Rethinking race as a risk factor for glaucoma

M. Roy Wilson, MD, MS, developed this article based on the 2025 Shaffer-Hetherington-Hoskins Lecture, which he delivered at the Glaucoma 360 meeting in San Francisco, California. Image credit: ©wavebreak3 – stock.adobe.com

More than three decades ago, Harvard historian Evelyn Brooks Higginbotham quipped, “When we talk about the concept of race, most people believe that they know it when they see it but arrive at nothing short of confusion when pressed to define it.”¹ Although there exists widespread consensus among the scientific community that race is a sociopolitical construct that has limited biologic significance, most of society believes it to be biologically real. Even among biomedical scientists, misunderstandings persist regarding the appropriate, and inappropriate, use of race and ethnicity in medical research and medicine. This was the topic of the 2025 Shaffer-Hetherington-Hoskins Lecture I delivered at the Glaucoma 360 meeting in San Francisco, California, in January 2025.

In October of 2024, the National Academies of Sciences, Engineering, and Medicine released a consensus study report on the use and misuse of race in biomedical research.² Drawing heavily on this report, in my lecture, I defined race in the current context of 2025, deconstructed conflated terms of race and genetic ancestry, and explored the role of role of race in society and its impact on health and disease. I noted that race and ethnicity often serve as a proxy for the true variable of interest and urged that factors more directly associated with health outcomes and disparities be explored.

Completed in 2003, the Human Genome Project demonstrated that human populations do not form distinct genetic categories; rather, genetic variation is continuous and overlaps racial and ethnic groups. There exists so much ambiguity between races, and so much variation within them, that two people of European descent (e.g., James Watson and Craig Venter, two of the first individuals to have their genome mapped) may be more genetically similar to an Asian person (Kim Seong-jin, the first Korean to have his genome mapped ) than they are to each other.³ The Human Genome Project’s finding that all humans are more than 99% genetically identical has, in the opinion of some, obviated the term race.

It is time to move beyond relying on race and search for more precise causes, including potential biomarkers, underpinning disparities.

Yet, race continues to play an outsize role in medicine, particularly in the assessment of risk for health outcomes. Consider, for example, variations in the CYP2C9 gene, which codes for a crucial drug-metabolising enzyme. Genetic polymorphisms in this gene lead to different levels of enzyme activity in individuals, potentially impacting how they respond to medications that are metabolised by this enzyme. Since level of enzyme activity is correlated to racial groups, with Asian populations being poor metabolisers and White populations being extensive metabolisers, race is often used to assess the risk of adverse drug reactions in the clinical setting. However, race is imprecise and relying on it to make such a determination can be problematic: Craig Venter, a White man, is an extensive metaboliser but James Watson, who is also White, is a poor/intermediate metaboliser.⁴

Another example is when sickle cell disease is viewed as a disease of Black people rather than as a disease endemic to populations concurrently at risk for malaria.⁵ While it is true that sickle disease disproportionately impacts Black individuals, the global distribution of sickle hemoglobin mirrors that of malaria, and the selective advantage of this blood disorder in protecting against malaria in heterozygotes is the important factor in determining who gets the disease. Thus the correlation between Black populations and sickle cell is confounded by genetic ancestry and geography, constructs related to but different from constructs of race and ethnicity.

Race and ethnicity categories used in biomedical research and clinical practice are broad and less precise than ancestry. Racial and ethnic differences in risk for disease and response to treatments are partially related to genetic and epigenetic variants. These polymorphisms can be mapped on the non-recombining region of the Y chromosome to trace paternal ancestry and on mitochondrial DNA to trace maternal lines, and geographic regions where a specific variation originated and how it spread can be inferred. Using ancestry as a variable can thus capture and explain a portion of the biologic variation seen between and within groups.

Race is often used clinically to assess risk of disease and may sometimes be helpful, particularly in considering a differential diagnosis. Some scientists object to this practice, concerned that doing so may falsely infer causality. Not withstanding what may be a matter of semantics—a factor does not have to be causal to be considered a risk factor—it is nonetheless time to move beyond relying on race and search for more precise causes, including potential biomarkers, underpinning disparities. For example, race has long been considered a risk factor for glaucoma, with Black individuals bearing a disproportionate burden of the disease. An unexpected finding from the landmark Ocular Hypertension Treatment Study was that having a thin central cornea was associated with increased risk of developing glaucoma.⁶ Further, Black individuals had thinner central corneal thickness (CCT) than White individuals, and the effect of race was weakened when CCT was controlled for in the analyses. Thus, researchers and clinicians should examine other concepts and factors (biological, social, environmental) that have more direct effects on health instead of relying on race and ethnicity as shorthand.

At the same time, race is not irrelevant in medicine. Despite its limited usefulness in biology or genetics, race is an important consideration in our society. Socially constructed as a hierarchal human-grouping system, it continues to influence the distribution of societal resources and opportunities. Though not biological, race shapes social realities and lived experiences. These, in turn, have downstream impacts on health outcomes. These factors, commonly referred to as social determinants of health (SDOH), overlap with race.

The data on SDOH and glaucoma has historically been sparse, but recent interest in SDOH has generated a number of studies on the association of various SDOH measures and glaucoma testing, prevalence and severity. SDOH are the conditions in the environments where people live, learn, work, play and age that affect a wide range of health, functioning and quality-of-life outcomes. More common SDOH include healthcare access and quality, education, income, food security and housing.

The increased focus on social determinants of health, rather than on race per se, is a welcomed development.

Elam and colleagues examined the likelihood of obtaining visual fields, fundus photographs, and other optic imaging in White, Black, and Latino patients who had Medicaid insurance versus commercial health insurance.⁷ Overall, Medicaid patients, who are generally poorer than those with commercial insurance, were less likely to receive any of these glaucoma evaluations. For each type of evaluation, Black patients were less likely to be tested than White or Latino patients, underscoring the overlap between race and wealth.

For his PhD thesis in epidemiology, Ken Kitayama, a resident at the Jules Stein Eye Institute of UCLA, examined the influence of socio-economic status (SES) and race on incisional glaucoma surgical outcomes.⁸ All racially minoritised groups had an increased risk of surgical failure compared to non-Latinx White patients, ranging from 18% in Asian patients to 32% in patients of "other race and ethnicity." SES accounted for varying proportions of the total disparity in outcomes, ranging from 22% of the disparity in Asian patients to 54% in Black patients. When SES was artificially assigned as non-low for all patients, varying amounts of the surgical outcome disparities were eliminated, ranging from 0% for Asian patients and 97% for Black patients. SES thus mediates racial and ethnic disparities in incisional glaucoma surgical outcomes.

The association between social vulnerability index (SVI) and glaucoma has been explored in several recently published studies. SVI is a place-based index, database and mapping application designed to identify and quantify communities experiencing social vulnerability. In a cross-sectional study of data extracted from a large electronic health record database, Swaminathan and Medeiros examined socioeconomic disparities in glaucoma severity at initial diagnosis and found that higher SVI scores (higher vulnerability) were associated with more severe disease at presentation.⁹ Other factors associated with severity of disease included Black race, Hispanic ethnicity, and non-commercial insurance or uninsured status, again underscoring the intersection of race, ethnicity, and measures of SDOH.

In a retrospective longitudinal study by Swaminathan, Medeiros and Gedde, living in areas associated with greater social vulnerability was found to be a risk factor for developing glaucoma-related severe visual impairment or blindness.¹⁰

Using a similar study design, Almidani and colleagues found a significant link between increased SVI scores and worse functional visual field (VF) loss at baseline, higher rates of structural worsening over time (as per optical coherence tomography) and higher VF variability.¹¹ The study also found that the effect of IOP on retinal nerve fibre layer loss was more pronounced in individuals with higher SVI.

The construct of race is complex and its relevance in medicine and biomedical research continues to evolve. The increased focus on SDOH, rather than on race per se, is a welcomed development in this evolution. Race as a variable will become increasingly less relevant in medicine as the era of big data and personalised medicine will shift focus of disease risk at the population level to the individual level. Large-scale analyses will ideally incorporate myriad other variables, including genomics, socio-environmental exposures, genetic ancestry, personal habits and SDOH, among others.

Ophthalmologists must be appropriately cautious in using race and ethnicity in their clinical decision-making. Yes, race is a risk factor for glaucoma and for many other diseases. But these other factors—particularly SDOH—are really what matters.

References

1. Higginbotham EB. African-American women's history and the metalanguage of race. Signs. 1992;17(2):251-274.

2. Wilson MR, Beachy SH, Schumm SN. Rethinking race and ethnicity in biomedical research: consensus study report. National Academies of Sciences, Engineering, and Medicine. National Academies Press. 2025.

3. Schaare D, Abenavoli L, Boccuto L. Race: how the post-genomic era has unmasked a misconception promoted by healthcare. Medicina (Kaunas). 2023:59 (5):861.

4. Callaway E. Watson vs Venter: The Loser is Race-based Medicine. New Scientist. 2008.

5. Winny A. How Sickle Cell Disease and Malaria Defined Evolution. Global Health Now. 2004.

6. Brandt JD, Beiser JA, Kass MA, Gordon MO. Central Corneal Thickness in the Ocular Hypertension Treatment Study (OHTS). Ophthalmology. 2001;108: 1779-1788.

7. Elam AR, Andrews C, Musch DC, et al. Large Disparities in Receipt of Glaucoma Care between Enrollees in Medicaid and Those with Commercial Health Insurance. Ophthalmology. 2017; 124: 1442-1448.

8. Kitayama K. Racial and Ethnic Disparities in Glaucoma Surgery in the United States. Doctoral thesis. University of California, Los Angeles; 2023.

9. Swaminathan SS, Medeiros FA. Socioeconomic Disparities in Glaucoma Severity at Initial Diagnosis: A Nationwide Electronic Health Record Cohort Analysis. Am J Ophthalmol. 2024; 263: 50-60.

10. Swaminathan SS, Medeiros FA, Gedde SJ. Impact of Social Vulnerability Index on the Development of Severe Visual Impairment or Blindness from Glaucoma. Am J Ophthalmol. 2024; 267: 172-181.

11. Almidani L, Bradley C, Herbert P, et al. The Impact of Social Vulnerability on Structural and Functional Glaucoma Severity, Worsening, and Variability. Ophthalmology Glaucoma. 2024; 7: 380-390.

M. Roy Wilson, MD, MS | E: mrw@wayne.edu

Wilson is president emeritus and the distinguished professor of opthamology at Wayne State University in Detroit, Michigan, where he served as president from 2012 to 2023. He is a member of the National Academy of Medicine.