Association Between Microvascular Retinal Signs and Age-Related Hearing Loss in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) | Ophthalmology | JAMA Otolaryngology–Head & Neck Surgery | JAMA Network
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Figure.  Multivariable-Adjusted Estimates and 95% CIs of the Association Between Microvascular Retinal Signs at Visit 5 (2011-2013) and Hearing Impairment at Visit 6 (2016-2017) by Diabetes Status Among 1458 Individuals in the Atherosclerosis Risk in Communities Neurocognitive Study
Multivariable-Adjusted Estimates and 95% CIs of the Association Between Microvascular Retinal Signs at Visit 5 (2011-2013) and Hearing Impairment at Visit 6 (2016-2017) by Diabetes Status Among 1458 Individuals in the Atherosclerosis Risk in Communities Neurocognitive Study

Adjusted for age, sex, race, study site, educational level, body mass index, hypertension, diabetes, cigarette smoking status, and noise exposure (visit 5 time-varying covariate measures). For hearing impairment, pure-tone average (PTA) of air conduction speech thresholds at 0.5, 1, 2, and 4 kHz in the better-hearing ear were used for analysis, with higher PTAs indicating worse hearing. AV indicates arteriovenous; CRAE, central retinal arteriolar equivalent.

Table 1.  Baseline Characteristics by the Presence of Retinopathy Among 1458 Participants in the Atherosclerosis Risk in Communities Neurocognitive Study at Visit 5 (2011-2013)
Baseline Characteristics by the Presence of Retinopathy Among 1458 Participants in the Atherosclerosis Risk in Communities Neurocognitive Study at Visit 5 (2011-2013)
Table 2.  Crude Better-Hearing Ear Thresholds at Visit 6 (2016-2017) by the Presence of Microvascular Retinal Signs at Visit 5 (2011-2013) and Audiometric Test Frequency Among 1458 Participants in the Atherosclerosis Risk in Communities Neurocognitive Study
Crude Better-Hearing Ear Thresholds at Visit 6 (2016-2017) by the Presence of Microvascular Retinal Signs at Visit 5 (2011-2013) and Audiometric Test Frequency Among 1458 Participants in the Atherosclerosis Risk in Communities Neurocognitive Study
Table 3.  Multivariable-Adjusted Association Between the Presence of Microvascular Retinal Signs at Visit 5 (2011-2013) and Hearing Impairment at Visit 6 (2016-2017) Among 1458 Participants in the Atherosclerosis Risk in Communities Neurocognitive Studya
Multivariable-Adjusted Association Between the Presence of Microvascular Retinal Signs at Visit 5 (2011-2013) and Hearing Impairment at Visit 6 (2016-2017) Among 1458 Participants in the Atherosclerosis Risk in Communities Neurocognitive Studya
Table 4.  Mean Differences in Better-Hearing Ear Thresholds at Visit 6 (2016-2017) by the Presence of Microvascular Retinal Signs at Visit 5 (2011-2013) and Audiometric Test Frequency Among 1458 Participants in the Atherosclerosis Risk in Communities Neurocognitive Study
Mean Differences in Better-Hearing Ear Thresholds at Visit 6 (2016-2017) by the Presence of Microvascular Retinal Signs at Visit 5 (2011-2013) and Audiometric Test Frequency Among 1458 Participants in the Atherosclerosis Risk in Communities Neurocognitive Study
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    Original Investigation
    December 26, 2019

    Association Between Microvascular Retinal Signs and Age-Related Hearing Loss in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)

    Author Affiliations
    • 1Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins School of Medicine, Baltimore, Maryland
    • 2Cochlear Center for Hearing and Public Health, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
    • 3Department of Biostatistics, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
    • 4Department of Ophthalmology, Johns Hopkins School of Medicine, Baltimore, Maryland
    • 5Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
    JAMA Otolaryngol Head Neck Surg. 2020;146(2):152-159. doi:10.1001/jamaoto.2019.3987
    Key Points

    Question  Is there an association between microvascular retinal signs and age-related hearing loss among older adults in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS)?

    Findings  In this cohort study of a subset of the ARIC-NCS participants who underwent retinal fundus photography in 2011-2013 and hearing assessment in 2016-2017 (n = 1458), there was an association between retinopathy and hearing loss in a small group of individuals without diabetes (n = 42) and in the total cohort.

    Meaning  Among individuals without diabetes, a diagnosis of retinopathy may potentially be used to identify those at higher risk for hearing loss.

    Abstract

    Importance  Given that age-related hearing loss is highly prevalent and treatable, understanding its causes may have implications for disease prevention.

    Objective  To investigate whether microvascular retinal signs are associated with age-related hearing loss attributable to a hypothesized underlying shared pathologic entity involving microvascular disease.

    Design, Setting, and Participants  The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) is a community-based prospective cohort study of 15 792 men and women aged 45 to 64 years at baseline. The ARIC-NCS participants returned for a fifth clinic visit in 2011-2013 and a sixth clinic visit in 2016-2017. Participants were recruited from 4 US communities (Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis suburbs, Minnesota). Participants included a subset of the ARIC-NCS cohort with complete covariate data who underwent retinal fundus photography at visit 5 (2011-2013) and completed hearing assessment at visit 6 (2016-2017) (N = 1458). Overall, 453 participants had diabetes; of those, 68 had retinopathy. Of 1005 participants without diabetes, 42 had retinopathy.

    Exposures  Microvascular retinal signs included retinopathy, arteriovenous (AV) nicking, and generalized arteriolar narrowing measured using the central retinal arteriolar equivalent (CRAE).

    Main Outcomes and Measures  Hearing was measured using the better-hearing ear pure-tone average (PTA) of air conduction speech thresholds (0.5, 1, 2, and 4 kHz). Multivariable-adjusted linear and ordered logistic regression was used to estimate the association between microvascular retinal signs and age-related hearing loss to describe the precision of the estimates and provide a plausible range for the true association.

    Results  After full adjustment among 1458 individuals in the analytic cohort (mean [SD] age, 76.1 [5.0] years [age range, 67-90 years]; 825 women [56.6%]; 285 black [19.5%]), the difference in PTA per dB hearing level in persons with and without retinopathy was 2.21 (95% CI, −0.22 to 4.63), suggesting that retinopathy is associated with poorer hearing, although the width of the 95% CI prevents definitive conclusions about the strength of the observed association. Restricting the analysis to participants without diabetes, the difference in PTA associated with retinopathy was even greater (4.14; 95% CI, 0.10-8.17 dB hearing level), but the large width of the 95% CI prevents definitive conclusions about the association. In analyses quantifying the mean differences in hearing thresholds at individual frequencies by retinopathy status, the estimates trended toward retinopathy being associated, contrary to expectation, with better high-frequency hearing. At 8 kHz, the estimated difference in hearing thresholds in persons with retinopathy vs those without was −4.24 (95% CI, −7.39 to −1.09).

    Conclusions and Relevance  In this population-based study, an association between the presence of microvascular retinal signs and hearing loss was observed, suggesting that retinopathy may have the potential to identify risk for hearing loss in persons without diabetes. The precision of these estimates is low; therefore, additional epidemiologic studies are needed to better define the degree of microvascular contributions to age-related hearing loss.

    Introduction

    Age-related hearing loss is an increasingly pervasive public health issue that is of national importance.1 Affecting almost two-thirds of adults 70 years and older in the United States,2 hearing loss prevalence is expected to double in the United States by 2060 to more than 73 million adults.3,4

    Hearing loss is a cause of communication difficulty and reduced hearing-related quality of life in older adults. Furthermore, in light of findings that suggest hearing impairment is a risk factor for various adverse health outcomes,5-8 including cognitive decline and dementia,9 understanding the pathogenesis of hearing loss may be important in developing effective methods for prevention of disease and functional decline in older adults. For example, hearing loss is a potentially modifiable dementia risk factor, and treatment of hearing loss in mid- to late life could possibly prevent 9% of dementia cases globally.10 In addition to cognitive decline, hearing loss is also independently associated with poorer physical functioning,5 limited mobility,6 increased falls,7 and greater depressive symptoms.8 Because only a minority of people with hearing loss are either diagnosed or treated,11 focusing efforts on hearing loss prevention could thus minimize possible negative downstream consequences associated with hearing loss.

    However, well-established risk factors for hearing loss, such as increasing age, male sex, and white race, are nonmodifiable.2 Vascular disease has known prevention strategies and is thought to contribute to hearing loss through a diminished cochlear blood supply. Microvascular disease in particular may have a role in the development of hearing loss, but this potential association has not been well investigated in epidemiologic studies.

    In addition to possible prevention opportunities, understanding risk factors for hearing loss is important because the mechanism underlying the association between hearing loss and cognitive decline and dementia9,12-15 remains uncertain. Given that retinal microvasculature (which may serve as an index of cerebral microvasculature16-18) is associated with cognitive decline and dementia,19-21 the association between hearing loss and cognitive decline could potentially be explained in part if they are both sequelae of an underlying microvascular etiology. However, previous studies on hearing loss and cognitive decline have not adjusted for this potential association.

    Retinal fundus photography is a noninvasive method of measuring changes in the cerebral microvasculature.16-18,22 It is possible that these changes may also extend to the cochlear microvasculature, which is not amenable to direct measurement in vivo. However, the number of studies investigating the role of microvascular pathology in hearing loss is limited.23,24 To measure the magnitude of the association between microvascular retinal signs and age-related hearing loss attributable to a hypothesized underlying shared pathology involving microvascular disease, we examined retinal data collected in the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) at visit 5 (2011-2013) and hearing data collected at visit 6 (2016-2017).

    Methods
    Study Population

    The ARIC-NCS is a community-based prospective cohort study of 15 792 men and women aged 45 to 64 years in 1987-1989 recruited from 4 US communities (Washington County, Maryland; Forsyth County, North Carolina; Jackson, Mississippi; and Minneapolis suburbs, Minnesota). In this cohort study, participants were examined every 3 years from 1987-1989 to 1996-1998 (visits 1-4). As part of the ARIC-NCS, participants returned for a fifth clinic visit in 2011-2013 and a sixth clinic visit in 2016-2017. During the fifth visit, a full neurocognitive battery was administered to all participants. Participants with evidence of cognitive impairment or decline were invited to stage 2 of the examination, as well as a random sample of the remaining participants.25 A retinal examination was administered as part of the stage 2 examination.

    Participants in this analysis included a subset of the ARIC-NCS cohort with complete covariate data who underwent retinal fundus photography at visit 5 (2011-2013) and completed hearing assessment at visit 6 (2016-2017) (n = 1458). From the initial cohort of 15 792 individuals, participants were excluded if they did not complete visit 5 (n = 9254) or did not have a gradable retinal fundus photograph at visit 5 (n = 3912). In addition, participants who did not complete visit 6 (n = 1081) or did not have complete audiometric data to calculate the better-hearing ear 4-frequency pure-tone average (PTA) (n = 41) were excluded. Participants were also excluded if race was other than black or white or if nonwhite from Washington County or Minneapolis field sites (n = 8) or if they were missing retinopathy severity level (n = 1), diabetes status (n = 12), or other covariate data (n = 25). The final analytic sample was 1458 for analyses of retinopathy, 1386 for analyses of arteriovenous (AV) nicking, and 1348 for analyses of the central retinal arteriolar equivalent (CRAE).

    Institutional review boards at each study site approved the ARIC-NCS. Written informed consent was obtained from all participants at each study visit.

    Hearing Assessment

    The primary outcome was hearing loss as measured with pure-tone conduction audiometry. Pure-tone audiometry was offered to participants at all field centers at visit 6 for frequencies 0.5, 1, 2, 4, 6, and 8 kHz. For the primary analysis, a PTA of air conduction speech thresholds at 0.5, 1, 2, and 4 kHz in the better-hearing ear was used as a continuous variable. In secondary analyses, we modeled the association of microvascular retinal signs with each individual audiometric test frequency. The PTA was categorized according to World Health Organization definitions for hearing loss (≤25 dB hearing level [HL] for normal hearing, 26-40 dB HL for mild hearing loss, and >40 dB HL for moderate or greater hearing loss).26

    Retinal Grading and Definitions

    Two retinal fundus photographs were taken of each eye at visit 5 using a digital camera. All photographs were graded by trained, certified graders at the Ocular Epidemiology Reading Center at the University of Wisconsin–Madison, who were masked to participant characteristics, including diabetes status and hypertension status. The retinal variables of interest included measures associated with loss of vascular integrity (eg, retinopathy) and measures associated with changes in the arteriolar wall (AV nicking and generalized arteriolar narrowing as measured by the CRAE).

    Retinopathy was defined as the definite presence of at least 1 of the following lesions: retinal microaneurysms, soft exudates, hard exudates, retinal hemorrhages, macular edema, intraretinal microvascular abnormalities, venous beading, new vessels, vitreous hemorrhage, disc swelling, or laser photocoagulation scars. Retinopathy was defined using the Arlie House classification and was classified as none (retinopathy severity level, <14), mild (14-34), moderate (35-46), or severe (≥47).27 Worse-eye retinopathy level was used for analysis and was categorized as none vs mild or greater because the number of participants with moderate or severe retinopathy was too small to model as its own category.

    The AV nicking was defined as absent, definite, or questionable based on the number and grading of at least 1 venous blood column that was tapered on both sides of its crossing underneath an arteriole.27 For the present analysis, AV nicking was considered to be present when given a grade of definite.

    Generalized arteriolar narrowing was evaluated using enhanced digital images and image processing software. Arteriolar diameters within a prespecified zone surrounding the optic nerve were combined and quantified as the CRAE using the following formula to adjust for branching27:

    Image description not available.

    where Wc indicates the caliber of the trunk vessel; Wa, the caliber of the smaller branch; and Wb, the caliber of the larger branch. The presence of generalized narrowing was defined as the lowest 25th percentile of the CRAE.21

    Definition of Other Variables

    Demographic information was collected at visit 1. This included birth date (to calculate age in years), sex, race, educational level (defined as less than high school vs high school or greater for analysis), and study site.

    Potential vascular confounding disease and health behavior covariates collected at visit 5 included body mass index (calculated as weight in kilograms divided by height in meters squared) and self-reported cigarette smoking status (never, former, or current). Hypertension was defined as diastolic blood pressure of at least 90 mm Hg, systolic blood pressure of at least 140 mm Hg, or antihypertensive medication use. Diabetes was considered present if fasting blood glucose level was at least 126 mg/dL, nonfasting blood glucose level was at least 200 mg/dL (to convert glucose level to millimoles per liter, multiply by 0.0555), or the participant self-reported a physician diagnosis of diabetes or medication use for diabetes. Noise exposure was collected at visit 6 and was considered present if the participant self-reported ever being exposed to 1 or more of the following: (1) firearm use (target shooting, hunting, military, job, or other), (2) a job with very loud sounds or noise for more than 10 hours per week, or (3) very loud noise or music more than 10 hours per week outside of a job.

    Statistical Analysis

    Multivariable-adjusted linear and ordinal logistic regression was used to estimate the magnitude of the association between microvascular retinal signs with PTA and hearing loss categories, respectively. Because the proportional odds assumption was not met for the ordinal logistic regression, we modeled the magnitude of the association between microvascular retinal signs and level of hearing loss (none, mild, or moderate or greater) using a generalized ordered logistic model with the gologit2 package.28 Analyses using sampling weights to account for visit 5 selection factors for retinal fundus photography (so that inference from results is generalizable to the entire ARIC-NCS population) were similar and inference unchanged, so the unweighted results are presented.

    Linear mixed models were used to estimate the magnitude of the association between microvascular retinal signs and hearing thresholds at each audiometric test frequency (0.5-8 kHz), accounting for the correlation of thresholds within an individual. An interaction term between audiometric test frequency and microvascular retinal signs status was included in the model to test if the association between audiometric thresholds and microvascular retinal signs varied by audiometric test frequency.

    We adjusted for potential demographic confounders, including age, sex, educational level, and (because race is so tightly connected to study site in this cohort) a combination variable incorporating race and study site (Washington County whites, Forsyth blacks, Forsyth whites, Jackson blacks, and Minneapolis whites). The models also adjusted for potential confounders measured at the time when the retinal fundus photographs were taken, including body mass index, hypertension status, diabetes status (in nonstratified models), self-reported cigarette smoking status (never, former, or current), and noise exposure. Stratification by diabetes status was also considered in light of the substantial vascular implications of diabetes on microvascular retinal signs. Analyses were performed using Stata, version 15, statistical software (StataCorp LLC).

    Results

    Of the 1458 individuals in the analytic cohort, 83 (5.7%) had mild retinopathy and 27 (1.9%) had moderate or greater retinopathy for a total of 110 individuals (7.5%) with retinopathy at visit 5 (Table 1). The mean (SD) age was 76.1 (5.0) years [age range, 67-90 years], which was similar across participants with and without retinopathy; 825 were female (56.6%), and 285 were black (19.5%). On average, participants with at least mild (vs no) retinopathy were more likely to be female (65.5% [72 of 110] vs 55.9% [753 of 1348]) and to have greater body mass index (mean [SD], 30.0 [6.3] vs 28.7 [5.6]). Sixty-two percent (68 of 110) of participants with mild or greater retinopathy had diabetes compared with only 28.6% (385 of 1348) of those without retinopathy.

    In the overall sample, crude better-hearing ear thresholds increased with higher frequencies, ranging from a mean (SD) of 24.7 (12.7) dB HL at 0.5 kHz to 61.9 (19.0) dB HL at 8 kHz. Similar trends were seen in participants with retinopathy, AV nicking, and CRAE (Table 2).

    After full adjustment, the difference in PTA per dB HL in persons with vs without retinopathy was 2.21 (95% CI, −0.22 to 4.63), suggesting that retinopathy is associated with poorer hearing, although the width of the 95% CI prevents definitive conclusions about the strength of the observed association (Table 3). When hearing loss was categorized as mild vs moderate or greater, the strength of the association between retinopathy and hearing loss was greater for more severe levels of hearing loss (odds ratio [OR] for microvascular retinal signs with mild hearing loss, 1.30; 95% CI, 0.79-2.13; OR for moderate or greater hearing loss, 1.53; 95% CI, 0.98-2.39), but again the imprecision of the estimates prevents definitive conclusions (Table 3).

    Uncertainty surrounding the estimated associations for AV nicking and hearing, and for CRAE and hearing, prevents firm conclusions. However, the estimates suggested a protective association (ie, the presence of microvascular retinal signs associated with better hearing) (Table 3).

    Overall, 453 participants had diabetes; of those, 68 had retinopathy. Of 1005 participants without diabetes, 42 had retinopathy. Among participants with diabetes, the estimated association between retinopathy and hearing was 2.53 (95% CI, −0.83 to 5.90). However, restricting the analysis to participants without diabetes, the difference in PTA per dB HL associated with retinopathy (participants with vs without retinopathy) was even greater (4.14; 95% CI, 0.10-8.17), but the large width of the 95% CI prevents definitive conclusions about the association (Figure).

    In analyses quantifying the mean differences in hearing thresholds at individual frequencies by retinopathy status (Table 4), the estimates trended toward retinopathy being associated with better high-frequency hearing, contrary to our expectation. At 8 kHz, the estimated difference in hearing thresholds in persons with vs without retinopathy was −4.24 (95% CI, −7.39 to −1.09). For AV nicking, the estimates trended toward better hearing at low frequencies and worse hearing at high frequencies. The estimated difference in hearing threshold for AV nicking was 3.10 (95% CI, 0.01-6.19) at 8 kHz and 2.41 (95% CI, −0.61 to 5.43) at 6 kHz. For the CRAE, there was no observed association between individual audiometric test frequency and the mean differences in hearing thresholds.

    Discussion

    In this community-based cohort study of adults after full adjustment for age, demographics, and clinical factors, the presence of retinopathy was associated with hearing loss. The magnitude of the hearing loss associated with the presence of retinopathy was greater among participants without diabetes. Because of the small number of events and participants with specific clinical conditions, the estimates of the magnitude of the hearing loss were imprecise, so definitive conclusions are not possible. The magnitude of hearing loss observed in the present study is clinically modest in light of previous findings of a mean hearing loss progression of 1.35 dB per year in older adults.29 For perspective, regarding a difference in PTA that is associated with clinically meaningful outcomes, a 10-dB HL increase was associated with a 14% increase in risk of dementia in the Health, Aging, and Body Composition (Health ABC) Study.30 Inference must also be tempered given the small number of participants without diabetes who had retinopathy (n = 42). Neither AV nicking nor CRAE was associated with hearing loss in the audiometric test frequencies. Unexpectedly, when examining hearing thresholds at individual frequencies by retinopathy status, the estimates suggested that retinopathy was associated with better high-frequency hearing. The AV nicking showed the opposite trend, trending toward better hearing at low frequencies and worse hearing at high frequencies. However, the imprecision of the estimates prevents definitive conclusions. For the CRAE, there was no observed association with hearing loss. A possible explanation for the lack of definitive conclusions is that AV nicking and CRAE are considered to indicate less severe microvascular damage compared with retinopathy.31

    Few epidemiologic studies investigating the association between microvascular signs and age-related hearing loss are available for direct comparison. A prior cross-sectional, population-based study23 found that retinopathy was associated with hearing loss exceeding a 40-dB HL in women (OR, 2.10; 95% CI, 1.09-4.06) but not in men (OR, 0.61; 95% CI, 0.27-1.37). In line with the present study, retinal variables included retinopathy, AV nicking, focal arteriolar narrowing, and retinal vessel caliber, with hearing loss measured using PTA of air conduction speech thresholds at 0.5, 1, 2, and 4 kHz in the better-hearing ear. Notably, the strongest association between retinal microvascular signs and hearing loss was seen at lower frequencies (0.25-1 kHz) (OR, 3.00; 95% CI, 1.25-7.19) but was absent at higher frequencies (OR, 0.71; 95% CI, 0.43-1.18).23 More recently, a retrospective study among 175 veterans32 found that diabetic retinopathy was associated with hearing loss severity in both ears after adjusting for glycated hemoglobin level and creatinine level. The current literature is limited by investigations of small sample sizes and few outcome events. For example, a study33 of 33 participants with diabetic retinopathy did not find a difference in hearing thresholds between a retinopathy group and a control group, highlighting the potential for false-negative results given the small sample size of the study. Although our findings support the potential role of microvascular disease in hearing loss suggested by previous studies, the currently limited epidemiologic evidence base highlights the need for further prospective studies examining this association.

    The association of hearing loss with diseases such as diabetes suggests that they may share a common microvascular pathology.34 Microvascular disease may result in a diminished blood supply to the striae vascularis, which is the metabolic driver of cochlear function.35 Given that retinopathy is a marker of microvascular disease and has been associated with cerebral microvascular health,36 the consequences of microvascular disease may extend to the cochlea, and microvascular retinal signs may offer a window to examining these changes. This hypothesis is further supported by previous animal models documenting diabetic microangiopathy in the inner ear, with damage to the capillary base of the cochlea potentially causing high-frequency hearing loss.32,37

    Based on the proposed biological mechanism of hearing loss, we hypothesized that retinal microvasculature may serve as a proxy for general cerebral microvascular health, extending to the cochlear microvasculature. Given that the cochlear microvasculature cannot be directly measured in vivo, retinal imaging may offer an alternative using simple instrumentation. Although previous studies16-18 have supported the use of retinal microvasculature as a window into general cerebral microvascular health, and we found an association between retinopathy and hearing loss in persons without diabetes, microvascular retinal signs may not adequately reflect all microvascular changes in the cochlea. We recognize that the imprecision of the estimated association prevents us from making definitive conclusions about the likely true difference. The audiometric test frequency–specific trends seen in those with retinopathy (poorer low frequencies) and AV nicking (poorer high frequencies) is a novel finding of this study. Although cochlear microcirculation is poorly understood, the pathogenesis of retinopathy suggests reduced blood flow from alterations of the small blood vessels stemming from the central retinal artery.38 This model may parallel the metabolic presbycusis model of hearing loss characterized by low-frequency hearing loss from reduced blood supply to the lateral wall, particularly the stria vascularis.39,40 Conversely, AV nicking corresponds to changes in the arteriolar and venular junctions and could reflect changes in a specific blood vessel, such as the vestibulocochlear artery, which supplies the basal end of the cochlea that is responsible for high-frequency signal encoding.41

    Strengths and Limitations

    Strengths of our study include a large sample size, biracial population, and 5-year prospective follow-up at multiple sites. To date, previous studies on this topic have only been cross-sectional or retrospective in nature. This study also has limitations. Although this study was a large epidemiologic investigation, the small number of events and participants with specific clinical conditions (eg, diabetes) led to wide 95% CIs around the estimated association, which in turn prevented us from making definitive conclusions regarding the observed associations. An additional limitation of this study is that we did not include focal arteriolar narrowing as a retinal variable because of the small number of participants with this condition in the analytic cohort. Given that hearing loss was only measured at visit 6, we were unable to assess the progression of hearing loss over time. Although retinal fundus photographs were taken only in a subset of participants, we used survey weights to account for generalizability to the entire ARIC-NCS cohort and found similar estimates and inferences. In addition, although the better-hearing ear was used for analysis, worse-eye microvascular retinal signs were used in keeping with prior work in this cohort.42 However, inferences were the same when we repeated the analysis using worse-ear hearing.

    Conclusions

    In this community-based cohort study, we identified an association between age-related hearing loss and retinopathy, but the small number of participants in certain clinical categories and outcome events prevented us from making definitive conclusions. Therefore, retinopathy may have the potential to identify a group at higher risk for age-related hearing loss, particularly among individuals without diabetes. Given that age-related hearing loss is a highly prevalent and modifiable risk factor for dementia and other adverse health outcomes,10 further epidemiologic studies are needed to better characterize microvascular contributions to age-related hearing loss.

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    Article Information

    Accepted for Publication: October 25, 2019.

    Corresponding Author: Jennifer A. Deal, PhD, Department of Otolaryngology–Head and Neck Surgery, Johns Hopkins School of Medicine, 2024 E Monument St, Ste 2-700, Baltimore, MD 21205 (jdeal1@jhu.edu).

    Published Online: December 26, 2019. doi:10.1001/jamaoto.2019.3987

    Author Contributions: Dr Deal had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

    Concept and design: Reed, Abraham, Deal.

    Acquisition, analysis, or interpretation of data: All authors.

    Drafting of the manuscript: Kim, Betz.

    Critical revision of the manuscript for important intellectual content: Reed, Betz, Abraham, Lee, Sharrett, Lin, Deal.

    Statistical analysis: Kim, Betz, Abraham, Lee, Deal.

    Obtained funding: Lin, Deal.

    Supervision: Abraham, Lin, Deal.

    Conflict of Interest Disclosures: Dr Reed reported being a scientific advisory board member for SHOEBOX Ltd. Dr Abraham reported receiving grants from the National Institutes of Health. Dr Lin reports being a consultant to Amplifon, receiving speaker honoraria from Caption Call, and receiving sponsored travel from Cochlear Ltd. No other disclosures were reported.

    Funding/Support: The Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) has been funded in whole or in part by federal funds from the National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health (NIH), and Department of Health and Human Services (contracts HHSN268201700001I, HHSN268201700002I, HHSN268201700003I, HHSN268201700005I, and HHSN268201700004I). Neurocognitive data are collected under contracts U012U01HL096812, 2U01HL096814, 2U01HL096899, 2U01HL096902, and 2U01HL096917 from the NIH (NHLBI, National Institute of Neurological Disorders and Stroke, National Institute on Aging [NIA], and National Institute on Deafness and Other Communication Disorders), and previous brain magnetic resonance imaging examinations were funded by grant R01-HL70825 from the NHLBI. Dr Deal was supported by grant K01AG054693 from the NIH/NIA.

    Role of the Funder/Sponsor: The funding sources had no role in the design and conduct of the study; collection, management, analysis, and interpretation of the data; preparation, review, or approval of the manuscript; and decision to submit the manuscript for publication.

    Additional Contributions: We thank the staff and participants of the ARIC-NCS for their important contributions.

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