Children with permanent unilateral hearing loss (UHL) are an understudied population, with limited data to inform the guidelines on clinical management. There is a funding gap in healthcare provision for the children with UHL in the United Kingdom, where genetic screening, support services, and devices are not consistently provided or fully funded in all areas. They are a disparate population with regard to aetiology and their degree of hearing loss, and hence their device choice and use. Despite having one “good ear”, some children with UHL can have similar outcomes, socially, behaviourally, and academically, to children with bilateral hearing loss, highlighting the importance of understanding this population. In this longitudinal cohort study, we aimed to characterise the management of the children with UHL and the gaps in the support services that are provided for the children in Nottingham, United Kingdom.A cohort study was conducted collecting longitudinal data over 17 years (2002–2019) for 63 children with permanent congenital confirmed UHL in a large tertiary regional referral centre for hearing loss in Nottingham, United Kingdom. The cases of UHL include permanent congenital, conductive, mixed, or sensorineural hearing loss, and the degree of hearing loss ranges from mild to profound. The data were taken from their diagnostic auditory brainstem responses and their two most recent hearing assessments. Descriptors were recorded of the devices trialled and used and the diagnoses including aetiology of UHL, age of first fit, degree of hearing loss, when and which type of device was used, why a device was not used, the support services provided, concerns raised, and who raised them.Most children  trialled a device, and the remaining 18 children had no device trial on record. Most children  trialled a bone-conduction device, followed by contralateral routing of signal aid  and conventional hearing aids . Most children  who had a device indicated that they wore their device “all day” or every day in school. Few children  reported that they wore their device rarely, and the reasons for this included bullying (3/8), feedback from the device (2/8), and discomfort from the device (2/8). Only one child reported that the device was not helping with their hearing. The age that the children were first fitted with their hearing device varied a median of 2.5 years for hearing aids and bone-conduction devices and 7 years for a contralateral routing of signal aid. The length of time that the children had the device also varied widely ; the children had their bone-conduction hearing aid for the longest period of time (median of 32.5 months). There was a significant trend where more recent device fittings were happening for children at a younger age. Fifty-one children were referred by the paediatric audiologist to a support service, 72.5% (37/51) were subsequently followed up by the referred service with no issue, whilst the remaining 27.5% (14/51) encountered an issue leading to an unsuccessful provision of support. Overall, most children  had no reported concerns, and 28.5% (18/63) of the children went on to have a documented concern at some point during their audiological care: five with hearing aid difficulties, five with speech issues, four with no improvement in hearing, three facing self-image or bullying issues, and one case of a child struggling to interact socially with friends. Three of these children had not trialled a device. We documented every concern reported from the parents, clinicians, teachers of the deaf, and from the children themselves. Where concerns were raised, more than half  were by schools and teachers, the remaining four concerns were raised by the family, and further four concerns were raised by the children themselves.To discover what management will most benefit which children with permanent UHL, we first must characterise their treatment, their concerns, and the support services available for them. Despite the children with UHL being a highly disparate population—in terms of their aetiology, their device use, the degree of hearing loss, and the age at which they trial a device—the majority report they use their device mostly in school. In lieu of available data and in consideration of the devices that are available to them, it could be useful to support families and clinicians in understanding the devices which are most used and where they are used. Considering the reasons for cessation of regular device use counselling and support services would be vital to support the children with UHL. Within the United Kingdom , there is a current lack of national management guidelines for clinicians looking after children with unilateral hearing loss (UHL), and treatment is widely debated –3. NumerUptake of devices for UHL can be variable with as few as 31% of children 9–18 years) with UHL using a hearing device . Low dev–18 yearsIn 50% of the cases, the aetiology of UHL is unknown . There aThe listening difficulties that the children with UHL experience can mainly be explained by their loss of bilateral input. The range of loss of input can range from a child having no available hearing in their affected ear, often called SSD (weak or absent nerve for example), to very mild losses where they have some, albeit asymmetrical bilateral input. Their degree of hearing loss and aetiology will impact their device choice. The choice for a child to use a device and their device choice are also likely to be indicative of having an ear that works well and the ability of the child to use that monaural input to good effect. It can also reflect their listening environment, for example, if their device helps them in background noise or whether they are predominately in a quiet home and are able to position themselves for optimal listening. Counselling by a multidisciplinary team is advocated to avoid treatment bias for children with conductive UHL , and thiIn a small study of children with Trisomy 13 and conductive UHL (mostly moderate hearing loss), the conservative approach of watchful waiting was often adopted, and when hearing aids were implemented, they were on the whole successful .Where there is a lack of auditory input, this will impede binaural summation of loudness, the head shadow effect, and binaural release from masking which affects their ability to decode speech in noise and localise sound in space –19. In aThe morbidity of UHL can be similar to bilateral hearing loss (BHL), and there is a wealth of evidence that UHL can affect preverbal vocalisation, speech and language development, and cognition , 21–25. There are a number of hearing devices that will not restore bilateral input but can be used to help the children with UHL—contralateral routing of signal (CROS) aids and bone-conduction devices help alleviate the head shadow effect as they re-route the sound via air or bone-conduction, respectively. BCDs and CROS-aids are commonly used for severe losses, fluctuating hearing loss, profound conductive losses or where the auditory nerve is absent or weak, whereas mild to moderate losses are often treated with conventional hearing aids.The data from adult studies often imply that BCDs are better than CROS-aids but both devices impair speech perception when the noise emanates from the impaired ear side. Also, it has been shown that a BCD does not improve sound localisation abilities , but it A study assessing orienting head-movement responses in people with SSD investigated whether a BCD would jeopardise their directional hearing based on monaural spectral and/or level cues. They found that 5 out of 19 participants could localise certain sounds (broad-band and high-pass but not low-pass filtered noises) in the horizontal plane in the unaided condition and that a BCD did not deteriorate their localisation abilities .The outcomes for the children with UHL can be as disparate as the aetiology and their type of hearing loss. For example, evidence of the impact of unilateral conductive hearing loss in children can be varied and sometimes mild, and there is limited evidence to indicate that hearing devices benefit every child in relation to their speech and language development. Aetiology is important since listeners with conductive UHL can activate the auditory pathways of their impaired ear through their own voice, and through bone and tissue conduction . If the It was postulated that some listeners with congenital conductive UHL have adapted to their UHL and learned to rely on the spectral shape cues and monaural head shadow effect cues . In summCollation and comparison of data sets for paediatric UHL studies in the current literature can be difficult; a systematic review and consensus paper noted no firm evidence for the efficacy of current available devices nor evidence to inform decisions as to which devices are most suitable , 37. TheSeveral adult studies have demonstrated the long-term implications of uncorrected hearing loss; with an increased likelihood of experiencing social isolation and emotional distress as well as an increased risk of developing dementia in later life –41. WhilFuture research may highlight the importance of early detection and appropriate treatment for some children with UHL.To promote consistent and effective care for the children with UHL, it is important to both identify the current standard of care and support provided, as well as characterise the affected cohort of patients. It is also important to identify gaps in the funding and support for the children with UHL.Moreover, an understanding of the respective thoughts of patients, parents, and clinicians on the care provided is essential to ensure a unified approach to UHL management.In this current longitudinal cohort study, we describe all aspects, we can reliably ascertain from their data over 17 years in a large tertiary centre, on the management of children with confirmed permanent UHL. Consequently, there is a potential for further research into the future development of evidence-based management guidelines and promoting informed treatment decisions for clinicians, parents, and children.1.demography and aetiology of UHL in children in a tertiary referral centre.Establish a database from the advent of NHSP (2002) to document the 2.management of UHL—e.g., type of device trialled, the age of the child when they first trial a device, when and how long they use their current device, and why they do not use their device.Characterise 3.support services for the children with UHL and the documentation of any concern related to the impact of their hearing loss.Additional The objectives of this study are the following:The routinely recorded and collected data in this study formed part of a service evaluation 2002–2019 at Nottingham University Hospitals. The data was also used from the Nottingham research database (NEAT) under ethical approval to analyse routinely collected data (REC project ID: 292263), South Central Berkshire Research Ethics Committee.The criteria for inclusion included the patient referred on the NHSP and having a diagnosis of permanent UHL (hearing loss in one ear lasting for greater than 6 months). Children who did not speak English as a first language were also included.The criteria for exclusion included children with acquired, fluctuating, or bilateral hearing losses as well as any child who did not have their new-born hearing screening (NHS) conducted in Nottingham.Of the 89 cases identified as having UHL from the new-born hearing screening or referred from the UHL clinic, 26 (29.2%) cases were excluded as they were acquired or progressive, leaving a total of 63 cases of permanent congenital confirmed UHL. Of the 26 excluded, 13 cases were excluded for the reason that the hearing loss was progressive and developed to a bilateral hearing loss, 11 were acquired UHL, 1 case was both acquired and bilateral, and 1 case was excluded as the child did not have their new-born hearing screening in Nottingham.The cases of UHL include permanent congenital, conductive, mixed, or sensorineural hearing loss, and the degree of hearing loss range from mild to profound. The aetiology and severity of hearing loss could be identified in many cases, but we could not reliably determine the number of cases with conductive UHL since the tympanometry data were viewed to be not of high enough quality. The guidelines of the British Society of Audiology (BSA) were used to classify the severity of UHL in the poorer hearing ear . Hearing loss in each ear was recorded and averaged over four frequencies . Occasionally, only the hearing level at two frequencies was recorded (most often 1 and 4 kHz) usually due to the attention or ability of the child to remain engaged in the testing (depending on their age or degree of development). Hearing loss in the affected ear was classified as Mild: between 20 and 40 dBHL; Moderate: 41–70 dBHL; Severe: 71–95 dBHL; or Profound: over 95 dBHL.The data were entered into an Excel spreadsheet from 89 patient paper notes (2002–2019) and electronic hospital databases  in a regional referral centre, Children's Audiology at Ropewalk House in Nottingham. The patient demographics included date of birth, sex, age at diagnosis of hearing loss, formal diagnosis of hearing loss, aetiology of UHL, and birth history. The results from the NHSP hearing test of the child and their diagnostic auditory brainstem response (ABR) as well as the two most recent hearing test results were recorded for frequencies 0.25, 0.5, 1, 2, 4, and 8 kHz, if present. When the data permitted, this was recorded for both ears. The age of the child at the hearing tests was recorded as was the method of testing—pure tone audiometry (PTA), visual reinforcement audiometry (VRA), and play audiometry. If the child had a hearing device, the device type, ear fitted, make and model, and date of first fit were recorded. For the patients who stopped using a device, the reasons for this were documented, and for those who had no device, the reasons why no trial was undertaken were noted. For device use, we catalogued when the device was worn and for how long, for example, none of the time, some of the time, at school, at home, or all the time, alongside any relevant quantification if present. The data-logging information from the hearing devices was not available. The support service data was also documented and included the teachers of the deaf (ToD), speech and language therapy (SLT), missed appointments, and comments made by the relevant parties relating to the management of the child and their respective outcomes.We documented every concern reported from parents, clinicians, ToD, or the children themselves. Where data were of poor quality, verbatim quotes were lifted from patient notes.The cases of UHL may have been missed if the NHSP of the child took place out of the area, or if the child was not referred for diagnostic follow-up following a UHL found on the new-born hearing screening. The data were not available if the parents did not engage with audiology services after the initial appointment and diagnosis of UHL for their child.current severity of hearing loss remained unknown and these cases are documented as severe-profound*. These are listed separately in The onset of hearing loss was categorised as congenital or acquired. Those with an acquired hearing loss were defined as developing hearing loss after having passed their new-born hearing screening. Congenital hearing loss was defined as children who were referred on the NHS as a neonate and then went on to have a confirmed permanent hearing loss by ABR and then later VRA or play audiometry . The average of the hearing loss of the child  was recorded for both ears, and the data were used from the most recent hearing test (most often PTA). Where this information was not available, then the data from the second latest hearing test were used. In a number of cases, the most recent hearing tests only documented the data from the better-hearing ear , in which cases the r) were performed using SPSS version 28.0. The GraphPad Prism version 8.0 was used to graph the data.The software used included Microsoft Excel (Internet) version 2302 to record the data. The Kruskal–Wallis (K–W) non-parametric ANOVA for multiple comparisons and Pearson correlation  were male and 49.2% (31/63) female. Birth complications were recorded in 34.9% (22/63) of the cases where the most common were C-sections  and NICU involvement 31.8% (7/22). The aetiology of the hearing loss and the number of birth complications reported are shown in Of the total 89 cases of children with hearing loss identified between February 2002 and March 2019 analysed in this study, 77 children had permanent congenital hearing loss, 12 had an acquired hearing loss, and 63 children were identified with permanent congenital UHL.The known aetiologies for UHL in the children were documented in 50.7% (32/63) of the cases. The aetiologies were broadly classed into categories and described in the notes as follows: craniofacial—structural malformation 56.3% (18/32) including atresia, microtia, and poor development of labyrinthine structures; malformation or absence of auditory nerve 21.9% (7/32); post-infection 12.5% (4/32); and genetic 9.38% (4/32).The genetic testing revealed four pathogenic variants, and two had variants of unknown significance. The genetics data have previously been cited in a recent study .With regard to the hearing severity of the poorer ear of the child, 1.6% 1/63) was mild, 31.7% (20/63) moderate, 15.9% (10/63) severe, and 15.9% (10/63) profound. In the remaining 34.9% (22/63), the degree of severity of their hearing loss was not documented in their most recent two hearing tests. In these 22 cases, the poorer ear remained untested for a prolonged period, sometimes since the diagnostic ABR as in the majority of the cases, it was recognised that the ear was effectively “dead” due to a number of reasons. We do not have the current degree of hearing loss recorded for this group, so we have labelled this group separately in  was mildn = 1) or moderate (n = 4) loss in their poorer ear but who never trialled a device. Only the children who owned and reported that they wore a hearing aid (HA) had a moderate degree of hearing loss (n = 9); however, there were children with moderate losses who also used a BCD (n = 5) or a CROS-aid (n = 2) (n = 11), and eight children used a CROS-aid  or were in the severe-profound category of hearing loss . Most of those not trialling a device had severe hearing losses 44.4% (8/18) . There w (n = 2) . Of the CROS-aid .Forty-five children  with UHL trialled a device with the remaining 18  children having had no device trial . Twenty n = 41). The ages of the child when they are first fit with their first device are plotted individually in K = 8.4; P = 0.015). The medians and minimum–maximum ranges (in months) for age of first fit within device types were the following: HA , BCD , and CROS-aid .The range of ages at first device fit was wide with a mean age of 56 months or 4.7 years . Across device types, the length of time a device is used is widely varying  (The children kept their BCDs for longer periods of time (median 32.5 months), but this was not statistically significantly longer than for HAs (median 24 months) or length of time they kept their CROS-aids (median 22 months)  —useful tThere were eight children who have had device trials and currently wear their device but only infrequently. For the three children, it was documented that infrequent wearing was because they experienced bullying wearing their hearing devices (and/or appearance of their ear), two children experienced feedback from their device, two found them uncomfortable to wear , and one found their HA not helpful with their hearing.n = 5), two have auditory neuropathy spectrum disorder (ANSD), three have sensorineural hearing loss, one had CMV, and one had a skull fracture as an infant. In the six cases, the aetiology was unknown or not documented.In terms of their aetiology, the majority who have not trialled a device in this group have external or inner ear abnormalities  of the cases, the parent decided for the child not to trial a device, and it was an ENT clinician-led decision (mild UHL) in one case . A further two cases were joint clinician and parent-led decisions, and six cases had no documented reason. However, despite there being no documented reason for “no trial of a device,” it was reported in three cases of the child doing well, having a good understanding of speech and no developmental concerns. One child was lost to follow-up.The percentage of children who had a documented referral to a support service was 81.6% (51/63); the remainder had no documented support referral.Of the 51 children who were referred, 72.5% (37/51) received their intended support with no issue, whilst the remaining 27.5% (14/51) encountered an issue leading to an unsuccessful provision of support. The documented obstructions to this support were 86% (12/14) due to the child not meeting referral criteria and 14% (2/14) due to parental refusal of support. Overall, 93 support referrals were made: 74% (69/93) for a teacher of the deaf and 20.4% (19/93) for speech and language therapy. A further 5.38% (5/93) to “other” services. Within these 51 children with referrals, most, 37/51 (72.5%), had combined referrals to several support services and 14/51 (27.5%) had a single referral to a specific service.A total of 65% (41/63) of the children with UHL had no reported concerns, and 28.5% (18/63) of the children had a documented concern: 5 children reported difficulties with their hearing devices, 5 had problems with their speech, 4 had no improvement in their hearing, 3 faced self-image or bullying issues, and 1 case of a child struggling to interact socially with friends. In three cases, the reason for the concern was not documented.Where a concern was raised during audiological care, the hearing level severity included 0% (0/18) mild, 17% (3/18) moderate, 17% (3/18) severe, 17% (3/18) profound, and 50% (9/18) of the cases had an unknown degree of hearing loss—likely to be severe-profound*. Furthermore, in the 18 children where a concern was reported most trialled a device, 8 children had trialled a BCD, 4 an HA, 3 a CROS-aid, and 3 children had no device trial on record. Within these 3 cases with no documented device trial, 2 cases received documented support service input. Only in one case did a child with raised concerns has no device trial and no support.Half, 56% (10/18), of the concerns were raised by schools and teachers, 22% (4/18) of the concerns were raised by the family, and a further 22% (4/18) of the concerns were raised by the children themselves.A number of organisations have established candidacy guidelines for paediatric amplification, but the guidelines for the children with UHL remain more ambiguous, and recommendations vary . CurrentMost children with permanent congenital UHL in our cohort wore a device, most often a BCD or a CROS-aid; they wore it at school or all day indicating that, at least for school age children, a trial of a device should be prioritised. In our cohort, it was the parents who usually made the decision for their child to trial a device. Many children with UHL are at high risk of certain adverse developmental outcomes , 23, thuThe prevalence of hearing loss in one ear is estimated at 0.3–1 per 1,000 births ; our estTo improve the current standard of care, it is first important to identify the cohort of patients affected and to understand the treatment provided. This study provides much needed information about current practice and the reasons behind the interventions and choices made by the care team of the children and their families in this central tertiary regional referral centre over a 17-year period.Similar to previous studies, we found that the aetiology of UHL was documented in half of the cases and over half of these were structure abnormalities related to the ear, 22% had absent or malformed auditory nerve, 12% post-infection, and 9% genetic causes. The aetiology and degree of hearing loss are very important to ascertain as they can impact device choice for the child with UHL. It is established in the literature that congenital anomalies, for example, craniofacial abnormalities and ear malformations, are common in this population , and thePrevious studies have revealed that the percentage of UHL associated with a family history is approximately 3.7%–13% , 50, 51,n = 34 children; 68%) had trialled a hearing device. Fewer, however,  continued to use their device. In a study of 31 children with congenital, acquired, or unknown onset UHL (age range: 1–10 years), it was reported that 81% of the children with moderately severe or better UHL accepted the use of a hearing aid. However, when the UHL was severe or profound, the parents reported very poor or no use of the hearing aid  children with UHL trialled a device, which in some cases is higher than pre-existing literature. In Purcell's study of 50 children, aged 5–19 years, a similar number to our study  and speech discrimination, and an improved hearing in noise, but findings for sound localisation were inconsistent. Similarly, Liu et al. systematically reviewed the role of BCDs and found consistent gain in SRT and speech discrimination, but inconsistent results with sound localisation. The measurement of the quality of life showed a high rate of usage and benefit in the learning domain.The age of the first device trial was disparate and depended on the device type. It also depended on the age of the child where the children who have been seen more recently (younger) were fitted earlier, most likely due to change in management over time. The average age of fitting of a device was around school age (4.7 years); BCD and HA can be fitted earlier and were fitted around preschool age. This age of fit was later in comparison with other studies for children with BHL, for example, Walker et al. reported an average age of fitting at 10.99 months  within a cohort of 211 children identified with BHL . HoweverOne interpretation of the wide range of the ages of first fit in this study indicates that the children with UHL are followed up, and when they have trouble, they have no problem returning to audiology services and requesting a trial even into their teenage years.all the children with UHL, there is some evidence to suggest that wearing a hearing device can improve the quality of life, especially in those suffering with speech and language or academic and behavioural issues. A few studies have shown that early intervention may be crucial particularly for speech reception thresholds and speech discrimination, especially in noisy environments . CROS-aids have a very different role, and evidence for the benefit of the early fitting of CROS-aids for children is not available . CROS-aids do not stimulate the unaided ear and only provide access to the acoustically blind area, so there is no binaural access to sound. It is thought that CIs for severe-profound losses and hearing aids for mild–moderate losses are vital to stimulate the auditory pathway during the crucial periods of neural development for the acquisition of speech and language , 56, 57.With regard to the devices used by the children in this study, nearly half wore BCDs, a third wore CROS-aids, and a fifth wore conventional hearing aids often reflecting the age of the child, aetiology, and type of hearing loss experienced. No children in this cohort had a cochlear implant despite their associated benefits seen in children and adults with severe-profound UHL , 61. ThiMost children who wore a device reported that they wore it all day or at school. A parent-led decision for device trial was most often documented (51%), followed by child-led decision (13%) and clinician-led decision (9%). For the children who did not trial a device, half were documented as a parent-led decision, very few were clinician- or child-led decisions. With regard to “decision to trial a device,” specific decision making and counselling were often poorly documented and unclear. It is likely that the decision to trial a device is complex and child-specific; further investigation would be useful into how we could better understand both parental and child concerns. This may be particularly important in cases where device was not trialled or parents were not engaged with audiological services. Funding is also a point of concern as with limited resources, a CROS-aid or hearing aid is much more economical than a BCD. There are no official recommendations in the United Kingdom for CROS-aids, but there is a practical consideration when fitting them to young children. CROS-aids are best fitted on open fit slim tubes so that the sound to the better ear is not attenuated. Young children do not have the appropriate size of ear canal to enable fitting of open slim tubes, and hearing aid manufacturers do not make domes/slim tubes small enough for the ear canals of children. Furthermore, due to the small removable components , there are choking hazards for small children. If CROS-aids were fit to a small child, an occluding ear mould would be required to aid retention , and the occlusion effect would need to be overcome in the hearing aid programming. For these reasons, CROS-aids are not fit for children under 6 years old in Nottingham, United Kingdom. The children with severe and profound losses are not usually fitted with conventional hearing aids because of interaural attenuation due to the high levels of gain required, resulting in a cross-hearing into the better ear and therefore likely distortion of the sound perceived in the normal hearing ear.Our data illustrate the importance of BCD and CROS-aids and are in contrast to an early study where 27 children with UHL who were fitted with an HA but usually did not wear it, 26% reported wearing it all of the time, 4% reported wearing it only in school, and 50% reported never wearing it .n = 31; 81%) but only for users with moderately severe or better levels of hearing loss, whereas children with severe or profound UHL had poor or no use of hearing aids   . It is d= 0.015) .n = 46, ages 6–12 years) (n = 14) encountered an issue leading to an unsuccessful provision of support. The majority (86%) of documented obstructions to this support were due to the child not meeting referral criteria, defined by local support teams, only two cases were due to parental refusal of support. The criteria for referral are defined by the support service rather than audiologists—this is an area of inconsistency that needs further evaluation.More than half of all children in our cohort had a referral to a support service; this is in keeping with most of the current literature. A previous study indicated that 39% of the children with permanent UHL received speech therapy, 54% had received an individualised education programme (IEP), and 36% had received additional educational assistance (2 years) . In a la2 years) . Three qA fifth of the children with UHL went on to have documented concerns; these included speech and language problems, self-image or bullying issues, hearing aid difficulties, and/or poor social interactions with friends. The majority (40/51) of the children with UHL that had a referral to a support service had trialled a hearing device. Whilst the struggles faced by each child differ, thematic analysis , using aGiven the lack of UK National Health Service and NICE guidelines for the management of paediatric UHL, audiologists often use SLT or a diagnosis of developmental impairment to guide them on their treatment plan, and to suggest to the parents that their child should trial a device. Unfortunately, by the time the child requires SLT, this may be too late, especially when early device trials may impact speech and language acquisition, as has been noted by the LOCHI study . Most deMore than half of the concerns about a child with UHL were raised by teachers, and a fifth were raised by the family, and a further fifth were raised by the children themselves. This is likely due to teachers spending most of the day with the child in an environment wherein auditory cues are paramount, and they may also be highlighting the developmental delay of the child and paucity of support in school. The parents/families/clinicians may also seek their advice from specialist interest groups, social media, and charitable web sources such as the National Deaf Children's Society.The recognition of hearing impairments within schools and the consequent supporting facilities they can provide is also likely to affect the response of the child. Prior to the NHSP, the school hearing screening programme (SHSP) was used throughout the United Kingdom to recognise the children with undiagnosed hearing impairments . School This study has a number of strengths and limitations.It is important to note that for the children and families in this study, although there are no national guidelines for treatment of UHL, there are some guidelines about device candidacy see the . Thus, dA further limitation to this study is potential sampling bias since many children with mild losses can be missed; they may either not be picked up on UNHS or the parent may not follow up with audiological services following diagnosis.Another limitation of the study is that we are not able to make inferences about device benefits since one cannot extrapolate from the reporting of wearing a particular device to the device being beneficial for the child in all environments.A strength of this study is that there are advantages to following the same children over time in a single large centre, and the continuity of care for these children are reflected in consistently documented follow-up notes over a prolonged period. There was a consistency to record keeping, which contrasts to the data that are amalgamated from multiple sites and have different local policies and different record keeping regimens.We do not know why some children with UHL go on to require speech and language services and struggle to develop academically and behaviourally whilst others do not. The fitting of the hearing device, degree of hearing loss, and maternal education are key , but resFuture research into how the brains processing of monaural cues are impacted by late identification of hearing loss or later aiding is needed, as these could impact the outcomes of the children . This isLong-term follow-up into adulthood would be beneficial for this cohort to examine which and when are the best devices to trial for a child and the most favourable support services. It will also be important to understand the reasons the families do not engage with hearing services and to quantify the outcomes of their children. Setting up anti-bullying campaigns within schools could be vital for children with hearing loss as they are particularly vulnerable, and their device use is likely most useful in school. A core-outcome set of what is important for the children with UHL and their families is important to define.It will be important to determine why particular children with UHL struggle in school, and whether instructional training for the parents and teachers improves the likelihood of a positive outcome for the child. This may be particularly important for the parents of the children with UHL who in a recent study underestimated the fatigue of their child .Future research should concern the items that enable the children with UHL to succeed and discover biomarkers that can accurately quantify stress and the quality of life. These factors are likely to be complex, multi-faceted, and relate to their frustration, attention, anxiety, fatigue, peer relations, social confidence, independence in the classroom, and emotional maturity, which are the important variables in educational success for children. Researching these aspects of a child's education could be key to understanding their struggles and thus providing specific support they need to help them succeed.In our study, most children with UHL wore a BCD or a CROS-aid and reported they wore it for the duration of their school day. There was a very wide-ranging age of first device fit, but on average, it happened at school age (4.7 years). The children who trialled a BCD or hearing aid were fitted earlier at around 2.5 years. Additional support with speech and language via support services were available for three quarters of this cohort, but for those who were unable to access this support, it was primarily because the child did not meet the referral criteria. Several areas of provision of support services provided for the children with UHL are currently under resourced. Individualised treatment plans are essential for this distinct cohort but where devices are not trialled or worn then sound-field amplification systems in the nursery and school would improve all the outcomes of the children regardless of their hearing status.The funding for genetic testing and consistent provision of support services, counselling, and anti-bullying campaigns within schools for this understudied group is vital.


GSTM1, GSTP1 c.313A>G), DNA repair , and apoptosis-related proteins  presented up to 32.22 higher odds of moderate or severe ototoxicity. These findings reinforce the importance of inherited nucleotide variants involved in cisplatin metabolism as candidate variables for predictive models of adverse events. Cisplatin is recognized as the standard agent for head and neck squamous cell carcinoma therapy, despite the relevant risk of permanent hearing damage. The aim of this study was to evaluate the possible associations of the clinicopathological features and inherited genotypes encoding cisplatin metabolism in eighty-nine patients undergoing chemoradiation with the risk of hearing loss. We were able to confirm race, body mass index, and cumulative cisplatin dose as independent clinical risk factors. Patients with specific isolated and combined genotypes encoding cisplatin efflux (2. Moderate/severe ototoxicity occurred in 26 (29%) patients, particularly related to hearing loss at frequencies over 3000 Hertz. Race, body-mass index, and cumulative CDDP were independent risk factors. Patients with specific isolated and combined genotypes of GSTM1, GSTP1 c.313A>G, XPC c.2815A>C, XPD c.934G>A, EXO1 c.1762G>A, MSH3 c.3133A>G, FASL c.-844A>T, and P53 c.215G>C SNVs had up to 32.22 higher odds of presenting moderate/severe ototoxicity. Conclusions: Our data present, for the first time, the association of combined inherited nucleotide variants involved in CDDP efflux, DNA repair, and apoptosis with ototoxicity, which could be potential predictors in future clinical and genomic models.Background: Cisplatin (CDDP) is a major ototoxic chemotherapy agent for head and neck squamous cell carcinoma (HNSCC) treatment. Clinicopathological features and genotypes encode different stages of CDDP metabolism, as their coexistence may influence the prevalence and severity of hearing loss. Methods: HNSCC patients under CDDP chemoradiation were prospectively provided with baseline and post-treatment audiometry. Clinicopathological features and genetic variants encoding glutathione S-transferases , nucleotide excision repair , mismatch repair , and apoptosis -related proteins were analyzed regarding ototoxicity. Results: Eighty-nine patients were included, with a cumulative CDDP dose of 260 mg/m Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide, with 878,348 new cases and 444,347 deaths estimated in 2020 ,2. ApproEvery year, one in five patients submitted to CDDP-based chemotherapy will suffer severe to profound hearing loss ,12,13. RNumerous proteins act in the mechanisms of CDDP cellular detoxification, as well as in the pathways of damage repair and apoptosis ,22 Figu. GSTM1), Theta1 (GSTT1), and Pi1 (GSTP1) genes [XPC, XPD, and XPF) [ERCC1) genes [MLH1) [MSH2) [MSH3), and exonuclease 1 (EXO1) genes [P53, Caspase 8 (CASP8), CASP9, CASP3, Fas cell surface death receptor (FAS), and Fas ligand (FASL) tumor necrosis factors [The detoxification of CDDP occurs mainly through its conjugation with glutathione, encoded by the Mu1 (1) genes , in whic1) genes . The cyt1) genes , mediateand XPF) ,27 and e1) genes , as wells [MLH1) , MutS ho) [MSH2) , MutS ho1) genes . If the  factors ,31. Defe factors .ACYP2), involved in calcium homeostasis [WFS1 genes [TPMT) and cathecol-O methyltransferases (COMT) have also been described as potential risk factors [GSTM1, GSTT1 [GSTP1 c.313A>G [XPC c.2815A>C SNV influenced ototoxicity in osteosarcoma patients [Genome-wide studies have described SNVs in acylphosphatase 2  in the ototoxicity of HNSCC treated with CDDP chemoradiation was previously conducted by our group, and the functional roles of each SNV described in the literature are presented in GSTT1 [EXO1 [XPC [FASL [To our knowledge, the only cohort that evaluated SNVs in genes of distinct pathways of CDDP metabolism, damage repair, and apoptosis  performance status of equal to or less than 1 , creatinPatients received high-dose CDDP   associatThe study was approved by the local institutional review board (Protocol 274/2011 and 62870722.1.0000.5404), and all patients enrolled in the study agreed to participate and declared consent in accordance with the Declaration of Helsinki. The results of this study were reported following the Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) guidelines .Data related to age, gender, race, history of tobacco and alcohol use , ECOG stPatients were submitted to otoscopic examination before any audiometric measurements. If there were identifiable diseases of the external acoustic meatus, tympanic membranes, middle ears, or other conditions that could interfere with the audiological evaluation, patients received treatment and were followed up until resolution. Audiometric evaluations were performed on two occasions, before treatment initiation and up to 30 days after therapy completion in an acoustic booth previously calibrated to meet the specifications of internal noise levels allowed according to the International Organization for Standardization ((ISO) 8253-1:2010 criteria, using the Interacoustics audiometer model AC 30 .Pure tone audiometry was conducted in air and bone conduction for both the left and right sides. For the air conduction assessment, the tonal auditory thresholds were measured at sound frequencies 0.25, 0.50, 1, 2, 3, 4, 6, and 8 kHz, with earphones model TDH 39, applying the descending–ascending technique. In each test, the smallest sound stimulus perceived by the patient in at least 50% of the presentations was considered. Bone conduction evaluation was performed in a similar descending–ascending manner, registering minimum dB thresholds at frequencies 0.25, 0.50, 1, 2, 3, and 4 kHz through a conduction receiver bow fixed on the mastoid . The corresponding hearing thresholds for each frequency in both ears were collected, considering that the normal expected range was lower than 15 dB .Speech audiometry was performed when applicable, assessing the speech recognition threshold (SRT) in dB for the repetition of 50% disyllabic words for left and right ears. The speech discrimination score (SDS), calculating the percentage of syllables repeated correctly, was also registered for each side when possible . SRT is The GBD Hearing Loss Classification was performed, assessing the ISO threshold average for 0.5, 1, 2, and 4 kHz in dB, as recommended by the World Health Organization , pre- anHearing loss in the right and left ears were also classified based on grades (G) 1 to 4, according to the NCI CTCAE v4.0 criteria  followinGSTM1 and GSTT1 variants [® SNP Genotyping Assays , as follows: GSTP1 c.313A>G (rs1695) [XPC c.2815A>C (rs2228001) [XPD c.934G>A (rs1799793) [XPD c.2251A>C (rs13181) [XPF c.2505T>C (rs1799801) [ERCC1 c.354C>T (rs11615) [MLH1 c.-93G>A (rs1800734) [MSH2 c.211 +9G>C (rs2303426) [MSH3 c.3133A>G (rs26279) [EXO1 c.1762G>A (rs1047840) [FAS c.-1378G>A (rs2234767) [FAS c.-671A>G (rs1800682) [FASL c.-844C>T (rs763110) [CASP3 c.-1191A>G (rs12108497) [CASP3 c.-182-247G>T (rs4647601) [Genetic variants were selected for study based on the National Center for Biotechnology Information database, minor allele frequency greater than 10%, previous association with risk/outcome of solid tumors and/or CDDP metabolism, and the availability of financial resources . For genvariants  were obtrs1695) , XPC c.22228001) , XPD c.91799793) , XPD c.2rs13181) , XPF c.21799801) , ERCC1 crs11615) , MLH1 c.1800734) , MSH2 c.5 , XPC crs26279) , EXO1 c.1047840) , P53 c.21047840) , FAS c.-1800682) , FASL c.s763110) , CASP3 c2108497) , and CASDescriptive statistics were performed according to the variables under study, with mean values and standard deviation (SD) in normal distribution or median and interquartile ranges (IQR) when applicable.Pre- and post-treatment pure tone thresholds were described individually, as well as the averages of high-frequency minimum thresholds  and ISO averages  in each ear. Wilcoxon’s signed-rank test for paired data was applied in the comparison of speech audiometry, pure tone averages, and frequency thresholds before and after chemoradiation, with the latter controlling for false discovery rates with the Benjamini–Hochberg correction in multiple testing . Cochranp-value of under 0.10 in univariate regression. The main endpoint of this study was the proportion of patients with NCI CTCAE hearing loss G equal to or greater than 3 during follow-up based on audiometry monitoring. Multiple logistic regression was used to obtain the odds ratio (ORs) adjusted for any specific discrepancies for each independent variable, considering a 95% confidence interval (CI). Variables were selected using a conditional stepwise approach, permitting a p-value and CI as the measures of statistical significance [p ≤ 0.05 were validated using bootstrap [Post hoc power analyses (PA) were also conducted for associations, taking into consideration ificance ,79. Afteootstrap  to verifAll tests were performed using the Statistical Analysis System (SAS) for Windows, version 9.4  and Stata Statistical Software: Release 15 .In a median follow-up of 142 days, 152 patients were enrolled, of whom 89 were included in the analysis with the completion of baseline and post-treatment audiometry .2. Eighty-eight patients received 2D RT, with a total dose of 70 Gy. The clinicopathological aspects of patients enrolled in the study are further detailed in The median age was 56 years, and most patients were male and white, with a high rate of tobacco and alcohol consumption. Median BMI was within the normally acceptable range, most presented an ECOG status of 0, and the proportion of diabetes and hypertension was 10 and 26.9%, respectively. Most primary tumors were in the oral cavity or oropharynx, evenly distributed between the right and left sides of the head and neck, well or moderately differentiated, and at advanced stages (III or IV). The median cumulative CDDP dose among patients was 260 mg/mAnalyzing the median thresholds for each frequency upon baseline, we were able to observe a normal range below 2 kHz and a trend toward higher thresholds, starting from 3 kHz in both conduction modalities .After treatment, there was significant damage regarding higher frequencies over 2 kHz, which was more evident in air conduction analysis. Hearing thresholds for each frequency in pure tone audiometry are further detailed in p < 0.001) on the right side and 6.25 dB (p < 0.001) on the left side was observed when comparing baseline to post-treatment assessments. For bone conduction, there was a median increase of 6.25 (p < 0.001) on the right side and 6.25 dB (p < 0.001) on the left side, respectively  on the right and 19 dB (p < 0.001) on the left sides observed after exposure to CDDP and RT.Regarding high-frequency average thresholds for pure tone air conduction audiometry, there was a median increase of 18 dB . The median baseline SRT was 10 and 15 dB in the right and left ears, respectively. Pre- and post-treatment median differences were null on both sides . Regardi2 20.16, p < 0.001 for air; chi2 18.24, p < 0.001 for bone conduction), although a severe degree of hearing loss was not observed throughout the study . The ototoxicity of G1 and G2 was observed in 23 (25.8%) and 19 (21.3%) patients, respectively. G3 or moderate/severe ototoxicity occurred in 26 (29.3%) participants, and G4 was not identified in this study.p = 0.02), where the higher the dose of CDDP, the greater the hearing impairment , as represented in GSTM1 null plus EXO1 c.1762GA or AA  and with GSTP1 c.313AG or GG plus XPC c.2815AA  in comparison to other related variants. The analyses of isolated and combined SNVs with biological significance with hearing loss at high frequencies are presented in When SNVs were analyzed individually, it was observed that patients with p = 0.02) in multivariate analysis. BMI was also a potential predictor, as participants with grade 3 hearing impairment presented lower median BMI (17.8 versus 19.7), with the OR = 0.82 higher for every decrease in BMI  in multivariate analysis.Race and BMI were significantly associated with the risk of G3 ototoxicity in univariate and multivariate analyses, but potential clinical risk factors such as age, gender, diabetes, hypertension, smoking, alcohol consumption, tumor stage, tumor side, and CDDP cumulative dose did not alter the risk of ototoxicity in univariate analysis . The occGSTP1 c.313AG or GG genotypes had about 4.20 higher odds of having grade 3 or greater ototoxicity. Moreover, XPC c.2815AA genotype was associated with greater odds of severe hearing impairment, with a reported OR of 3.13 (p = 0.01) in the multivariate regression model. In associations of SNVs, it was observed that patients with GSTM1 null plus the XPC c.2815AA genotype had 8.19 greater odds of having moderate/severe hearing impairment . GSTP1 c.313AG or GG genotypes plus XPC c.2815AA, XPD c.934AA and EXO1 c.1762AA had ORs of 32.22 , 19.44 , and 12.08 , respectively. In addition, we observed relevant associations amongst DNA repair and apoptosis-related SNVs in patients with XPC c.2815AA genotype plus MSH3 c.3133A>G and FASL c.-844CC, where individuals with the respective profile had OR 17.09  and 22.29 . Finally, patients with the combined genotypes EXO1 c.1792GA or AA and P53 c.215 CC had OR 20.97 . Further details of other SNVs and their combinations are summarized in When analyzed individually , two SNVIn this clinical and pharmacogenetic cohort, it was possible to reaffirm the clinical relevance of hearing loss induced by CDDP. CDDP induces ototoxicity through the promotion of oxidative stress and inflammation in the cochlea, with the increased generation of reactive oxygen species (ROS) . The lonFirstly, substantial hearing loss before treatment was observed in our cohort; high-frequency minimum thresholds were higher at baseline, ranging from 35 to 40 dB over 4 kHz. This may be attributable to the high proportion of smokers in our sample since smoking is a reported risk factor for loss at high frequencies ,83,84. AWhen accounting for the 0.25 to 4 kHz interval, there was also a significant relative increase in mild and moderate hearing loss after CDDP in our analysis, following GBD classification. The percentage of 64.1% with a threshold ≥ 20 dB after treatment is markedly superior to the overall prevalence reported in the literature for the general population (19.3%) , pointinOn the other hand, median outcomes from speech audiometry (SRT and SDS) were practically unchanged after platinum exposure. One possible explanation for this may be related to the fact that human speech usually ranges from 0.25 to 4 kHz , while CNCI CTCAE criteria for the classification of hearing loss, the proportion of 29.5% moderate/severe ototoxicity was marginally higher than previously reported literature data, ranging from 20 to 25% in adults [p = 0.029) and hearing loss (p = 0.007) amongst patients with higher distress scores [When considering the n adults ,37. Excen adults . A crosss scores . Due to GSTP1 c313AG or GG and XPC c.2815 AA genotypes increased the odds of moderate/severe ototoxicity 4.20- and 3.13-fold, respectively. Preclinical studies have demonstrated that GSTP1 c313 A>G encodes a change from isoleucine to valine in codon 105, leading to reduced protein activity and detoxification [GSTP1 c313AG or GG was associated with an increased risk of moderate/severe hearing impairment in 106 [GSTP1 c313A>G [XPC c.2815A>G [XPC c.2815AA genotype was associated with an increased risk of any grade of toxicity [In this study, fication , while tfication . There it in 106  and 64 ct in 106 , respectt in 106  but not t in 106 . Even tht in 106  are simi c313A>G , this SN c313A>G , while i c313A>G . Reporte.2815A>G . The XPCtoxicity  in a pretoxicity . Nonethetoxicity  did not toxicity  did not GSTM1 null plus XPC c.2815AA, GSTP1 c.313AG or GG plus XPC c.2815AA, XPD c.934AA or EXO1 c.1762AA, or XPC c.2815AA plus MSH3 c.3133AA or FASL c.-844CC (XPD c.934 (A) [EXO1 c.1762 (A) [MSH3 c.3133 (A) [FASL c.-844 is located within the enhancer-biding region of FASL, and luciferase assays have described the variant genotype TT to promote protein affinity twice lower than wild CC donors, leading to less protein expression and, as such, reduced apoptosis [The metabolism of CDDP is known to involve cellular efflux, NER, and MMR damage repair, as well as apoptosis . We werec.-844CC  intensif.934 (A) , EXO1 c.1762 (A) , and MSH3133 (A)  have beepoptosis . Hence, EXO1 c.1762GA or AA and P53 c.215CC genotypes increased the risk for events with OR 20.97. The P53 c.215 wild allele encoding arginine (G) was described as more efficient in inducing apoptosis than the proline (C) variant [EXO1 c.1792GA or AA and P53 c.215CC combined genotypes were more efficient in promoting cell cycle arrest and senescence of sensory cells after injury by CDDP and, consequently, were at greater risk of hearing loss when compared to patients carrying other genotypes.An association with MMR and apoptosis mechanisms was also noted in this study, as the combination of  variant . The P53 variant . In addi variant . Cellula variant . In vitr variant . Moreove variant  observed variant . Thus, wACYP2 [TPMT [COMT [WFS1 [ACYP2 is known to influence ATP-dependent calcium signaling, which may play a role in sensorineural hearing loss [WSF1 is included, encode proteins reported to control endothelial reticulum stress response, thus influencing inner ear cellular damage [We are aware that this study is limited for its sample size; thus, similarly to previous studies, lacking power for further SNVs combinations or polygenic evaluations and correction for other possible confounders. Though statistical tools were used to stabilize risk, such as bootstrap and power post hoc calculations, there may still be unknown influential factors not identifiable in this sample. It must also be considered that not all SNVs in the genes related to CDDP detoxification, DNA repair, and the apoptosis of damaged cells were evaluated in this study; only those recognized with a greater potential to induce ototoxicity were evaluated here. Thus, it is possible that other SNVs with equal or even greater importance in CDDP ototoxicity will be identified in future studies. Furthermore, other known SNVs for CDDP-induced ototoxicity unrelated to stages regarding drug absorption, distribution, metabolism, and excretion were not assessed and could be additional confounders. There is evidence supporting additional SNVs as risk factors for ototoxicity induced by CDDP related to ACYP2 ,34, TPMTP2 [TPMT , COMT [3MT [COMT , and WFSMT [WFS1  genes. Aing loss . TPMT anr damage . Apart fr damage  and distr damage , were alIt is also important to consider distinct patient characteristics when assessing the generalizability of this study for other tumors since the population was predominantly male, with a high frequency of smokers and alcohol users, as well as locally advanced stages of HNSCC. Treatment approaches in the field of RT may also be distinct and could influence the prevalence and severity of adverse events, mainly in institutions with more frequent use of intensity-modulated RT. Though prespecified treatment protocols were strictly followed, therefore preventing confounding to some extent, heterogeneity in therapy protocols could affect the generalizability of these results.The results of this cohort suggest, for the first time, the interactions of inherited genetic abnormalities involved in CDDP metabolism as potential candidate targets for future risk models in ototoxicity. The development of genetic and clinical risk prediction tools is essential, not only for optimizing treatment selection based on efficacy but also to assist in supportive care during therapy. We believe these results may be included in future polygenic and clinical predictive models.


This study aims to explore the association between coffee consumption and the prevalence of hearing loss in American adults based on a national population-based survey.Cross-sectional analysis of reported audiometric status and coffee intake from the 2003–2006 National Health and Nutrition Examination Survey (NHANES). Multivariate logistic regression, forest plots and restricted cubic spline (RCS) analyses were used to explore the associations and dose–response relationships between coffee consumption frequency and hearing loss.The USA.This study included 1894 individuals aged ≥ 20 from the 2003–2006 NHANES.Ptrend = 0·001). This association of HFHL was similar for participants aged 20–64 (Ptrend = 0·001), non-Hispanic White (Ptrend = 0·002), non-noise exposure participants (Ptrend = 0·03) and noise-exposed participants (Ptrend = 0·003). The forest plots analysis found that the association between 1 cup-increment of daily coffee consumption and the prevalence of HFHL was statistically significant in males. RCS model supported a positive linear association of coffee consumption with SFHL  and a positive non-linear association of coffee consumption with HFHL .In this study, the prevalence of speech-frequency hearing loss (SFHL) and high-frequency hearing loss (HFHL) among the participants was 35·90 % and 51·54 %, respectively. Compared with those who no consumed coffee, non-Hispanic White who consumed ≥ 4 cups/d had higher prevalence of SFHL . And a positive trend of coffee consumption frequency with the prevalence of HFHL was found (Our findings suggested that coffee consumption was associated with higher prevalence of hearing loss. Further cohort studies in larger population are needed to investigate these findings. In America, nearly a quarter of people aged 12 years and over have hearing loss, including mild and unilateral hearing loss. The WHO has estimated that hearing loss will be one of the main causes of disease burden globally by 2030. Hearing loss may be associated with a variety of diseases. Evidence from epidemiological studies showed that hearing loss is related to the increased risks of depressive symptoms, falls, total mortality and heart disease mortality–6. The traditional risk factors, including age, noise exposure, family history of hearing loss, exposure to ototoxic medications, smoking and diabetes, could only partially explain the causes of hearing loss. Recently, accumulating studies have suggested that diet is related to hearing loss, and this effect can be attributed to specific dietary patterns or some special bioactive compounds, such as PUFA, vitamin A, isoflavone, riboflavin, niacin and retinol–11.Hearing loss is a major global public health problem. Approximately, one-fifth of the global population currently suffer from hearing loss. Coffee trigonelline has anti-microbial, anti-carcinogenic and anti-hyperglycemic effects. Coffee chlorogenic acid has some anti-cancer effects. Caffeine has protective effect on neurodegenerative disease due to its strong antioxidant, anti-inflammatory and adenosine receptor antagonist properties. It may also be related to increased risk of fractures and decreased sleep quality,17. Additionally, polyphenols, such as caffeic acid and caffeic acid phenethyl ester, have antioxidant effects and prevent hearing loss,19. However, caffeine are often considered a cause of tinnitus. Large population-based studies on the association between coffee consumption and hearing loss are limited.Coffee is one of the most popular beverages in the world. Coffee and its compounds, such as caffeine, trigonelline, polyphenols and chlorogenic acid, have various impacts on human health,41. Contrary, previous animals studies have shown that caffeine in coffee can interfere with hearing recovery after acoustic overstimulation events,32. Moreover, a previous study based on the National Health and Nutrition Examination Survey (NHANES) has reported no significant association between urinary caffeine metabolites and hearing thresholds. Therefore, in this study, we have investigated the association of coffee consumption with the hearing loss in adults from America according to the NHANES database.Currently, study about the effect of coffee consumption on hearing loss is scarce, and the results remain controversial. Two previous population-based studies have suggested a negative association between coffee consumption frequency and hearing lossn 451) and coffee consumption data (n 1284). Of the remaining 3188 participants, additional 1294 were eliminated because they aged < 20 years (adolescents aged 12–19 years in NHANES). Finally, 1894 subjects were recruited for analyses in this study . This survey investigated about 10 000 representative samples of the general American population per cycle using a complex, multistage, probability sampling design. The data from the 2003–2006 were used in our study, because the information on coffee consumption and audiometry data of adult participants were collected in the same period. In the 2003–2006 NHANES, a total of 4923 subjects participated in the audiometry component. Among 1735 subjects were excluded because they lacked audiometry test data  based on the NCI Diet History Questionnaire. Participants were asked to review and fill in their coffee consumption in the past 12 months. The question on coffee consumption frequency in the questionnaire was: ‘How many cups of caffeinated or decaffeinated coffee did you drink’. The possible responses were none, ≤ 1 cup/m, 1–3 cups/m, 1 cup/w, 2–4 cups/w, 5–6 cups/w, 1 cup/d, 2–3 cups/d, 4–5 cups/d, ≥ 6 cups/d. If they select other option than ‘none’, participant need to answer the following question: ‘How often was you drank the decaffeinated coffee’. The possible responses were ‘almost never or never, about 1/4 of the time, about 1/2 of the time, about 3/4 of the time, almost always or always’. In this survey, a cup of coffee was 8oz according to the Measuring Guides for the Dietary Recall InterviewIn present analysis, total coffee consumption frequency was categorised into five groups: none, ≤ 1 cup/d, 1 cup/d, 2–3 cups/d and ≥ 4 cups/d. Then coffee consumption frequency data were further converted to quantitative data (e.g. 1–3 cups/m was converted to 0·07 cups/d). The prevalence of hearing loss related to caffeinated and decaffeinated coffee consumption was also investigated..All hearing measurements were conducted by a well-trained physicians in a dedicated, sound-isolating room at a mobile examination centre. The test equipment included AD226 audiometer , TDH-39 standard headphones  and EARtone 3A insert earphones . The hearing threshold for each ear was measured at frequencies of 500, 1000, 2000, 3000, 4000, 6000 and 8000 Hz across an intensity range of –10 to 120 dB using the modified Hughson-Westlake procedure and invoking the automated testing mode of the audiometer. More details of audiometric measures are displayed on NHANES website. In our study, speech-frequency hearing loss (SFHL) was defined as pure-tone average of hearing thresholds at 500, 1000, 2000 and 4000 Hz is > 25 dB in either ear, and high-frequency hearing loss (HFHL) was defined as pure-tone average of hearing thresholds at 3000, 4000 and 6000 Hz is > 25 dB in either ear. BMI status was classified as BMI < 25, BMI 25–30 and BMI ≥ 30. The question on non-occupational noise exposure was: ‘Outside of a job, have you ever been exposed to steady loud noise or music for 5 or more hours a week? This is noise so loud that you have to raise your voice to be heard’. The possible responses were ‘yes’ or ‘no’. The question on occupational noise exposure was: ‘have you ever had a job where you were exposed to loud noise for 5 or more hours a week (you had to raise your voice to be heard)’. The possible responses were ‘yes’ or ‘no’. In addition, diagnoses of diabetes mellitus and hypertension and history of ear infection were self-reported by the subjects.Covariates were obtained from the questionnaire survey, including general characteristics , lifestyles , noise exposure and history of diseases (hypertension and diabetes mellitus). Ethnicity was classified as non-Hispanic White, non-Hispanic Black and other. Smoking status was categorised as never smoker, former smoker and current smoker. Drinking status was categorised as never drinker, low to moderate drinker (drinking < 1 drink/d in women and < 2 drinks/d in men) and heavy drinker sd for the normal distribution and as median  for skewed distribution and analysed by Student’s t tests. Categorical variables were expressed as frequency (%) and analysed by χ2 test or Wilcoxon rank-sum test.Given the design of complex, multistage, probability sampling in the NHANES, we implemented sampling weight, cluster and strata in the analysis. Continuous variables were expressed as mean and P for non-linearity < 0·05 suggested a non-linear association; otherwise, a linear association was indicated. RCS analyses was conducted using SAS macro program %RCS_Reg. All statistical analyses were performed using SAS software .Multivariate logistic regression models were applied to assess the relationships between coffee consumption frequency and the prevalence of SFHL and HFHL. The ‘None’ group were considered as the reference groups. Covariates including ethnicity, BMI, ear infection, occupational noise exposure, non-occupational noise exposure, smoking status, drinking status, hypertension and diabetes mellitus were adjusted. The trend test was conducted by taking the median of each coffee consumption frequency group as a continuous variable in these models. We also transformed coffee consumption frequency into continuous variable to explore the linear dose–response relationship. We also conducted subgroup analyses stratified by demographic characteristics , ethnicity  and sex ), noise exposure source (including Yes (at work exposure Yes and/or outside work exposure Yes), No (at work exposure No and outside work exposure No), noise exposure unknown (outside work exposure No and at work exposure data missing)) and coffee type . Moreover, we created forest plots to estimate the OR (95 % Cl) of hearing loss related to a 1-cup/d increment for the different types of coffee separately in men and women. Furthermore, restricted cubic splines (RCS) regression model was conducted to further explore the dose–response relationship of coffee consumption with the prevalence of SFHL and HFHL in the multivariable-adjusted binary logistic regression analyses for sex, ethnicity and noise exposure status separately, with four knots of at the 5th, 35th, 65th and 95th percentiles. Adjusted factors were consistent with multivariate logistic regression model. P > 0·05).As shown in Table Ptrend = 0·001), but this trend has insignificant after full adjustments (Ptrend = 0·25). Besides, a positive trend and association of coffee consumption frequency with the prevalence of HFHL in crude model was found (Ptrend < 0·05), while only the trend remained after full adjustments (Ptrend < 0·05)As shown in Table S1 and S2. In non-Hispanic White subgroup, only participants who consumed ≥ 4 cups/d had a higher prevalence of SFHL compared to non-coffee drinker group . Similarly, the positive trend of coffee consumption frequency with the prevalence of HFHL in Model 1 was also found in subgroups of loud noise exposure (yes and no). In addition, no significant correlations were also found between coffee consumption frequency and the prevalence of SFHL and HFHL in all coffee type subgroups (online Supplementary Table S2).The results of subgroup analyses were shown in Table The relationship between coffee consumption and the prevalence of SFHL and HFHL appeared to be more pronounced in male subgroup. However, only in caffeinated coffee subgroup, the association between per 1 cup-increment of daily coffee consumption and HFHL was statistically significant in male Fig. .P overall association = 0·02, P nonlinearity = 0·48; Fig. P overall association = 0·001, P nonlinearity = 0·001; Fig. P overall association = 0·03, P nonlinearity = 0·47; online Supplementary Fig. S1 (a)). Likewise, positive linear associations of coffee consumption with the prevalence of HFHL were found in male subgroup and non-noise exposure subgroup –(g)), while positive non-linear associations of coffee consumption with the prevalence of HFHL were found in the age 20–64 years, non-Hispanic White, female and noise exposure subgroup .RCS model also showed a linear positive associations of coffee consumption with the prevalence of SFHL  HI genes varies from race to race, and African Americans/African Americans receive the least impact. In addition, we also found that even after adjusting for covariates related to hearing loss, there was still a sex difference in the relationship between coffee and hearing loss, the association between per 1 cup-increment of daily coffee consumption and HFHL was statistically significant in men, but no significant association was found among women, which was similar to a previous study. In this study, the proportion of male coffee consumers is higher than that of female (78·26 % v. 74·82 %). Coffee drinking is widespread in the USA, and men consumed more coffee,44. Previous studies have shown that men may have a higher hearing threshold. It may be due to the great differences between men and women in brain biochemistry, physiology, structure and function. In physiological structure, the length of the cochlea in men was longer than that in women, which could affect the auditory brainstem responses. Besides, oestrogen also plays a protective role in the cochlear function. Oestrogen may play an important role in modulating the pathophysiological mechanisms in the hearing system, and it could enhance the expression of antioxidant superoxide dismutase and decrease apoptosis by upregulating Bcl-2/Bcl-xL and inhibiting the JNK pathway, and it also could inhibit glutamate excitotoxicity to regulate cochlear homoeostasis. Thus, in women, the effect of nutrition on auditory function may not be as relevant as in men. Besides, we found a positive trend and relationship between coffee consumption frequency with the prevalence of HFHL in non-noise exposure subgroup, suggesting that caffeine may have a potential effect on hearing. A previous study reported that caffeine significantly suppressed the compound action potential of the auditory nerve after infusing caffeine into the perilymph compartment. Noteworthy, we found a positive trend and relationship of coffee consumption frequency with the prevalence of SFHL and HFHL in the noise-exposed participants. Noise-induced hearing loss mainly refers to the apoptosis of cochlear hair cells caused by noise through mechanical damage and metabolic damage . The interaction between coffee and noise may aggravate the apoptosis of cochlear hair cells. Given the biological plausibility, it will be very meaningful to conduct further studies to establish the potential role of coffee consumption combined with noise exposure on hearing loss.Of note, our study showed a positive trend and association of coffee consumption frequency with the prevalence of SFHL and HFHL in non-Hispanic Whites, and participants who consumed ≥ 4 cups/d coffee had a 1·87-fold higher prevalence of SFHL than non-coffee drinkers. Similar to our finding, another study based on the NHANES database also showed that the odds of hearing loss are substantially higher in non-Hispanic White Americans than in other ethnic individuals . Finally, this was an observation study, so causality between coffee consumption and hearing loss could not be shown.This study has several advantages. First, the data are from NHANES, which have been implemented in the USA for a long time, and the survey implementation process is rigorous and mature, so the results of this study are relatively reliable. Second, given that the survey design was complex, multistage, probability sampling in the NHANES, we conducted sampling weight, cluster and strata to solve the deviation of variance estimation caused by such clustering data in the statistical analyses. Besides, we explored the association between the prevalence of SFHL and HFHL with coffee consumption frequency. This study also has several limitations. First, since only two circles (2003–2006) in the NHANES have collected the information on coffee consumption frequency and audiometry test of American adults, the sample size was relatively small; thus, the extrapolation of this result to the general population should be more cautious. Secondly, coffee consumption is obtained through questionnaires, which may have participants’ recall bias, and it is difficult to accurately obtain information about coffee consumption, such as individual coffee intake, type of coffee consumption and preparation process. Therefore, the error of coffee consumption between measured exposure and actual exposure cannot be completely eliminatedThis finding suggested that the positive trend and association of coffee consumption frequency with the prevalence of hearing loss in US adults. And this association was found in non-Hispanic Whites, men, aged 20–64 participants and noise-exposed individuals. This association may be independent of the coffee type or the preparation method. Further cohort studies in larger population are needed to validate these findings, and the underlying mechanism also remains to be elucidated.


Glaucoma is a multifactorial degenerative optic neuropathy characterized by the irreversible loss of retinal ganglion cells. Vascular, genetic, anatomical and immune factors are present in etiopathogenic mechanisms. Being the second cause of blindness worldwide after cataract, and with an irreversible character, glaucoma has turned into a disease with a significant impact on public health. Patients with primary open-angle glaucoma (POAG) may have central neurodegenerative changes, such as sensorineural hearing loss and static changes.Aim: The aim of this study was to estimate the connections between visual and auditory functional changes in glaucoma. The subjects were grouped as follows: patients with glaucoma compared with patients without glaucoma, while trying to identify the functional defect of the optic nerve  and a hearing testing (audiogram).Materials and methods: The prospective, cross-sectional study included 32 eyes of 16 subjects with POAG in a group of study and 24 eyes of 12 healthy subjects in the other group, with a mean age of both groups between 61,64 ± 6,53 years old. Both groups were examined from ophthalmological, audiological and radioimaging perspectives with Pure-tone audiometry (PTA) and magnetic resonance imaging (MRI) for brain. All patients had ophthalmologic assessments according to a standardized protocol. Moreover, auditory functional parameters (audiometry) were recorded.Results: Female cases, over 65 years old, with residency in a city, predominated in the group of study. Compared to the control group, patients in the group of study had average levels of the PTA and modified visual field (VF) parameters. Multivariate analysis demonstrated that the correlation of PTA was indirect, reduced in intensity, both with MD , Cal HOV  and the slope profile of the right eye. Multivariate analysis demonstrated that there was a correlation of the right PTA, which was indirect, reduced in intensity, both with MD , Cal HOV  and the slope profile of the right eye. The left ear PTA correlation was indirect, moderate in intensity, statistically significant with both MD  and slope profile  and reduced as intensity with Cal HOV  of the left eye.Conclusions: Patients with POAG showed changes in audiometry in connection with ophthalmological parameters, a fact suggesting that the auditory system might have been affected in POAG. This study highlighted the interdisciplinarity of the medical field with the aim of ensuring the quality of life of glaucoma patients. A good collaboration between the ophthalmologist and the otolaryngologist was very important for our patients.Abbreviations: RE = Right eye, LE = Left Eye, POAG = Primitive Open Angle Glaucoma, PTA = Pure-tone audiometry, VF = visual field, MRI = magnetic resonance imaging, IOP = Intraocular pressure, BVAC = best visual acuity corrected, MD = mean defect, CNS = central nervous system, SAP = standard automated perimetry, CCT = central corneal thickness, ONH = Optic nerve head, CDR = Cup/ Disc ratio, RNFL = Retinal fiber layers Glaucoma is a multifactorial and degenerative optic neuropathy characterized by the irreversible loss of retinal ganglion cells. Vascular, genetic, anatomical and immune factors are involved in etiopathogenic mechanisms. Glaucoma is a significant public health problem, being the second leading cause of blindness in the world after cataract, but, which is irreversible.1].People aged over 60 years with pathological heredo-collateral antecedents of glaucoma, steroid users, diabetics, patients with high myopia, high blood pressure, central corneal thickness <5 mm, and eye injuries, are at an increased risk of glaucoma [1].In 2020, approximately 76 million people suffered from glaucoma and their number is expected to grow to 111.8 million by 2040 . Dual sensory impairment, hearing and vision, compromises the two main ways of communication, listening and reading speech, and can determinate social isolation , which can affect the quality of life. The double sensory loss affects the cognitive function greater than the unilateral loss of vision or hearing [5-9], the two functions being interconnected cerebrally. In perspective, the aging of population will be associated with the prevalence of glaucoma that will increase, and the loss of the two senses will become more frequent, the two functions being functionally interconnected [10].Visual impairment affects physical functioning, while hearing impairment greatly affects the social functioning .MD (mean defect) specifies the loss of ocular sensitivity and is the average difference between the “ideal” profile calculated by the computer for a given patient based on the results of his evaluation and appropriate age norm. The MD calculation is the average value of the locations on the Total Deviation graph – for 24, 30 fields and from the Age deviation graph - for radial maps. The MD index shows how far the patient’s visual field has deviated from normal values. For below-normal vision, the MD index is negative .Audiometry is a way of evaluating hearing thresholds. The audiogram evaluates and records graphically the type of hearing loss . Several etiological situations that generate hearing changes develop characteristic patterns on the audiogram. Audiograms are the golden standard evaluation for the identification of hearing deficits. The audiogram is a functional test that measures both conduction air and bone. Air conduction assesses the transmission of sound through the outer, middle, and inner ear to the central nervous system (CNS) for auditory integration. Bone conduction represents the transmission from the inner ear only to the CNS [14]. PTA, “pure tone average”, is the arithmetic mean of air conduction thresholds at 500, 1000, and 2000 Hz, which is calculated for each patient. However, PTA does not inform about high-frequency hearing loss. For each frequency, PTA is a graphic representation, in which the X-axis represents the frequency of the sound in hertz and the Y-axis represents the (inverse) sound intensity in decibels. ASHA (American Speech-Language-Hearing Association) set standardized levels for hearing loss.Since the 1920s, threshold audiometric data (pure tone testing) have been used clinically to classify the degree and type of hearing loss. Audiometry uses different intensities of sound emitted over a range of frequencies to determine possible hearing loss, and the results are represented graphically as an audiogram. A typical audiogram shows thresholds at frequencies over a slightly wider range than human speech: 250, 500, 1000, 2000, 3000, 4000, 6000, and 8000 Hz. Primary speech frequencies range from 500 to 4000 Hz, although normal human hearing works from ~20 Hz to ~20,000 Hz [15].The auditory pathway has the auditory cortex as its central projection, which is primary located in the superotemporal region of the gyrus superior temporal with extension on the extern surface of the temporal lobe, on an extension of the insular cortex and included in the lateral region of the parietal operculum. For association, the auditory cortex receives information both from the primary cortex, the thalamic areas located adjacent to the medial geniculate bodies, but also from other visual areas located adjacent to the primary area. The primary somatosensory areas, which are areas of association that receive information both from the primary and secondary areas, from the subthalamic structures necessary for the complex integration of information, are located at the cortical level, additionally to the primary and secondary motor cortical areas. Among these association areas, the parieto-occipital-temporal has a great role. Wernicke’s area, located at this level, is involved in understanding language. Behind this, is the area for language read processing at the level of the angular gyrus, in the lateral side of the occipital lobe. At this level, numerous areas of association with the auditory, visual analyzer with major implication in thought and language processes, are located. The face recognition area is located on the medial face of the occipital and parietal lobes. All the somatic, auditory and visual association areas forms are complex mechanisms in the interpretation of sensory experiences and send information to the posterosuperior Wernicke’s area in the temporal lobe, which informs Broca’s language area located in the frontal area (complex integrative systems) . If initial testing was deemed unreliable, audiometry testing was repeated.A specialist otolaryngologist examined all the participants, who underwent bilateral ear examination prior to hearing testing with Heine beta 200 otoscope. Audiometry evaluation was performed using pure-tone audiometry in a special double-walled soundproof booth quit room. Air-condition pure-tone thresholds audiometry was performed using the MAICO MA53 Audiometer, two channels , Noah 9 software, or each ear at six frequencies , by a well-trained examiner, and the results were recorded. Hearing loss was a pure-tone average threshold of >40 dB at 125, 250, 500, 1000, 2000, 4000 and 8000 Hz, averaged for both ears. Hearing impairment was mild or moderate-to-profound. ASHA recommendations thresholds classify normal hearing at 0-25 dB (decibels), mild hearing loss at 26-40 dB, moderate hearing loss at 41-55 dB, moderate-severe hearing loss at 56-70 dB, severe hearing loss at 70-90 dB, and a profound hearing loss at more than 90 dB a : if the correlation coefficient tended to +1 (direct correlation), or to -1 (indirect correlation), there was a strong linear dependence of the parameters; the closer the correlation coefficient was to 0, the lower the intensity of the link. Multiple linear regression aims to highlight the relationship between a dependent variable  and a set of independent variables .Epidemiologic characteristicsGender distributionFig. 1).In the study/ control group, female patients predominated (71.4%), the F/ M ratio being 2.5/ 1. The percentage distribution of both groups was homogeneous  : the average age in the study group was significantly higher compared to the control group .The series of values for age were homogeneous, which suggested that the tests of statistical significance could be applied .Participants from the city predominated (urban) (82.1%), the U/ R ratio being 4.6/ 1 in the study/ control group. It was observed that all the patients in the control group and 68.8% of the study group came from the urban environment (p=0.011) .In the case study presented, more than 70% of the patients had secondary education (32.1%) or higher education (39.3%). It was noted that over 58% of the patients in the control group and 25% in the study group had higher education (p=0.05) Table 1).Because PTA was a homogeneous variable in both the right and the left ear, we were able to apply statistical significance tests , and the result of the Skewness test = 0.441;- Left ear PTA varied from 5 to 52 dB, the average level being 19.29 dB ± 10.87, close to the median value (18 dB), and the Skewness test result = 1.292 .VF parameters: MD, Cal HOV, slope profileBecause VF was a homogeneous variable in both the right and the left eye, we were able to apply statistical significance tests. After these analyses, we were able to state that the data were in accordance with the grading of the glaucomatous disease.MD: Comparative MD by study groups (dB) (Table 2):- in the study group, the MD in the RE varied from -0,44 to 0,30, the average level being -0,156 ± 0,201, close to the median value , and the result of the Skewness test = 0.949;- in the study group, the MD in the LE varied from -0,59 to 0,31, the average level being -0,186 ± 0,246, close to the median value , and the result of the Skewness test = 0.564;- in the control group, the MD in the RE varied from -0,10 to 0,07, the average level being -0,025 ± 0,06, close to the median value , and the result of the Skewness test = 0.326;- in the control group, the MD in the LE varied from -0,16 to 0,10, the average level being -0,003 ± 0,08, close to the median value , and the result of the Skewness test = -0,468;Cal HOV: Comparative Cal HOV by study groups (dB) (Table 3):- in the study group, the Cal HOV in the RE varied from 18 to 21, the average level being 20,44 ± 1,209, close to the median value 21, and the result of the Skewness test = 0.564;- in the study group, the Cal HOV in the LE varied from 18 to 21, the average level being 20,06 ± 1,784, close to the median value 21, and the result of the Skewness test = 0.637;- in the control group, the Cal HOV in the RE varied from 18 to 24, the average level being 20,67 ± 2,015, close to the median value 21, and the result of the Skewness test = 0.637;- in the control group, the Cal HOV in the LE varied from 18 to 24, the average level being 20,05 ± 1,784, close to the median value 21, and the result of the Skewness test = 0,441;Slope profile: Comparative slope profile by study groups (dB) (Table 4):- in the study group, the slope profile in the RE varied from 1,1 to 4,5, the average level being 2,588 ± 1,006, close to the median value 2,45, and the result of the Skewness test = 0.564;- in the study group, the slope profile in the LE varied from 1 to 4,5, the average level being 2,894 ± 1,256, close to the median value 2,750, and the result of the Skewness test = 0.564;- in the control group, the slope profile in the RE varied from 2,4 to 3,3, the average level being 2,908 ± 0,303, close to the median value 2,800, and the result of the Skewness test = 0.637;- in the control group, the slope profile in the LE varied from 1,8 to 3,6, the average level being 2,725 ± 0,666, close to the median value 2,750, and the result of the Skewness test = 0,637;Right ear PTA with RE: MD function, Cal HOV level, slope profileFig. 5).The correlation of the right ear PTA was indirect, reduced in intensity, both with MD , Cal HOV , or slope profile  .The left ear PTA correlation was indirect, moderate in intensity, statistically significant with both MD  and slope profile  and reduced as intensity with Cal HOV  , compared to men (28.6%), resulted from the demographic analysis of the patients in this study. The statistical analysis showed a high percentage of patients with above-average education  in the studied groups. As a result, it could be affirmed that the female patients were more compliant and that the studies above the average made it easier for them to accept to participate in the study. Also, the increased number of functional investigations  and brain MRI have further reduced the acceptance rate beyond the inclusion criteria, which were quite restrictive, and justified the low number of participants included in the study. Analyzing the area of origin, it was found that the majority was the percentage of those from the urban environment compared to those from the rural environment (82.1% versus 17.9%). Each patient’s expertise had to be obtained through some functional tests, and the cognitive ability acquired through experience and own exercise had a key role. As a first conclusion deriving from the primary demographic analysis, it could be affirmed that women presented to the doctor more quickly and more frequently, and that the urban origin combined with the level of schooling made it easier to understand the performance of the functional tests that required a considerable amount of understanding and completion from the patients.The cognitive and functional decline of the body were associated with the loss of hearing and vision, but also with the dual impairment (both hearing and vision deficiency) .- The inner ear, which contains the organ of Corti that translates acoustic signals into neural impulses, derives from the ectoderm and is the first of the three anatomical parts of the ear. The development begins on the ectoderm surface, because the otic placode or otic disc is one of the first sensory placodes involved in the development of the special sensory organs . The optic vesicle develops from the optic grooves and optic stalk will develop from the optic vesicle (the future optic nerve), and will generate the necessary modifications in the ectoderm surface to develop the placode lens. At four weeks of gestation, the optic vesicle invaginates and creates the optic cup [22], which will become the retina.- The visual analyzer starts growing in the 3rd week of gestation with the optic grooves of neuroectodermal origin in the forebrain , because the neurons cannot function alone, although in complex organisms, neurons specialized for various functions are present. In complex organisms, the CNS can create types of behaviors that recognize subsystems and neural pathways that include sensory afferents coming from the retina, but considering that each specific cortical region is interconnected in both directions with other regions that ensure the primary functions of the motor example, the cortical integration of visual information becomes a complex mechanism closely connected with other motor, auditory, and vestibular cortical areas [23]. The light information transformed into nerve signals leaves the retina through the optic nerves made up of ganglion cell axons. At the level of the optic chiasm, located near the pituitary gland, the fibers of the optic nerve from the nasal part cross and continue their path along with the fibers that collect information from the temporal part of the retina of the contralateral eye to the lateral dorsal geniculate nuclei and later form the geniculocalcarine tract, while the optic radiations reach the primary visual cortex located on the edges of the calcarine sulcus, in the medial area of the occipital lobe. Neural circuits responsible for receiving related impulses, processing information and generating other efferent responses are present in the central nervous system (CNS). A key role is played by neuronal patterns .The primary somatosensory areas receive afferents from the visual and auditory analyzers and play the role of detecting specific visual and auditory sensations. The secondary somatosensory areas decipher the sense of the impulses reaching the primary areas. They generate their interpretation, initiate the evaluation of specific sensory impulses that include: the understanding of the shape or texture of an object, the analysis of colors, light intensity, the direction of lines, angles and different aspects of visual perception, the interpretation of tones, their intensity and the sequence of tones contained by auditory nerve impulses. Association areas, which receive and analyze impulses from several areas of the motor and sensory cortex, as well as from the subcortical areas, are also present at the cortical level, besides the primary and secondary or somatosensory areas. The significant association areas are the following: parieto-occipital-temporal, prefrontal and limbic. The parieto-occipital-temporal association area is situated at the level of the parietal and occipital cortex, being delimited anteriorly by the somatosensory cortex, posteriorly by the visual cortex, and laterally by the auditory cortex. At the level of this area, the sense of the impulses coming from all the nearby somatosensory areas are interpreted [Considering all the complex interrelations between the primary, secondary and cortical association areas, in which visual and auditory information are processed, the connections between the changes in the function of the optic and auditory nerve become possible. Neuroconnectivity of the brain can explain many of the connections between the visual and auditory analyzer.Unfortunately, the study had a series of limitations that must be mentioned: low number of patients included, the fact that the study was monocentric and had a cross-sectional nature, short follow-up period, severe inclusion criteria that generated few enrollments. Also, patients with mild glaucomatous damage were enrolled in our study, and starting from this point, it would be interesting to develop further studies considering groups with different glaucomatous damage, but which would allow the performing of functional evaluations.The observations were interesting, challenging and opened opportunities for further study. The association of changes in VF parameters, light sensitivity at 10°  and the profile of the decrease in light sensitivity from the core to the periphery (slope profile), with hearing values on the same side, could be explained from an embryological, anatomical and physiological evolution, if the visual and auditory pathway was analyzed functionally and structurally. But, due to the limitations of the study, the final conclusions could not be drawn. These changes and associations must be noticed within a general context, together with the evaluation of the structure of the optic nerve and its changes in glaucoma, while opening new opportunities and approaches with a longitudinal design to observe how these parameters change over time. Ensuring the quality of life is still the main objective since the aging of the population has a global character and implies an increase in the glaucomatous disease. The multidisciplinary nature of glaucoma respects once again the idea issued in 1922 by Felix Lagrange that the eye with glaucoma is “a sick eye in a sick body”.Conflict of Interest statementThe authors state no conflict of interest.Informed Consent and Human and Animal Rights statementInformed consent has been obtained from all individuals included in this study.Authorization for the use of human subjectsEthical approval: The research related to human use complies with all the relevant national regulations, institutional policies, is in accordance with the tenets of the Helsinki Declaration, and has been approved by the Ethics Committee of Clinical County Emergency Hospital of Brăila, Romania (no. 1/ 3.09.2021).AcknowledgementsNone.Sources of FundingNone.DisclosuresNone.