. At the 2-week aided assessment (T1), 21 (65.6%) of the participants in the audiologist-fitted group requested fine-tuning compared with 2 (6.3%) of participants in the self-fitting group requesting remote support from the call center. All fine-tuning for the audiologist-fitted participants was conducted at the first follow-up appointment (T1).Two days following hearing aid fitting, 1 participant in the self-fitting group developed a middle ear infection, a medical contraindication for using a self-fitting OTC or audiologist-fitted hearing aid. The participant was asked to discontinue the intervention. No other adverse events were observed during the 6-week trial.In this randomized clinical effectiveness trial, the self-fitting group performed comparably with the audiologist-fitted group. At 2 weeks, the self-fitting group had a small but meaningful advantage on 2 of the 4 outcome measures. After support and fine-tuning were provided to the self-fitting (remote support) and audiologist-fitted groups, no clinically meaningful differences were evident in any outcome measures at the end of the 6-week trial.33 If this clinical model is the standard to which self-fitting OTC hearing aids are to be held, a key matter is whether the outcomes are similar. Self-reported hearing aid outcomes are standard outcome measures in hearing aid trials, especially since they are associated with consistent hearing aid use.34Audiologists fitted participants with hearing aids by matching the hearing aid gain according to prescriptive targets based on the audiometric results. Counseling and hearing aid orientation was provided in person at the fitting stage (T0), and hearing aids were fine-tuned based on the patient report at the 2-week (T1) follow-up appointment. We considered this characteristic of clinical best practice, aligned with the American Speech-Language-Hearing Association guidelines.21 showed similar findings. The study by Humes et al19 in 2017 used an alternative OTC method where users selected from different preprogrammed hearing aids, compared with an audiologist-fitted hearing aid and placebo control. Two self-reported outcome measures (Profile of Hearing Aid Benefit and the Hearing Handicap Inventory for the Elderly) were equivalent between the preprogrammed OTC and audiologist-fitted hearing aid groups. However, a slight nonsignificant advantage was found for the audiologist-fitted group. These findings were replicated in 2019 using less restrictive participant selection.20 Sabin et al21 compared an audiologist-fitted best practice group with a self-fitting group using SoundControl hearing aids (Bose). Here, users could select their own fitting parameters, including gain and spectral tilt. The APHAB global scores and the short form of the Speech, Spatial, and Qualities of Hearing Scale showed no significant differences between the groups. The latter study is closely aligned with the present study through inclusion of an OTC hearing aid currently in the market. The weight of the evidence thus far supports self-reported benefits for a self-fitting OTC model to be comparable to an audiologist-fitted model for mild to moderate hearing loss.We found better self-reported outcomes for the self-fitting compared with the audiologist-fitted groups after 2 weeks of field use that was clinically meaningful. Specifically, the APHAB self-reported background noise performance was better for the self-fitting group, as was the global benefit score. The self-fitting group also showed a longer duration of daily hearing aid use on the IOI-HA, along with the total score. However, after 6 weeks of hearing aid use, the self-reported outcomes were not meaningfully different between the groups. Three previous effectiveness trials35 However, a recent systematic review indicates that although real-ear–verified hearing aids are positively associated with better speech recognition in noise, the pooled effect sizes are small,35 and the absolute decibel SNR benefit is slight and clinically not meaningful.36 Our study showed little differences in speech-in-noise performance  between the audiologist-fitted group matched to the prescriptive target and the self-fitting groups at 2 and 6 weeks post hearing aid fitting. Similarly, Sabin et al21 found no significant differences in speech recognition benefit (QuickSIN) between the audiologist-fitted best practice and self-fitting groups when fitted with the same hearing aid. Considering the results of this and other studies, the present study suggests that target-matched hearing aids are not likely to produce functionally different outcomes in speech recognition in noise when compared with good self-fitting algorithms. Furthermore, observations presented herein (eFigure 1 in 21 showed that participants preferred their self-selected fitting parameters, which were generally lower than the audiologist-selected gain. A few other studies on self-fitting hearing aids37 have similarly shown a preference for lower gain, especially in the higher-frequency region. The OTC hearing aid in this study also applied lower gain in high frequencies (eFigure 1 in There is a prevailing assumption that hearing aids matched to prescriptive targets through probe tube verification result in better speech recognition in noise.This study has some limitations. First, blinding was not possible. Furthermore, we investigated only 1 self-fitting OTC device with 1 fitting method. Other devices and fitting methods may produce outcomes with variable success. The sample size did not allow for subgroup analysis, such as age, which could influence self-fitting outcomes if there are varying levels of digital proficiency; this limits the ability of the study to identify and resolve potential problems in the self-fitting model. Possible recall bias for the wear time of the hearing aids may be present since the actual duration of use was not captured using data logging. Finally, the results only report outcomes up to 6 weeks post fitting. Further field research investigating long-term outcomes is needed.In this randomized clinical effeciveness trial, the short-term outcomes of self-fitting OTC hearing aids for people with mild to moderate hearing loss were comparable to those obtained from audiologist-fitted hearing aids using best practices. Affordable self-fitting OTC hearing aids may be an accessible hearing intervention option with outcomes similar to those of audiologist-fitted hearing aids.


A cochlear implant is a neuroprosthetic device that can restore speech perception for people with severe to profound hearing loss. Because of recent evolutions, a growing number of people with a cochlear implant have useful residual acoustic hearing. While combined electro-acoustic stimulation has been shown to improve speech perception for this group of people, some studies report limited adoption rates. Here, we present electro-vibrational stimulation as an alternative combined stimulation strategy that similarly targets the full cochlear reserve. This novel strategy combines the electrical stimulation by the cochlear implant with low-frequency bone conduction stimulation. In a first evaluation of electro-vibrational stimulation, speech perception in noise was assessed in 9 subjects with a CI and symmetrical residual hearing. We demonstrate a statistically significant and clinically relevant improvement for speech perception in noise of 1.9 dB signal-to-noise ratio. This effect was observed with a first prototype that provides vibrational stimulation to both ears with limited transcranial attenuation. Future integration of electro-vibrational stimulation into one single implantable device could ultimately allow cochlear implant users to benefit from their low-frequency residual hearing without the need for an additional insert earphone. For people with moderately severe to profound levels of hearing loss, speech perception can be restored by a cochlear implant (CI)2. A CI is a surgically implantable device that replaces the function of the hearing organ by converting the sound waves of speech and music into electrical pulses. These electrical pulses are then conveyed to the brain via the auditory nerve.Worldwide more than 430 million people are suffering from disabling hearing loss with the need for rehabilitation3. In situations with multiple competing talkers or background noise, however, speech perception remains much more difficult5. For example, even CI users with excellent word recognition in quiet need at least 5–10 dB better signal-to-noise ratio (SNR) to reach the same speech perception as normal hearing listeners6. These difficulties with speech perception in background noise have been attributed to the lower spectral resolution with a CI resulting from, among other factors, the limited numbers of electrodes and current spread inside the cochlea7.CIs are considered among the most successful implantable medical devices and can provide excellent speech perception in quiet8. In the majority of cases, the residual hearing is located in the low-frequency range from 125 to 1000 Hz. Moreover, due to advances in electrode designs and surgical techniques, long-term preservation of this residual hearing after implantation has been shown to be possible in about 70% of patients9. In the future, integration of new technologies such as real-time monitoring during CI insertion may further increase hearing preservation rates10.As a result of the recently evolving CI indication criteria, there is a growing number of CI candidates with useful residual acoustic hearing at the time of the implantation13. The benefits of this combination have been attributed to a better representation of voicing and manner of articulation, allowing the user to narrow down the potential word candidates in the lexicon15. Furthermore, in background noise, the voicing cues can provide acoustic landmarks for when to listen to the target speaker15. Nevertheless, despite the benefits and high adoption rates of EAS observed in clinical trials16, a recent survey in a population with a low EAS adoption rate identified that about half of the users reject EAS for non-audiological reasons, with the need for an extra insert earphone being the most cited17.Interestingly, combining low-frequency acoustic amplification with the electrical stimulation by the CI, so-called electro-acoustic stimulation (EAS), has consistently been shown to improve speech perception, especially in background noiseElectro-Vibrational Stimulation (EVS) as an alternative combined stimulation strategy for the first time. EVS combines the electrical stimulation by the CI with vibrational stimulation provided by a bone conduction (BC) actuator. With EVS, we aim to improve speech perception in the growing group of CI users with residual hearing, while overcoming the limitations of EAS.In the present study, we explore the potential of 18. In contrast to hearing aids that amplify sounds via a speaker in the ear canal, BC actuators convert the sound into mechanical vibrations. These vibrations are then transferred directly to the inner ear, largely bypassing the outer and middle ear. Recently, implantable actuators have been developed20. By integrating implantable actuator technology into the CI housing, in the future, EVS could be delivered by a single implantable device. This would allow CI users to benefit from the high spectral and temporal resolution of their low-frequency residual hearing without the need for an additional insert earphone.Nowadays, BC devices are widely used in clinical practiceThe aim of this study was to assess speech perception in noise with a non-invasive EVS prototype for the first time. In a within-subject repeated measures design, the speech reception threshold (SRT) with EVS was compared to the SRT with the CI alone (E-only) in CI users with symmetrical residual low-frequency hearing. We hypothesized that speech perception in noise would improve by adding low-frequency vibrational stimulation to the electrical stimulation of the CI.In 7/10 ears the pattern of hearing loss was continuously down-sloping from low to high frequencies, while in 3/10 the most profound hearing loss was located in the mid frequencies . The mean (n = 10) SRT with the E-only condition was 1.4 dB SNR  compared to − 0.5 dB SNR  with the EVS condition. The mean EVS benefit was 1.9 dB SNR (SD: 2.0 dB SNR). On an individual level, each of the participants benefited from EVS compared to E-only, except subject 9.Individual SRTs in different conditions are plotted in Fig. In the subgroup with a restricted CI frequency spectrum (n = 3) the SRT with E only and EVS were on average − 1.4 and − 3.2 dB SNR, respectively. In the subgroup with a full CI frequency spectrum (n = 7) the SRT with E-only was 2.6 dB SNR compared to 0.6 dB SNR with EVS.We observed no correlation between the degree of low-frequency residual hearing, measured as LFPTA-AC or low-frequency pure tone average with BC (LFPTA-BC), and SRTs with E-only, SRTs with EVS or EVS benefit  we observed a non-significant average improvement in speech perception with EAS over E-only—i.e., EAS effect—of 0.17 dB SNR. The average improvement with EVS compared to EAS in the same subgroup was 1.8 dB SNR.13. In contrast to EAS, however, this benefit was achieved by providing BC stimulation at the level of the skull, without the need for insert earphones.We have shown for the first time that EVS can improve speech perception in steady-state noise compared to E-only. In a population of experienced CI users with symmetrical low-frequency hearing the SRT improved on average 1.9 dB SNR with EVS compared to E-only. The observed effect size is considered clinically significant and in line with the improvement of 2 dB SNR observed with EAS over E-only in a large multi-center study13. Moreover, given the bilateral BC stimulation of EVS , a comparison with unilateral EAS should be interpreted with caution. Individually, 8 out of the 9 subjects benefited from the addition of vibrational stimulation. Individual effect sizes ranged from 0.3 to 5.3 dB SNR. Only subject 9 did not experience an EVS benefit and performed even worse compared to E-only (− 2.3 dB SNR). This lack of improvement in subject 9 may be due to multiple factors. One potential factor that stands out is the level of the low-frequency BC thresholds in this particular subject. At each of the frequencies between 250 and 1000 Hz, the BC thresholds matched or exceeded the MPO of the BC device used in this study. As a consequence, the effective dynamic range of the BC device—i.e., the difference between the BC threshold and the loudest hearing level that can be obtained with the device21—was close to zero for this subject.Also, in the subgroup of participants with EAS (n = 4), we observed a better speech perception with EVS compared to EAS. However, this result should be interpreted with caution because of the small sample size and the relatively smaller EAS effect  of 0.17 dB SNR in this subgroup group compared to what is typically observed in larger EAS studies21. There are two primary reasons for the limited effective dynamic range of the BC device used in this study. First, we repurposed a commercially available BC device. While this device was the most powerful commercially available BC device at the time of this study, it has not been designed for the specific purpose of the present study to generate high-output low-frequency stimulation. Moreover, because of the exploratory nature of the study including human participants, we opted for a non-invasive setup via transcutaneous stimulation. This stimulation method is associated with skin attenuation of the BC vibrations, albeit limited in the frequency range < 1000 kHz22. Nevertheless, despite this limited effective dynamic range, we did observe a significant benefit of EVS on speech perception in noise. The effective dynamic range of EVS could further increase with a dedicated BC actuator designed for higher output in the low frequencies and direct coupling to the skull bone. Based on the results from previous studies24 that showed improved speech perception with higher output power BC devices, this could result in even larger effect sizes with EVS vs E-only. However, it remains unclear how the findings from these studies showing the benefit of an increased broadband output would translate to higher low-frequency stimulation at the electro-vibrational cross-over frequency.While in each of the other participants, the effective dynamic range of the BC device was > 0 for at least one frequency, the typically desired 30–35 dB effective dynamic range was obtained only for two subjects  at 250 Hz15.For the subjects that did benefit from EVS with the current setup Fig. , we hypo25. Previous studies showed that low-frequency tactile stimulation at the wrist or fingertip can improve speech perception in noise when combined with the electrical stimulation by the CI27. Though this electro-haptic effect was not specifically assessed in the current experiment, it may have contributed to the improved speech perception in noise. However, the study by Fletcher et al. only showed a significant average increase in word recognition of 8.3% with haptic stimulation after a training window of 20 min which is longer than the total duration of EVS use in the present study experiments26. Based on the data obtained with the current patient population, we cannot differentiate the exact contribution of the electro-haptic effect. In future studies, this isolated effect can be measured by applying the same methodology of EVS in participants with a CI and the absence of residual hearing in both ears.Furthermore, two mechanisms specific to EVS could contribute to improved speech perception in noise. First, EVS could potentially provide haptic cues. It is known that, especially for the low-frequency range, the MPO levels of the present BC actuator are well above the vibrotactile thresholds at the mastoid28. Since all the participants in the present study had symmetrical low-frequency residual hearing, this could result in binaural summation. This phenomenon of binaural summation has been shown to improve speech perception in steady-state noise up to 1.3 dB SNR in normal-hearing listeners30. The impact of binaural summation in bone conduction stimulation, however, is less clear.A second mechanism specific to EVS is the bilateral stimulation with little transcranial attenuation, especially in the low frequenciesThe present within-subject repeated measures design has the advantage of limiting the inter-subject variability that is typically observed with CI users. Yet, this also implies that subjects are tested in device conditions that differ from their usual rehabilitation. Therefore, to further limit the number of modifications from the rehabilitation strategy of a single participant, we chose to keep the CI fitting map unaltered.This unaltered CI fitting could negatively impact speech perception E-only condition in EAS users. In 3 out of the 4 EAS users included in this study, the frequency range covered by the CI was restricted at the low-frequency end. As a result, these subjects miss out on a small part—i.e., 188–313 Hz or 188–438 Hz—of the frequency spectrum in the E-only condition. The restricted frequency spectrum in the E-only condition could negatively impact speech perception and result in an artificially high EVS effect (SRT EVS—SRT E-only). While we cannot exclude the effect of the altered frequency map completely, posthoc analyses comparing the SRT with E-only, SRT with EVS, and EVS benefit in the group with a full CI frequency spectrum (n = 7) to those with a restricted frequency spectrum (n = 3) support the idea that EVS benefit is substantial and not solely based on an unfavorable E-only condition. While the results should be interpreted with caution given the small sample sizes, we did even observe opposite trends with better SRTs in E-only condition and lower EVS benefit in the group with the restricted E-only frequency spectrum.32. While it is unclear if these findings can be generalized to EVS, we hypothesize that individualization of the allocation of the frequency spectra could further increase EVS benefit.The fitting parameters of the vibrational component in EVS were identical for all subjects Fig. . BecauseIn the present study, stimuli were presented in free field without the use of ear plugs or ear defenders to block the AC pathway. Some of the subjects with excellent residual hearing and thresholds of up to 15 dB HL may have benefited from unamplified low-frequency acoustic cues in the E-only condition, therefore resulting in a smaller observed EVS effect than would be the case if the air conduction pathway was blocked. However, since no condition with occlusion of the AC pathway was included in this study, we do not have data to support this hypothesis. In any respect, the reported EVS effect sizes in the present study really show the potential impact of adding a vibrational component in CI users with residual hearing that currently use only their CI (E-only).34.Finally, it should be noted that the experiments concerned an acute in-hospital evaluation and that the speech perception tests with EVS occurred after only a short accommodation time of 5–10 min. Based on the improvements in speech perception over time observed in previous studies with E-only or electro-tactile stimulation, even larger effect sizes may be expected if the subjects have a longer adaptation time to the new EVS condition before testingOne of the main limitations of the present study is the size and heterogeneity of the study population. Nevertheless, each individual participant except the one participant with the poorest BC thresholds has been shown to benefit from EVS. The current sample does not allow further analysis of the impact of different electrode types, fitting maps, or the use of a contralateral hearing aid. Future studies should aim to recruit a larger homogenous sample to further explore these effects.In summary, our result show for the first time that EVS can improve speech perception in noise for CI users with symmetrical residual low-frequency hearing and could be an alternative to EAS. Even larger effect sizes can be expected with an individualized frequency spectrum allocation and a longer adaptation time. Future integration of EVS into one single implantable device could ultimately allow CI users to benefit from their low-frequency residual hearing without the need for an additional insert earphone.Nine adults with a CI, 6 females and 3 males, were prospectively recruited from the University Hospitals Leuven. The following inclusion criteria were applied: (1) Low-frequency residual hearing—i.e., at least one frequency between 125 and 1000 Hz in the ipsilateral ear with a pure tone audiometric threshold ≤ 65 dB HL; (2) Minimum of 6 months of experience with the CI; (3) Stable fitting of the CI over the last month before testing; (4) Native Dutch speaker. This study was approved by the Ethics Committee of the UZ Leuven (S65654) and performed in accordance with the Declaration of Helsinki. Informed consent was obtained before the start of the experiments.Participant demographics are displayed in Table At the start of the experiment, air conduction thresholds  were obtained for both ears. Only participants with a difference in LFPTA-AC between the two ears of < 15 dB HL were included in this study. BC thresholds were obtained with the RadioEar B71/81. Otomicroscopy and tympanometry were performed to rule out middle ear effusion or external ear canal occlusion as potential causes of conductive hearing loss.Cochlear™ Baha® 5 SuperPower, the most powerful commercially available BC in terms of MPO at the time of the study. To keep the BC device in place at the mastoid ipsilateral to the CI, the participants wore an elastic headband , EVS , and EAS . The EAS condition was only tested if used by the participant in daily life. No changes were made to the fitting of the acoustical component of the EAS or the acoustical HAs in the contralateral ear. In this first preliminary assessment of EVS, a non-invasive stimulation combination is used. The previously implanted CI provided the electrical stimulation. The vibrational component was delivered by a transcutaneous BC device. More specifically, we used the and Fig. . This noBC Direct) were obtained with the transcutaneous BC device using the commercially available fitting software (Baha® Fitting Software 5.4) provided by the manufacturer. These thresholds are unmasked and, because of the limited attenuation of BC stimulation, represent the lowest threshold of the ipsilateral and contralateral ear combined. The LFPTA-BC was calculated based on thresholds at 250, 500, 750, and 1000 Hz. The output of the BC actuator was fitted similarly for each participant with maximum gain at frequencies below 1 kHz and minimal output at higher frequencies  and asking the participant for a score on a 7-levels scale as used for the assessment of T and C levels in CI fitting. This loudness assessment showed that the device conditions were perceived equally loud within one level difference on the 7-levels scale. Given the fixed BC output  sentences were used as speech stimuli. The LIST set is a Dutch speech material containing 35 equivalent lists of each 10 sentences uttered by a female speaker. Each sentence contains three to four keywords. The LIST speech material was specifically designed for testing people with severe hearing impairment and CI usersThe EVS condition was fitted at the beginning of the experimental procedure. The participants had a short period of 5–10 min to get accustomed to the new rehabilitation strategy before the start of the measurements.36, routed via an RME Hammerfall DSP Multiface II sound card to a single speaker (Genelec 8020B) placed at a distance of 1.35 m in front of the participant at 0°.The measurements were performed in a double-walled soundproof room. The stimuli were presented from a PC using APEX softwareSpeech perception was assessed in a within-subjects repeated measurements design. Between different tests, only the device condition  differed. In one experimental session with the same participant, up to three device conditions  were tested. During the experimental session, the participants did not use a contralateral device. In this acute experimental setup, there was only a short interval of about 5–10 min to get accustomed to the next device condition. The order of the device conditions was randomized between participants. Experiments with one participant were performed during a single session. The research design was unmasked to both participants and researchers.37. While the intensity of the speech stimulus was kept constant at 60 dB SPL, the SNR varied in a 1-up 1-down procedure by changes in the intensity of the masker in steps of 2 dB SPL. The SRT was calculated as the mean of the SNRs of the last 6 trials. The initial SNR at the beginning of the experiment  was set at a level about 5 dB SNR lower than the SRT measured with E-only during previous testing at the clinic, resulting in a speech perception level close to 0%. The first sentence was repeated at increasing SNRs in steps of 2 dB SNR until correct. Each test with a specific device condition was repeated at least twice (test–retest). If the difference between the test and retest was > 2 dB, an additional retest was performed. The final SRT was calculated by averaging the two lowest  SRTs.In each specific test, SRT was determined via an adaptive procedureIn none of the conditions ear plugs or ear defenders were used.Statistical testing was performed with SPSS version 28.0.1.1. We compared the within-subject effect of the device condition  on SRTs with a paired t-test (two-sided). The Kolmogorov–Smirnov test with Lilliefors modification was used to assess normality. Correlations were assessed with Pearson correlation. Significance levels were set at 0.05.EVS and EAS benefits were defined as the difference in SRT between EVS and E-only condition or EAS and E-only condition, respectively.Supplementary Information 1.Supplementary Figure 1.Supplementary Figure 2.Supplementary Figure 3.


The aim of this study was to investigate hearing outcome of stapes surgery, considering the post-operative air and bone conduction (AC&BC) changes, in a frequency specific approach.This was a retrospective cohort study. A total of 245 ears (231 patients), who underwent Stapedotomy at our tertiary referral center in a period of 5 years were enrolled in the study. Pure tone audiometry (PTA) was evaluated preoperatively and one month postoperatively. AC, BC, and Air-bone gap (ABG) were documented. Moreover, one-year post-op PTA was also recorded for more than a quarter of the cases.Overall, significant improvements were observed in AC thresholds with a mean AC gain of 20.44±13.64 dB. At higher frequencies the results were poorer (AC gain of 27 dB at 250 Hz vs 7 dB at 8000 Hz). ABG significantly improved at all frequencies after one month. BC thresholds were typically better after surgery. However, there appears to be a worsening trend in BC thresholds at frequencies higher than 2000 Hz. In 68 patients with 1-year follow-up, BC thresholds were slightly worse  at most frequencies, in comparison to the one-month results. Stapes surgery significantly improves air and bone conduction hearing, particularly at lower frequencies. Nonetheless, there exists a potential for sensorineural hearing loss (SNHL) at high frequencies. However, the changes are insignificant and not within the speech frequencies. Therefore, patients are typically satisfied with the hearing outcome of the surgery. Otosclerosis represents a unique disorder involving endochondral bone remodeling that specifically affects the otic capsule, potentially resulting in conductive, mixed, or even sensorineural hearing loss due to cochlear sclerosis ,4,5. SomThis phenomenon can be attributed to multiple factors, including reduction in the extent of ossicular fixation, alteration in middle-ear biomechanics and cochlear fluid dynamics, reduction in the degree of conductive hearing loss and consequent refinement in BC threshold measurement, as postulated by the Carhart effect and the overclosure theory . Historical data on stapes surgeries have indicated that stapedotomy offers superior gains in high-frequency hearing and reduces the risk of sensorineural hearing loss (SNHL) , an infrIt is evident that the post-surgical auditory outcomes exhibit variability across different frequency ranges. Multiple investigations have been conducted on the hearing outcome following otosclerosis surgery so far. Nonetheless, while these studies have provided valuable insights, there exists a degree of inconsistency in their findings pertaining to postoperative changes in BC thresholds across various frequencies. To address this uncertainty, we have undertaken a frequency-specific survey approach, aimed at obtaining a comprehensive understanding of this intricate phenomenon.The retrospective cohort study was conducted on otosclerosis patients who underwent Stapedotomy over a five-year period (2015-2020) at our tertiary referral center. Eligible participants exhibited conductive or mixed hearing loss, diagnosed through clinical history, otoscopy, tuning fork tests, pure tone audiometry (PTA), and impedance findings. Exclusion criteria encompassed individuals under 18 years old, those who had undergone revision stapes surgery, patients with congenital middle ear anomalies, and those with specific risk factors for hearing loss, such as diabetes mellitus, chronic otitis media, rheumatologic disorders, temporal bone trauma, exposure to ototoxic agents, noise-induced hearing loss, and those who failed to complete their 1-month follow-up. The cases with intra-operative findings other than otosclerosis were also excluded from the study. Ethical approval was obtained from the local ethics committee (code: IR.MUMS.MEDICAL.REC.1398.883), and patients provided written informed consent before participation.Small fenestration stapedotomy was performed in all patients via the transcanal approach. The prosthesis used was a Teflon Piston in all the cases. A lobular fat graft was used for sealing the Oval Window around the prosthesis shaft. Surgical details, including prosthesis length and diameter, footplate thickness, extent of Oval Window opening and other significant occurrences, were meticulously documented.Preoperative and 1-month postoperative standard pure tone audiometry (PTA) was conducted for all participants, with additional one-year post-op PTA data available for a subset of cases. Audiometry was administered by qualified audiologists in a sound-treated room using a calibrated audiometer (Interacoustics AC 40). Air conduction (AC) and bone conduction (BC) thresholds were determined via TDH 49 supra-aural headphones and B-71 bone vibrator, respectively. Postoperative air-bone gap (ABG) was calculated by subtracting postoperative BC thresholds from postoperative AC thresholds, in line with the guidelines established by the Committee on Hearing and Equilibrium of the American Academy of Otolaryngology-Head and Neck Surgery (AAO-HNS) . Due to Data analysis was executed using SPSS software (version 16). Descriptive statistics were employed, including calculation of relative frequencies for categorical variables and mean±SD for continuous variables. The normality of continuous data was assessed with the Kolmogorov–Smirnov test, followed by paired t-tests and other descriptive measures to evaluate changes in target variables. Pearson correlation coefficients were also computed, and statistical significance was set at a p-value of less than 0.05.A total of 245 ears (from 231 patients), comprising 82(%35) men and 149(65%) women, were included in the study. The average patient age was 42.41 years (±11.06), spanning 18 to 75 years.Significant improvements in AC thresholds were observed across all frequencies after one month, reaching maximum at 250 Hz. Notably, the magnitude of AC improvement diminished with higher frequencies, as detailed in .The mean AC gain was 20.44 dB (±13.64). ABG also exhibited noteworthy improvement across all frequencies one month postoperatively, as outlined in BC thresholds displayed remarkable improvement within the 250-4000 Hz range, with the most substantial improvement (~12 dB) occurring at 2000 Hz, potentially attributable to the Carhart effect . The treThe study did not record any cases of postoperative dead ear. However, a significant postoperative sensorineural hearing loss (SNHL) was observed in 4 cases (1.4%), characterized by BC deterioration of ≥15 dB at speech frequencies. No significant correlations emerged between hearing outcomes and age, patient gender, prosthesis length & diameter, or footplate thickness (p>0.05).Nonetheless, a noteworthy positive correlation surfaced between preoperative BC and BC improvement one-month post-surgery, as reflected by the correlation coefficient testing r , . This suggests that greater preoperative BC values corresponded to more substantial improvements in postoperative BC across all frequencies. However, the correlation was comparatively weaker at higher frequencies.Around 25% of cases (68 out of 245) returned for their one-year follow-up. Analysis of this subset revealed slightly worsening in one-year post-operative BC thresholds across all frequencies, except at 1000 Hz, compared to one-month values . NeverthIn designing our study, we aimed to investigate the possibility of persistant high-frequency sensorineural hearing loss (SNHL) following stapedotomy, challenging the prevailing notion of its transience. Our findings revealed noteworthy improvements in air conduction (AC) thresholds at all frequencies within one month after surgery, with the most remarkable gains noted at 250 Hz. However, the degree of hearing recovery (AC gain) was less substantial at higher frequencies, as evident by the lower AC gain at 8000 Hz compared to 250 Hz . InteresBone conduction (BC) thresholds exhibited improvements after surgery, particularly at 2000 Hz, attributed to the Carhart effect and the phenomenon of "overclosure",18-21. TOur study uncovered a significant positive correlation between preoperative BC values and BC improvement one month post-surgery. Higher preoperative BC values were linked with greater postoperative BC improvements across all frequencies, similar to the findings of Sharaf et al. . Martin 11 But Vincent et al. found correlation between obliterative otosclerosis and higher rate of postoperative SNHL  and bone conduction (BC) hearing, particularly at lower frequencies. Nonetheless, there exists a potential for sensorineural hearing loss (SNHL) to manifest at high frequencies. Importantly, these changes, although present, do not achieve statistical significance and are not within the range of speech frequencies. As such, overall patient satisfaction with the hearing outcomes of the surgery remains high. However, our study highlights the need for continued investigation into potential adverse changes within the inner ear and basal turn of the cochlea, offering further exploration in future research endeavors.


This study examines the relationship between the early identification of hearing loss and language outcomes for deaf/hard of hearing (D/HH) children, with bilateral or unilateral hearing loss and with or without additional disabilities. It was hypothesized that hearing loss identified by 3 months of age would be associated with better language outcomes. Using a prospective, longitudinal design, 86 families completed developmental instruments at two time points: at an average age of 14.8 months and an average age of 32.1 months. Multiple regression examined how hearing loss identified by 3 months of age contributed to later language outcomes while controlling for developmental level at the first time point. Hearing loss identified by 3 months of age was positively associated with better language outcomes for D/HH children at 32 months of age; however, D/HH children still exhibited language delays, compared to normative scores for same-aged hearing peers for reported measures. Language outcomes of children with unilateral hearing loss were not better than those of children with mild-to-moderate bilateral hearing loss. Children with additional disabilities and more severe bilateral hearing loss had lower language scores than those without. Before The Joint Committee on Infant Hearing (JCIH) published a 2019 position statement emphasizing early hearing screening (by 1 month of age), evaluation (by 3 months of age), and intervention (by 6 months of age) for all children . SeveralThe purpose of this paper is to examine the relationship between timing of hearing loss identification and language development for children with permanent hearing loss in Wisconsin who were recruited as part of a larger prospective, longitudinal study of developmental outcomes for D/HH children. Identity-first and person-first language are used throughout this paper to reflect terms preferred by both deaf individuals and individuals with hearing loss. To expand on previous research, this study included children with either unilateral or bilateral hearing loss, as well as participants with and without additional disabilities. Other co-variates were examined, such as degree of hearing loss and maternal level of education.2.2.1.In 2008, a partnership between the Wisconsin EHDI program and researchers at the University of Wisconsin-Madison and the University of Colorado-Boulder created the Assessment of Early Intervention Outcomes (AEIOu) study. UW-Madison was the Institutional Review Board (IRB) of record. Recruitment began when children were around 12 months of age. Initially, all D/HH children who were enrolled before 12 months of age in the Wisconsin Part C early intervention program, called the Birth to 3 Program, were eligible to participate in the study. After 2013, inclusion criteria were expanded to include all children reported to the WI EHDI program with a diagnosis of hearing loss regardless of enrollment in the Birth to 3 Program. Exclusion criteria included temporary hearing loss . A study team member contacted eligible families by phone around the time the child was 12 months of age and provided information about the AEIOu study. If the family agreed to participate, they were mailed both the study consent and developmental questionnaires. Because each participant was to be assessed at 2 time points , several strategies were used to reduce attrition and improve timely return of the completed forms. First, 3 weeks after parents were sent the forms, a phone and/or email reminder was sent. If the evaluation forms were not returned, up to 3 contact attempts were made, with the last contact attempt approximately 1 month before the participant was close to aging out of the target age ranges.2.2.The AEIOu study protocol was designed collaboratively with the CDC-funded National Early Childhood Assessment Project (NECAP) at the University of Colorado-Boulder , which aAt both Phase 1 and Phase 2, families were asked to complete demographic and developmental questionnaires. Demographic information included the child’s sex, age, hearing device used, communication method at home, and co-occurring conditions. Maternal demographic information collected included race, ethnicity, presence of parental hearing loss, and parent rating on the effect of co-occurring conditions on the child’s speech and/or language development.Results from two norm-referenced developmental instruments were analyzed for this paper, the MacArthur-Bates Communicative Development Inventories  and the Developmental forms were scored at the University of Colorado-Boulder by trained undergraduate students, checked for accuracy by a second scorer, and errors were corrected by consensus.Quotient scores were calculated using the following equation:A quotient of 100 indicates a child’s developmental age is exactly commensurate with their chronological age. Quotients below 80 are considered to indicate a clinically significant delay, relative to other children of the same age. Additionally, the manual for the CDI indicates that scores between 70–80 are suggestive of borderline delay .2.3.Data collection occurred over ten years (2009–2019) with a total of 118 children completing Phase 1 and 86 of those children completing Phase 2. This study focuses on the 86 children for whom both Phase 1 and Phase 2 data were available. Although there was some attrition due to losing contact with families or families choosing not to complete Phase 2, children completing Phase 2 did not differ from the group completing Phase 1 on important study group characteristics, such as communication method used at home, hearing status of parents, maternal level of education, types of childhood comorbidities, and degree of hearing loss.Demographic information for the study cohort of 86 children, as reported at Phase 2, is shown in Self-identified race in this study cohort was 90% White, and no families reported Hispanic ethnicity. Mothers reported a relatively high level of maternal education . The pre2.4.p > 0.05) for children in these two groups. The only variables that were significantly different between the two groups were age of diagnosis, age of receiving hearing amplification, and age of receiving early intervention, as shown in To examine whether meeting the EHDI recommendation for identification of hearing loss by 3 months of age influenced language development, children were considered to have “met” the 3 months diagnostic recommendation if their hearing loss was identified before 3.5 months of age. Sixty-two children 72%) met this criterion. This categorical variable (“met” or “not met”) was used as one of the predictors for the analyses. % met thiOutcome variables used in the regression model were the expressive vocabulary quotient from the MacArthur Bates Communicative Development Inventories  (Mac_LQ)To examine the impact of co-occurring conditions , 2 groups were created for analysis using parent-reported impact of co-occurring conditions on speech/language development. The first group was composed of children with no additional co-occurring conditions or who have a condition that parents reported as having no impact on speech/language development. The second group was composed of children with additional conditions that parents reported had a mild-to-significant impact on speech/language development.The transition regression model  was usedAs a follow up to the previous analyses, we applied hierarchical regression to determine if the age of intervention and the age of amplification could contribute significantly to the variation in developmental outcomes when children’s age of hearing diagnosis and other covariates were considered. Hierarchical regression is commonly used to evaluate the contributions of a variable above and beyond previously entered variables . The ord3.The subscale means and SDs are shown in f2 ≥ 0.02) [p values were less than or close to 0.05 after controlling for the other covariates. This model also demonstrates that the developmental quotient at Phase 1 was highly correlated with the same quotient at Phase 2 (p < 0.001) for most developmental quotients. After controlling for the developmental score at Phase 1, as well as the other covariates in the analysis model, hearing loss identification by 3 months of age was still significantly related to better outcomes at Phase 2. There were no interactions between identification by the age of 3 months and any of the other covariates, indicating identification of hearing loss by the age of 3 months was independently related to outcomes measured.As seen in  ≥ 0.02)  for assoThe identification of hearing loss must come before intervention for hearing loss can be initiated. Utilizing a hierarchical regression method, neither the age of intervention nor the age of amplification had a significant relationship with developmental quotients at Phase 2 when the identification of hearing loss by age 3 months and covariates were controlled (entered in the model first). The following analyses focused only on the models using hearing loss identified by age 3 months.Of additional interest is that laterality of hearing loss  did not have a separate relationship with these developmental quotients. However, having a moderately severe-to-profound bilateral hearing loss was associated with lower developmental quotients for the four outcomes shown on Predictive mean values at Phase 2 were computed to visualize the longitudinal trajectory when hearing loss was identified before or after 3 months using the four developmental quotients in 4.Analyses reported here consistently demonstrate that hearing loss identified by 3 months of age is associated with better developmental outcomes, at least up to an average of 32 months of age, as measured by the MacArthur vocabulary quotient (Mac_LQ) and three subscales of the CDI  shown in Children with additional disabilities and also those with moderately severe-to-profound bilateral hearing loss, predictably had more significant developmental delays than those who had lesser degrees of hearing loss independent of age of identification of hearing loss . There wAlmost all children were enrolled in intervention at some point in the study, since this was initially one of the criteria for study participation. The hierarchical regression indicated that the general age of enrollment in intervention services  did not have a significant unique contribution to the longitudinal language outcomes in this cohort when the age of early hearing loss identification was controlled. This finding may relate to the heterogeneity of interventions that participants received, which were not exclusive to language. For example, fewer than half of the children in this cohort received speech-language pathology services at either Phase 1 (45%) or Phase 2 (49%). The timing of audiological and speech and language intervention ,23, fittp < 0.05) associations with the CDI language quotient (Rec_LQ), CDI social skills quotient (Soc_Q), and CDI general development quotient (Gen_Q) but not for the MacArthur vocabulary quotient (Mac_LQ) . Further research is needed with culturally and linguistically diverse groups to examine associations between early identification of hearing loss and language outcomes.


Diabetic retinopathy (DR) is a microvascular lesion that occurs as a complication of diabetes mellitus. Many studies reveal that retinal neurodegeneration occurs early in its pathogenesis, and abnormal retinal function can occur in patients without any signs of microvascular abnormalities. The gut microbiota is a large, diverse colony of microorganisms that colonize the human intestine. Studies indicated that the gut microbiota is involved in the pathophysiological processes of DR and plays an important role in its development. On the one hand, numerous studies demonstrated the involvement of gut microbiota in retinal neurodegeneration. On the other hand, alterations in gut bacteria in RD patients can cause or exacerbate DR. The present review aims to underline the critical relationship between gut microbiota and DR. After a brief overview of the composition, function, and essential role of the gut microbiota in ocular health, and the review explores the concept of the gut-retina axis and the conditions of the gut-retina axis crosstalk. Because gut dysbiosis has been associated with DR, the review intends to determine changes in the gut microbiome in DR, the hypothesized mechanisms linking to the gut-retina axis, and its predictive potential. AccorDR has been considered a microvascular complication, a known complication of DM –9. Studiin vivo, disrupt the function of the intestinal epithelial barrier, and cause metabolic disorders  . Followiisorders , 31. Dysisorders .Moreover, dysbiosis of the gut microbiota can result in various gastrointestinal diseases and processes in distal tissues other than the intestine, such as joints, mucous membranes, and the eyes, which are common sites of invasion –35.In adSince Rowan  et al. iOn the one hand, an increasing number of studies have demonstrated that gut microbiota plays a role in retinal neurodegeneration , 43, in The present review aims to highlight the importance of gut microbiota in DR. The critical role of gut dysbiosis in the development and progression of DR is discussed briefly. Subsequently, the concept of the gut-retina axis and the mediators and conditions that allow gut-retina crosstalk will be investigated, focusing on the mechanisms involved in regulating DR by the intestinal microbiota. Finally, diet and antibiotics strategies for treating DR via the regulated intestinal microbiota and, thus, the treatment of DR will be described.22.1Firmicutes and Bacteroidetes, which account for more than 90% of the entire community, and other subdominant phyla such as Proteobacteria, Aspergillus, Actinomycetes, and Clostridium Firmicutestridium , and uvestridium . In addistridium . In humaividuals , 46.2.2Firmicutes and Bacteroidetes  is a potential diagnostic biomarker for DM  tract and the brain, and numerous studies have confirmed the existence of the brain-gut axis. The “gut-brain axis” refers to the specific linkage between the GI tract and the central nervous system (CNS), which consists of a bidirectional exchange between the two . The preThe possibility of an interconnection between the eye and CNS has long been debated because the retina is an extension of the brain . The retMany features of neurodegenerative processes in the CNS are similar to those observed in the retina, and some CNS neurodegenerative diseases can affect the retina and vice versa . RetinalSubsequent studies have confirmed the existence of the gut-retina axis and demonstrated that dysregulation of the gut microbiota contributes to the development of ocular diseases –97. More4The gut-retina axis is an emerging concept that describes a strong interaction between the gut host-microbiota interface and the retina. Because the retina is immune-privileged, a critical question is how this gut-retina crosstalk can be validated. The retina is a ten-layer complex composed of numerous cells, including glial cells , retinal microvascular endothelial cells (RMECs), retinal pigment epithelium (RPE), and all types of neurons , 103. RPThe interaction between microbes, gut-derived products, and the retina can be explained by the disruption of the BRB, which is common in retinal diseases , 106. ThShort-chain fatty acids (SCFAs) are beneficial microbial metabolites produced only in the gut. Chen et al.  demonstr5The studies described in the preceding sections support a causative role of microbiota in triggering DR, but the specific mechanisms involved remain elusive. Gut dysbiosis has been associated with DM and DR. The gut-retina axis could be a potential target for preventing DR, a well-known complication of DM. A critical question now is how the gut microbiota influences the development and treatment of DR through the gut-retina axis. We reviewed the literature and identified that the hypothesized mechanisms relating to the gut-retina axis include disruption of intestinal barrier function, activation of the stimulator of interferon genes (STING) signaling pathway, production of lipopolysaccharide (LPS), angiotensin-converting enzyme 2 (ACE2) deficiency, and affecting gut microbiota metabolites Figure 15.1Bifidobacterium and other bacteria found in the deep layer and Peptostreptococcus in the intermediate layer, which accounts for more than 99% of intestinal bacteria. These intrinsic intestinal bacteria act as a biological barrier by pre-empting colonization sites, competing for nutrients, producing organic acids and SCFAs to lower intestinal pH, producing bacterins, and inducing a moderate inflammatory response  and systemically . In this5.2In various inflammatory diseases, aberrant regulation of the STING pathway has emerged as a critical pathogenic mechanism . STING i5.3LPS, a gut microbial-derived product composed of lipid A-based glycolipid found on the outer membrane of gram-negative bacteria, is thought to be a pro-inflammatory mediator of insulin resistance. It is challenging to shed from the outer membrane of gram-negative bacteria in healthy populations, but it becomes detached and toxic when bacteria are lysed or damaged . LPS is Lactobacillus, Bacteroides, Faecalibacterium, Akkermansia muciniphila (A. muciniphila), and Roseburia are known to down-regulate the pro-inflammatory cytokines in the intestine. Bacteroides and A. muciniphila improve intestinal barrier function. Bacteroides reduce intestinal permeability, decrease LPS production, and improve endotoxemia by up-regulating the colonic tight junction gene expression , a potent activator of Takeda-G-protein-receptor-5 (TGR5) in the retinal ganglion cell layer and can act as a neuroprotective agent. IF also improves intestinal vascular barrier function and lowers plasma peptidoglycan levels. Peptidogly can activates TLR2-mediated signaling cascades and exacerbates DR by interfering with the integrity of retinal endothelial cell junctions (Genetic factors have a limited impact on the composition of the host gut microbiota. For example, diets can influence gut microbes in healthy individuals. A high-fat diet is associated with an increased abundance of evotella . The dieevotella . Beli etevotella  reportedunctions . In concunctions .7The gut-retina axis concept was developed in response to the dysregulation of gut microbiota observed in patients with retinal diseases such as AMD, DR, and glaucoma. Researchers used antibiotics, probiotics, and diet to reshape the gut microbiota, and the results improved eye disease, providing the link between the gut microbiota and the retina. Subsequent studies revealed further crosstalk between the eye and the gut.The specificity of the abundance and function of microorganisms and their metabolites in retinal diseases is slowly being elucidated. Scientists have made several advances in the enumeration, characterization, and classification of the human microbiota since the advent of high-throughput sequencing and culture group technologies . The mosThe link between microbiota and DR is now well established, and identifying pathogenic or protective microbes is an important step to follow in future. In conclusion, the concept of a gut-retina axis driven by various pathways is being actively investigated, and available data in animals and humans suggest possible therapeutic applications for disease through targeted manipulation of the microbiome.HZ reviewed the literature and drafted this review. YM reviewed the literature, gave critical comments, and revised the manuscript. All authors contributed to the article and approved the submitted version.


This study aimed to investigate the relationship among changes in corneal topography, retinal vascular density, and retinal thickness in myopic children who underwent orthokeratology for 3 months.p < 0.05.Thirty children with myopia wore orthokeratology lenses for 3 months. Using optical coherence tomography angiography (OCTA), the retina was imaged as 6 × 6 mm en-face images at baseline and 3 months after orthokeratology. Cornea data was acquired by topography and analyzed by customer MATLAB software. The cornea was divided into 3 zones and 9 sectors. The relative corneal refractive power shift (RCRPS) was used in this study. Changes in retinal vascular density (RVDC) and retinal thickness change (RTC) were associated with RCRPS by using spearman test. Statistical significance was set at p value <0.05). Significant positive correlations were found between RVDC in inner and outer temple regions with RCRPS at inner and outer nasal sectors. There were no significant correlations between RTC and RCRPS in other sectors except in the central cornea and the outer nasal retina . At baseline and 3 months after wearing the orthokeratology lens, no significant differences in the retinal microvasculature or thickness (p > 0.05) were observed at any regions.A significant correlation was observed between the RVDC and the RCRPS in many regions (the r was 0.375 ~ 0.548, all The correlation between the cornea and the retina was observed after orthokeratology. Cornea changes may affect regional retinal responses accordingly，which may explain how orthokeratology delays myopia progression partially. The prevalence of myopia has increased rapidly, particularly in Asia . StudiesIn addition, orthokeratology affects the retina and choroid , which wIn subjects wearing OK lenses, corneal changes after wearing lens were the optical factor of retinal defocus. A more specific and direct way is the relative corneal refractive power (RCRP), which was described by Wang et al. . In theiA total of 30 children with myopia, aged 8–14 years, with corrected distance visual acuity (VA) better than 20/20, no cycloplegic subjective refraction and a spherical equivalent refractive error between −5.00 diopters (D) ~ −0.75 D in either eye, rule of astigmatism no greater than 1.50 D, anisometropia no greater than 1.50 D, and no previous experience of using contact lenses were included in this study. Prescreening ocular examinations, including anterior segment bio-microscopy, non-cycloplegic and subjective refraction, and retinal vasculature and thickness were conducted on all participants using OCTA . None of the participants had any other ophthalmic or systemic diseases. Only data from the right eye were analyzed. Age, sex, and spherical equivalent (SE) were recorded at baseline. The participants were instructed to return for study visits 1 day, 1 week, 1 month, and 3 months after wearing orthokeratology lenses. Ocular health, visual acuity, and corneal topography were re-assessed during these visits. The OCTA was operated only at baseline and 3 months after lens wearing, the other parameters of these two time points were used for statistical analysis accordingly.Using the Lenstar LS900 , the axial length (AL) and biometric data, such as anterior chamber depth (ACD) and lens thickness (LT), were measured simultaneously at baseline and 3 months after wearing orthokeratology lens. Data analysis was performed on the first five readings with signal-to-noise ratios greater than 3 and intrasession differences of no greater than 0.02 mm.Each participant and their parents were informed of all possible risks and written informed consent was obtained before commencing the study. The Institutional Human Research Ethics Committee of Artificial Eye Hospital, Wenzhou Medical University approved this study, and the study was conducted in accordance with the tenets of the Declaration of Helsinki. The study’s registration number on the Chinese Clinical Trial Registry web is ChiCTR1800019893.In accordance with the manufacturer’s guidelines, all participants were fitted with orthokeratology lenses . The material used for lens fabrication was Boston XO (Dk ISO/Fat 141). The lenses were worn overnight. The total lens diameter (s), was approximately 10.5–10.9 mm with a 6 mm optic zone diameter. The lens was designed as 4-zoned. The clinical optometrist chose the spherical or tori lens based on the corneal parameters and the manufacturer’s fitting guidelines. Orthokeratology lens that fit well had a typical bullseye fluorescein pattern, with the lens movement between 1.0 mm and 1.5 mm. The OK lens was centered on the cornea. The corneal topography after treatment was not more than 1 mm decentration.The Medmont E300  with the software of Medmont Studio 6 was used in this study. Each eye was imaged four times at each visit, and a score of >95% was recorded for statistical analysis. The axial corneal refractive power was automatically measured with chord lengths of approximately 11 mm. The corneal topography raw data within a radius of 5.5 mm including 32 rings were exported directly from the instrument, and then imported into the customized MATLAB software. The corneal axial keratometry raw data were used to reconstruct the cornea topography map, which was divided into 3 zones and 9 sectors. The radius of center zone was up to 1.67 mm including 10 rings, the inner zone was from the 1.67–3.3 mm apart from the apex including 11–20 rings, and the outer zone was from the 3.3–5.5 mm including 21–32 rings. Both of the inner and outer zones were divided into four sectors include superior, inferior, nasal and temple sectors. The sectors were named as center (C), inner inferior (II), inner superior (IS), inner temple (IT), inner nasal (IN), outer inferior (OI), outer superior (OS), outer temple (OT), outer nasal (ON). The detail of the corneal sectors is shown in the Optical coherence tomography angiography scans were performed using an AngioVue XR Avanti device  in the angio-retina scan mode (6 × 6 mm) centered on the fovea. With a wavelength of 840 nm, the device can perform 70,000 A-scans per second using a super luminescent diode. By split-spectrum amplitude correlation angiography (SSADA), vascular information is optimized for the algorithm. The OCTA images define vascular density as the percentage of the image occupied by vascular tissue. Using the OCTA instrument, the superficial macular vascular density is automatically calculated. The detailed operation of OCTA had been described in many reports . Specifip of 0.05 was used to denote statistically significant results.Statistical analysis was performed using the statistical package for the social science (SPSS) software . All variables underwent normality testing by Schapiro Wilk test. All results are expressed as the mean and standard deviation (SD). During preoperative and postoperative periods, the central refraction, corneal refractive power, and retinal density were compared using the paired t-tests for normally distributed data, and Mann–Whitney U tests were used for nonnormally distributed data. The relationships between the changes in corneal topography, retinal vasculature, and retinal thickness were analyzed by Spearman correlation analysis. A critical value of p < 0.05), whereas the LT(3.38 ± 0.15 vs. 3.43 ± 0.18 mm) and WTW (12.05 ± 0.39 vs. 12.05 ± 0.38 mm) increased (p < 0.05). The AL showed a non-statistically significant increasing tendency . During the follow-up period, the corrected visual acuity gradually improved and stabilized at a naked eye visual acuity of 20/20 or higher after wearing lenses for 10 days to 1 month. Ocular health was checked at each follow-up visit, and there were no serious health events during the entire follow-up process.In total, 14 boys and 16 girls  who underwent orthokeratology were enrolled in this study. All the children completed the 3-month follow-up. The spherical equivalent (SE) at baseline was −2.69 ± 0.96 D. Ocular parameters such as axial length (AL), anterior chamber depth (ACD), lens thickness (LT), corneal diameter of white to white (WTW), and anterior corneal Keratometry in the steepest and flattest meridians  were calculated using Lenstar . After 3p > 0.05). The total retinal layer thickness (RTC) showed central foveal macular thicknesses of 248.62 ± 13.73 at baseline and 249.17 ± 14.05 at 3 months after wearing orthokeratology lenses (p > 0.05). There was no significant change in microvascular density or retinal thickness after 3 months of wearing orthokeratology lens compared to that observed preoperatively .The superficial retinal layer showed a central foveal macular vascular density (RVD)of 21.34 ± 6.39 at baseline and 20.21 ± 6.04 at 3 months after wearing an orthokeratology lens (p < 0.05). While in the outer zone, the corneal power decreased only in the ON sector (p < 0.05). The remaining sectors had no significant change both in the inner and outer zones of the cornea . The comparing corneal data at baseline, and 3 months after lens wearing, are shown in The corneal axial refractive powers at different sectors in baseline were the steepest in the central cornea (43.35 ± 1.39D), and flattest in the outer inferior sector (40.56 ± 1.43D). After 3 months of lens wearing, the steepest data was 42.87 ± 1.35D in inner temple sector, and the flattest data was 40.66 ± 1.38D in the outer inferior sector. Comparing the cornea refractive power change, the corneal power significant decreased in the central cornea, and the inner zone including IN, IS, and IT after 3-month of lens wearing , shown in r 0.375 ~ 0.548, all p value <0.05). At the temple retina, both the inner and outer zones, had positive correlations with more than five sectors of RCRPS. The correlation between RVDC in the temple retina and RCRPS was found to be significant for the nasal corneal region, but not for the temple cornea region, which was an interesting phenomenon.After 3 months, there was no significant correlation between the RCRPS and retina thickness changes at any zones except in the central cornea (C) and the outer nasal retina (ON)  and RVDC . The relationships of the RCRPS and RVDC existed in the temple retina. The RCRPS in the central cornea had positive correlation with regional RTC only in the outer nasal region. Based on this phenomenon, RCRPS caused by orthokeratology had varied regional effect on the retina.Orthokeratology is a safe and effective method of correcting low-to-moderate myopia by flattening the central cornea overnight with special design reverse geometry rigid gas permeable lenses , 33. In In this study, the RCRPS were all positive at all sectors, which mean that relative to the central area of the cornea, the diopter is larger, and its ability to converge light is stronger, that is, the relative myopic defocus state in cornea.The RCRPS was reported by Wang et al. to describe the change of corneal power. In their reports, myopic control appears to be related to a larger RCRP modulation, specific 4.5D .The RCRPOrthokeratology affects the cornea and the retina. Increasing research concerning fundus changes after orthokeratology exist; however, few studies have described retinal thickening or microvascular changes as a response to orthokeratology lens use. In this study, microvascular density decreased, whereas retinal thickness increased mildly; however, they were not statistically significant. The possible reasons for the non-significant changes in retinal thickness and vascular density before and after wearing OK lens in this study are speculated to be the relatively short follow-up period of only 3 months. A longer follow-up time may be required in future studies to investigate this further. Another possible reason is that the degree of myopia correction in our study was mild to moderate, which may result in weaker changes.Recent studies have shown that the retina plays a crucial role in the development and progression of myopia. The retina is a complex and highly specialized neural tissue that contains several distinct layers of cells, including photoreceptors, bipolar cells, ganglion cells, and glial cells, which work together to convert light signals into electrical impulses that are transmitted to visual centers. The retina is also supplied with a rich vessel network that provide nutrients and oxygen. The fundus response is thought to be a part of the retina-choroid-sclera signaling pathway, which is one of the various theories proposed to explain myopia control interventions. Several neurochemicals and receptors have been implicated in the cascade of reactions within the retina, some of which are related to refractive error . New indThe retina operates independently and selectively regionally, which implies that different regions of the retina may have different levels of control over myopia. The regional difference of retinal morphology in the human eye has been described in previous studies. Several studies have shown that myopic atrophy is more likely to occur in the superior and temporal regions of the retina, which are also regions that exhibit significant regional variability in thickness and vascular density distribution.These regional differences in the thickness and vascular density distribution of the retina may have important implications for the development of myopia. Specifically, in animal experiments, the choroid and retina of myopic animals have been found to become thinner during the myopia induction process , 40. ResPeripheral retinal defocus is believed to play a key role in myopia control . Myopia A study by Wallman et al. suggested that local defocus may control the local eye growth and progression of myopia, based on the assumption that the peripheral retina defocuses asymmetrically . A studyDespite the lack of statistical difference in the absolute data of RVD and RT, there was a positive and mild to medium correlation between RCRPS and RVDC in this study. As we know, orthokeratology lenses can cause significant changes in corneal topography and refractive power zones, which can lead to retinal myopia defocus. Retinal myopia defocus was thought to be the mechanisms by which orthokeratology controls myopia. In this study, the changes of retinal vascular density in many regions had significant correlation with the relative defocus of corneal change. Anatomical differences between the nasal and temporal sides of the retina may account for this change.The correlation in retinal vascular density in the temporal and superior regions and the multi-position RCRPS suggest that the changes in the retina in response to corneal changes vary regionally. Myopia arc, posterior staphyloma, and choroidal atrophy are prone to occur in the temporal region. Therefore, such correlations may imply that under the induction of optical signals, the vascular density on the temporal side of the retina might change correspondingly, which may delay the occurrence of choroidal atrophy and reduce or delay the occurrence of myopia arc.In our study, there was a significant association between the outer superior and temple retinal vascular and nasal topographic changes. This localized association may be due to the photoelectric or photochemical reaction of the retina caused by the direction of light. The electrophysiological responses at the retinal center and periphery may alter myopia progression . Active According to this study, the correlation was in the inner temple and outer temple retina superior retina, as myopia atrophy often occurs in the temple retina and inferior retina around the optic disc. Myopia may have an atrophic arc on the temporal side of the optic disc, which corresponds to the nasal side of the macula anatomically. Therefore, in this study, the refraction of light from the cornea showed no such correspondence, or the correspondence exists but the response of retina vascular density was focus on the temple regions. If the position and amount of the RCRPS correspond to the retinal changes in the corresponding region, the position and amount must be confirmed, which needs further research.This study has several limitations. First, follow-up period was short. A longer follow-up period should be used in future studies. Second, the sample size was relatively small. Future studies with lager sample sizes are warranted.As an explorative study to assess RCRPS in relation to RVDC and RTC, the results showed that RCRPS correlated with the RVDC mostly in the inner temple region after a short time of OK lens wearing. OK lens causes changes in the cornea regionally, which directly leads to regional changes in the corneal topographic map. The changes of the cornea lead to corresponding defocusing at the retinal level, which may also lead to regional changes in the fundus. The regional changes in retinal vascular density may be related to retinal signal transduction. Such a chain reaction may be a mechanism for myopia control.The original contributions presented in the study are included in the article/The studies involving human participants were reviewed and approved by Institutional Human Research Ethics Committee of Artificial Eye Hospital, WenZhou Medical University. Written informed consent to participate in this study was provided by the participants' legal guardian/next of kin.QL, RC, AX, LM, and WZ collected and analyzed the data. YL, WL, and WJ designed and supervised the study. YL analyzed the data and wrote the manuscript. All authors contributed to the article and approved the submitted version.This study was supported by the Science and Technology Project of Wenzhou .The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article, or claim that may be made by its manufacturer, is not guaranteed or endorsed by the publisher.