Elevated allostatic load, which indicates greater physiological wear and tear due to chronic stress, can precede glaucoma by several years, study finds. Yoga and other forms of relaxation are among the interventions recommended to mitigate such effects. Photo: Getty Images. Click image to enlarge.

The leading modifiable risk factor for glaucoma is intraocular pressure, though recent research suggests that certain systemic and modifiable lifestyle factors, including chronic stress, may also play a significant role in its pathogenesis. One new study, published last week in American Journal of Ophthalmology, aimed to evaluate the relationship between glaucoma and allostatic load (AL), a framework used to quantify the physiologic effects of chronic stress via measurements of systemic biomarkers. It found that higher AL scores were significantly associated with a diagnosis of glaucoma, and it also revealed substantial racial and ethnic disparities; higher AL scores more significantly predicted glaucoma in Black and Hispanic populations compared to non-Hispanic Whites.

Study participants were drawn from the National Institutes of Health All of Us Research Program—“a nationwide, longitudinal research initiative with emphasis on recruiting populations underrepresented in biomedical research,” the authors explained in their paper. They identified 349 (16.1%) glaucoma cases and 1,819 (83.9%) controls (52.7% female, 2.2% Asian, 10.7% Black, 10.0% Hispanic and 72.5% non-Hispanic white) with complete AL biomarker data between December 1984 and June 2022. The researchers calculated AL scores using a measure called the adapted Seeman AL scale, which consists of 10 systemic biomarkers: body mass index, systolic blood pressure, diastolic blood pressure, total cholesterol, triglycerides, glomerular filtration rate, albumin, C-reactive protein and homocysteine.

At the earliest measured AL score, taken a median of 6.4 years before diagnosis, those with glaucoma showed higher AL scores than controls (scores of three vs. two, respectively). Through multivariable analysis, it was found that a higher AL score increased the risk of glaucoma by 9% per each point increment.

Subgroup analysis also revealed that higher AL scores increased the risk of primary open-angle glaucoma by 11%, though no significant association was found with primary angle-closure glaucoma.

“Establishing the relationship between AL and glaucoma could help contextualize and advance research advocating for stress-reducing, lifestyle interventions among patients with or at risk for glaucoma,” the researchers explained in their AJO paper. “For example,” they wrote, “previous work proposed the benefit of relaxation-based exercises for mitigating glaucoma risk, whether directly through AL score reduction or indirectly through interactions with other lifestyle modifications.” Some of these exercises that may lower AL include physical therapy, breathing techniques, aerobic exercise and yoga, the research team noted, adding that prior studies have also “reported associations between mindfulness-based relaxation exercises and reductions in serum measurements of stress-related biomarkers, such as cortisol, TNF alpha and IL-6.” However, they caution, “the effectiveness of these interventions requires further validation in real-world practice settings.”

In their paper, the researchers also discussed the racial and ethnic disparities the data highlighted. It revealed that being of Black race increased the glaucoma risk 2.58 times, and Hispanic ethnicity 2.12 times. The AL score was found to partly mediate the increased risk of glaucoma in Black and Hispanic populations by 7.5% and 5.0%, respectively, compared to non-Hispanic white individuals. Furthermore, despite controlling for race and ethnicity, AL score remained independently associated with glaucoma, suggesting other influencing factors likely tied to socioeconomic conditions, such as neighborhood deprivation, food and housing insecurity and discrimination, further affect glaucoma risk among these groups.

“Differences in glaucoma prevalence have been primarily attributed to non-modifiable genetic or biometric factors, and differences in glaucoma outcomes have been primarily attributed to modifiable factors, including healthcare access, treatment adherence and social determinants of health,” the study authors wrote in their paper. “Our findings provide a possible link between environmental factors and glaucoma risk that suggests racial and ethnic differences in glaucoma prevalence may be partially modifiable by addressing disparities in allostatic load.”

There are several limitations of this study, the most relevant one being the dependence on EHR codes that poses the risk of some glaucoma cases being incorrectly diagnosed or coded. Nonetheless, given the growing body of evidence to suggest a relationship between chronic stress and glaucoma, prospective studies are warranted to further explore the role of the lifestyle factor in the pathogenesis of the progressive ocular disease.