Findings from a recent study published in Scientific Reports shed light on the potential clinical utility of retinal biomarkers for early detection of hearing loss (HL).
Give me some background.
HL is a prevalent health issue, with a 2024 World Health Organization report indicating that ~430 million individuals globally experience HL—making up more than 5% of the world’s population.
- By 2050 this number is expected to reach 2.45 billion.
As such: There is a significant global burden of HL and an urgent need for early detection and intervention to improve quality of life and health for impacted individuals.
Further: Recent studies have suggested that microvascular pathology in the stria vascularis—a key structure in the cochlea—may contribute to HL.
- Why: Disruption of cochlea homeostasis that adversely affects the functionality of sensory hair cells and leads to progressive HL.
Now bring in retinal microvasculature.
Due to the anatomical and physiological similarities between retinal microvasculature and other body microvessels, it is frequently used as a surrogate marker for systemic microcirculation in various diseases, including:
Moreover: Previous studies have identified a correlation between retinal microvascular abnormalities and HL, indicating that common vascular pathologies may affect the blood flow of both the retina and the cochlea, potentially contributing to HL in older individuals.
Now talk about the study.
In this retrospective cross-sectional study, investigators reviewed data from 575 participants who underwent ophthalmological and audiological assessments at the Shanghai Health and Medical Center in Wuxi, China between October 2014 and January 2024.
What they evaluated:
- Retinal vascular fractal dimension (FD) was measured using nonmydriatic fundus photography and analyzed using Singapore I Vessel Assessment software
- Hearing thresholds were assessed by air-conduction pure-tone audiometry, with the high Fletcher index (hFI) used to evaluate hearing acuity
Note: Retinal FD comprehensively evaluates vascular branching intricacy and density, with a reduced FD value indicating a less dense vascular network (potentially reflecting significant microvascular changes associated with systemic illnesses).
And the findings?
Higher retinal FD values were significantly associated with better hearing acuity.
- Specifically: Each standard deviation (SD) increase in arteriolar FD (FDa) was correlated with a 2.85 dB decrease in the hearing threshold at 1 kHz (β = -2.85, 95% confidence interval [CI]: -4.47 to -1.23, p = < 0.001)
Further: Each 1-SD increase in venular FD (FDv) was correlated with a 2.61 dB decrease at 2 kHz (β = -2.61, 95% CI: -4.42 to -0.80, p = 0.005).
- Note: β determines whether the independent variable (retinal FD) has an effect on the dependent variable (hearing threshold), where:
- β = 0 if the independent variable has no effect on the dependent variable
- β < 0 means there is a negative correlation
- β > 0 indicates a positive correlation
Meaning: Higher values (i.e., a denser vascular network) for any of the three FD measures (FDa, FDv, and FD) were associated with better hearing acuity, as reflected in lower hearing thresholds.
Expert opinion?
The study authors highlighted two hypotheses for the potential mechanisms behind these observed associations, such as:
- A deficit in neurovascular cupping: Pericytes along capillary walls regulate vessel tone and local blood flow in response to neuronal activity, thus loss or dysfunction of these pericytes can impair neurovascular coupling and reduce oxygen delivery.
- Thus: A similar mechanism could exist in the cochlea, where pericytes are densely distributed and disruption of pericyte-mediated regulation in the cochlear microvasculature may result in transient ischemia, potentially accelerating HL.
- A deficit in glymphatic-like clearance: The cochlea has been reported to contain a glymphatic-like system that removes metabolic waste via paravascular fluid transport.
- Hence: As indicated by lower retinal FD, a reduction in systemic microvascular complexity may compromise this clearance mechanism, leading to toxin accumulation and damage to auditory structures.
Any limitations to note?
A few … these included:
- The cross-sectional design limited the ability to establish causal relationships between retinal vascular changes and age-related HL
- Residual confounding variables, such as nutrition, physical activity, and medication usage may have persisted despite adjustments for major confounders
- The absence of bone conduction audiometry limited the capacity to differentiate between sensorineural and conductive HL
- While the observed effect sizes were small, even modest associations may hold clinical relevance at the population level
Take home.
These findings suggest that retinal FD may serve as a noninvasive biomarker for early detection of HL and could assist in the development of preventative strategies.
Moving forward: Longitudinal studies are warranted to establish causation and determine whether retinal microvascular changes occur before HL and should incorporate bone conduction audiometry to discern between sensorineural and conductive HL.